Exploring the Relationship Between Morphea and Malignancy: A Decade-Long Single- Center Study of 204 Patients

Exploring the Relationship Between Morphea and Malignancy: A Decade-Long Single- Center Study of 204 Patients | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Exploring the Relationship Between Morphea and Malignancy: A Decade-Long Single- Center Study of 204 Patients Keren Lyakhovitsky, Giovanni Damiani, Daniel Mimouni, Anna Aronovich This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4772917/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 8 You are reading this latest preprint version Abstract The association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7 ± 20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7 ± 15.1 years vs. 50.3 ± 20 years, p < 0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p = 0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study highlights a bidirectional link between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Vigilant monitoring for malignancy, early detection, and effective management strategies are crucial for improving outcomes in morphea patients. Localized scleroderma morphea mortality malignancy neoplasms Introduction Morphea (localized scleroderma), a rare, chronic inflammatory connective tissue disorder that manifests with inflammation and fibrosis affecting the skin and underlying soft tissue, with possible extension to adjacent structures (e.g., lungs, gastrointestinal tract) 1 . Despite being primary recognized as a condition confined to the skin, some subtypes of morphea exhibit extra-cutaneous manifestations, involving the musculoskeletal and central nervous systems 1 . The annual incidence of morphea varies from 4 to 27 new cases per million, with approximately two-thirds occurring in adults 1 . There are two incidence peaks: between ages 2 to 14 and in the 5th decade of life 1 . Morphea predominantly affects females, with a female-to-male ratio of 4:1, and is most common among Caucasians, followed by Hispanics and Latin Americans 2 . The five main clinical types of morphea include limited, generalized, linear, deep, and mixed, with plaque-type and generalized morphea being prevalent in adults, while the linear form is more common in children 3 . Morphea's pathogenesis involves a complex interplay of genetic predisposition, vascular dysfunction, environmental triggers, and autoimmune dysregulation 1 . Possible triggers for morphea include cancer treatments like radiotherapy, chemotherapy, and immunotherapy 1 . It unfolds in three phases: an initial inflammatory phase, a fibrotic phase marked by excessive collagen deposition, and an atrophic phase. Th1/Th2 imbalance and the upregulation of profibrotic pathways are key factors, with an initial proinflammatory Th1/Th17-associated cytokine response followed by a shift towards Th2 cytokines during disease progression 4 . Diagnosing morphea relies primarily on clinical features, with skin biopsy reserved for atypical cases. Treatment options vary based on disease severity 5 . Topical corticosteroids are used for limited disease, while systemic corticosteroids and methotrexate are most commonly utilized in more extensive cases. Additional options for topical therapies include calcineurin inhibitors, vitamin D derivatives, and imiquimod 6 . For more severe cases, systemic treatment options encompass mycophenolate mophetil, hydroxychloroquine, retinoids, anti-interleukin-6 receptor antibody and janus kinase inhibitors 6 . Other treatment modalities include various phototherapy types and laser treatments 7 . Emerging antifibrotic and anti-inflammatory agents continue to shape the therapeutic landscape 6 . The association between morphea and malignancy is an evolving research area. While systemic sclerosis (SSc) patients are known to have an elevated susceptibility to malignancy, attributed to shared risk factors, chronic inflammation, premature immunosenescence, impaired DNA repair, and therapy-related immunosuppression, limited data is available for morphea 8 . Some studies suggest an increased risk of secondary malignancies, particularly in those with generalized disease 9 . Additionally, there have been reported cases of morphea induced by cancer treatments such as radiotherapy, chemotherapy, and immunotherapy 9 . Nevertheless, the majority of previous studies have concentrated on specific patient subgroups and types of malignancy 10,11 . This study aimed to assess the incidence and types of malignancies among patients diagnosed with morphea. Additionally, the study sought to analyze the demographics, medical histories, clinical characteristics, treatment modalities, and mortality rates in morphea patients, distinguishing between those with and without malignancy. Materials and Methods Study Design This retrospective cohort study analyzed the medical records of patients diagnosed with morphea. Patients were diagnosed, treated, and monitored in the dermatology department and outpatient clinic at the Rabin Medical Center, a tertiary care facility, from January 2012 to December 2023. The study was conducted with approval from the institutional review board (Approval Number [2021 − 1401]). Patient data were retrieved from the Hospital Chameleon System electronic medical records and subsequently reviewed. Study Population Inclusion criteria encompassed patients of all ages with a confirmed diagnosis of morphea, established through typical clinical presentation and histopathological confirmation with atypical presentation. Patients were required to have a minimum follow-up duration of 6 months post-diagnosis. Exclusion criteria involved patients with misdiagnoses or incomplete medical records. Data Collection Demographic data, comorbidities (including general conditions and malignancies), clinical parameters (comprising clinical subtypes and symptoms), treatment modalities, and follow-up durations were collected. For patients diagnosed with malignancies, details regarding the type of malignancy, timing of diagnosis relative to morphea diagnosis, and mortality rates were recorded. Data Analysis All patients were divided into two principal groups: individuals lacking malignancies and those with malignancies (either diagnosed before or after the onset of morphea), followed by a thorough comparative analysis. Following this, subgroups comprising patients with malignancies were further delineated into those who developed malignancy before the diagnosis of morphea and those who did so after. The time interval between diagnoses was carefully assessed. Statistical Analysis Categorical variables were reported as numbers and percentages, and continuous variables were presented as mean and standard deviation (SD). Chi-square tests were utilized for comparing dichotomous variables, whereas unpaired Student's t-tests were applied for dichotomous and quantitative variables such as age and follow-up duration. All statistical tests were two-sided and conducted at a significance level of 0.05. Data analysis was performed using IBM SPSS Statistics version 25 (IBM Corp., Armonk, NY, USA). Results Patient demographics and comorbidities Data are presented in Table 1 . The study encompassed a total of 204 patients in its final analysis, after excluding 238 individuals due to misdiagnosis or uncertain diagnostic criteria, 10 due to lack of access to data, and 20 due to insufficient follow-up. Table 1 Comparison of Demographic Characteristics and Medical Backgrounds in Morphea Patients with and without Malignancy Variable Morphea with malignancy (n = 47) Morphea without malignancy (n = 157) Total (n = 204) p-value Female gender, n (%) 37 (78.7%) 117 (74.5%) 154 (75.5%) 0.556936 Male gender, n (%) 10 (21.3%) 40 (25.5%) 50 (24.5%) Age at onset, year, mean (SD) 64.7±15.1 50.3±20 53.7±20 > 0.0001 Age range 27–89 4–86 4–89 - Time to morphea diagnosis, years, mean (SD) 2.93±5.7 3.39±5.3 3.25±5.4 0.6086 Ethnicity, n (%) Jews 45 (95.7%) 151 (96.2%) 196 (96%) 0.913484 Arabs 2 (4.3%) 6 (3.8%) 8 (4%) Smoking, n (%) 9 (19.1%) 27 (17.2%) 36 (17.6%) 0.758178 Comorbidities, n (%) Obesity 13 (27.6%) 38 (24.2%) 51 (25%) 0.63124 Hypertension 26 (55.3%) 52 (33.1%) 78 (38.2%) 0.00601 Hyperlipidemia 24 (51%) 74 (47.1%) 98 (48%) 0.636145 Diabetes mellitus type 2 14 (29.8%) 32 (20.4%) 46 (22.5%) 0.175886 Cardiovascular 12 (25.5%) 24 (15.3%) 36 (17.6%) 0.106021 Atopy 9 (19.1%) 35 (22.3%) 44 (21.5%) 0.645699 Systemic autoimmune disorders Lupus Erythematosus Systemicus 0 (%) 1 (0.64%) 1 (0.49%) 1 Rheumatoid arthritis 0 (0%) 3 (1.91%) 3 (1.47%) 1 Sarcoidosis 0 (0%) 1 (0.64%) 1 (0.49%) 1 Organ specific autoimmune disorders Endocrine Diabetes mellitus type 1 0 (0%) 1 (0.64%) 1 (0.49%) 1 Dysthyroidisms 10 (21.3%) 30 (19.1%) 40 (19.6%) 0.742563 Neurological (Multiple Sclerosis) 0 (0%) 2 (1.3%) 2 (1%) 1 Gastrointestinal 2 (4.3%) 4 (2.5%) 6 (2.9%) 0.543303 Hematological* 0 (0%) 6 (3.8%) 6 (2.9%) 0.3398 Dermatological Psoriasis 4 (8.5%) 5 (3.2%) 9 (4.4%) 0.118806 Vitiligo 1 (2.1%) 4 (2.5%) 5 (2.4%) 0.870199 Alopecia areata 0 (0%) 3 (1.91%) 3 (1.47%) 1 Family history of atopy 6 (12.7%) 21 (13.4%) 27 (13.2%) 0.913811 Family history of rheumatological disorders 0 (0%) 7 (4.4%) 7 (3.4%) 0.3559 Family history of other autoimmune disorders 2 (4.3%) 12 (7.6%) 14 (6.8%) 0.420264 SD-standard deviation. *Hematological: neutropenia, IgA deficiency, Immune thrombocytopenic purpura. Statistically significant p -values are highlighted in bold. Among all patients, 47 developed malignancies, while 157 did not. The average time period from symptom onset to morphea diagnosis was 3.25 ± 5.4 years, indicating a significant delay without notable differences between patients with and without malignancy. Among the 204 included patients, 154 were women and 50 were men, yielding a female-to-male ratio of 3.08. The patients' ages varied considerably, with an overall mean age at the time of morphea diagnosis of 53.7 ± 20 years. The mean age was 54.6 ± 18.6 years for women and 51.5 ± 22.4 years for men, with no significant gender differences (p = 0.39). Patients with malignancy were significantly older than those without (64.7 ± 15.1 vs. 50.3 ± 20, p < 0.0001). No differences in gender or ethnicity were observed between the groups. Except for a higher prevalence of hypertension in patients with malignancy, medical backgrounds were similar. Clinical characteristics, treatments, and outcomes The data are summarized in Table 2 . The clinical subtypes of morphea were distributed as follows: limited in 113 (55.4%) patients, generalized in 72 (35.3%), linear in 16 (7.8%), and deep in 3 (1.47%). Among limited morphea subtypes, atrophoderma of Pasini and Pierini was more common in patients with malignancy than in those without (8.5% vs. 1.9%, p = 0.029). No differences were observed in the frequency of other clinical subtypes between groups. Most patients were asymptomatic (68.2%), 25% reported itchiness (only 2 patients, or 1%, had an atopic background), and 6.8% experienced pain, with no significant differences in symptoms between groups. Topical treatments alone were administered to 45.6% of patients, with topical corticosteroids being the most frequently prescribed, given to 77.9% of patients. The most commonly employed systemic treatments included methotrexate, administered to 12.7% of patients, followed by intravenous corticosteroids (10.7%), and hydroxychloroquine (5.4%). In the comparison of systemic treatments, a lower proportion of patients in the morphea group associated with malignancy received methotrexate. Table 2 Comparison of Clinical