Characterization of patients with cutaneous squamous cell carcinoma arising in hidradenitis suppurativa from a racially and ethnically diverse population

Characterization of patients with cutaneous squamous cell carcinoma arising in hidradenitis suppurativa from a racially and ethnically diverse population | 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 Characterization of patients with cutaneous squamous cell carcinoma arising in hidradenitis suppurativa from a racially and ethnically diverse population Michelle Toker, Lindsay Pattison, Pooja Srivastava, Bijal Amin, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3340723/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Cutaneous squamous cell carcinoma (cSCC) is a lethal consequence of longstanding hidradenitis suppurativa (HS), yet there is limited knowledge regarding this complication. While some risk factors have been identified, including human papillomavirus and smoking, other variables such as obesity, socioeconomic status (SES), and human immunodeficiency virus, have yet to be assessed. Furthermore, previous studies of HS-associated cSCC have predominantly examined White individuals. We evaluate the comorbidities and clinical characteristics of patients with cSCC arising in HS who received their care at a diverse medical center, thereby adding to the limited racial and ethnic representation of this rare, potentially life-threatening neoplasm. Screening a total of 6960 patients with HS, we identified 7 (approximately 0.1%) patients who met criteria for cSCC-in situ or cSCC in the setting of pre-existing HS lesions. All patients were Black or Hispanic and the majority were female, smoked tobacco, experienced metabolic syndrome, required multiple cutaneous biopsies for a definitive diagnosis of cSCC, and had low SES. Compared to previous cohorts, our skin of color patients had diminished rates of cSCC metastasis and mortality, and shorter time intervals between HS and cSCC diagnoses. Assessing the clinical and prognostic features of this complication in diverse patient populations is essential given that HS may be more prevalent in patients of color. We also explore numerous unique risk factors to better understand the pathogenesis of this grave complication. cutaneous squamous cell carcinoma hidradenitis suppurativa malignancy metastasis skin of color diversity Figures Figure 1 Introduction Hidradenitis suppurativa (HS) is a chronic inflammatory disorder of follicular biology. It manifests with painful nodules, abscesses, sinus tracts, and scarring that predominantly involve the axillary, inframammary, suprapubic, inguinal, upper inner thigh, and buttock skin [ 3 , 13 ]. One of the most ominous complications of HS, cutaneous squamous cell carcinoma (cSCC), may arise in longstanding sites of disease activity, particularly those in the perineum and gluteal regions [ 3 ]. It is postulated that chronic inflammation and lymphatic disruption in the sinus tracts drive malignant transformation [ 2 ]. While this complication is rare, the cSCCs are typically aggressive with substantial local invasion, as well as increased risk of metastasis [ 3 ]. In a recent literature review, the rate of metastasis was 54.0% and disease-specific mortality 58.7% [ 13 ]. The poor prognosis may be partially attributed to the delay in diagnosis of cSCC as clinical differentiation from the underlying HS is often difficult [ 3 , 7 ]. While current guidelines recommend a low threshold for biopsy of suspicious lesions, small samples of large, heterogeneous lesions can easily camouflage a malignant focus [ 7 ]. Once identified, cSCC staging is followed by positron emission tomography (PET) imaging and sentinel lymph node biopsy. Most patients undergo surgical excision of the primary focus with 2 cm margins, which in the perineum and gluteal region can result in functional and aesthetic complications including contractures, incontinence, impotence, and the potential need for colostomy [ 13 ]. The prevalence of HS in the United States is reportedly 3-fold greater in Black patients and 2-fold greater in biracial patients, compared to White patients [ 6 ]. Previous reports of cSCC arising in HS were comprised of 83.3% White and 14.3% Black patients [ 11 ]. Whether this reflects White skin as a risk factor for cSCC or a reporting bias is unknown. Many prior studies do not address race or ethnicity [ 10 ]. It is noteworthy that socioeconomic status (SES), body mass index (BMI), and history of diabetes have not been specifically explored as potential risk factors. In the current study, we evaluate the comorbidities and clinical characteristics of patients with cSCC arising in HS who received care at a racially/ethnically diverse urban medical center. Methods We performed an institutional review board-approved (Einstein IRB #2022–14585) retrospective, observational cohort study of adult patients ≥ 18 years of age with cSCC or cSCC-in situ (-is) in the setting of HS at our institution between January 1st, 2015 and September 30th, 2022. Screening a total of 6960 patients with HS (ICD-9: 705.83 and ICD-10: L73.2 codes), we sought to identify those with both HS and cutaneous cSCC(-is) (ICD-9: 173.92 and ICD-10: C44.92 and C44.5). Electronic medical records were used to retrieve demographic and clinical information and refine the total number cSCC(-is) cases to those anatomically associated with HS. Data on race and ethnicity were obtained through patient-reported demographic information, and SES was based on insurance status with Medicaid insurance serving as a proxy for low SES [ 5 ]. Results Our search identified 33 patients with both HS and cSCC(-is). Seven patients (approximately 0.1%) met criteria for cSCC(-is) in the setting of pre-existing HS lesions (Table 1 ). The mean age at cSCC(-is) diagnosis was 55.7 ± 7.1 years (range 44–66), 57% were female, 6 identified as Black or African American and 1 identified as Spanish/Hispanic/Latino. Low SES was observed in 4 (57%) patients. Other comorbidities, tobacco and alcohol use, and treatments are listed in the Table 1 . No patient had a documented history of human papilloma virus (HPV) or human immunodeficiency virus (HIV) infection. Table 1 Patient demographics and clinical characteristics Pt Age Sex Race/ Ethnicity BMI (kg/m 2 ) PMH Smoker HS severity HS treatment Time from HS