Recurrent Cutaneous Manifestation in Multiple Myeloma: A Case Report and Management Approach

Recurrent Cutaneous Manifestation in Multiple Myeloma: A Case Report and Management Approach | 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 Case Report Recurrent Cutaneous Manifestation in Multiple Myeloma: A Case Report and Management Approach Mohammad Saad Salim Naviwala, Mariam Hina, Munira Moosajee, Nasir Ali This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3882128/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 Background Cutaneous involvement in multiple myeloma (MM) is an uncommonly encountered manifestation, more commonly observed in patients with aggressive subtypes, and often resistant to conventional therapies. Owing to its infrequency, reported clinical characteristics have been diverse and relatively nonspecific. Particularly uncommon is lower extremity involvement, where cutaneous MM is found. Case presentation In this report, we present a unique case of a middle age lady with refractory IgG lambda MM, who subsequently developed recurrent cutaneous plasmacytoma in the lower leg, while being on systemic therapy. Initially, the lesion resembled squamous cell carcinoma, posing a diagnostic challenge. Through meticulous histopathological and immunohistochemical studies, cutaneous involvement by multiple myeloma was conclusively confirmed. Conclusion This case highlights the importance of maintaining a high clinical suspicion for cutaneous MM in patients with MM who present with new skin lesions, as early diagnosis is crucial for appropriate management. Cutaneous plasmacytoma multiple myeloma radiotherapy chemotherapy wedge resection Figures Figure 1 Figure 2 Figure 3 Introduction MM is an infrequent type of blood cancer, comprising only 1 to 2% of all cancer cases and 17% of all hematological malignancies ( 1 ). It is a plasma cell dyscrasia, characterized by neoplastic proliferation of plasma cells in bone marrow leading to over production of monoclonal immunoglobulins called M-proteins or para-proteins. Cutaneous lesions in MM are rare and are found in fewer than 2% of patients with systemic MM ( 2 ). At the time of initial diagnosis, approximately 7% of patients with MM present with extramedullary plasmacytoma. However, 6% of patients may subsequently develop extramedullary symptoms at a later stage of disease. Patients with MM who had direct cutaneous involvement experienced a notable decrease in overall survival ( 3 ). The most common cause of cutaneous involvement in MM is metastasis and direct extension of the disease from nearby tumor sites.This typically presents as palpable violaceous nodules on the trunk and extremities. Frequently, cutaneous involvement in MM is observed during advanced stages of the disease, attributed to a higher tumor cell burden ( 3 ). These lesions are found in various anatomical locations, with the extremity, trunk and abdomen being the most frequently affected areas ( 4 ). Limited medical literature has discussed cutaneous involvement in MM. We present a rare case of a recurrent red, violaceous, and non-tender nodule on the left lower leg in a patient diagnosed with IgG lambda MM and currently undergoing systemic treatment. Case Presentation A middle aged female with a medical history of hypertension, Eastern Cooperative Oncology Group (ECOG) performance status of 2, and past pulmonary tuberculosis, presented with the complain of pain in left lower leg in tibial region for two months. Imaging revealed an 8.4 x 4.3 x 3.5 cm focal lesion in the proximal metaphysis of the left tibia, leading to a pathological fracture for which intramedullary nailing was done. PET-CT scan indicated hypermetabolic activity in various regions including the left tibia, soft tissue of the neck, right posterior iliac bone, L5 vertebra, multiple left ribs, and manubrium sterni. She was diagnosed with R-ISS Stage II, Immunoglobulin G (IgG) lambda Multiple Myeloma (MM) with 80% plasma cells observed in the initial bone marrow biopsy. No high-risk chromosomal abnormalities were detected in Fluorescence in Situ Hybridization (FISH) testing. She was started on treatment and underwent eight cycles of lenalidomide, bortezomib, and dexamethasone, accompanied by monthly intravenous (IV) zoledronic acid. Additionally, 2000 cGy of palliative external beam radiation therapy via Three–dimensional radiation therapy (3CDRT) technique was administered to L4 vertebrae and sacral region to alleviate pain. Clinically patient responded very well and pain subsided. Subsequently, maintenance therapy was started at 10 mg daily dose of lenalidomide, which was later tapered to alternate days. Over the course of two years, her monthly disease assessments showed a Very Good Partial Response (VGPR). However, she experienced a relapse with M spike, prompting a switch to bortezomib and dexamethasone for 5 cycles. Subsequently, she underwent bortezomib maintenance therapy but it was later changed to lenalidomide maintenance due to gastro-intestinal side effects. (Lenalidomide not discontinued) After seven months of maintenance therapy with lenalidomide and approximately 2 years after initial diagnosis, a well-circumscribed polypoidal soft tissue lesion appeared on her left knee which was treated with wedge resection. (Fig.1). The microscopic examination confirmed a relapsed MM in soft tissue with characteristic features of plasmacytoid cells. Immunohistochemical staining confirmed MM with positive reactivity for Mum-1 and CD56. (Fig.2). She