Melanoma of unknown primary with skeletal muscle metastasis. A case report

Melanoma of unknown primary with skeletal muscle metastasis. 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A case report Ny Ony Tiana Florence Andrianandrasana, Rova Malala Fandresena Randrianarisoa, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1861692/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 12 Mar, 2023 Read the published version in Journal of Medical Case Reports → Version 1 posted You are reading this latest preprint version Abstract Background: Melanoma is usually discovered from an irregular skin patch or a modification of a pre-existing patch. Cutaneous and lymph node metastases are common. Muscle metastasis are rare. We report a case of melanoma with infiltration of the gluteus maximus, which had normal dermatological examination. Case presentation: A 43-year-old man with no history of skin surgery was admitted with progressively worsening dyspnea. On admission, he presented with superior vena cava syndrome, painless cervical lymphadenopathy and a painful swelling in the right buttock. Skin and mucous membrane examination did not reveal any abnormal or suspicious lesions. The biology was limited to a C-reactive protein of 40 mg/L, a white blood cell count of 23 G/L and a lactate dehydrogenase level of 1705 U/L. The computed tomography scan showed several lymphadenopathies, compression of the superior vena cava and a tissue mass at the expense of the gluteus maximus. Cervical lymph node biopsy and cytopuncture of the gluteus maximus were consistent with a secondary melanoma location. A stage III melanoma of unknown primary origin associated with lymph node metastases and extension to the right gluteus maximus was suggested. Conclusions: Melanoma of unknown primary accounts for 3% of diagnosed melanomas. Diagnosis is difficult in the absence of a skin lesion. Patients are diagnosed with multiple metastases. Muscle involvement is unusual and may suggest a benign pathology. In this context, biopsy remains essential for diagnosis. Biopsy Melanoma Melanoma of unknown primary Muscle metastasis Figures Figure 1 Figure 2 Figure 3 Figure 4 Background Melanoma is one of the most aggressive forms of skin cancer, accounting for about three quarters of all deaths. Over the past two decades, the incidence of melanoma has been steadily increasing [ 1 ]. According to the Global Cancer Observatory, the incidence was 3.4 cases per 100,000 population in 2020 with 57,043 deaths [ 2 ]. The diagnosis of melanoma is usually made in the presence of an irregular skin patch or a change in a pre-existing patch. The diagnosis is then based on histological examination. Cutaneous and lymph node metastases are common. Hematogenous spread is possible, often involving the lungs, liver and brain [ 3 ]. Striated muscle metastases are unusual [ 4 ]. In the absence of a skin lesion, melanoma represents a diagnostic challenge that can delay therapeutic management. We report a case of melanoma with infiltration of the right gluteus maximus, which had a normal dermatological examination. Our objectives are to discuss the frequency, pathophysiological mechanism and prognosis of this type of melanoma in relation to the literature. Case Presentation A 43-year-old man of Malagasy nationality with black skin was admitted to the oncology department for dyspnea which had been evolving for a few weeks with progressive worsening. He reported dysphonia, dysphagia and associated episodes of dry cough. He had asthenia and weight loss without fever. He was followed by the thoracic surgery team for a right cervical lymphadenopathy which had been evolving for 4 months and for which the histological result of the biopsy was pending. He had a history of alcoholism and chronic weaned smoking. He had no history of skin pigmentation or skin surgery and no personal or family history of cancer. On admission, hemodynamic parameters were stable. General condition was impaired with a World Health Organization performance status score of 3. Examination revealed facial oedema and venous collateral circulation in the neck. He had painless right cervical lymphadenopathy and a swelling in the right buttock that was painful to palpation and firm in consistency (Fig. 1 ). Careful examination of the skin and mucous membranes did not reveal any abnormal or suspicious lesions. The rest of the examination was normal. The blood count showed a white blood cell count of 23 G/L with a predominance of neutrophils. The C-reactive protein was 40 mg/L. Serum ionogram, calcium and creatinine levels and liver function tests were normal. HIV and hepatitis B and C serologies were negative. The lactate dehydrogenase level was 1705 U/L. The carcinoembryonic antigen test was negative. The thoracic-abdominal-pelvic computed tomography scan revealed cervical, mediastinal and retroperitoneal lymphadenopathy and compression of the superior vena cava (Fig. 2 ). The mass in the right buttock was well-limited, heterogeneous, measuring 63 x 127 mm and was located at the expense of the gluteus maximus muscle with low enhancement (Fig. 3 ). The result of the histological examination of the cervical lymph node biopsy showed invasion of the lymph node and capsular