to cSCC diagnosis (days) Body site Biopsy details Invasion/ Metastasis cSCC treatment Vital status 1 66 F AA, not Hispanic 44.6 DM, obesity, thalassemia No NA Oral antibiotics 2100 Thighs Punch (n = 1) Potential lymph node invasion None Deceased 2 57 F Hispanic 36.7 Pre-diabetes, hyper-cholesterolemia Yes NA Topical BP, clindamycin gel, hibiclens Longstanding subjective HS, formal diagnosis concurrent with SCC Breast Excision (n = 2) None Surgical resection Alive 3 51 M AA, not Hispanic 35.7 Pre-diabetes, hyper-cholesterolemia, alcohol use disorder Yes NA Topical BP, clindamycin gel, hibiclens, ILTAC, surgical excision 24 Anal/ perianal Excision (n = 4) None Surgical resection Alive 4 60 M AA, not Hispanic 18.0 Pulmonary HTN, HFrER Yes Hurley III Clindamycin gel, hibiclens, IV ertapenem, IV infliximab, finasteride, surgical excision 7414 Anal/ perianal Excision, punch, shave (n = 7); HPV RNA testing performed Potential lymph node invasion Surgical resection, chemotherapy, radiation Alive 5 59 M AA, not Hispanic 22.1 DM, HTN Yes NA Surgical excision, topical metronidazole 7080 Buttocks Punch (n = 1) Pulmonary SCC metastasis Chemotherapy, radiation Deceased 6 44 F AA, not Hispanic 36.6 DM, HTN, obesity, VIN Yes Hurley III Oral antibiotics, clindamycin gel, spironolactone, OCP, IV infliximab, surgical excision Longstanding subjective HS, formal diagnosis 471days prior to SCC diagnosis Anal/ perianal Excision (n = 9); p16 staining performed Potential lymph node invasion Surgical resection, chemotherapy, radiation Alive 7 53 F AA, not Hispanic 17.2 Anemia, arthritis No Hurley III Hibiclens, oral antibiotics, ILTAC, IV infliximab, surgical excision 12107 Thigh, buttocks Punch, excision (n = 11) Lymph node, perineum, pelvic bone, labia, vagina invasion Palliative care Deceased Table 1 Legend : Demographic information, risk factors, clinical features of hidradenitis suppurativa and cutaneous squamous cell carcinoma, and clinical outcomes of all 7 patients Table 1 Footnote : Pt: patient; F: female; M: male; AA: African American; BMI: body mass index; PMH: past medical history; DM: diabetes mellitus; HTN: hypertension; HFrEF: heart failure with reduced ejection fraction; VIN: vulvar intraepithelial neoplasia; HS: hidradenitis suppurativa; NA: not available; BP: benzoyl peroxide; ILTAC: intralesional triamcinolone; IV: intravenous; OCP: oral contraceptive pills; cSCC: cutaneous squamous cell carcinoma Hurley staging for HS was only available for 3 of 7 patients, all stage III disease. The average duration from HS diagnosis to the identification of cSCC(-is) was 11.4 ± 13 years (range 0-33.2). Affected body sites included the thigh (n = 2), breast (n = 1), anal/perianal region (n = 3), and buttocks (n = 2) (Fig. 1 ). Cutaneous cSCC(-is) was confirmed in all patients after biopsy of suspicious HS lesion morphology and/or imaging that showed lymphadenopathy. The average number of biopsies needed to establish a definitive diagnosis of cSCC(-is) was 5 ± 4 (range 1–11). The types of biopsies included punch, excision, and shave. On pathology, invasive cSCC was found in 4 patients, cSCC(-is) was found in 1 patient, and epidermal hyperplasia with atypia suspicious for cSCC was found in 2 patients. One patient with anal/perianal disease received p16 immunostaining, which was positive, and another patient with anal/perianal disease received HPV RNA in situ hybridization testing, which was negative. Five patients underwent diagnostic imaging including PET (n = 3), CT scan (n = 1), or MRI (n = 1); 4 exhibited potential lymph node invasion. No patient underwent lymph node biopsy. Sites of metastatic disease included lungs (n = 1) and bone (n = 1). Two patients were treated with surgical resection, 1 received chemotherapy and radiation, and 2 underwent surgery, chemotherapy, and radiation; 1 patient died due to septic shock 39 days following diagnosis, exacerbated by necrotizing fasciitis within the disease site before treatment of the cSCC; the last patient received palliative care and died 304 days following cSCC diagnosis. None of our patients were treated with immunotherapy. Four patients achieved a durable remission initially but 1 patient in this group died due to metastatic cSCC 276 days following cSCC diagnosis. Discussion The current literature on cSCC arising from HS describes 138 cases, with the largest consecutive case series comprising 13 patients from a single institution in France [ 1 , 3 , 4 , 7 – 9 , 11 – 13 ]. The mean duration between HS onset and cSCC transformation is approximately 25.5 years [ 13 ]. This is significantly longer than the average time between HS and cSCC(-is) diagnoses in our cohort, which was approximately 11.4 years. However, this time difference may be underestimated in our study as 2 patients with a documented, longstanding history of HS symptoms did not receive an official diagnosis until later in their clinical course. One of these patients was only formally diagnosed with HS after cSCC(-is) was detected. It is curious that in HS the reported F:M ratio is 3:1 but HS-associated cSCC is encountered more frequently in men [ 3 ]. In our cohort, 4 of 7 (57%) cases were women. Racanelli et al. conducted the most extensive investigation of prognostic characteristics among patients with cSCC arising in HS [ 11 ]. This systematic review and meta-analysis concluded the majority of affected patients were middle-aged White males with a history of tobacco smoking. By comparison, our cohort consisted of middle-aged patients (4 female; 3 male) with SOC; 5 of 7 reporting tobacco smoking. As smoking is an independent risk factor for both HS and cSCC, it is difficult to ascertain from our study whether smoking contributed to cSCC transformation of pre-existing HS lesions. Additionally, HPV is a common risk factor in HS-associated cSCC, especially in cases of anal disease, with HPV detection occurring in 30% or more of HS-associated cSCC cases [ 3 , 8 , 9 , 11 , 13 ]. It is postulated that patients with anogenital HS experience HPV autoinoculation, which, in addition to chronic HS-induced inflammation, may contribute to the preponderance of HS-associated cSCC in anogenital lesions [ 11 ]. However, none of our patients, including the 3 patients with anal/perianal disease, had a known history of HPV. Only 2 patients received pathologic HPV or p16 testing of a