was initiated on the 2nd line of treatment, which included two cycles of carfilzomib, lenalidomide, and dexamethasone. Carfilzomib was later substituted with pomalidomide due to financial limitations. However, the plasmacytoma continued to grow, causing pain and bleeding, a dose of 2000 cGy in 5 fractions was delivered to the left tibial soft tissue lesion via 3DCRT technique to control local symptoms. The disease responded very well and the lesion completely resolved along with palliation of other symptoms. A year later, while still on pomalidomide and dexamethasone, she developed another polypoidal soft tissue growth on her left leg, 4 cm above the medial malleolus. (Fig.3). An X-ray of the tibia showed lobulated soft tissue opacity but no involvement of underlying bone. She was planned for radiation therapy (RT) to the soft tissue lesion and received a dose of 2000 cGy in 5 fractions via electron beam therapy and responded very well and is being followed up. Meanwhile, she will continue on pomalidomide and dexamethasone. If the disease progresses, the next step will involve switching to third-line treatment. Discussion Extramedullary disease in MM may manifest in various anatomical sites such as in skin, pleura, lymph nodes, liver or central nervous system ( 5 ). Skin is the most frequently affected organ in relapsed MM cases ( 5 ). Cutaneous MM arises as a consequence of either hematogenous or lymphatic metastases or local spread of disease from adjacent malignant growth or cortical bone destruction ( 3 , 6 ). In some rare cases, its growth can be instigated by invasive procedures ( 5 ). Cutaneous involvement of MM depicts an aggressive nature of disease signifying the capacity of clonal plasma cells to proliferate outside the confines of bone marrow environment ( 5 ). It is associated with high-risk genetic features, augmented cellular proliferation, evasion of apoptosis and a history of extensive prior treatments as exemplified in our case ( 5 ). Typically, occurrence of cutaneous MM is observed in patients between ages of 50 to 71 years, as evidenced in our case as well ( 7 ). It has been reported that the earlier the disease manifests, the aggressive its course is ( 8 ). This condition may manifest on any region of skin, primarily observed on extremities, trunk and abdomen ( 3 , 7 ). Multiple lesion can be present at the same time ( 7 ). They are usually red, violaceous lesions characterized by a diameter of 1-5cm or more ( 9 ). Trauma might play a significant role in harboring plasma cells in skin nevertheless, in our patient’s case there was no history of trauma or instrumentation. Several studies have indicated that age, sex, light chain type, prior lines of therapy for MM, time elapsed from MM diagnosis to skin manifestation, and lesion location do not hold significant influence over the development of cutaneous MM ( 7 ). Simultaneously, certain studies have demonstrated a predisposition of cutaneous MM towards IgG, IgA, and IgD subtypes, as well as light chain disease ( 3 , 7 ). Our patient also presented with IgG lambda MM. Cutaneous MM does not exhibit any preferential cytogenetic abnormalities nor does it demonstrate any correlation with CD56 expression ( 7 ). Nonetheless, certain studies indicate that the absence of CD56 expression is a significant factor in disease development, as the loss of CD56 may contribute to disease dissemination and hinder the adherence of myeloma cells to the bone marrow ( 6 ). However, according to certain studies, more than 50% of cases show positive CD56 expression ( 3 ). Our patient also showed positive reactivity for MUM-1 and CD56. Management: Due to the rarity of cutaneous MM, there are currently no established treatment guidelines for its management. The most frequently employed approach for relapsed cutaneous MM involves palliative radiation therapy (RT) along with systemic therapy ( 3 ). Typically, patients present with cutaneous MM after undergoing an extensive treatment regimen, having already developed refractory disease ( 10 ). Radiation Therapy: As a local treatment modality, RT has demonstrated favorable responses, providing palliative effects and complete regression in cases of cutaneous MM ( 9 ). In a case report by Liu J. et al., a 75-year-old male with secondary cutaneous MM received both 3D conformal photon and electron therapy to multiple sites, resulting in a complete response and palliation of pain at the irradiated site ( 11 ). Dose of the therapy ranged from 3000 cGy in 10 fractions to 4140 cGy in 23 fractions ( 11 ). Nguyen also documented a near-complete treatment response of the right lower leg using a five-field 6 MeV electron beam with 0.5 cm bolus, administering a radiation dose of 2000 cGy in 5 fractions ( 12 ). A palliative total skin electron therapy employing the standard six-field technique with 6 MeV electron beams delivering 2000 cGy in two days, was reported in a 78-year-old male. The patient continued on systemic therapy and exhibited isolated progression in the right canthus, for which he subsequently received an additional 3000 cGy of electron beam therapy, resulting in a complete response at a later stage ( 13 ). Studies have shown that RT can effectively achieve complete or near-complete responses, providing palliation of pain and regression of lesions in affected areas. Although cutaneous multiple myeloma is a rare entity, radiation therapy has demonstrated favorable outcomes as a local treatment option, particularly in cases of relapsed disease. Systemic