Characteristics, Treatments, and Outcomes in Morphea Patients with and without Malignancy Variable Morphea with malignancy (n = 47) Morphea without malignancy (n = 157) Total (n = 204) p-value Clinical subtype , n (%) Limited Plaque-type morphea 23 (49%) 77 (49%) 100 (49%) 0.989593 Atrophoderma of Pasini and Pierini 4 (8.5%) 3 (1.91%) 7 (3.4%) 0.029218 Bullous 0 (0%) 3 (1.91%) 3 (1.47%) 1 Keloid 0 (0%) 3 (1.91%) 3 (1.47%) 1 Linear Morphea of the extremities 0 (0%) 4 (2.5%) 4 (2%) 0.5755 Morphea en coup de sabre 0 (0%) 11 (7%) 11 (5.4%) 0.0717 Progressive facial hemiatrophy (Parry-Romberg syndrome) 0 (0%) 1 (0.64%) 1 (0.49%) 1 Generalized 20 (42.5%) 52 (33.2%) 72 (35.3%) 0.235204 Deep 0 (0%) 3 (1.91%) 3 (1.47%) 1 Symptoms Pain 2 (4.3%) 12 (7.6%) 14 (6.8%) 0.420264 Itch 10 (21.3%) 41 (26.1%) 51 (25%) 0.501599 Asymptomatic 35 (74.4%) 104 (66.3%) 139 (68.2%) 0.288328 Treatment, n(%) Topical Corticosteroids 39 (83%) 120 (76.4%) 159 (77.9%) 0.342407 Calcineurin inhibitors 1 (2.1%) 8 (5%) 9 (4.4%) 0.384735 Other* 12 (25.5%) 32 (20.4%) 44 (21.5%) 0.451431 Topical treatment only 18 (38.3%) 75 (47.8%) 93 (45.6%) 0.252662 Systemic Oral corticosteroids 0 (0%) 3 (1.91%) 3 (1.47%) 1 IV corticosteroids 2 (4.3%) 20 (12.7%) 22 (10.7%) 0.099987 Tetracyclines 2 (4.3%) 2 (1.3%) 4 (2%) 0.195913 Hydroxychloroquine 3 (6.4%) 8 (5%) 11 (5.4%) 0.731735 Methotrexate 2 (4.3%) 24 (15.3%) 26 (12.7%) 0.046646 Mycophenolate Mophetil 2 (4.3%) 7 (4.4%) 9 (4.4%) 0.952526 Retinoids** 1 (2.1%) 5 (3.2%) 6 (2.9%) 0.706714 Other*** 0 (0%) 2 (1.3%) 2 (1%) 1 Phototherapy PUVA 12 (25.5%) 27 (17.2%) 39 (19.1%) 0.202406 NBUVB 7 (14.9%) 10 (6.4%) 17 (8.3%) 0.06361 BBUVB 1 (2.1%) 1 (0.64%) 2 (1%) 0.362848 UVA 2 (4.2%) 1 (0.64%) 3 (1.47%) 0.070626 Duration of follow up Range, months 6-132 6-174 6-174 - Mean + SD 32.2±35.4 28.3±34.2 29.1±34.6 0.4971 Remission rates, n(%) 20 (42.5%) 67 (42.7%) 87 (42.6%) 0.988166 Time to remission, months, mean (SD) 55.4±67.1 47.4±41.3 48.2±49 0.3214 Relapse, n(%) 0 (0%) 7 (4.4%) 7 (3.4%) 0.3559 All-cause mortality rate, n (%) 11 (23.4%) 6 (3.8%) 17 (8.3%) 0.00002 *Other topical treatment included: retinoids, calcipotriol, and crisaborole. **Retinoids included: isotretinoin (n = 2), acitretin (n = 4) ***Other included: biological medications (secukinumab, n = 1), and Janus kinase inhibitors (tofacitinib, n = 1). Statistically significant p -values are highlighted in bold. Various types of phototherapy were employed in approximately one-third of patients, with PUVA being the most commonly utilized, followed by NBUVB (19.1% and 8.3% of patients, respectively). There was a tendency for a higher rate of phototherapy use in the group associated with malignancy, but the differences were not statistically significant. The follow-up duration after morphea diagnosis ranged from 6 to 174 months, with a mean of 29.1 ± 34.6 months. During the follow-up, 42.6% of patients achieved remission with no significant differences between groups; 3.4% of those relapsed. The all-cause mortality rate was 8.3%, significantly higher in patients with associated malignancy compared to those without (23.4% vs. 3.8%, p = 0.00002). Mortality rates differed between patients who developed malignancy before and after morphea diagnosis. Of the 47 patients with both conditions, 11 (23.4%) died during follow-up. Among 29 patients with pre-morphea malignancy, 5 (17.2%) died, while 6 of 23 patients (26%) with pre-malignancy morphea died. Analysis of malignancy spectrum, incidence, and timing Of the 204 patients included in the study, 47 (23%) were diagnosed with malignancy. Within this subset of patients with both morphea and malignancy, 42 (89.4%) had one malignancy, 4 (8.5%) had two malignancies, and one (2.1%) had three malignancies. The data on malignancy rate, spectrum and timing from the diagnosis of morphea is detailed in Table 3 . In 29 (61.7%) of the 47 patients, malignancy occurred prior to the onset of morphea, while in 23 patients (48.9%), it manifested after the diagnosis of morphea. Five patients who presented with multiple types of malignancy experienced occurrences both before and after the diagnosis of morphea. Table 3 The Spectrum, Incidence, and Timing of Malignancies in Morphea Patients Malignancy type Patients n = 47 f = 37 m = 10 Morphea preceded malignancy (n = 23, f = 20, m = 3) Malignancy preceded morphea (n = 29, f = 21, m = 8) Patients, n (%) Time range, years, (mean±SD) Patients, n (%) Time range, years, (mean±SD) Solid organ Breast 12 (25.5%) 2 (8.7%) 3–7(5±2.8) 10 (34.5%) 1–30(7.1±8.4) Uterus 2 (4.2%) 1 (4.3%) 3 1 (3.4%) 4 Cervix 4 (8.5%) 3 (13%) 1–9(5.3±4) 1 (3.4%) 3 Vulva 2 (4.2%) 1 (4.3%) 7 1 (3.4%) 6 Colon 3 (6.4%) - - 3 (10.3%) 1–22(8.5±11.7) Stomach 2 (4.2%) 2 (8.7%) 1–8(4.5±4.9) - - Renal 1 (2.1%) - - 1 (3.4%) 7 Lung 3 (6.4%) 2 (8.7%) 2–10(6±5.6) 1 (3.4%) 6 Thyroid 1 (2.1%) - - 1 (3.4%) 48 Prostate 2 (4.2%) - - 2 (6.9%) 3–10(6.5±4.9) Testicle 2 (4.2%) - - 2 (6.9%) 2–20(11±12.7) Hematological Lymphoma 2 (4.2%) 1 (4.3%) 14 1 (3.4%) 3 Multiple myeloma 2 (4.2%) 1 (4.3%) 6 1 (3.4%) 9 AML 1 (2.1%) 1 (4.3%) 4 - - Cutaneous NMSC 12 (25.5%) 8 (34.8%) 2–8(4.6±2.4) 4 (13.8%) 3–11(6±3.3) Melanoma 1 (2.1%) 1 (4.3%) 8 - - f – female, m – male. AML- acute myeloid leukemia. NMSC – non-melanoma skin cancer. Female predominance was observed in both groups, though not statistically significant (p = 0.351). The time interval between the diagnosis of malignancy and morphea exhibited wide variation, spanning from 1 to 30 years. Specifically, in cases associated with breast cancer, when cancer preceded the diagnosis of morphea, the time from cancer onset to morphea ranged from 1 to 30 years, with an average of 7.1 ± 8.4 years. Conversely, when cancer followed the diagnosis of morphea, the time between diagnoses ranged from 3 to 7 years, averaging 5 ± 2.8 years. Patients diagnosed with malignancy after morphea diagnosis In this subgroup, the ages at morphea diagnosis ranged from 10 to 88 with a mean of 67.1 ± 14.6 years. There were no statistically significant differences in age compared to those who developed morphea after a cancer diagnosis (27 to 89 years, mean 63.6 ± 15.0 years; p = 0.401). The age range of cancer diagnosis was 31–92 years, with mean of 73.2 (± 12.4) years. The time to cancer diagnosis from morphea onset ranged from 1 to 14 years, with a mean of 5.43 years (± 3.15) years. There were 9 (39.1%) cases of generalized morphea and 14 (60.9%) cases of limited morphea. The most prevalent solid organ malignancy was cervical cancer found in 13% of patients, followed by breast, stomach, and lung cancers, each detected in 8.7% of patients. There was a trend toward a higher rate of non-melanoma skin cancer (34.8% vs. 13.8%) compared to those with malignancy preceding morphea, though it was not statistically significant (p = 0.07). Table 4 shows the types of treatment for morphea and the time interval from treatment to cancer diagnosis. Of the patients, 56.5% received only topical treatments, 35% underwent phototherapy, one was treated with methotrexate, and another with etretinate. Of the 8 patients who developed NMSC, 1 received NBUVB, 1 received both NBUVB and BBUVB, 1 received UVA, 1 received PUVA, and 3 did not receive phototherapy. The time period from phototherapy initiation to the development of NMSC ranged from 2 to 6 years. The patient who developed melanoma had previously been treated with PUVA for morphea Table 4 Treatment Modalities for Morphea in 23 Patients Who Developed Malignancy Post-Treatment: A Subgroup Analysis Type of treatment Patients, n (%) Time interval, range (years) Type of malignancy (n) Phototherapy NBUVB* 3 (13%) 1–6 NMSC (2) Stomach (1) UVA** 1 (4.3%) 7 NMSC (1) PUVA*** 3 (13%) 4–8 Breast (1) NMSC (1) Uterus (1) BBUVB**** 1 (4.3%) 2 NMSC (1) Systemic pharmacological therapy Methotrexate 1 (4.3%) 1 Cervix (1) Acitretin 1 (4.3%) 10 Lung (1) Topical treatment only 13 (56.5%) 2–14 NMSC (4) Cervix (2) Hematological (2) Lung (1) Vulvar (1) Breast (1) Melanoma (1) Stomach (1) *NBUVB-Narrowband ultraviolet B therapy, **UVA-Ultraviolet light A, ***PUVA-Psoralen plus UVA, ****BBUVB-Broadband ultraviolet B therapy. NMSC - non-melanoma skin cancer. Patients diagnosed with morphea after malignancy The mean age at cancer diagnosis in this subgroup was 58.6 (± 13.7) years, with 48.2% diagnosed with generalized morphea and 51.8% with limited morphea. Breast cancer was the most common, occurring in 34.3% of cases, followed by colon cancer at 10.3%, and prostate and testicular cancers at 6.9% each. Breast cancer was significantly more frequent in this subgroup compared to those diagnosed with morphea before cancer (p = 0.028). Among the treatment modalities for all breast cancer patients, all 10 received radiation therapy, one underwent chemotherapy, and four were treated with hormone therapy. Of these 10 patients, 6 had limited plaque-type morphea, and 4 had generalized morphea. In cases with limited plaque-type morphea, it affected sites that were exposed to radiation. One patient with colon cancer received radiotherapy, chemotherapy, and immunotherapy, while two were treated solely with surgery. Table 5 provides details on cancer treatment modalities and the interval between cancer treatment initiation and morphea diagnosis. Table 5 Cancer Treatment Modalities in 29 Patients Diagnosed with Morphea Following Malignancy Cancer treatment modality Patients, n (%) Time interval, years, range (mean±SD) Surgery 23 (79.3%) 1–48 (9.46±10.96) Chemotherapy 4 (13.8%) 2–9 (4.63±3.2) Radiotherapy 13 (44.8%) 1–30 (6.12±7.58) Hormone therapy 5 (17.2%) 1–6 (3.6±1.95) Immunotherapy 2 (6.9%) 2.5-9 (5.75±4.6) Multimodal treatment* 12 (41.3%) 1–30 (6.96±7.75) *Multimodal treatment was defined as the use of at least two treatment modalities. Discussion Our retrospective cohort study unveils intriguing connections between morphea and various malignancies. Typically viewed as a dermatological condition, morphea demonstrates associations with cancer. This analysis provides valuable insights into malignancy types, their timing relative to morphea diagnosis, and potential mechanisms linking these conditions. Gender distribution exhibited a female predominance, consistent with prior studies 1,2 . However, no significant gender differences emerged between patients with and without malignancy, suggesting gender may not affect cancer risk in morphea patients 1,12 . Older age emerged as a critical risk factor for cancer in morphea patients, likely due to factors like cumulative genetic mutations, chronic inflammation, and immunological changes 13,14 . These findings emphasize the importance of monitoring and targeted risk management for older morphea patients. Significant diagnostic delays, averaging 3.25 years, were noted, consistent with previous research. These delays arise from factors such as limited awareness among patients and healthcare providers, restricted access to specialists, nonspecific symptoms, gradual disease progression, and variable presentations 1,15 . Addressing these delays requires enhanced awareness and improved diagnostics. Importantly, time to diagnosis didn’t correlate with malignancy status, indicating no significant impact on malignancy development in morphea patients. In our study, the most common malignancies in patients with pre-existing morphea were NMSC, cervical, breast, stomach, and lung cancers, differing from previous findings published by Joly-Chevrier et al. that reported pancreatic, skin, gynecological, and breast cancer as predominant 9 . These discrepancies may stem from geographic variations such as regional dietary