biopsied anal/perianal tissue sample, 1 of which was positive for p16 immunostaining. We recognize that lack of universal HPV testing in our cohort is a limitation, as HPV-related anal cancer cannot be ruled out. Similarly, testing for HIV, a risk factor for HPV infection, was also not performed. Delineating high-risk HPV-associated cSCC from non-HPV-associated cSCC arising from a chronic wound is important as these 2 entities have varying underlying pathophysiology. It is also important to consider that tumor necrosis factor alpha (TNF-α) inhibitors for severe HS, such as adalimumab and infliximab, have recently been linked to increased risk of malignant transformation [ 1 , 4 , 12 ]. In our cohort, 3 patients received TNF-α inhibitor therapy for HS management. Familial HS is another factor implicated in HS-associated cSCC; but none of our patients reported a family history of HS [ 14 ]. The role of other common HS comorbidities as risk factors for cSCC transformation, including obesity, diabetes, and HIV infection, remains largely unexplored. While cSCC arising from HS has a reported metastasis rate of greater than 50%, the rate in our cohort was 16.7%. Additionally, the disease-specific mortality rate in our cohort was 43%, which was lower than reported in the literature [ 13 ]. The lower metastasis and mortality rates we observed may be due to only 57% of patients having a pathologic diagnosis of invasive cSCC. Among the patients who expired, 1 chose palliative care, 1 expired prior to initiation of treatment, and 1 had pulmonary metastases managed with chemoradiation and expired during treatment. All 3 patients were African American and had a history of smoking, diabetes, or obesity. This study expands the racial and ethnic composition of patients with HS-associated cSCC(-is) and emphasizes the importance of considering this ominous complication regardless of race and ethnicity. The predominance of White patients in prior cSCC reports may be a selection bias rather than reflecting an accurate racial prevalence. We estimate that the period prevalence of HS-associated cSCC(-is) was 0.1% among patients with an ICD diagnosis of HS during our study period. It is recognized that some patients with an ICD diagnosis may not have had a clinical diagnosis, and others may have a clinical diagnosis without an ICD diagnosis. Larger epidemiologic studies are needed to characterize the impact of race on cSCC risk in patients with HS. Our cohort suggests that other risk factors for HS-associated cSCC, including obesity, diabetes, and low SES, should also be investigated in order to better understand the contribution of these factors to the development and clinical course of cSCC arising in HS. Identifying HS patients from all racial/ethnic backgrounds at high risk for malignant transformation will enable customization of screening protocols. Because of study limitations that include small sample size and a single institutional cohort, our findings are not intended to be generalized. Finally, while all of our cSCC cases were diagnosed from tissue specimens, the heterogenous nature of large wounds presents a considerable challenge to properly sampling for HS-associated cSCC, especially since the focus of cSCC is often deep, near the base of the sinus tracts, and there are typically many reactive changes on pathology. Accordingly, 5 (71%) of our patients required multiple biopsies to establish a diagnosis of cSCC. Therefore, in cases of high clinical suspicion, multiple biopsies, including incisional biopsy, as well as good communication with the pathologist, is necessary to establish the definitive diagnosis. In our patients who received radiographic imaging, bulky, hypermetabolic lymph nodes were a common finding. Accordingly, in patients with longstanding, severe HS with suspicious clinical findings, routine lymph node examination and possibly imaging with MRI or CT should be considered. The presence of enlarging lymphadenopathy in an area of concern may signal the development of cSCC. Future studies assessing the utility of imaging for monitoring and diagnostic purposes may facilitate improved prognosis of this grave complication in HS. Declarations Funding : None Competing Interests : None Author Contributions: All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by M.T. and L.P. The first draft of the manuscript was written by M.T. All authors commented on previous versions of the manuscript. All authors reviewed and approved the final manuscript. Ethics Approval: This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Institutional Review Board of the Albert Einstein College of Medicine (Einstein IRB #2022-14585) approved this study. References Bessaleli E, Scheinfeld N, Kroumpouzos G. Squamous cell carcinoma of the cervix arising in a patient on adalimumab – a need for cervical screenings in patients on tumor necrosis factor inhibitors. Dermatol Online J . May 15 2018;24(5) Caccavale S, Caccavale T, La Montagna M. Hidradenitis suppurativa associated with squamous cell carcinoma: an example of an isoscartopic response. Int J Dermatol . Dec 2016;55(12):e629-e631. doi:10.1111/ijd.13375 Chapman S, Delgadillo D, III, Barber C, Khachemoune A. Cutaneous squamous cell carcinoma complicating hidradenitis suppurativa: a review of the prevalence, pathogenesis, and treatment of this dreaded complication. Acta Dermatovenerol Alp Pannonica Adriat . Mar 2018;27(1):25-28. Cooper SD, Cowdrey MCE, Linos KD, Lefferts JA, Basic KK. Squamous Cell Carcinoma in Hidradenitis Suppurativa Lesions Following Tumor Necrosis Factor α Inhibitors. Cutis . Apr 2021;107(4):E5-e7. doi:10.12788/cutis.0233 Foraker RE, Rose KM, Whitsel EA, Suchindran CM, Wood JL, Rosamond WD. Neighborhood socioeconomic status, Medicaid coverage and medical management of myocardial infarction: atherosclerosis risk in communities (ARIC) community surveillance. BMC Public Health . Oct 21 2010;10:632. doi:10.1186/1471-2458-10-632 Garg A, Kirby JS, Lavian J, Lin G, Strunk A. Sex- and Age-Adjusted Population Analysis of Prevalence Estimates for Hidradenitis Suppurativa in the United States. JAMA Dermatology . 