Therapy: In subsequent lines of therapy for cutaneous multiple myeloma, drugs such as Bortezomib or Lenalidomide combined with dexamethasone, as well as novel agents like Carfilzomib and Pomalidomide, have exhibited promising responses. Additionally, the incorporation of Bortezomib has been associated with a notable increase in progression-free survival (PFS) and improved overall survival (OS) over a 4-year timeframe for patients presenting with extramedullary disease ( 10 ). Furthermore, it has demonstrated enhanced outcomes even in transplant ineligible patients. Carfilzomib, in combination with Lenalidomide and dexamethasone, has also exhibited superior results in achieving complete response (CR), partial response (pCR), and very good partial response (VGPR) ( 10 ). Cutaneous MM treatment also incorporates a range of proteasome inhibitors and immune-modulatory agents as part of the regimen ( 7 ). However, immune-modulatory agents may not exhibit substantial efficacy in targeting soft tissue lesions ( 10 ). According to the reported findings, more than 10% of patients undergo RT during their initial relapse treatment, while over 50% receive RT and immune-modulatory agents (IMIDs) during treatment for their second relapse. Additionally, it has been documented that more than 50% of individuals who receive second-line therapy will proceed to receive third-line therapy. However, no specific treatment modality has been associated with achieving complete or partial response in these cases ( 7 ). The overall survival rate for cutaneous MM is notably low, with majority of patients succumbing to the disease within 9 to 12 months of initial diagnosis ( 3 , 7 , 4 ). However, our patient exhibits a different outcome in this regard. Cutaneous MM has been identified as an independent prognostic factor for MM ( 3 ). The principal causes of mortality comprise disease progression, involving liver involvement, infections, and pancreatic obstruction ( 6 , 7 ). The absence of prospective studies renders it challenging to substantiate robust recommendations for any particular treatment approach. Conclusion In conclusion, cutaneous multiple myeloma presents as a rare and challenging entity with a poor overall survival rate. Skin is the most commonly affected organ in relapsed cases just as our case demonstrates. While radiation therapy and systemic therapies have shown promising responses, the lack of prospective studies limits the establishment of robust treatment recommendations. A multidisciplinary approach is crucial to tailor treatment plans according to each patient's unique clinical profile. The exploration of innovative treatment approaches exhibit promise in enhancing the overall outcomes for these patients. Abbreviations MM: Multiple Myeloma IgG: Immunoglobulin G 3CDRT: Three-Dimensional Conformal Radiation Therapy PET-CT: Positron Emission Tomography-Computed Tomography R-ISS: Revised International Staging System IV: Intravenous VGPR: Very Good Partial Response FISH: Fluorescence in Situ Hybridization RT: Radiation Therapy CR: Complete Response pCR: Partial Complete Response OS: Overall Survival PFS: Progression-Free Survival CD56: Cluster of Differentiation 56 IMIDs: Immune-Modulatory Agents ECOG: Eastern Cooperative Oncology Group Declarations Author Contribution M.S.S. Naviwala and M. Hina primarily contributed to writing the main manuscript text, while N. Ali and M. Moosajee focused on manuscript review and provided critical insights. All authors participated in the manuscript's overall review process. • Ethical Approval and Consent to participate: Has taken ethical approval and consent from Aga Khan University Hospital ethical review committee. Patients signed informed consent regarding publishing their data and photographs. • Consent for publication: I hereby provide consent for the publication of the manuscript detailed above, including any accompanying imag- es or data contained within the manuscript. • Availability of supporting data : On behalf of all the contributors I will act as guarantor and will correspond with the journal from this point onward.We hereby transfer, assign, or otherwise convey all copyright ownership, including any and all rights incidental thereto, exclusively to the journal, in the event that such work is published by the journal. • Competing interests/Authors' contributions : M.S.S. Naviwala and M. Hina primarily contributed to writing the main manuscript text, while N. Ali and M. Moosajee focused on manuscript review and provided critical insights. All authors participated in the manuscript's overall review process. • Funding: No funding received. References Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48.. Buntinx-Krieg T, McKee RM, Eichenfield DZ, Marsch A. Increased Risk of Cutaneous Diseases in Multiple Myeloma Patients. Cureus. 2020 Sep 10;12(9):e10356.. Woo YR, Kim JS, Lim JH, Hwang S, Kim M, Bae JM, Park YM, Min CK, Kim DW, Park HJ. Prevalence and clinicopathologic characteristics of multiple myeloma with cutaneous involvement: A case series from Korea. J Am Acad Dermatol. 2018 Mar;78(3):471-478.e4.. Clutter CA, Aneja S, Ivan D, Ciurea A, Silapunt S. Cutaneous Lesions of Multiple Myeloma of the Lower Extremity Masquerading as Squamous Cell Carcinoma. Cureus. 2020 Nov 3;12(11):e11313.. Bladé J, Beksac M, Caers J, Jurczyszyn A, von Lilienfeld-Toal M, Moreau P, Rasche L, Rosiñol L, Usmani SZ, Zamagni E, Richardson P. Extramedullary disease in multiple myeloma: a systematic literature review. Blood Cancer J. 2022 Mar 21;12(3):45.. Bladé J, de Larrea CF, Rosiñol L. Extramedullary involvement in multiple myeloma. Haematologica. 