habits or smoking rates, as well as methodological differences. Future studies should aim to standardize these factors to enable more consistent comparisons. NMSC predominated post-morphea diagnosis, consistent with prior research 10,11 . Extensive UV light exposure emerged as a significant risk factor. Notably, 5 out of the 8 NMSC patients in our cohort had received phototherapy. Although our data suggested a higher tendency for phototherapy use among patients who developed malignancy compared to those who did not, the differences were not statistically significant. Further research is necessary to confirm or refute this observation. Other potential factors contributing to NMSC risk include immunosuppressive therapy, whether used alone or in combination with UV light. Additionally, the persistent inflammation and fibrosis characteristic of morphea, accompanied by increased levels of cytokines such as IL-4, IL-13, and transforming growth factor β, may promote epithelial cell malignant transformation 10,11 . Genetic predisposition to autoimmune disorders could heighten cancer susceptibility, suggesting a common cause for both conditions 11 . Cervical cancer emerged as the second most frequent malignancy in morphea patients. Supporting this observation, Hemminki K et al. reported an elevated risk of cervical cancer in individuals with localized scleroderma. Factors underlying this association include chronic inflammation and fibrosis, which are known to drive oncogenesis; potential shared genetic or environmental risk factors; hormonal imbalances commonly seen in autoimmune disorders; and immune dysregulation, compromising defense against oncogenic viruses like HPV, thereby heightening the risk of cervical cancer 16 . Additional types of cancer that were more common in morphea patients who developed malignancy after diagnosis included breast, stomach, and lung cancers. Potential explanations include chronic inflammation, fibrosis, and immunosuppressive treatment. It is important to note, however, that Hemminki's study found no increased risk of breast cancer in morphea patients 16 . The number of cases per type of cancer was small; therefore, there is a need for larger sample sizes. Most patients with cancer did not receive systemic immunosuppressive therapy before their cancer diagnosis, thus indicating that the risk associated with this treatment seems to be less significant. Therefore, further research is needed to clarify this discrepancy. In patients with malignancies preceding morphea, the most common types were breast cancer, NMSC, colon, prostate, and testicular cancers. Breast cancer was the most prevalent, comprising 34.5% of cases. All those with prior breast cancer who developed morphea had received radiation therapy. Among these, 4 cases presented with generalized morphea and 6 with limited plaque-type morphea in irradiated areas, supporting prior studies linking morphea to radiation 17–20 . The relationship between breast cancer and morphea is multifaceted, involving several treatment modalities and biological responses. Radiation therapy, a common treatment for breast cancer, can induce fibrosis by damaging both cancerous and healthy cells, triggering a reactive increase in connective tissue. The tumor itself may also provoke an inflammatory response, contributing to fibrotic changes in the surrounding tissues. Surgical interventions can lead to scarring and fibrosis at the surgical site. Additionally, chemotherapy and hormone therapies used in breast cancer treatment can disrupt normal cellular and hormonal functions, potentially leading to further fibrotic developments. There are also rare cases of morphea linked to chemotherapy and immunotherapy treatments, including PD-1 and CTLA-4 inhibitors 9 . Each of these factors can individually or collectively contribute to morphea onset in breast cancer patients. Compared to Joly-Chevrier's review, our cohort's morphea patients with associated malignancy were notably older (64.7 vs. 38.8 years) and had a shorter time from morphea diagnosis to cancer onset (5.43 vs. 15 years) 9 . In our cohort, although not significant, there was a trend toward higher generalized morphea in the cancer-associated group, consistent with previous findings 9,21 . Atrophoderma of Pasini and Pierini (APP) was more prevalent in malignancy-associated patients, a novel observation requiring further validation. Research on the association between morphea subtypes and cancer is limited 9–11 . Case reports have linked APP with neoplastic conditions, necessitating additional investigation to elucidate these relationships, particularly regarding Borrelia burgdorferi infections 22–27 . The time interval between cancer treatment and morphea development varied from prior data: 4.6 vs. 1.6 years for chemotherapy, 6.1 vs. 3.1 years for radiotherapy, and 5.7 vs. 0.8 years for immunotherapy. Increased all-cause mortality in morphea patients with malignancy, particularly those diagnosed before their cancer, necessitates significant clinical focus. Morphea may activate biological pathways predisposing to aggressive or treatment-resistant cancers, a risk heightened by immunosuppressive treatments weakening immune defense. Chronic inflammation linked to morphea could enhance tumor growth, and overlapping symptoms might delay cancer diagnosis. Furthermore, treatments like radiation or chemotherapy could raise secondary cancer risks, with possible inherent genetic or molecular factors in morphea patients amplifying their vulnerability to malignancies. Strengths of our study include comprehensive data collection from a sizable patient cohort, encompassing diverse demographics to enhance relevance. Detailed clinical evaluations further enrich our analysis. However, limitations include the retrospective nature of the analysis, potentially introducing biases. Conducting the study in a single tertiary care center may limit generalizability, and limited sample sizes for subgroup analyses may reduce statistical power. Reliance on medical records hampers capturing comprehensive patient information, affecting outcomes. In conclusion, our study underscores the bidirectional link between morphea and malignancies, influenced by patient age, sequence of diagnoses, and treatments. Vigilant monitoring is crucial for morphea patients, especially those with associated cancers, emphasizing the importance of heightened awareness, early detection, and refined management strategies. Declarations Funding sources: None Conflict of interest: None Ethical approval: The study was conducted with approval from the institutional review board (Approval Number [2021-1401]). Ethics statement: Since the study didn’t include information or images that could identify patients, informed consent wasn’t required. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request. Authorship: All authors met the criteria for authorship. Author Contribution K. L. contributed to the conceptual idea, data collection, analysis, and wrote the draft of the manuscript. G. D. discussed the results, contributed to the interpretation of the results, and critically revised the manuscript. D. M. contributed to the design of the research, data interpretation, and critically revised the manuscript. A. A. planned and supervised the project, contributed to the interpretation of the results, and critically revised the manuscript. All authors reviewed and approved the final manuscript. References Papara C, De Luca DA, Bieber K, Vorobyev A, Ludwig RJ. Morphea: The 2023 update. Frontiers in Medicine 2023; 10 . Szczȩch J, Samotij D, Jaworecka K, Tobiasz A, Reich A. Quality of Life in Patients with Morphea: A Cross-Sectional Study and a Review of the Current Literature. Biomed Res Int 2020; 2020 . Careta MF, Romiti R. Localized scleroderma: Clinical spectrum and therapeutic update. An Bras Dermatol 2015; 90 . Abbas L, Joseph A, Kunzler E, Jacobe HT. Morphea: progress to date and the road ahead. Ann Transl Med 2021; 9 . Rodríguez-Salgado P, García-Romero MT. Morphea: a practical review of its diagnosis, classification and treatment. Gaceta Medica de Mexico 2019; 155 . Wenzel D, Haddadi NS, Afshari K, Richmond JM, Rashighi M. Upcoming treatments for morphea. Immunity, Inflammation and Disease 2021; 9 . Szczepanik-Kułak P, Michalska-Jakubus M, Krasowska D. Laser therapy for the treatment of morphea: A systematic review of literature. Journal of Clinical Medicine 2021; 10 . Lepri G, Catalano M, Bellando-Randone S, et al. Systemic Sclerosis Association with Malignancy. Clinical Reviews in Allergy and Immunology 2022; 63 . Joly-Chevrier M, Gélinas A, Ghazal S, et al. Morphea, Eosinophilic Fasciitis and Cancer: A Scoping Review. Cancers 2023; 15 . Heck J, Olk J, Kneitz H, Hamm H, Goebeler M. Long-standing morphea and the risk of squamous cell carcinoma of the skin. JDDG - Journal of the German Society of Dermatology 2020; 18 . Boozalis E, Shah AA, Wigley F, Kang S, Kwatra SG. Morphea and systemic sclerosis are associated with an increased risk for melanoma and nonmelanoma skin cancer. J Am Acad Dermatol 2019; 80 . Lagacé F, D’Aguanno K, Prosty C, et al. The Role of Sex and Gender in Dermatology - From Pathogenesis to Clinical Implications. Journal of Cutaneous Medicine and Surgery 2023; 27 . Li X, Li C, Zhang W, Wang Y, Qian P, Huang H. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduction and Targeted Therapy 2023; 8 . Lian J, Yue Y, Yu W, Zhang Y. Immunosenescence: a key player in cancer development. Journal of Hematology and Oncology 2020; 13 . Johnson W, Jacobe H. Morphea in adults and children cohort II: Patients with morphea experience delay in diagnosis and large variation in treatment. J Am Acad Dermatol 2012; 67 . Hemminki K, Liu X, Ji J, Försti A, Sundquist J, Sundquist K. Effect of autoimmune diseases on risk and survival in female cancers. Gynecol Oncol 2012; 127 . Ardern-Jones MR, Black MM. Widespread morphoea following radiotherapy for carcinoma of the breast. Clin Exp Dermatol 2003; 28 . Davis DA, Cohen PR, McNeese MD, Duvic M. Localized scleroderma in breast cancer patients treated with supervoltage external beam radiation: Radiation port scleroderma. J Am Acad Dermatol 1996; 35 . Bleasel NR, Stapleton KM, Commens C, Ahern VA. Radiation-induced localized scleroderma in breast cancer patients. Australasian Journal of Dermatology 1999; 40 . Partl R, Regitnig P, Lukasiak K, Winkler P, Kapp KS. Incidence of Morphea following Adjuvant Irradiation of the Breast in 2,268 Patients. Breast Care 2020; 15 . Desmond BL, Blattner CM, Young J. Generalized morphea as the first sign of breast carcinoma: A case report. Dermatol Online J 2016; 22 . Ravic-Nikolic A, Djurdjevic P, Mitrovic S, Milicic V, Petrovic D. Atrophoderma of Pasini and Pierini associated with extramedullary plasmacytoma. Clinical and Experimental Dermatology 2016; 41 . Kopeć-Medrek M, Kotulska A, Zycińska-Debska E, Widuchowska M, Kucharz EJ. Exacerbated course of atrophoderma of Pasini and Pierini in patient with papillary cancer of the thyroid gland. Wiad Lek 2010; 63 . Chang CM, Landgren O, Koshiol J, Björkholm M, Löve TJ, Kristinsson SY. Borrelia and subsequent risk of solid tumors and hematologic malignancies in Sweden. International Journal of Cancer 2012; 131 . Gaur G, Sawant JY, Chavan AS, et al. Effect of invasion of borrelia burgdorferi in normal and neoplastic mammary epithelial cells. Antibiotics 2021; 10 . Buechner SA, Rufli T. Atrophoderma of Pasini and Pierini: Clinical and histopathologic findings and antibodies to Borrelia burgdorferi in thirty-four patients. J Am Acad Dermatol 1994; 30 . Lee Y, Oh Y, Ahn SY, Park HY, Choi EH. A case of atrophoderma of Pasini and Pierini associated with Borrelia burgdorferi infection successfully treated with oral doxycycline. Ann Dermatol 2011; 23 . Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Revision requested 05 Aug, 2024 Reviews received at journal 01 Aug, 2024 Reviewers agreed at journal 01 Aug, 2024 Reviewers agreed at journal 31 Jul, 2024 Reviewers invited by journal 31 Jul, 2024 Editor assigned by journal 22 Jul, 2024 Submission checks completed at journal 22 Jul, 2024 First submitted to journal 20 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4772917","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":336307155,"identity":"cd8f4c7d-ac9c-46b0-8259-698c84e39824","order_by":0,"name":"Keren Lyakhovitsky","email":"","orcid":"","institution":"Rabin Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Keren","middleName":"","lastName":"Lyakhovitsky","suffix":""},{"id":336307156,"identity":"4f6f2b61-0c0f-4a71-a866-8cede9297b1f","order_by":1,"name":"Giovanni Damiani","email":"","orcid":"","institution":"Fondazione IRCCS Ca' Granda","correspondingAuthor":false,"prefix":"","firstName":"Giovanni","middleName":"","lastName":"Damiani","suffix":""},{"id":336307157,"identity":"9d6ee7f2-173d-4aaa-bc6a-9af7d36134b4","order_by":2,"name":"Daniel Mimouni","email":"","orcid":"","institution":"Rabin Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Daniel","middleName":"","lastName":"Mimouni","suffix":""},{"id":336307158,"identity":"18804589-217b-45d7-8e75-5ae50e48a216","order_by":3,"name":"Anna Aronovich","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA2klEQVRIiWNgGAWjYDADNgYexgdAmoePFC3MBiAtbCTYw8MmAdFLAPDPbn724eMOm8Q+9rPHKr/m2MmwMTA/fHQDjxaJO8eMZ848k5bYxpOXdlt2WzLQYWzGxjn4rLmRYMzM23bYmE2Cx+y25DZmoBYeNml8WuRvpH+GaymW3FZPWIvBjRywLXIgLYwftx0mrMXwRk4x48y2NDk2nhxjacZtx3nYmAn4Re5G+maGj202PPLtZww//txWbc/P3vzwMV7vIwNmHjBJrHIQYPxBiupRMApGwSgYMQAARq09QIuZOLYAAAAASUVORK5CYII=","orcid":"","institution":"Rabin Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Anna","middleName":"","lastName":"Aronovich","suffix":""}],"badges":[],"createdAt":"2024-07-20 11:36:43","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4772917/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4772917/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":62580079,"identity":"9e492d4c-d386-4387-95d2-a46e9425dea7","added_by":"auto","created_at":"2024-08-16 06:02:12","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1047370,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4772917/v1/dc117b04-5407-4bd2-93b2-716935ea8c6e.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Exploring the Relationship Between Morphea and Malignancy: A Decade-Long Single- Center Study of 204 Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMorphea (localized scleroderma), a rare, chronic inflammatory connective tissue disorder that manifests with inflammation and fibrosis affecting the skin and underlying soft tissue, with possible extension to adjacent structures (e.g., lungs, gastrointestinal tract)\u003csup\u003e1\u003c/sup\u003e. Despite being primary recognized as a condition confined to the skin, some subtypes of morphea exhibit extra-cutaneous manifestations, involving the musculoskeletal and central nervous systems\u003csup\u003e1\u003c/sup\u003e. The annual incidence of morphea varies from 4 to 27 new cases per million, with approximately two-thirds occurring in adults\u003csup\u003e1\u003c/sup\u003e. There are two incidence peaks: between ages 2 to 14 and in the 5th decade of life\u003csup\u003e1\u003c/sup\u003e. Morphea predominantly affects females, with a female-to-male ratio of 4:1, and is most common among Caucasians, followed by Hispanics and Latin Americans\u003csup\u003e2\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe five main clinical types of morphea include limited, generalized, linear, deep, and mixed, with plaque-type and generalized morphea being prevalent in adults, while the linear form is more common in children\u003csup\u003e3\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eMorphea's pathogenesis involves a complex interplay of genetic predisposition, vascular dysfunction, environmental triggers, and autoimmune dysregulation\u003csup\u003e1\u003c/sup\u003e. Possible triggers for morphea include cancer treatments like radiotherapy, chemotherapy, and immunotherapy\u003csup\u003e1\u003c/sup\u003e. It unfolds in three phases: an initial inflammatory phase, a fibrotic phase marked by excessive collagen deposition, and an atrophic phase. Th1/Th2 imbalance and the upregulation of profibrotic pathways are key factors, with an initial proinflammatory Th1/Th17-associated cytokine response followed by a shift towards Th2 cytokines during disease progression\u003csup\u003e4\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eDiagnosing morphea relies primarily on clinical features, with skin biopsy reserved for atypical cases. Treatment options vary based on disease severity\u003csup\u003e5\u003c/sup\u003e. Topical corticosteroids are used for limited disease, while systemic corticosteroids and methotrexate are most commonly utilized in more extensive cases. Additional options for topical therapies include calcineurin inhibitors, vitamin D derivatives, and imiquimod\u003csup\u003e6\u003c/sup\u003e. For more severe cases, systemic treatment options encompass mycophenolate mophetil, hydroxychloroquine, retinoids, anti-interleukin-6 receptor antibody and janus kinase inhibitors\u003csup\u003e6\u003c/sup\u003e. Other treatment modalities include various phototherapy types and laser treatments\u003csup\u003e7\u003c/sup\u003e. Emerging antifibrotic and anti-inflammatory agents continue to shape the therapeutic landscape\u003csup\u003e6\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe association between morphea and malignancy is an evolving research area. While systemic sclerosis (SSc) patients are known to have an elevated susceptibility to malignancy, attributed to shared risk factors, chronic inflammation, premature immunosenescence, impaired DNA repair, and therapy-related immunosuppression, limited data is available for morphea\u003csup\u003e8\u003c/sup\u003e. Some studies suggest an increased risk of secondary malignancies, particularly in those with generalized disease\u003csup\u003e9\u003c/sup\u003e. Additionally, there have been reported cases of morphea induced by cancer treatments such as radiotherapy, chemotherapy, and immunotherapy\u003csup\u003e9\u003c/sup\u003e. Nevertheless, the majority of previous studies have concentrated on specific patient subgroups and types of malignancy\u003csup\u003e10,11\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThis study aimed to assess the incidence and types of malignancies among patients diagnosed with morphea. Additionally, the study sought to analyze the demographics, medical histories, clinical characteristics, treatment modalities, and mortality rates in morphea patients, distinguishing between those with and without malignancy.\u003c/p\u003e"},{"header":"Materials and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design\u003c/h2\u003e \u003cp\u003eThis retrospective cohort study analyzed the medical records of patients diagnosed with morphea. Patients were diagnosed, treated, and monitored in the dermatology department and outpatient clinic at the Rabin Medical Center, a tertiary care facility, from January 2012 to December 2023. The study was conducted with approval from the institutional review board (Approval Number [2021\u0026thinsp;\u0026minus;\u0026thinsp;1401]). Patient data were retrieved from the Hospital Chameleon System electronic medical records and subsequently reviewed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eInclusion criteria encompassed patients of all ages with a confirmed diagnosis of morphea, established through typical clinical presentation and histopathological confirmation with atypical presentation. Patients were required to have a minimum follow-up duration of 6 months post-diagnosis. Exclusion criteria involved patients with misdiagnoses or incomplete medical records.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eData Collection\u003c/h2\u003e \u003cp\u003eDemographic data, comorbidities (including general conditions and malignancies), clinical parameters (comprising clinical subtypes and symptoms), treatment modalities, and follow-up durations were collected. For patients diagnosed with malignancies, details regarding the type of malignancy, timing of diagnosis relative to morphea diagnosis, and mortality rates were recorded.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData Analysis\u003c/h2\u003e \u003cp\u003eAll patients were divided into two principal groups: individuals lacking malignancies and those with malignancies (either diagnosed before or after the onset of morphea), followed by a thorough comparative analysis. Following this, subgroups comprising patients with malignancies were further delineated into those who developed malignancy before the diagnosis of morphea and those who did so after. The time interval between diagnoses was carefully assessed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eCategorical variables were reported as numbers and percentages, and continuous variables were presented as mean and standard deviation (SD). Chi-square tests were utilized for comparing dichotomous variables, whereas unpaired Student's t-tests were applied for dichotomous and quantitative variables such as age and follow-up duration. All statistical tests were two-sided and conducted at a significance level of 0.05. Data analysis was performed using IBM SPSS Statistics version 25 (IBM Corp., Armonk, NY, USA).\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePatient demographics and comorbidities\u003c/h2\u003e \u003cp\u003eData are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. The study encompassed a total of 204 patients in its final analysis, after excluding 238 individuals due to misdiagnosis or uncertain diagnostic criteria, 10 due to lack of access to data, and 20 due to insufficient follow-up.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Demographic Characteristics and Medical Backgrounds in Morphea Patients with and without Malignancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMorphea with malignancy (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMorphea without malignancy\u003c/p\u003e \u003cp\u003e (n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;204)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale gender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e37 (78.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e117 (74.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e154 (75.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.556936\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale gender, n (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e50 (24.5%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge at onset, year, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e64.7\u0026plusmn;15.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.3\u0026plusmn;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e53.7\u0026plusmn;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e\u0026gt;\u0026thinsp;0.0001\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge range\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27\u0026ndash;89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u0026ndash;86\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u0026ndash;89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime to morphea diagnosis, years, mean (SD)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.93\u0026plusmn;5.