2017;153(8):760-764. doi:10.1001/jamadermatol.2017.0201 Jourabchi N, Fischer AH, Cimino-Mathews A, Waters KM, Okoye GA. Squamous cell carcinoma complicating a chronic lesion of hidradenitis suppurativa: a case report and review of the literature. Int Wound J . Apr 2017;14(2):435-438. doi:10.1111/iwj.12671 Kohorst JJ, Shah KK, Hallemeier CL, Baum CL, Davis MDP. Squamous Cell Carcinoma in Perineal, Perianal, and Gluteal Hidradenitis Suppurativa: Experience in 12 Patients. Dermatol Surg . Apr 2019;45(4):519-526. doi:10.1097/dss.0000000000001713 Lavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. Dermatology . 2010;220(2):147-53. doi:10.1159/000269836 Pena ZG, Sivamani RK, Konia TH, Eisen DB. Squamous cell carcinoma in the setting of chronic hidradenitis suppurativa; report of a patient and update of the literature. Dermatol Online J . Apr 16 2015;21(4) Racanelli E, Jfri A, Gefri A, et al. Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa. Cancers (Basel) . Mar 8 2021;13(5). doi:10.3390/cancers13051153 Roy CF, Roy SF, Ghazawi FM, Patocskai E, Bélisle A, Dépeault A. Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: A case report. SAGE Open Med Case Rep . 2019;7:2050313x19847359. doi:10.1177/2050313x19847359 Sachdeva M, Mufti A, Zaaroura H, et al. Squamous cell carcinoma arising within hidradenitis suppurativa: a literature review. Int J Dermatol . Nov 2021;60(11):e459-e465. doi:10.1111/ijd.15677 Scheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. Dermatol Online J . Mar 17 2014;20(3) Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted 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. 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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-3340723","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":232253673,"identity":"7504a42a-f026-4d5c-bbaf-ef99e5287e45","order_by":0,"name":"Michelle Toker","email":"","orcid":"","institution":"Department of Medicine, Division of Dermatology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Michelle","middleName":"","lastName":"Toker","suffix":""},{"id":232253674,"identity":"9cda4f32-c93d-4fe3-b418-ab85fcd5fca4","order_by":1,"name":"Lindsay Pattison","email":"","orcid":"","institution":"Department of Medicine, Division of Dermatology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Lindsay","middleName":"","lastName":"Pattison","suffix":""},{"id":232253676,"identity":"ead04578-ed44-429c-82f5-cbcc3ccc5c36","order_by":2,"name":"Pooja Srivastava","email":"","orcid":"","institution":"Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Pooja","middleName":"","lastName":"Srivastava","suffix":""},{"id":232253677,"identity":"49c575e9-649c-49fb-9cf0-f78ba3466205","order_by":3,"name":"Bijal Amin","email":"","orcid":"","institution":"Department of Pathology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Bijal","middleName":"","lastName":"Amin","suffix":""},{"id":232253679,"identity":"0d7dceea-bbf9-44f7-a0bf-881a20d89576","order_by":4,"name":"Beth N. 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It manifests with painful nodules, abscesses, sinus tracts, and scarring that predominantly involve the axillary, inframammary, suprapubic, inguinal, upper inner thigh, and buttock skin [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. One of the most ominous complications of HS, cutaneous squamous cell carcinoma (cSCC), may arise in longstanding sites of disease activity, particularly those in the perineum and gluteal regions [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. It is postulated that chronic inflammation and lymphatic disruption in the sinus tracts drive malignant transformation [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. While this complication is rare, the cSCCs are typically aggressive with substantial local invasion, as well as increased risk of metastasis [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In a recent literature review, the rate of metastasis was 54.0% and disease-specific mortality 58.7% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The poor prognosis may be partially attributed to the delay in diagnosis of cSCC as clinical differentiation from the underlying HS is often difficult [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWhile current guidelines recommend a low threshold for biopsy of suspicious lesions, small samples of large, heterogeneous lesions can easily camouflage a malignant focus [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Once identified, cSCC staging is followed by positron emission tomography (PET) imaging and sentinel lymph node biopsy. Most patients undergo surgical excision of the primary focus with 2 cm margins, which in the perineum and gluteal region can result in functional and aesthetic complications including contractures, incontinence, impotence, and the potential need for colostomy [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe prevalence of HS in the United States is reportedly 3-fold greater in Black patients and 2-fold greater in biracial patients, compared to White patients [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Previous reports of cSCC arising in HS were comprised of 83.3% White and 14.3% Black patients [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Whether this reflects White skin as a risk factor for cSCC or a reporting bias is unknown. Many prior studies do not address race or ethnicity [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. It is noteworthy that socioeconomic status (SES), body mass index (BMI), and history of diabetes have not been specifically explored as potential risk factors. In the current study, we evaluate the comorbidities and clinical characteristics of patients with cSCC arising in HS who received care at a racially/ethnically diverse urban medical center.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003e We performed an institutional review board-approved (Einstein IRB #2022\u0026ndash;14585) retrospective, observational cohort study of adult patients\u0026thinsp;\u0026ge;\u0026thinsp;18 years of age with cSCC or cSCC-in situ (-is) in the setting of HS at our institution between January 1st, 2015 and September 30th, 2022. Screening a total of 6960 patients with HS (ICD-9: 705.83 and ICD-10: L73.2 codes), we sought to identify those with both HS and cutaneous cSCC(-is) (ICD-9: 173.92 and ICD-10: C44.92 and C44.5). Electronic medical records were used to retrieve demographic and clinical information and refine the total number cSCC(-is) cases to those anatomically associated with HS. Data on race and ethnicity were obtained through patient-reported demographic information, and SES was based on insurance status with Medicaid insurance serving as a proxy for low SES [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e].