2012 Nov;97(11):1618-9.. Jurczyszyn A, Olszewska-Szopa M, Hungria V, Crusoe E, Pika T, Delforge M, Leleu X, Rasche L, Nooka AK, Druzd-Sitek A, Walewski J, Davila J, Caers J, Maisnar V, Gertz M, Gentile M, Fantl D, Mele G, Vesole DH, Yee AJ, Shustik C, Lentzsch S, Zweegman S, Gozz.. Varricchio S, Pagliuca F, Travaglino A, Gallo L, Villa MR, Mascolo M. Cutaneous localization of plasmablastic multiple myeloma with heterotopic expression of CD3 and CD4: Skin involvement revealing systemic disease. J Cutan Pathol. 2019 Aug;46(8):619-622.. Saidane O, Slouma M, Haouet S, Abdelmoula L. Cutaneous and pleural involvement in a patient with multiple myeloma. BMJ Case Rep. 2015 Oct 5;2015:bcr2015211197.. Jagosky MH, Usmani SZ. Extramedullary Disease in Multiple Myeloma. Curr Hematol Malig Rep. 2020 Apr;15(2):62-71.. Liu J, Bakst R, Phelps R, Jagannath S, Blacksburg S. Radiation therapy for secondary cutaneous plasmacytomas. Case Rep Hematol. 2013;2013:739230.. Nguyen SK, Dagnault A. Radiotherapy for multiple myeloma with skin involvement. Curr Oncol. 2010 Oct;17(5):74-7.. Floyd SR, Pantanowitz L, McDermott DF, Yannucci J, Driver JA, Stevenson MA, Smith BD, Wilson LD, Richardson PG. Plasma cell problems: Case 1. Disseminated cutaneous plasmacytomas treated with total skin electron radiotherapy. J Clin Oncol. 2005 May 1;23(1.. 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. 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. 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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-3882128","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":268915099,"identity":"be1cbfb7-7d3c-4d21-9bb3-1aa67aad674c","order_by":0,"name":"Mohammad Saad Salim Naviwala","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA7klEQVRIiWNgGAWjYJACCRDBxsDAeIChgsEALkKMFoYDDGdI0QICBxjbiNAi33744Q3GHXaJfRLJDw78nGdnbHCA+eBtHjxaDM6kGVswnklObJNIMzjYuy3ZzOAAW7I1Xi0MCWYSjG3MxmzSCQYHeLcx2xgc4DGTxqdFvv/5N6CWeqCW9A8H/86pB2rh/4ZXC8ONHJAth+XYpHMMDvM2HAY6jIcNrxaDG2+KLRLbjsuxyb8pOCxz7Lix5GE2Y8s5eB2WvvHGx7ZqHvme4xsfvqmpNuw73vzwxht8DgOBBBQeMyHlo2AUjIJRMAoIAgAq1knsWnaadwAAAABJRU5ErkJggg==","orcid":"","institution":"Aga Khan University Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Mohammad","middleName":"Saad Salim","lastName":"Naviwala","suffix":""},{"id":268915100,"identity":"28da305b-0a19-47be-8a61-5f6e40326954","order_by":1,"name":"Mariam Hina","email":"","orcid":"","institution":"Aga Khan University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Mariam","middleName":"","lastName":"Hina","suffix":""},{"id":268915101,"identity":"eb0a73d9-5522-441b-8ebc-a3b0786dd26b","order_by":2,"name":"Munira Moosajee","email":"","orcid":"","institution":"Aga Khan University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Munira","middleName":"","lastName":"Moosajee","suffix":""},{"id":268915102,"identity":"82a246eb-80ba-4f3e-8222-30db317b89e4","order_by":3,"name":"Nasir Ali","email":"","orcid":"","institution":"Aga Khan University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Nasir","middleName":"","lastName":"Ali","suffix":""}],"badges":[],"createdAt":"2024-01-20 17:19:35","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3882128/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3882128/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":50175276,"identity":"a3c0ff81-d515-4fe4-822b-e523ad43c170","added_by":"auto","created_at":"2024-01-25 16:21:02","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":490547,"visible":true,"origin":"","legend":"\u003cp\u003eA and B illustrate the physical examination findings, showing polypoidal, violaceous soft tissue nodules situated on the medial surface of the patient's left knee. These nodules are indicative of cutaneous multiple myeloma.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3882128/v1/c211d0a4e5f1454d91785d71.png"},{"id":50175277,"identity":"cea6faf1-5687-4ea3-827b-733a1c3e24f0","added_by":"auto","created_at":"2024-01-25 16:21:02","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":348047,"visible":true,"origin":"","legend":"\u003cp\u003eA) Histopathological image of plasma cell neoplasm, left knee polypoidal mass (40× objective).The cell infiltrate shows eccentric nuclei with coarse chromatin and prominent nucleoli. Scattered mitotic figures are present. Immunohistochemical analysis demonstrated strong positivity for CD56 (B) and MUM1 (C) within the infiltrate.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3882128/v1/454163edbf41366dae77796d.png"},{"id":50175966,"identity":"819bb1d1-9974-4a39-91a4-74e94616c470","added_by":"auto","created_at":"2024-01-25 16:29:02","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":101747,"visible":true,"origin":"","legend":"\u003cp\u003ePolypoidal soft tissue growth on left leg, around 4 cm above the medial malleolus.\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3882128/v1/bec6e158896fccd6be9fad93.png"},{"id":50297048,"identity":"147ea4fe-8acc-4b09-9997-6af509cf554c","added_by":"auto","created_at":"2024-01-29 10:27:43","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1388963,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3882128/v1/477c4cae-b378-4ad0-9db3-e8bd702133ca.