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.39\u0026plusmn;5.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.25\u0026plusmn;5.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.6086\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEthnicity, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eJews\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e45 (95.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e151 (96.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e196 (96%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.913484\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eArabs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8 (4%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.758178\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eComorbidities, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eObesity\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (27.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e38 (24.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.63124\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypertension\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26 (55.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (33.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e78 (38.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.00601\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHyperlipidemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (51%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74 (47.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e98 (48%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.636145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus type 2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (29.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e46 (22.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.175886\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCardiovascular\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e36 (17.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.106021\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (22.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.645699\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic autoimmune disorders\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLupus Erythematosus Systemicus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRheumatoid arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSarcoidosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eOrgan specific autoimmune disorders\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEndocrine\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes mellitus type 1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDysthyroidisms\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e30 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40 (19.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.742563\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeurological (Multiple Sclerosis)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGastrointestinal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.543303\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHematological*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3398\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDermatological\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePsoriasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.118806\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVitiligo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5 (2.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.870199\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlopecia areata\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of atopy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21 (13.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e27 (13.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.913811\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of rheumatological disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3559\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history of other autoimmune disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.420264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eSD-standard deviation. *Hematological: neutropenia, IgA deficiency, Immune thrombocytopenic purpura. Statistically significant \u003cem\u003ep\u003c/em\u003e-values are highlighted in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAmong all patients, 47 developed malignancies, while 157 did not. The average time period from symptom onset to morphea diagnosis was 3.25\u0026thinsp;\u0026plusmn;\u0026thinsp;5.4 years, indicating a significant delay without notable differences between patients with and without malignancy. Among the 204 included patients, 154 were women and 50 were men, yielding a female-to-male ratio of 3.08. The patients' ages varied considerably, with an overall mean age at the time of morphea diagnosis of 53.7\u0026thinsp;\u0026plusmn;\u0026thinsp;20 years. The mean age was 54.6\u0026thinsp;\u0026plusmn;\u0026thinsp;18.6 years for women and 51.5\u0026thinsp;\u0026plusmn;\u0026thinsp;22.4 years for men, with no significant gender differences (p\u0026thinsp;=\u0026thinsp;0.39). Patients with malignancy were significantly older than those without (64.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1 vs. 50.3\u0026thinsp;\u0026plusmn;\u0026thinsp;20, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). No differences in gender or ethnicity were observed between the groups. Except for a higher prevalence of hypertension in patients with malignancy, medical backgrounds were similar.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eClinical characteristics, treatments, and outcomes\u003c/h2\u003e \u003cp\u003eThe data are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. The clinical subtypes of morphea were distributed as follows: limited in 113 (55.4%) patients, generalized in 72 (35.3%), linear in 16 (7.8%), and deep in 3 (1.47%). Among limited morphea subtypes, atrophoderma of Pasini and Pierini was more common in patients with malignancy than in those without (8.5% vs. 1.9%, p\u0026thinsp;=\u0026thinsp;0.029). No differences were observed in the frequency of other clinical subtypes between groups. Most patients were asymptomatic (68.2%), 25% reported itchiness (only 2 patients, or 1%, had an atopic background), and 6.8% experienced pain, with no significant differences in symptoms between groups. Topical treatments alone were administered to 45.6% of patients, with topical corticosteroids being the most frequently prescribed, given to 77.9% of patients. The most commonly employed systemic treatments included methotrexate, administered to 12.7% of patients, followed by intravenous corticosteroids (10.7%), and hydroxychloroquine (5.4%). In the comparison of systemic treatments, a lower proportion of patients in the morphea group associated with malignancy received methotrexate.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of Clinical Characteristics, Treatments, and Outcomes in Morphea Patients with and without Malignancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMorphea with malignancy (n\u0026thinsp;=\u0026thinsp;47)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMorphea without malignancy (n\u0026thinsp;=\u0026thinsp;157)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal (n\u0026thinsp;=\u0026thinsp;204)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eClinical subtype\u003c/b\u003e, \u003cb\u003en (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLimited\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlaque-type morphea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e77 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e100 (49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.989593\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtrophoderma of Pasini and Pierini\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.029218\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBullous\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eKeloid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLinear\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorphea of the extremities\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (2.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.5755\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMorphea en coup de sabre\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11 (7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0717\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProgressive facial hemiatrophy (Parry-Romberg syndrome)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1 (0.49%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eGeneralized\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (42.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52 (33.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e72 (35.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.235204\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDeep\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSymptoms\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (7.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14 (6.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.420264\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eItch\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (21.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41 (26.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e51 (25%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.501599\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAsymptomatic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (74.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e104 (66.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e139 (68.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.288328\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTreatment, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopical\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39 (83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e120 (76.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e159 (77.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.342407\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCalcineurin inhibitors\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.384735\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32 (20.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e44 (21.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.451431\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTopical treatment only\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18 (38.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e75 (47.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e93 (45.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.252662\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral corticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (1.91%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIV corticosteroids\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22 (10.