\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eOur search identified 33 patients with both HS and cSCC(-is). Seven patients (approximately 0.1%) met criteria for cSCC(-is) in the setting of pre-existing HS lesions (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The mean age at cSCC(-is) diagnosis was 55.7\u0026thinsp;\u0026plusmn;\u0026thinsp;7.1 years (range 44\u0026ndash;66), 57% were female, 6 identified as Black or African American and 1 identified as Spanish/Hispanic/Latino. Low SES was observed in 4 (57%) patients. Other comorbidities, tobacco and alcohol use, and treatments are listed in the Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. No patient had a documented history of human papilloma virus (HPV) or human immunodeficiency virus (HIV) infection.\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\u003ePatient demographics and clinical characteristics\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"15\"\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c11\" colnum=\"11\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c12\" colnum=\"12\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c13\" colnum=\"13\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c14\" colnum=\"14\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c15\" colnum=\"15\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePt\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAge\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eRace/\u003c/p\u003e \u003cp\u003eEthnicity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eBMI\u003c/p\u003e \u003cp\u003e(kg/m\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePMH\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSmoker\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHS severity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHS treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c10\"\u003e \u003cp\u003eTime from HS to cSCC diagnosis (days)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBody site\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c12\"\u003e \u003cp\u003eBiopsy details\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c13\"\u003e \u003cp\u003eInvasion/\u003c/p\u003e \u003cp\u003eMetastasis\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c14\"\u003e \u003cp\u003ecSCC treatment\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c15\"\u003e \u003cp\u003eVital status\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e66\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e44.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDM, obesity, thalassemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eOral antibiotics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eThighs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003ePunch (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePotential lymph node invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDeceased\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eHispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e36.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePre-diabetes,\u003c/p\u003e \u003cp\u003ehyper-cholesterolemia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTopical BP, clindamycin gel, hibiclens\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLongstanding subjective HS, formal diagnosis concurrent with SCC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eBreast\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eExcision (n\u0026thinsp;=\u0026thinsp;2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eSurgical resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e35.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePre-diabetes,\u003c/p\u003e \u003cp\u003ehyper-cholesterolemia, alcohol use disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eTopical BP, clindamycin gel, hibiclens, ILTAC, surgical excision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAnal/\u003c/p\u003e \u003cp\u003eperianal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eExcision (n\u0026thinsp;=\u0026thinsp;4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eSurgical resection\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e60\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e18.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ePulmonary HTN, HFrER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHurley III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eClindamycin gel, hibiclens, IV ertapenem, IV infliximab, finasteride, surgical excision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7414\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAnal/\u003c/p\u003e \u003cp\u003eperianal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eExcision, punch, shave\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;7); HPV RNA testing performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePotential lymph node invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eSurgical resection, chemotherapy, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e22.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDM, HTN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eNA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eSurgical excision, topical metronidazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e7080\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eButtocks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003ePunch (n\u0026thinsp;=\u0026thinsp;1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePulmonary SCC metastasis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eChemotherapy, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDeceased\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e36.