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eRecurrent Cutaneous Manifestation in Multiple Myeloma: A Case Report and Management Approach\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMM is an infrequent type of blood cancer, comprising only 1 to 2% of all cancer cases and 17% of all hematological malignancies (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). It is a plasma cell dyscrasia, characterized by neoplastic proliferation of plasma cells in bone marrow leading to over production of monoclonal immunoglobulins called M-proteins or para-proteins. Cutaneous lesions in MM are rare and are found in fewer than 2% of patients with systemic MM (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). At the time of initial diagnosis, approximately 7% of patients with MM present with extramedullary plasmacytoma. However, 6% of patients may subsequently develop extramedullary symptoms at a later stage of disease. Patients with MM who had direct cutaneous involvement experienced a notable decrease in overall survival (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The most common cause of cutaneous involvement in MM is metastasis and direct extension of the disease from nearby tumor sites.This typically presents as palpable violaceous nodules on the trunk and extremities. Frequently, cutaneous involvement in MM is observed during advanced stages of the disease, attributed to a higher tumor cell burden (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). These lesions are found in various anatomical locations, with the extremity, trunk and abdomen being the most frequently affected areas (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). Limited medical literature has discussed cutaneous involvement in MM. We present a rare case of a recurrent red, violaceous, and non-tender nodule on the left lower leg in a patient diagnosed with IgG lambda MM and currently undergoing systemic treatment.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA middle aged female with a medical history of hypertension, Eastern Cooperative Oncology Group (ECOG) performance status of 2, and past pulmonary tuberculosis, presented with the complain of pain in left lower leg in tibial region for two months. Imaging revealed an 8.4 x 4.3 x 3.5 cm focal lesion in the proximal metaphysis of the left tibia, leading to a pathological fracture for which intramedullary nailing was done. PET-CT scan indicated hypermetabolic activity in various regions including the left tibia, soft tissue of the neck, right posterior iliac bone, L5 vertebra, multiple left ribs, and manubrium sterni.\u003c/p\u003e\n\u003cp\u003eShe was diagnosed with R-ISS Stage II, Immunoglobulin G (IgG) lambda Multiple Myeloma (MM) with 80% plasma cells observed in the initial bone marrow biopsy. No high-risk chromosomal abnormalities were detected in Fluorescence in Situ Hybridization (FISH) testing.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eShe was started on treatment and underwent eight cycles of lenalidomide, bortezomib, and dexamethasone, accompanied by monthly intravenous (IV) zoledronic acid. Additionally, 2000 cGy of palliative external beam radiation therapy via Three–dimensional radiation therapy (3CDRT) technique was administered to L4 vertebrae and sacral region to alleviate pain. Clinically patient responded very well and pain subsided. Subsequently, maintenance therapy was started at 10 mg daily dose of lenalidomide, which was later tapered to alternate days.\u003c/p\u003e\n\u003cp\u003eOver the course of two years, her monthly disease assessments showed a Very Good Partial Response (VGPR). However, she experienced a relapse with M spike, prompting a switch to bortezomib and dexamethasone for 5 cycles. Subsequently, she underwent bortezomib maintenance therapy but it was later changed to lenalidomide maintenance due to gastro-intestinal side effects. (Lenalidomide not discontinued)\u003c/p\u003e\n\u003cp\u003eAfter seven months of maintenance therapy with lenalidomide and approximately 2 years after initial diagnosis, a well-circumscribed polypoidal soft tissue lesion appeared on her left knee which was treated with wedge resection. (Fig.1).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe microscopic examination confirmed a relapsed MM in soft tissue with characteristic features of plasmacytoid cells. Immunohistochemical staining confirmed MM with positive reactivity for Mum-1 and CD56. (Fig.2).\u003c/p\u003e\n\u003cp\u003eShe was initiated on the 2nd line of treatment, which included two cycles of carfilzomib, lenalidomide, and dexamethasone. Carfilzomib was later substituted with pomalidomide due to financial limitations. However, the plasmacytoma continued to grow, causing pain and bleeding, a dose of 2000 cGy in 5 fractions was delivered to the left tibial soft tissue lesion via 3DCRT technique to control local symptoms. The disease responded very well and the lesion completely resolved along with palliation of other symptoms.\u003c/p\u003e\n\u003cp\u003eA year later, while still on pomalidomide and dexamethasone, she developed another polypoidal soft tissue growth on her left leg, 4 cm above the medial malleolus. (Fig.3).\u003c/p\u003e\n\u003cp\u003eAn X-ray of the tibia showed lobulated soft tissue opacity but no involvement of underlying bone. She was planned for radiation therapy (RT) to the soft tissue lesion and received a dose of 2000 cGy in 5 fractions via electron beam therapy and responded very well and is being followed up. Meanwhile, she will continue on pomalidomide and dexamethasone. If the disease progresses, the next step will involve switching to third-line treatment.