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.099987\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTetracyclines\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4 (2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.195913\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHydroxychloroquine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11 (5.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.731735\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e24 (15.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26 (12.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.046646\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMycophenolate Mophetil\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.952526\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRetinoids**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (3.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6 (2.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.706714\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (1.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePhototherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePUVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e39 (19.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.202406\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNBUVB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (14.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.06361\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBBUVB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2 (1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.362848\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUVA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (0.64%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3 (1.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.070626\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"5\" nameend=\"c5\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eDuration of follow up\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRange, months\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6-132\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6-174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6-174\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMean\u0026thinsp;+\u0026thinsp;SD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.2\u0026plusmn;35.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28.3\u0026plusmn;34.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e29.1\u0026plusmn;34.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4971\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRemission rates, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20 (42.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e67 (42.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87 (42.6%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.988166\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTime to remission, months, mean (SD)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.4\u0026plusmn;67.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.4\u0026plusmn;41.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e48.2\u0026plusmn;49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3214\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRelapse, n(%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (4.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3559\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAll-cause mortality rate, n (%)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (23.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (3.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17 (8.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.00002\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e*Other topical treatment included: retinoids, calcipotriol, and crisaborole.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e**Retinoids included: isotretinoin (n\u0026thinsp;=\u0026thinsp;2), acitretin (n\u0026thinsp;=\u0026thinsp;4)\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e***Other included: biological medications (secukinumab, n\u0026thinsp;=\u0026thinsp;1), and Janus kinase inhibitors (tofacitinib, n\u0026thinsp;=\u0026thinsp;1). Statistically significant \u003cem\u003ep\u003c/em\u003e-values are highlighted in bold.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eVarious types of phototherapy were employed in approximately one-third of patients, with PUVA being the most commonly utilized, followed by NBUVB (19.1% and 8.3% of patients, respectively). There was a tendency for a higher rate of phototherapy use in the group associated with malignancy, but the differences were not statistically significant. The follow-up duration after morphea diagnosis ranged from 6 to 174 months, with a mean of 29.1\u0026thinsp;\u0026plusmn;\u0026thinsp;34.6 months. During the follow-up, 42.6% of patients achieved remission with no significant differences between groups; 3.4% of those relapsed. The all-cause mortality rate was 8.3%, significantly higher in patients with associated malignancy compared to those without (23.4% vs. 3.8%, p\u0026thinsp;=\u0026thinsp;0.00002). Mortality rates differed between patients who developed malignancy before and after morphea diagnosis. Of the 47 patients with both conditions, 11 (23.4%) died during follow-up. Among 29 patients with pre-morphea malignancy, 5 (17.2%) died, while 6 of 23 patients (26%) with pre-malignancy morphea died.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eAnalysis of malignancy spectrum, incidence, and timing\u003c/h2\u003e \u003cp\u003eOf the 204 patients included in the study, 47 (23%) were diagnosed with malignancy. Within this subset of patients with both morphea and malignancy, 42 (89.4%) had one malignancy, 4 (8.5%) had two malignancies, and one (2.1%) had three malignancies.\u003c/p\u003e \u003cp\u003eThe data on malignancy rate, spectrum and timing from the diagnosis of morphea is detailed in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In 29 (61.7%) of the 47 patients, malignancy occurred prior to the onset of morphea, while in 23 patients (48.9%), it manifested after the diagnosis of morphea. Five patients who presented with multiple types of malignancy experienced occurrences both before and after the diagnosis of morphea.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Spectrum, Incidence, and Timing of Malignancies in Morphea Patients\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eMalignancy type\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003ePatients\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;47\u003c/p\u003e \u003cp\u003ef\u0026thinsp;=\u0026thinsp;37\u003c/p\u003e \u003cp\u003em\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e \u003cp\u003eMorphea preceded malignancy (n\u0026thinsp;=\u0026thinsp;23, f\u0026thinsp;=\u0026thinsp;20, m\u0026thinsp;=\u0026thinsp;3)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c6\" namest=\"c5\"\u003e \u003cp\u003eMalignancy preceded morphea (n\u0026thinsp;=\u0026thinsp;29, f\u0026thinsp;=\u0026thinsp;21, m\u0026thinsp;=\u0026thinsp;8)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTime range, years, (mean\u0026plusmn;SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eTime range, years, (mean\u0026plusmn;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid organ\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u0026ndash;7(5\u0026plusmn;2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10 (34.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;30(7.1\u0026plusmn;8.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUterus\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCervix\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (8.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;9(5.3\u0026plusmn;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVulva\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eColon\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3 (10.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1\u0026ndash;22(8.5\u0026plusmn;11.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eStomach\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u0026ndash;8(4.5\u0026plusmn;4.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRenal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLung\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (6.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (8.7%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u0026ndash;10(6\u0026plusmn;5.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eThyroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eProstate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u0026ndash;10(6.5\u0026plusmn;4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTesticle\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2\u0026ndash;20(11\u0026plusmn;12.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHematological\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultiple myeloma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (4.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1 (3.4%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAML\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eCutaneous\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNMSC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (25.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (34.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u0026ndash;8(4.6\u0026plusmn;2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3\u0026ndash;11(6\u0026plusmn;3.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMelanoma\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1 (2.1%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003ef \u0026ndash; female, m \u0026ndash; male. AML- acute myeloid leukemia. NMSC \u0026ndash; non-melanoma skin cancer.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eFemale predominance was observed in both groups, though not statistically significant (p\u0026thinsp;=\u0026thinsp;0.351). The time interval between the diagnosis of malignancy and morphea exhibited wide variation, spanning from 1 to 30 years. Specifically, in cases associated with breast cancer, when cancer preceded the diagnosis of morphea, the time from cancer onset to morphea ranged from 1 to 30 years, with an average of 7.1\u0026thinsp;\u0026plusmn;\u0026thinsp;8.4 years. Conversely, when cancer followed the diagnosis of morphea, the time between diagnoses ranged from 3 to 7 years, averaging 5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.8 years.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003ePatients diagnosed with malignancy after morphea diagnosis\u003c/h2\u003e \u003cp\u003eIn this subgroup, the ages at morphea diagnosis ranged from 10 to 88 with a mean of 67.1\u0026thinsp;\u0026plusmn;\u0026thinsp;14.6 years. There were no statistically significant differences in age compared to those who developed morphea after a cancer diagnosis (27 to 89 years, mean 63.6\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0 years; p\u0026thinsp;=\u0026thinsp;0.401). The age range of cancer diagnosis was 31\u0026ndash;92 years, with mean of 73.2 (\u0026plusmn;\u0026thinsp;12.4) years. The time to cancer diagnosis from morphea onset ranged from 1 to 14 years, with a mean of 5.43 years (\u0026plusmn;\u0026thinsp;3.15) years. There were 9 (39.1%) cases of generalized morphea and 14 (60.9%) cases of limited morphea. The most prevalent solid organ malignancy was cervical cancer found in 13% of patients, followed by breast, stomach, and lung cancers, each detected in 8.7% of patients. There was a trend toward a higher rate of non-melanoma skin cancer (34.8% vs. 13.8%) compared to those with malignancy preceding morphea, though it was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.07). Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e shows the types of treatment for morphea and the time interval from treatment to cancer diagnosis. Of the patients, 56.5% received only topical treatments, 35% underwent phototherapy, one was treated with methotrexate, and another with etretinate. Of the 8 patients who developed NMSC, 1 received NBUVB, 1 received both NBUVB and BBUVB, 1 received UVA, 1 received PUVA, and 3 did not receive phototherapy. The time period from phototherapy initiation to the development of NMSC ranged from 2 to 6 years. The patient who developed melanoma had previously been treated with PUVA for morphea\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTreatment Modalities for Morphea in 23 Patients Who Developed Malignancy Post-Treatment: A Subgroup Analysis\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType of treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime interval, range (years)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eType of malignancy (n)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhototherapy\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNBUVB*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNMSC (2)\u003c/p\u003e \u003cp\u003eStomach (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUVA**\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNMSC (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePUVA***\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (13%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4\u0026ndash;8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eBreast (1)\u003c/p\u003e \u003cp\u003eNMSC (1)\u003c/p\u003e \u003cp\u003eUterus (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBBUVB****\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNMSC (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSystemic pharmacological therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMethotrexate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCervix (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcitretin\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (4.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eLung (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eTopical treatment only\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (56.5%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2\u0026ndash;14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNMSC (4)\u003c/p\u003e \u003cp\u003eCervix (2)\u003c/p\u003e \u003cp\u003eHematological (2)\u003c/p\u003e \u003cp\u003eLung (1)\u003c/p\u003e \u003cp\u003eVulvar (1)\u003c/p\u003e \u003cp\u003eBreast (1)\u003c/p\u003e \u003cp\u003eMelanoma (1)\u003c/p\u003e \u003cp\u003eStomach (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"4\"\u003e*NBUVB-Narrowband ultraviolet B therapy, **UVA-Ultraviolet light A, ***PUVA-Psoralen plus UVA, ****BBUVB-Broadband ultraviolet B therapy. NMSC - non-melanoma skin cancer.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003ePatients diagnosed with morphea after malignancy\u003c/h2\u003e \u003cp\u003eThe mean age at cancer diagnosis in this subgroup was 58.6 (\u0026plusmn;\u0026thinsp;13.7) years, with 48.2% diagnosed with generalized morphea and 51.8% with limited morphea. Breast cancer was the most common, occurring in 34.3% of cases, followed by colon cancer at 10.3%, and prostate and testicular cancers at 6.9% each. Breast cancer was significantly more frequent in this subgroup compared to those diagnosed with morphea before cancer (p\u0026thinsp;=\u0026thinsp;0.028). Among the treatment modalities for all breast cancer patients, all 10 received radiation therapy, one underwent chemotherapy, and four were treated with hormone therapy. Of these 10 patients, 6 had limited plaque-type morphea, and 4 had generalized morphea. In cases with limited plaque-type morphea, it affected sites that were exposed to radiation. One patient with colon cancer received radiotherapy, chemotherapy, and immunotherapy, while two were treated solely with surgery. Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e provides details on cancer treatment modalities and the interval between cancer treatment initiation and morphea diagnosis.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCancer Treatment Modalities in 29 Patients Diagnosed with Morphea Following Malignancy\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCancer treatment modality\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePatients, n (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eTime interval, years, range (mean\u0026plusmn;SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSurgery\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e23 (79.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;48 (9.46\u0026plusmn;10.96)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChemotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e4 (13.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2\u0026ndash;9 (4.63\u0026plusmn;3.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRadiotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e13 (44.8%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;30 (6.12\u0026plusmn;7.58)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHormone therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e5 (17.2%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;6 (3.6\u0026plusmn;1.95)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunotherapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2 (6.9%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.5-9 (5.75\u0026plusmn;4.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultimodal treatment*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e12 (41.3%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1\u0026ndash;30 (6.96\u0026plusmn;7.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003e*Multimodal treatment was defined as the use of at least two treatment modalities.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eOur retrospective cohort study unveils intriguing connections between morphea and various malignancies. Typically viewed as a dermatological condition, morphea demonstrates associations with cancer. This analysis provides valuable insights into malignancy types, their timing relative to morphea diagnosis, and potential mechanisms linking these conditions.\u003c/p\u003e \u003cp\u003eGender distribution exhibited a female predominance, consistent with prior studies\u003csup\u003e1,2\u003c/sup\u003e. However, no significant gender differences emerged between patients with and without malignancy, suggesting gender may not affect cancer risk in morphea patients\u003csup\u003e1,12\u003c/sup\u003e. Older age emerged as a critical risk factor for cancer in morphea patients, likely due to factors like cumulative genetic mutations, chronic inflammation, and immunological changes\u003csup\u003e13,14\u003c/sup\u003e. These findings emphasize the importance of monitoring and targeted risk management for older morphea patients.\u003c/p\u003e \u003cp\u003eSignificant diagnostic delays, averaging 3.25 years, were noted, consistent with previous research. These delays arise from factors such as limited awareness among patients and healthcare providers, restricted access to specialists, nonspecific symptoms, gradual disease progression, and variable presentations\u003csup\u003e1,15\u003c/sup\u003e. Addressing these delays requires enhanced awareness and improved diagnostics. Importantly, time to diagnosis didn\u0026rsquo;t correlate with malignancy status, indicating no significant impact on malignancy development in morphea patients.\u003c/p\u003e \u003cp\u003eIn our study, the most common malignancies in patients with pre-existing morphea were NMSC, cervical, breast, stomach, and lung cancers, differing from previous findings published by Joly-Chevrier et al. that reported pancreatic, skin, gynecological, and breast cancer as predominant\u003csup\u003e9\u003c/sup\u003e. These discrepancies may stem from geographic variations such as regional dietary habits or smoking rates, as well as methodological differences. Future studies should aim to standardize these factors to enable more consistent comparisons.\u003c/p\u003e \u003cp\u003eNMSC predominated post-morphea diagnosis, consistent with prior research\u003csup\u003e10,11\u003c/sup\u003e. Extensive UV light exposure emerged as a significant risk factor. Notably, 5 out of the 8 NMSC patients in our cohort had received phototherapy. Although our data suggested a higher tendency for phototherapy use among patients who developed malignancy compared to those who did not, the differences were not statistically significant. Further research is necessary to confirm or refute this observation. Other potential factors contributing to NMSC risk include immunosuppressive therapy, whether used alone or in combination with UV light. Additionally, the persistent inflammation and fibrosis characteristic of morphea, accompanied by increased levels of cytokines such as IL-4, IL-13, and transforming growth factor β, may promote epithelial cell malignant transformation\u003csup\u003e10,11\u003c/sup\u003e. Genetic predisposition to autoimmune disorders could heighten cancer susceptibility, suggesting a common cause for both conditions\u003csup\u003e11\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eCervical cancer emerged as the second most frequent malignancy in morphea patients. Supporting this observation, Hemminki K et al. reported an elevated risk of cervical cancer in individuals with localized scleroderma. Factors underlying this association include chronic inflammation and fibrosis, which are known to drive oncogenesis; potential shared genetic or environmental risk factors; hormonal imbalances commonly seen in autoimmune disorders; and immune dysregulation, compromising defense against oncogenic viruses like HPV, thereby heightening the risk of cervical cancer\u003csup\u003e16\u003c/sup\u003e. Additional types of cancer that were more common in morphea patients who developed malignancy after diagnosis included breast, stomach, and lung cancers. Potential explanations include chronic inflammation, fibrosis, and immunosuppressive treatment. It is important to note, however, that Hemminki's study found no increased risk of breast cancer in morphea patients\u003csup\u003e16\u003c/sup\u003e. The number of cases per type of cancer was small; therefore, there is a need for larger sample sizes. Most patients with cancer did not receive systemic immunosuppressive therapy before their cancer diagnosis, thus indicating that the risk associated with this treatment seems to be less significant. Therefore, further research is needed to clarify this discrepancy.