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eDM, HTN, obesity, VIN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHurley III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eOral antibiotics, clindamycin gel, spironolactone, OCP, IV infliximab, surgical excision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003eLongstanding subjective HS, formal diagnosis 471days prior to SCC diagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eAnal/\u003c/p\u003e \u003cp\u003eperianal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003eExcision (n\u0026thinsp;=\u0026thinsp;9); p16 staining performed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003ePotential lymph node invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003eSurgical resection, chemotherapy, radiation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eAlive\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eF\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAA, not Hispanic\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e17.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eAnemia, arthritis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003eHurley III\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eHibiclens, oral antibiotics, ILTAC, IV infliximab, surgical excision\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e12107\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c11\"\u003e \u003cp\u003eThigh, buttocks\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c12\"\u003e \u003cp\u003ePunch, excision (n\u0026thinsp;=\u0026thinsp;11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c13\"\u003e \u003cp\u003eLymph node, perineum, pelvic bone, labia, vagina invasion\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c14\"\u003e \u003cp\u003ePalliative care\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c15\"\u003e \u003cp\u003eDeceased\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e\u003cstrong\u003eTable 1 Legend\u003c/strong\u003e: Demographic information, risk factors, clinical features of hidradenitis suppurativa and cutaneous squamous cell carcinoma, and clinical outcomes of all 7 patients\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1 Footnote\u003c/strong\u003e: Pt: patient; F: female; M: male; AA: African American; BMI: body mass index; PMH: past medical history; DM: diabetes mellitus; HTN: hypertension; HFrEF: heart failure with reduced ejection fraction; VIN: vulvar intraepithelial neoplasia; HS: hidradenitis suppurativa; NA: not available; BP: benzoyl peroxide; ILTAC: intralesional triamcinolone; IV: intravenous; OCP: oral contraceptive pills; cSCC: cutaneous squamous cell carcinoma\u003c/p\u003e\u003cp\u003eHurley staging for HS was only available for 3 of 7 patients, all stage III disease. The average duration from HS diagnosis to the identification of cSCC(-is) was 11.4\u0026thinsp;\u0026plusmn;\u0026thinsp;13 years (range 0-33.2). Affected body sites included the thigh (n\u0026thinsp;=\u0026thinsp;2), breast (n\u0026thinsp;=\u0026thinsp;1), anal/perianal region (n\u0026thinsp;=\u0026thinsp;3), and buttocks (n\u0026thinsp;=\u0026thinsp;2) (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Cutaneous cSCC(-is) was confirmed in all patients after biopsy of suspicious HS lesion morphology and/or imaging that showed lymphadenopathy. The average number of biopsies needed to establish a definitive diagnosis of cSCC(-is) was 5\u0026thinsp;\u0026plusmn;\u0026thinsp;4 (range 1\u0026ndash;11). The types of biopsies included punch, excision, and shave. On pathology, invasive cSCC was found in 4 patients, cSCC(-is) was found in 1 patient, and epidermal hyperplasia with atypia suspicious for cSCC was found in 2 patients. One patient with anal/perianal disease received p16 immunostaining, which was positive, and another patient with anal/perianal disease received HPV RNA in situ hybridization testing, which was negative. Five patients underwent diagnostic imaging including PET (n\u0026thinsp;=\u0026thinsp;3), CT scan (n\u0026thinsp;=\u0026thinsp;1), or MRI (n\u0026thinsp;=\u0026thinsp;1); 4 exhibited potential lymph node invasion. No patient underwent lymph node biopsy. Sites of metastatic disease included lungs (n\u0026thinsp;=\u0026thinsp;1) and bone (n\u0026thinsp;=\u0026thinsp;1). Two patients were treated with surgical resection, 1 received chemotherapy and radiation, and 2 underwent surgery, chemotherapy, and radiation; 1 patient died due to septic shock 39 days following diagnosis, exacerbated by necrotizing fasciitis within the disease site before treatment of the cSCC; the last patient received palliative care and died 304 days following cSCC diagnosis. None of our patients were treated with immunotherapy. Four patients achieved a durable remission initially but 1 patient in this group died due to metastatic cSCC 276 days following cSCC diagnosis.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe current literature on cSCC arising from HS describes 138 cases, with the largest consecutive case series comprising 13 patients from a single institution in France [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan additionalcitationids=\"CR8\" citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR12\" citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The mean duration between HS onset and cSCC transformation is approximately 25.5 years [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. This is significantly longer than the average time between HS and cSCC(-is) diagnoses in our cohort, which was approximately 11.4 years. However, this time difference may be underestimated in our study as 2 patients with a documented, longstanding history of HS symptoms did not receive an official diagnosis until later in their clinical course. One of these patients was only formally diagnosed with HS after cSCC(-is) was detected. It is curious that in HS the reported F:M ratio is 3:1 but HS-associated cSCC is encountered more frequently in men [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In our cohort, 4 of 7 (57%) cases were women.