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eExtramedullary disease in MM may manifest in various anatomical sites such as in skin, pleura, lymph nodes, liver or central nervous system (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Skin is the most frequently affected organ in relapsed MM cases (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Cutaneous MM arises as a consequence of either hematogenous or lymphatic metastases or local spread of disease from adjacent malignant growth or cortical bone destruction (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). In some rare cases, its growth can be instigated by invasive procedures (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Cutaneous involvement of MM depicts an aggressive nature of disease signifying the capacity of clonal plasma cells to proliferate outside the confines of bone marrow environment (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). It is associated with high-risk genetic features, augmented cellular proliferation, evasion of apoptosis and a history of extensive prior treatments as exemplified in our case (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Typically, occurrence of cutaneous MM is observed in patients between ages of 50 to 71 years, as evidenced in our case as well (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). It has been reported that the earlier the disease manifests, the aggressive its course is (\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). This condition may manifest on any region of skin, primarily observed on extremities, trunk and abdomen (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Multiple lesion can be present at the same time (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). They are usually red, violaceous lesions characterized by a diameter of 1-5cm or more (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Trauma might play a significant role in harboring plasma cells in skin nevertheless, in our patient\u0026rsquo;s case there was no history of trauma or instrumentation. Several studies have indicated that age, sex, light chain type, prior lines of therapy for MM, time elapsed from MM diagnosis to skin manifestation, and lesion location do not hold significant influence over the development of cutaneous MM (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Simultaneously, certain studies have demonstrated a predisposition of cutaneous MM towards IgG, IgA, and IgD subtypes, as well as light chain disease (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Our patient also presented with IgG lambda MM. Cutaneous MM does not exhibit any preferential cytogenetic abnormalities nor does it demonstrate any correlation with CD56 expression (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). Nonetheless, certain studies indicate that the absence of CD56 expression is a significant factor in disease development, as the loss of CD56 may contribute to disease dissemination and hinder the adherence of myeloma cells to the bone marrow (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). However, according to certain studies, more than 50% of cases show positive CD56 expression (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Our patient also showed positive reactivity for MUM-1 and CD56.\u003c/p\u003e\n\u003ch3\u003eManagement:\u003c/h3\u003e\n\u003cp\u003eDue to the rarity of cutaneous MM, there are currently no established treatment guidelines for its management. The most frequently employed approach for relapsed cutaneous MM involves palliative radiation therapy (RT) along with systemic therapy (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). Typically, patients present with cutaneous MM after undergoing an extensive treatment regimen, having already developed refractory disease (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eRadiation Therapy:\u003c/h2\u003e \u003cp\u003eAs a local treatment modality, RT has demonstrated favorable responses, providing palliative effects and complete regression in cases of cutaneous MM (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). In a case report by Liu J. et al., a 75-year-old male with secondary cutaneous MM received both 3D conformal photon and electron therapy to multiple sites, resulting in a complete response and palliation of pain at the irradiated site (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Dose of the therapy ranged from 3000 cGy in 10 fractions to 4140 cGy in 23 fractions (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Nguyen also documented a near-complete treatment response of the right lower leg using a five-field 6 MeV electron beam with 0.5 cm bolus, administering a radiation dose of 2000 cGy in 5 fractions (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). A palliative total skin electron therapy employing the standard six-field technique with 6 MeV electron beams delivering 2000 cGy in two days, was reported in a 78-year-old male. The patient continued on systemic therapy and exhibited isolated progression in the right canthus, for which he subsequently received an additional 3000 cGy of electron beam therapy, resulting in a complete response at a later stage (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). Studies have shown that RT can effectively achieve complete or near-complete responses, providing palliation of pain and regression of lesions in affected areas. Although cutaneous multiple myeloma is a rare entity, radiation therapy has demonstrated favorable outcomes as a local treatment option, particularly in cases of