\u003c/p\u003e \u003cp\u003eIn patients with malignancies preceding morphea, the most common types were breast cancer, NMSC, colon, prostate, and testicular cancers. Breast cancer was the most prevalent, comprising 34.5% of cases. All those with prior breast cancer who developed morphea had received radiation therapy. Among these, 4 cases presented with generalized morphea and 6 with limited plaque-type morphea in irradiated areas, supporting prior studies linking morphea to radiation\u003csup\u003e17\u0026ndash;20\u003c/sup\u003e. The relationship between breast cancer and morphea is multifaceted, involving several treatment modalities and biological responses. Radiation therapy, a common treatment for breast cancer, can induce fibrosis by damaging both cancerous and healthy cells, triggering a reactive increase in connective tissue. The tumor itself may also provoke an inflammatory response, contributing to fibrotic changes in the surrounding tissues. Surgical interventions can lead to scarring and fibrosis at the surgical site. Additionally, chemotherapy and hormone therapies used in breast cancer treatment can disrupt normal cellular and hormonal functions, potentially leading to further fibrotic developments. There are also rare cases of morphea linked to chemotherapy and immunotherapy treatments, including PD-1 and CTLA-4 inhibitors\u003csup\u003e9\u003c/sup\u003e. Each of these factors can individually or collectively contribute to morphea onset in breast cancer patients.\u003c/p\u003e \u003cp\u003eCompared to Joly-Chevrier's review, our cohort's morphea patients with associated malignancy were notably older (64.7 vs. 38.8 years) and had a shorter time from morphea diagnosis to cancer onset (5.43 vs. 15 years)\u003csup\u003e9\u003c/sup\u003e. In our cohort, although not significant, there was a trend toward higher generalized morphea in the cancer-associated group, consistent with previous findings\u003csup\u003e9,21\u003c/sup\u003e. Atrophoderma of Pasini and Pierini (APP) was more prevalent in malignancy-associated patients, a novel observation requiring further validation. Research on the association between morphea subtypes and cancer is limited\u003csup\u003e9\u0026ndash;11\u003c/sup\u003e. Case reports have linked APP with neoplastic conditions, necessitating additional investigation to elucidate these relationships, particularly regarding Borrelia burgdorferi infections\u003csup\u003e22\u0026ndash;27\u003c/sup\u003e. The time interval between cancer treatment and morphea development varied from prior data: 4.6 vs. 1.6 years for chemotherapy, 6.1 vs. 3.1 years for radiotherapy, and 5.7 vs. 0.8 years for immunotherapy.\u003c/p\u003e \u003cp\u003eIncreased all-cause mortality in morphea patients with malignancy, particularly those diagnosed before their cancer, necessitates significant clinical focus. Morphea may activate biological pathways predisposing to aggressive or treatment-resistant cancers, a risk heightened by immunosuppressive treatments weakening immune defense. Chronic inflammation linked to morphea could enhance tumor growth, and overlapping symptoms might delay cancer diagnosis. Furthermore, treatments like radiation or chemotherapy could raise secondary cancer risks, with possible inherent genetic or molecular factors in morphea patients amplifying their vulnerability to malignancies.\u003c/p\u003e \u003cp\u003eStrengths of our study include comprehensive data collection from a sizable patient cohort, encompassing diverse demographics to enhance relevance. Detailed clinical evaluations further enrich our analysis. However, limitations include the retrospective nature of the analysis, potentially introducing biases. Conducting the study in a single tertiary care center may limit generalizability, and limited sample sizes for subgroup analyses may reduce statistical power. Reliance on medical records hampers capturing comprehensive patient information, affecting outcomes.\u003c/p\u003e \u003cp\u003eIn conclusion, our study underscores the bidirectional link between morphea and malignancies, influenced by patient age, sequence of diagnoses, and treatments. Vigilant monitoring is crucial for morphea patients, especially those with associated cancers, emphasizing the importance of heightened awareness, early detection, and refined management strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eFunding sources: None\u003c/p\u003e\n\u003cp\u003eConflict of interest: None\u003c/p\u003e\n\u003cp\u003eEthical approval: The study was conducted with approval from the institutional review board (Approval Number [2021-1401]).\u003c/p\u003e\n\u003cp\u003eEthics statement: Since the study didn\u0026rsquo;t include information or images that could identify patients, informed consent wasn\u0026rsquo;t required.\u003c/p\u003e\n\u003cp\u003eData availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003eAuthorship: All authors met the criteria for authorship.\u003c/p\u003e\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eK. L. contributed to the conceptual idea, data collection, analysis, and wrote the draft of the manuscript. G. D. discussed the results, contributed to the interpretation of the results, and critically revised the manuscript. D. M. contributed to the design of the research, data interpretation, and critically revised the manuscript. A. A. planned and supervised the project, contributed to the interpretation of the results, and critically revised the manuscript. All authors reviewed and approved the final manuscript.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003ePapara C, De Luca DA, Bieber K, Vorobyev A, Ludwig RJ. Morphea: The 2023 update. Frontiers in Medicine 2023;\u003cstrong\u003e10\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eSzczȩch J, Samotij D, Jaworecka K, Tobiasz A, Reich A. 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Immunosenescence: a key player in cancer development. Journal of Hematology and Oncology 2020;\u003cstrong\u003e13\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eJohnson W, Jacobe H. Morphea in adults and children cohort II: Patients with morphea experience delay in diagnosis and large variation in treatment. \u003cem\u003eJ Am Acad Dermatol\u003c/em\u003e 2012;\u003cstrong\u003e67\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eHemminki K, Liu X, Ji J, F\u0026ouml;rsti A, Sundquist J, Sundquist K. Effect of autoimmune diseases on risk and survival in female cancers. \u003cem\u003eGynecol Oncol\u003c/em\u003e 2012;\u003cstrong\u003e127\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eArdern-Jones MR, Black MM. Widespread morphoea following radiotherapy for carcinoma of the breast. \u003cem\u003eClin Exp Dermatol\u003c/em\u003e 2003;\u003cstrong\u003e28\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eDavis DA, Cohen PR, McNeese MD, Duvic M. 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International Journal of Cancer 2012;\u003cstrong\u003e131\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eGaur G, Sawant JY, Chavan AS, \u003cem\u003eet al.\u003c/em\u003e Effect of invasion of borrelia burgdorferi in normal and neoplastic mammary epithelial cells. \u003cem\u003eAntibiotics\u003c/em\u003e 2021;\u003cstrong\u003e10\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eBuechner SA, Rufli T. Atrophoderma of Pasini and Pierini: Clinical and histopathologic findings and antibodies to Borrelia burgdorferi in thirty-four patients. \u003cem\u003eJ Am Acad Dermatol\u003c/em\u003e 1994;\u003cstrong\u003e30\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eLee Y, Oh Y, Ahn SY, Park HY, Choi EH. A case of atrophoderma of Pasini and Pierini associated with Borrelia burgdorferi infection successfully treated with oral doxycycline. \u003cem\u003eAnn Dermatol\u003c/em\u003e 2011;\u003cstrong\u003e23\u003c/strong\u003e.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Localized scleroderma, morphea, mortality, malignancy, neoplasms","lastPublishedDoi":"10.21203/rs.3.rs-4772917/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4772917/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eThe association between systemic scleroderma and malignancy is well-documented, but there is limited data on the relationship between morphea and malignancy. This study aims to assess the incidence and types of malignancies in morphea patients, comparing demographics, clinical characteristics, treatments, and outcomes between those with and without malignancy. We conducted a retrospective study of 204 morphea patients treated at Rabin Medical Center between 2012 and 2023. Data on demographics, clinical subtypes, comorbidities, treatments, and outcomes were collected. Patients were categorized based on malignancy status and the timing of malignancy relative to their morphea diagnosis. Among the 204 patients (154 women and 50 men, mean age 53.7\u0026thinsp;\u0026plusmn;\u0026thinsp;20 years), 47 (23%) developed malignancies. In 29 patients (61.7%), malignancy occurred before the onset of morphea; in 23 patients (48.9%), it occurred after morphea. Five patients (10.6%) had malignancies both before and after the diagnosis of morphea. Patients with malignancy were significantly older than those without (64.7\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1 years vs. 50.3\u0026thinsp;\u0026plusmn;\u0026thinsp;20 years, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001). The all-cause mortality rate was higher in the malignancy group compared to those without malignancy (23.4% vs. 3.8%, p\u0026thinsp;=\u0026thinsp;0.00002). Moreover, mortality was higher in patients whose malignancy occurred after morphea than in those whose malignancy preceded morphea (26% vs. 17.2%). The most common post-morphea malignancies included non-melanoma skin cancer, cervical cancer, breast cancer, stomach cancer, and lung cancer. The most common pre-morphea malignancies included breast cancer, non-melanoma skin cancer, colon cancer, prostate cancer, and testicular cancer. This study highlights a bidirectional link between morphea and malignancies, influenced by patient age, sequence of diagnosis, and treatment regimens. Vigilant monitoring for malignancy, early detection, and effective management strategies are crucial for improving outcomes in morphea patients.\u003c/p\u003e","manuscriptTitle":"Exploring the Relationship Between Morphea and Malignancy: A Decade-Long Single- Center Study of 204 Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-16 05:54:05","doi":"10.21203/rs.3.rs-4772917/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-08-05T17:17:01+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-08-01T17:45:04+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"205151596333668603573298013239689067734","date":"2024-08-01T17:08:47+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"261248193229569700867086874696245885035","date":"2024-07-31T22:34:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-07-31T18:00:18+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-22T07:45:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-22T07:44:18+00:00","index":"","fulltext":""},{"type":"submitted","content":"Archives of Dermatological Research","date":"2024-07-20T11:35:19+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"archives-of-dermatological-research","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"","sideBox":"Learn more about [Archives of Dermatological Research](https://www.springer.com/journal/403)","snPcode":"403","submissionUrl":"https://submission.nature.com/new-submission/403/3","title":"Archives of Dermatological Research","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5e940f48-ab81-441d-a6c3-fc1a7bffd22b","owner":[],"postedDate":"August 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2024-08-26T23:52:11+00:00","versionOfRecord":[],"versionCreatedAt":"2024-08-16 05:54:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4772917","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4772917","identity":"rs-4772917","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}