\u003c/p\u003e \u003cp\u003eRacanelli et al. conducted the most extensive investigation of prognostic characteristics among patients with cSCC arising in HS [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. This systematic review and meta-analysis concluded the majority of affected patients were middle-aged White males with a history of tobacco smoking. By comparison, our cohort consisted of middle-aged patients (4 female; 3 male) with SOC; 5 of 7 reporting tobacco smoking. As smoking is an independent risk factor for both HS and cSCC, it is difficult to ascertain from our study whether smoking contributed to cSCC transformation of pre-existing HS lesions. Additionally, HPV is a common risk factor in HS-associated cSCC, especially in cases of anal disease, with HPV detection occurring in 30% or more of HS-associated cSCC cases [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. It is postulated that patients with anogenital HS experience HPV autoinoculation, which, in addition to chronic HS-induced inflammation, may contribute to the preponderance of HS-associated cSCC in anogenital lesions [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, none of our patients, including the 3 patients with anal/perianal disease, had a known history of HPV. Only 2 patients received pathologic HPV or p16 testing of a biopsied anal/perianal tissue sample, 1 of which was positive for p16 immunostaining. We recognize that lack of universal HPV testing in our cohort is a limitation, as HPV-related anal cancer cannot be ruled out. Similarly, testing for HIV, a risk factor for HPV infection, was also not performed. Delineating high-risk HPV-associated cSCC from non-HPV-associated cSCC arising from a chronic wound is important as these 2 entities have varying underlying pathophysiology. It is also important to consider that tumor necrosis factor alpha (TNF-α) inhibitors for severe HS, such as adalimumab and infliximab, have recently been linked to increased risk of malignant transformation [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In our cohort, 3 patients received TNF-α inhibitor therapy for HS management. Familial HS is another factor implicated in HS-associated cSCC; but none of our patients reported a family history of HS [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The role of other common HS comorbidities as risk factors for cSCC transformation, including obesity, diabetes, and HIV infection, remains largely unexplored.\u003c/p\u003e \u003cp\u003eWhile cSCC arising from HS has a reported metastasis rate of greater than 50%, the rate in our cohort was 16.7%. Additionally, the disease-specific mortality rate in our cohort was 43%, which was lower than reported in the literature [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. The lower metastasis and mortality rates we observed may be due to only 57% of patients having a pathologic diagnosis of invasive cSCC. Among the patients who expired, 1 chose palliative care, 1 expired prior to initiation of treatment, and 1 had pulmonary metastases managed with chemoradiation and expired during treatment. All 3 patients were African American and had a history of smoking, diabetes, or obesity.\u003c/p\u003e \u003cp\u003eThis study expands the racial and ethnic composition of patients with HS-associated cSCC(-is) and emphasizes the importance of considering this ominous complication regardless of race and ethnicity. The predominance of White patients in prior cSCC reports may be a selection bias rather than reflecting an accurate racial prevalence. We estimate that the period prevalence of HS-associated cSCC(-is) was 0.1% among patients with an ICD diagnosis of HS during our study period. It is recognized that some patients with an ICD diagnosis may not have had a clinical diagnosis, and others may have a clinical diagnosis without an ICD diagnosis. Larger epidemiologic studies are needed to characterize the impact of race on cSCC risk in patients with HS. Our cohort suggests that other risk factors for HS-associated cSCC, including obesity, diabetes, and low SES, should also be investigated in order to better understand the contribution of these factors to the development and clinical course of cSCC arising in HS. Identifying HS patients from all racial/ethnic backgrounds at high risk for malignant transformation will enable customization of screening protocols.\u003c/p\u003e \u003cp\u003eBecause of study limitations that include small sample size and a single institutional cohort, our findings are not intended to be generalized.\u003c/p\u003e \u003cp\u003eFinally, while all of our cSCC cases were diagnosed from tissue specimens, the heterogenous nature of large wounds presents a considerable challenge to properly sampling for HS-associated cSCC, especially since the focus of cSCC is often deep, near the base of the sinus tracts, and there are typically many reactive changes on pathology. Accordingly, 5 (71%) of our patients required multiple biopsies to establish a diagnosis of cSCC. Therefore, in cases of high clinical suspicion, multiple biopsies, including incisional biopsy, as well as good communication with the pathologist, is necessary to establish the definitive diagnosis. In our patients who received radiographic imaging, bulky, hypermetabolic lymph nodes were a common finding. Accordingly, in patients with longstanding, severe HS with suspicious clinical findings, routine lymph node examination and possibly imaging with MRI or CT should be considered. The presence of enlarging lymphadenopathy in an area of concern may signal the development of cSCC. Future studies assessing the utility of imaging for monitoring and diagnostic purposes may facilitate improved prognosis of this grave complication in HS.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests\u003c/strong\u003e: None\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions:\u0026nbsp;\u003c/strong\u003eAll authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by M.T. and L.P. The first draft of the manuscript was written by M.T. All authors commented on previous versions of the manuscript. All authors reviewed and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u003c/strong\u003e This retrospective chart review study involving human participants was in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The Institutional Review Board of the Albert Einstein College of Medicine (Einstein IRB #2022-14585) approved this study.