relapsed disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eSystemic Therapy:\u003c/h2\u003e \u003cp\u003eIn subsequent lines of therapy for cutaneous multiple myeloma, drugs such as Bortezomib or Lenalidomide combined with dexamethasone, as well as novel agents like Carfilzomib and Pomalidomide, have exhibited promising responses. Additionally, the incorporation of Bortezomib has been associated with a notable increase in progression-free survival (PFS) and improved overall survival (OS) over a 4-year timeframe for patients presenting with extramedullary disease (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Furthermore, it has demonstrated enhanced outcomes even in transplant ineligible patients. Carfilzomib, in combination with Lenalidomide and dexamethasone, has also exhibited superior results in achieving complete response (CR), partial response (pCR), and very good partial response (VGPR) (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Cutaneous MM treatment also incorporates a range of proteasome inhibitors and immune-modulatory agents as part of the regimen (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). However, immune-modulatory agents may not exhibit substantial efficacy in targeting soft tissue lesions (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eAccording to the reported findings, more than 10% of patients undergo RT during their initial relapse treatment, while over 50% receive RT and immune-modulatory agents (IMIDs) during treatment for their second relapse. Additionally, it has been documented that more than 50% of individuals who receive second-line therapy will proceed to receive third-line therapy. However, no specific treatment modality has been associated with achieving complete or partial response in these cases (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe overall survival rate for cutaneous MM is notably low, with majority of patients succumbing to the disease within 9 to 12 months of initial diagnosis (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e). However, our patient exhibits a different outcome in this regard. Cutaneous MM has been identified as an independent prognostic factor for MM (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). The principal causes of mortality comprise disease progression, involving liver involvement, infections, and pancreatic obstruction (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e). The absence of prospective studies renders it challenging to substantiate robust recommendations for any particular treatment approach.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eIn conclusion, cutaneous multiple myeloma presents as a rare and challenging entity with a poor overall survival rate. Skin is the most commonly affected organ in relapsed cases just as our case demonstrates. While radiation therapy and systemic therapies have shown promising responses, the lack of prospective studies limits the establishment of robust treatment recommendations. A multidisciplinary approach is crucial to tailor treatment plans according to each patient\u0026apos;s unique clinical profile. The exploration of innovative treatment approaches exhibit promise in enhancing the overall outcomes for these patients.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eMM: Multiple Myeloma\u003c/p\u003e\n\u003cp\u003eIgG: Immunoglobulin G\u003c/p\u003e\n\u003cp\u003e3CDRT: Three-Dimensional Conformal Radiation Therapy\u003c/p\u003e\n\u003cp\u003ePET-CT: Positron Emission Tomography-Computed Tomography\u003c/p\u003e\n\u003cp\u003eR-ISS: Revised International Staging System\u003c/p\u003e\n\u003cp\u003eIV: Intravenous\u003c/p\u003e\n\u003cp\u003eVGPR: Very Good Partial Response\u003c/p\u003e\n\u003cp\u003eFISH: Fluorescence in Situ Hybridization\u003c/p\u003e\n\u003cp\u003eRT: Radiation Therapy\u003c/p\u003e\n\u003cp\u003eCR: Complete Response\u003c/p\u003e\n\u003cp\u003epCR: Partial Complete Response\u003c/p\u003e\n\u003cp\u003eOS: Overall Survival\u003c/p\u003e\n\u003cp\u003ePFS: Progression-Free Survival\u003c/p\u003e\n\u003cp\u003eCD56: Cluster of Differentiation 56\u003c/p\u003e\n\u003cp\u003eIMIDs: Immune-Modulatory Agents\u003c/p\u003e\n\u003cp\u003eECOG: Eastern Cooperative Oncology Group\u003c/p\u003e"},{"header":"Declarations","content":"\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eM.S.S. Naviwala and M. Hina primarily contributed to writing the main manuscript text, while N. Ali and M. Moosajee focused on manuscript review and provided critical insights. All authors participated in the manuscript's overall review process.\u003c/p\u003e\n\u003cp\u003e•\u003cstrong\u003e\u0026nbsp;Ethical Approval and Consent to participate:\u003c/strong\u003e Has taken ethical approval and consent from Aga Khan University Hospital ethical review committee.\u0026nbsp;Patients signed informed consent regarding publishing their data and photographs.\u003c/p\u003e\n\u003cp\u003e• \u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eI hereby provide consent for the publication of the manuscript detailed above,\u0026nbsp;including\u0026nbsp;any accompanying imag- es or data contained within the manuscript.\u003c/p\u003e\n\u003cp\u003e• \u003cstrong\u003eAvailability of supporting data\u003c/strong\u003e: On behalf of all the contributors I will act as guarantor and will correspond with the journal from this point onward.We hereby transfer, assign, or otherwise convey all copyright ownership, including any and all rights incidental thereto, exclusively to the journal, in the event that such work is published by the journal.