\u003c/p\u003e"},{"header":"References","content":"\u003col start=\"1\" type=\"1\"\u003e\n\u003cli\u003eBessaleli E, Scheinfeld N, Kroumpouzos G. Squamous cell carcinoma of the cervix arising in a patient on adalimumab \u0026ndash; a need for cervical screenings in patients on tumor necrosis factor inhibitors. \u003cem\u003eDermatol Online J\u003c/em\u003e. May 15 2018;24(5)\u003c/li\u003e\n\u003cli\u003eCaccavale S, Caccavale T, La Montagna M. Hidradenitis suppurativa associated with squamous cell carcinoma: an example of an isoscartopic response. \u003cem\u003eInt J Dermatol\u003c/em\u003e. Dec 2016;55(12):e629-e631. doi:10.1111/ijd.13375\u003c/li\u003e\n\u003cli\u003eChapman S, Delgadillo D, III, Barber C, Khachemoune A. Cutaneous squamous cell carcinoma complicating hidradenitis suppurativa: a review of the prevalence, pathogenesis, and treatment of this dreaded complication. \u003cem\u003eActa Dermatovenerol Alp Pannonica Adriat\u003c/em\u003e. Mar 2018;27(1):25-28.\u003c/li\u003e\n\u003cli\u003eCooper SD, Cowdrey MCE, Linos KD, Lefferts JA, Basic KK. Squamous Cell Carcinoma in Hidradenitis Suppurativa Lesions Following Tumor Necrosis Factor \u0026alpha; Inhibitors. \u003cem\u003eCutis\u003c/em\u003e. Apr 2021;107(4):E5-e7. doi:10.12788/cutis.0233\u003c/li\u003e\n\u003cli\u003eForaker RE, Rose KM, Whitsel EA, Suchindran CM, Wood JL, Rosamond WD. Neighborhood socioeconomic status, Medicaid coverage and medical management of myocardial infarction: atherosclerosis risk in communities (ARIC) community surveillance. \u003cem\u003eBMC Public Health\u003c/em\u003e. Oct 21 2010;10:632. doi:10.1186/1471-2458-10-632\u003c/li\u003e\n\u003cli\u003eGarg A, Kirby JS, Lavian J, Lin G, Strunk A. Sex- and Age-Adjusted Population Analysis of Prevalence Estimates for Hidradenitis Suppurativa in the United States. \u003cem\u003eJAMA Dermatology\u003c/em\u003e. 2017;153(8):760-764. doi:10.1001/jamadermatol.2017.0201\u003c/li\u003e\n\u003cli\u003eJourabchi N, Fischer AH, Cimino-Mathews A, Waters KM, Okoye GA. Squamous cell carcinoma complicating a chronic lesion of hidradenitis suppurativa: a case report and review of the literature. \u003cem\u003eInt Wound J\u003c/em\u003e. Apr 2017;14(2):435-438. doi:10.1111/iwj.12671\u003c/li\u003e\n\u003cli\u003eKohorst JJ, Shah KK, Hallemeier CL, Baum CL, Davis MDP. Squamous Cell Carcinoma in Perineal, Perianal, and Gluteal Hidradenitis Suppurativa: Experience in 12 Patients. \u003cem\u003eDermatol Surg\u003c/em\u003e. Apr 2019;45(4):519-526. doi:10.1097/dss.0000000000001713\u003c/li\u003e\n\u003cli\u003eLavogiez C, Delaporte E, Darras-Vercambre S, et al. Clinicopathological study of 13 cases of squamous cell carcinoma complicating hidradenitis suppurativa. \u003cem\u003eDermatology\u003c/em\u003e. 2010;220(2):147-53. doi:10.1159/000269836\u003c/li\u003e\n\u003cli\u003ePena ZG, Sivamani RK, Konia TH, Eisen DB. Squamous cell carcinoma in the setting of chronic hidradenitis suppurativa; report of a patient and update of the literature. \u003cem\u003eDermatol Online J\u003c/em\u003e. Apr 16 2015;21(4)\u003c/li\u003e\n\u003cli\u003eRacanelli E, Jfri A, Gefri A, et al. Cutaneous Squamous Cell Carcinoma in Patients with Hidradenitis Suppurativa. \u003cem\u003eCancers (Basel)\u003c/em\u003e. Mar 8 2021;13(5). doi:10.3390/cancers13051153\u003c/li\u003e\n\u003cli\u003eRoy CF, Roy SF, Ghazawi FM, Patocskai E, B\u0026eacute;lisle A, D\u0026eacute;peault A. Cutaneous squamous cell carcinoma arising in hidradenitis suppurativa: A case report. \u003cem\u003eSAGE Open Med Case Rep\u003c/em\u003e. 2019;7:2050313x19847359. doi:10.1177/2050313x19847359\u003c/li\u003e\n\u003cli\u003eSachdeva M, Mufti A, Zaaroura H, et al. Squamous cell carcinoma arising within hidradenitis suppurativa: a literature review. \u003cem\u003eInt J Dermatol\u003c/em\u003e. Nov 2021;60(11):e459-e465. doi:10.1111/ijd.15677\u003c/li\u003e\n\u003cli\u003eScheinfeld N. A case of a patient with stage III familial hidradenitis suppurativa treated with 3 courses of infliximab and died of metastatic squamous cell carcinoma. \u003cem\u003eDermatol Online J\u003c/em\u003e. Mar 17 2014;20(3)\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"cutaneous squamous cell carcinoma, hidradenitis suppurativa, malignancy, metastasis, skin of color, diversity","lastPublishedDoi":"10.21203/rs.3.rs-3340723/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3340723/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eCutaneous squamous cell carcinoma (cSCC) is a lethal consequence of longstanding hidradenitis suppurativa (HS), yet there is limited knowledge regarding this complication. While some risk factors have been identified, including human papillomavirus and smoking, other variables such as obesity, socioeconomic status (SES), and human immunodeficiency virus, have yet to be assessed. Furthermore, previous studies of HS-associated cSCC have predominantly examined White individuals. We evaluate the comorbidities and clinical characteristics of patients with cSCC arising in HS who received their care at a diverse medical center, thereby adding to the limited racial and ethnic representation of this rare, potentially life-threatening neoplasm. Screening a total of 6960 patients with HS, we identified 7 (approximately 0.1%) patients who met criteria for cSCC-in situ or cSCC in the setting of pre-existing HS lesions. All patients were Black or Hispanic and the majority were female, smoked tobacco, experienced metabolic syndrome, required multiple cutaneous biopsies for a definitive diagnosis of cSCC, and had low SES. Compared to previous cohorts, our skin of color patients had diminished rates of cSCC metastasis and mortality, and shorter time intervals between HS and cSCC diagnoses. Assessing the clinical and prognostic features of this complication in diverse patient populations is essential given that HS may be more prevalent in patients of color. We also explore numerous unique risk factors to better understand the pathogenesis of this grave complication.\u003c/p\u003e","manuscriptTitle":"Characterization of patients with cutaneous squamous cell carcinoma arising in hidradenitis suppurativa from a racially and ethnically diverse population","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-09-14 17:50:51","doi":"10.21203/rs.3.rs-3340723/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6b8cad79-d3ab-43d2-a063-c54b42690d15","owner":[],"postedDate":"September 14th, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-06T04:29:25+00:00","versionOfRecord":[],"versionCreatedAt":"2023-09-14 17:50:51","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3340723","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3340723","identity":"rs-3340723","version":["v1"]},"buildId":"cBFmMYwuxLRRLfASyISRj","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}