\u003c/p\u003e\n\u003cp\u003e• \u003cstrong\u003eCompeting interests/Authors' contributions\u003c/strong\u003e\u003cstrong\u003e:\u003c/strong\u003eM.S.S. Naviwala and M. Hina primarily contributed to writing the main manuscript text, while N. Ali and M. Moosajee focused on manuscript review and provided critical insights. All authors participated in the manuscript's overall review process.\u003c/p\u003e\n\u003cp\u003e• \u003cstrong\u003eFunding:\u003c/strong\u003e No funding received.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSiegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023 Jan;73(1):17-48..\u003c/li\u003e\n \u003cli\u003eBuntinx-Krieg T, McKee RM, Eichenfield DZ, Marsch A. Increased Risk of Cutaneous Diseases in Multiple Myeloma Patients. Cureus. 2020 Sep 10;12(9):e10356..\u003c/li\u003e\n \u003cli\u003eWoo YR, Kim JS, Lim JH, Hwang S, Kim M, Bae JM, Park YM, Min CK, Kim DW, Park HJ. Prevalence and clinicopathologic characteristics of multiple myeloma with cutaneous involvement: A case series from Korea. J Am Acad Dermatol. 2018 Mar;78(3):471-478.e4..\u003c/li\u003e\n \u003cli\u003eClutter CA, Aneja S, Ivan D, Ciurea A, Silapunt S. Cutaneous Lesions of Multiple Myeloma of the Lower Extremity Masquerading as Squamous Cell Carcinoma. Cureus. 2020 Nov 3;12(11):e11313..\u003c/li\u003e\n \u003cli\u003eBlad\u0026eacute; J, Beksac M, Caers J, Jurczyszyn A, von Lilienfeld-Toal M, Moreau P, Rasche L, Rosi\u0026ntilde;ol L, Usmani SZ, Zamagni E, Richardson P. Extramedullary disease in multiple myeloma: a systematic literature review. Blood Cancer J. 2022 Mar 21;12(3):45..\u003c/li\u003e\n \u003cli\u003eBlad\u0026eacute; J, de Larrea CF, Rosi\u0026ntilde;ol L. Extramedullary involvement in multiple myeloma. Haematologica. 2012 Nov;97(11):1618-9..\u003c/li\u003e\n \u003cli\u003eJurczyszyn A, Olszewska-Szopa M, Hungria V, Crusoe E, Pika T, Delforge M, Leleu X, Rasche L, Nooka AK, Druzd-Sitek A, Walewski J, Davila J, Caers J, Maisnar V, Gertz M, Gentile M, Fantl D, Mele G, Vesole DH, Yee AJ, Shustik C, Lentzsch S, Zweegman S, Gozz..\u003c/li\u003e\n \u003cli\u003eVarricchio S, Pagliuca F, Travaglino A, Gallo L, Villa MR, Mascolo M. Cutaneous localization of plasmablastic multiple myeloma with heterotopic expression of CD3 and CD4: Skin involvement revealing systemic disease. J Cutan Pathol. 2019 Aug;46(8):619-622..\u003c/li\u003e\n \u003cli\u003eSaidane O, Slouma M, Haouet S, Abdelmoula L. Cutaneous and pleural involvement in a patient with multiple myeloma. BMJ Case Rep. 2015 Oct 5;2015:bcr2015211197..\u003c/li\u003e\n \u003cli\u003eJagosky MH, Usmani SZ. Extramedullary Disease in Multiple Myeloma. Curr Hematol Malig Rep. 2020 Apr;15(2):62-71..\u003c/li\u003e\n \u003cli\u003eLiu J, Bakst R, Phelps R, Jagannath S, Blacksburg S. Radiation therapy for secondary cutaneous plasmacytomas. Case Rep Hematol. 2013;2013:739230..\u003c/li\u003e\n \u003cli\u003eNguyen SK, Dagnault A. Radiotherapy for multiple myeloma with skin involvement. Curr Oncol. 2010 Oct;17(5):74-7..\u003c/li\u003e\n \u003cli\u003eFloyd SR, Pantanowitz L, McDermott DF, Yannucci J, Driver JA, Stevenson MA, Smith BD, Wilson LD, Richardson PG. Plasma cell problems: Case 1. Disseminated cutaneous plasmacytomas treated with total skin electron radiotherapy. J Clin Oncol. 2005 May 1;23(1..\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 plasmacytoma, multiple myeloma, radiotherapy, chemotherapy, wedge resection","lastPublishedDoi":"10.21203/rs.3.rs-3882128/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3882128/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eCutaneous involvement in multiple myeloma (MM) is an uncommonly encountered manifestation, more commonly observed in patients with aggressive subtypes, and often resistant to conventional therapies. Owing to its infrequency, reported clinical characteristics have been diverse and relatively nonspecific. Particularly uncommon is lower extremity involvement, where cutaneous MM is found.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn this report, we present a unique case of a middle age lady with refractory IgG lambda MM, who subsequently developed recurrent cutaneous plasmacytoma in the lower leg, while being on systemic therapy. Initially, the lesion resembled squamous cell carcinoma, posing a diagnostic challenge. Through meticulous histopathological and immunohistochemical studies, cutaneous involvement by multiple myeloma was conclusively confirmed.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis case highlights the importance of maintaining a high clinical suspicion for cutaneous MM in patients with MM who present with new skin lesions, as early diagnosis is crucial for appropriate management.\u003c/p\u003e","manuscriptTitle":"Recurrent Cutaneous Manifestation in Multiple Myeloma: A Case Report and Management Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-01-25 16:20:57","doi":"10.21203/rs.3.rs-3882128/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":"9938e6ec-fb26-43f3-8eea-cc1d177da08e","owner":[],"postedDate":"January 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-01-29T10:19:36+00:00","versionOfRecord":[],"versionCreatedAt":"2024-01-25 16:20:57","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3882128","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3882128","identity":"rs-3882128","version":["v1"]},"buildId":"rHA-KDH7Qsr4HCuvH75dn","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}