architecture by globular cells with abundant cytoplasm, cytonuclear atypia and melanin pigments (Fig. 4 ). A cytopuncture of the gluteus maximus was performed and cytology showed an infiltration of neutrophils and macrophages, tattooed with melanin pigments. BRAF V600 mutation testing could not be performed due to the technical platform. A stage III malignant melanoma with lymph node metastases and extension to the right gluteus maximus was suggested. No primary skin site was identified. The dyspnea was related to the superior vena cava syndrome, secondary to lymph node compression. A brain scan was performed and showed no secondary lesions. Corticosteroid therapy with methylprednisolone and preventive anticoagulation with enoxaparin were undertaken for superior vena cava syndrome. After multidisciplinary discussion, mediastinal radiotherapy for decompression and systemic chemotherapy with dacarbazine were planned. The short-term course was marked by rapid regression of the superior vena cava syndrome and improvement in respiratory symptomatology. No suspicious skin patches appeared during follow-up. Discussion And Conclusions Melanoma is an aggressive melanocyte tumour with easy and early metastasis. In the case of a metastatic melanoma, a primary lesion must be rapidly identified. Assessment should include a full dermatological examination and anorectal, genital and ophthalmological examination. The primary lesion commonly presents as skin, mucous membrane or ocular lesions. In some cases, it is not identified and is referred to as a melanoma of unknown primary (MUP) origin. The first entity of MUP was proposed by Das Gupta et al. in 1963 [ 5 ]. It is defined by the presence of histologically confirmed melanoma in skin/subcutaneous tissue, lymph nodes or viscera, without manifestation of a primary lesion. MUP is rare, accounting for approximately 3% of diagnosed melanomas [ 6 ]. It usually occurs in people in their 40s and 50s, with a male predominance. The pathophysiological mechanism of MUP is not fully understood. Two hypotheses have been suggested: complete spontaneous regression of the primary lesion after metastasis and primary origin from ectopic melanocytes in lymph nodes or viscera [ 5 , 7 ]. The spontaneous regression hypothesis is the most supported, secondary to an immunological response [ 8 ]. Metastases from MUP may be subcutaneous, lymph node or visceral [ 3 ]. Lymph node metastases are the most common, occurring in 60% of cases. Muscle metastases are rare and solitary forms occur in 0.8% of cases [ 4 ]. This low incidence may be attributed to the hostile environment of the muscles for cancer progression. In small series and single case reports, muscle metastases from melanoma often manifest as a palpable and painful mass. The paravertebral and proximal limb muscles are most affected [ 4 ]. Some cases were initially misdiagnosed as a lipoma [ 9 ]. However, the diagnosis of certainty is anatomopathological from a muscle or lymph node biopsy. Due to the lack of precision in the American Joint Committee on Cancer staging system, the authors classified MUP as stage III or IV [ 3 , 10 ]. Patients with lymph node, skin/subcutaneous or soft tissue metastases are classified as stage III. Other forms are classified as stage IV. In our case, the melanoma was classified as stage III. The prognosis of MUP has been shown to be better than melanoma of known origin at the corresponding stage [ 11 , 12 ]. In other studies, the clinical outcome is worse for patients with MUP [ 7 , 13 ]. These results remain inconclusive as the data are contradictory. Furthermore, treatment depends on the staging of the lesion and is generally similar in both forms of melanoma. The diagnosis of melanoma is difficult in the absence of a skin lesion. MUP is thus evoked. Patients are diagnosed with subcutaneous, lymph node or visceral metastases. Invasion of striated muscles is rare in melanoma but also in cancer in general. Muscle metastases usually present as a painful mass and may suggest a benign pathology. Biopsy plays an important role in the diagnosis of certainty and should be performed systematically for any adenopathy or muscle mass. Abbreviations MUP melanoma of unknow primary Declarations Ethics approval and consent to participate Not applicable. Consent for publication Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Availability of data and materials All data generated are included in this published article. Conflicts of interest The authors declare that they have no conflicts of interest. Funding The authors declare that they do not have a grant from any specific organisation. Authors' contributions ANOTF: patient follow-up, visualisation, critical revision. RRMF: patient follow-up, writing. NP, RMAC: patient follow-up, clinical data collection. VHMD, RF: validation, monitoring. All authors have read and approved the final version of the article. Acknowledgements The authors would like to thank all the staff of the Oncology, Thoracic Surgery, Pathological Anatomy and Cytology and Medical Imaging departments of the Joseph Raseta Befelatanana Hospital, Antananarivo, Madagascar. References O’Neill CH, Scoggins CR. Melanoma. J Surg Oncol 2019; 120(5):873-81. doi:10.1002/jso.25604 World Health Organization. Melanoma of skin. Global Cancer Observatory 2020. [online]. Available on : https://gco.iarc.fr/today/data/factsheets/cancers/16-Melanoma-of-skin-fact-sheet.pdf [Accessed 02/07/2022] Gershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67(6):472-92. doi:10.3322/caac.21409 Gómez-León N, Pacheco-Barcia V, Ballesteros AI, Fraga J, Colomer R, Friera A. Skeletal muscle and solitary bone metastases from malignant melanoma: multimodality imaging and oncological outcome. Melanoma Res 2018; 28(6):562-70. doi:10.1097/CMR.0000000000000466 Das Gupta T, Bowden L, Berg JW. Malignant melanoma of unknown primary origin. Surg Gynecol Obstet 1963; 117:341-45. Verver D, van der Veldt A, van Akkooi A, Verhoef C, Grünhagen DJ, Louwman WJ. Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population-based study. Int J Cancer 2020; 146(1):26-34. doi:10.1002/ijc.32229 Song Y, Karakousis GC. Melanoma of unknown primary. J Surg Oncol 2019; 119(2):232-41. doi:10.1002/jso.25302 Cervinkova M, Kucerova P, Cizkova J. Spontaneous regression of malignant melanoma - is it based on the interplay between host immune system and melanoma antigens? Anticancer Drugs 2017; 28(8):819-30. doi:10.1097/CAD.0000000000000526 Grech A, Mercieca N, Calleja-Agius J, Abela R. Metastatic malignant melanoma of unknown primary in temporalis muscle. J Surg Case Rep 2020; 2020(6):1-3. doi:10.1093/jscr/rjaa202 Balch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27(36):6199-206. doi:10.1200/JCO.2009.23.4799 Bae JM, Choi YY, Kim DS, Lee JH, Jang HS, Lee JH, et al. Metastatic melanomas of unknown primary show better prognosis than those of known primary: A systematic review and meta-analysis of observational studies. J Am Acad Dermatol 2015; 72(1):59-70. doi:10.1016/j.jaad.2014.09.029 van der Ploeg AP, Haydu LE, Spillane AJ, Scolyer RA, Quinn MJ, Saw RP, et al. Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease. Ann Surg Oncol 2014; 21(9):3108-16. doi:10.1245/s10434-014-3679-5 Milton GW, Shaw HM, McCarthy WH. Occult primary malignant melanoma: factors influencing survival. Br J Surg 1977; 64(11):805-8. doi:10.1002/bjs.1800641114 Supplementary Files CAREchecklist.pdf Cite Share Download PDF Status: Published Journal Publication published 12 Mar, 2023 Read the published version in Journal of Medical Case Reports → 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. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1861692","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":121828121,"identity":"c1a24949-bafb-47b4-a455-6232da40ddfc","order_by":0,"name":"Ny Ony Tiana Florence Andrianandrasana","email":"","orcid":"","institution":"Universite d'Antananarivo Faculte de Medecine","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ny","middleName":"Ony Tiana Florence","lastName":"Andrianandrasana","suffix":""},{"id":121828122,"identity":"247f2eb7-1dce-48f8-b43e-6d5f93632250","order_by":1,"name":"Rova Malala Fandresena 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buttock\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"FIGURE1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/4a4de9e8359553d5e863b248.jpg"},{"id":24060133,"identity":"22974156-fa0e-4caf-ae7b-a850cb5ba6cb","added_by":"auto","created_at":"2022-07-19 19:56:29","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1277755,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan with injection in axial (A) and coronal (B) sections. \u003c/p\u003e\u003cp\u003eMediastinal lymph node complex and compression of the right superior vena cava\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"FIGURE2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/07d30f15978a539a1005021e.jpg"},{"id":24060134,"identity":"e1538ffb-590e-4399-9e6f-fbeb8bcae3ea","added_by":"auto","created_at":"2022-07-19 19:56:29","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":1366898,"visible":true,"origin":"","legend":"\u003cp\u003eCT scan in axial (A) and coronal (B) sections. \u003c/p\u003e\u003cp\u003eMass at the expense of the gluteus maximus muscle\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"FIGURE3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/508c0182f72cb8b91219759e.jpg"},{"id":24060422,"identity":"40c034fc-8da7-4414-880e-7a66dbcd85e2","added_by":"auto","created_at":"2022-07-19 20:01:29","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":3185890,"visible":true,"origin":"","legend":"\u003cp\u003eHistology of lymph node biopsy. \u003c/p\u003e\u003cp\u003eCell infiltration and melanin pigments (HE x 40)\u003c/p\u003e\u003cp\u003e\u003cbr\u003e\u003c/p\u003e","description":"","filename":"FIGURE4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/720417ffb9c785324cb03748.jpg"},{"id":44721860,"identity":"81a0d4e5-b665-45b3-92a4-ca1ec77a45df","added_by":"auto","created_at":"2023-10-16 19:40:17","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":880048,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/5fb3a6f6-6dca-4164-b0c5-147f5eb54d95.pdf"},{"id":24060136,"identity":"c9534d8a-ef13-4f17-b0d1-834e00ed1102","added_by":"auto","created_at":"2022-07-19 19:56:29","extension":"pdf","order_by":8,"title":"","display":"","copyAsset":false,"role":"supplement","size":284223,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklist.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1861692/v1/38db0fa476a282a4b1847884.pdf"}],"financialInterests":"","formattedTitle":"Melanoma of unknown primary with skeletal muscle metastasis. A case report","fulltext":[{"header":"Background","content":"\u003cp\u003eMelanoma is one of the most aggressive forms of skin cancer, accounting for about three quarters of all deaths. Over the past two decades, the incidence of melanoma has been steadily increasing [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. According to the Global Cancer Observatory, the incidence was 3.4 cases per 100,000 population in 2020 with 57,043 deaths [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe diagnosis of melanoma is usually made in the presence of an irregular skin patch or a change in a pre-existing patch. The diagnosis is then based on histological examination. Cutaneous and lymph node metastases are common. Hematogenous spread is possible, often involving the lungs, liver and brain [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Striated muscle metastases are unusual [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn the absence of a skin lesion, melanoma represents a diagnostic challenge that can delay therapeutic management. We report a case of melanoma with infiltration of the right gluteus maximus, which had a normal dermatological examination. Our objectives are to discuss the frequency, pathophysiological mechanism and prognosis of this type of melanoma in relation to the literature.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 43-year-old man of Malagasy nationality with black skin was admitted to the oncology department for dyspnea which had been evolving for a few weeks with progressive worsening. He reported dysphonia, dysphagia and associated episodes of dry cough. He had asthenia and weight loss without fever. He was followed by the thoracic surgery team for a right cervical lymphadenopathy which had been evolving for 4 months and for which the histological result of the biopsy was pending.\u003c/p\u003e \u003cp\u003eHe had a history of alcoholism and chronic weaned smoking. He had no history of skin pigmentation or skin surgery and no personal or family history of cancer.\u003c/p\u003e \u003cp\u003eOn admission, hemodynamic parameters were stable. General condition was impaired with a World Health Organization performance status score of 3. Examination revealed facial oedema and venous collateral circulation in the neck. He had painless right cervical lymphadenopathy and a swelling in the right buttock that was painful to palpation and firm in consistency (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Careful examination of the skin and mucous membranes did not reveal any abnormal or suspicious lesions. The rest of the examination was normal.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe blood count showed a white blood cell count of 23 G/L with a predominance of neutrophils. The C-reactive protein was 40 mg/L. Serum ionogram, calcium and creatinine levels and liver function tests were normal. HIV and hepatitis B and C serologies were negative. The lactate dehydrogenase level was 1705 U/L. The carcinoembryonic antigen test was negative.\u003c/p\u003e \u003cp\u003eThe thoracic-abdominal-pelvic computed tomography scan revealed cervical, mediastinal and retroperitoneal lymphadenopathy and compression of the superior vena cava (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mass in the right buttock was well-limited, heterogeneous, measuring 63 x 127 mm and was located at the expense of the gluteus maximus muscle with low enhancement (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe result of the histological examination of the cervical lymph node biopsy showed invasion of the lymph node and capsular architecture by globular cells with abundant cytoplasm, cytonuclear atypia and melanin pigments (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). A cytopuncture of the gluteus maximus was performed and cytology showed an infiltration of neutrophils and macrophages, tattooed with melanin pigments.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eBRAF V600 mutation testing could not be performed due to the technical platform.\u003c/p\u003e \u003cp\u003eA stage III malignant melanoma with lymph node metastases and extension to the right gluteus maximus was suggested. No primary skin site was identified. The dyspnea was related to the superior vena cava syndrome, secondary to lymph node compression. A brain scan was performed and showed no secondary lesions.\u003c/p\u003e \u003cp\u003eCorticosteroid therapy with methylprednisolone and preventive anticoagulation with enoxaparin were undertaken for superior vena cava syndrome. After multidisciplinary discussion, mediastinal radiotherapy for decompression and systemic chemotherapy with dacarbazine were planned.\u003c/p\u003e \u003cp\u003eThe short-term course was marked by rapid regression of the superior vena cava syndrome and improvement in respiratory symptomatology. No suspicious skin patches appeared during follow-up.\u003c/p\u003e"},{"header":"Discussion And Conclusions","content":"\u003cp\u003eMelanoma is an aggressive melanocyte tumour with easy and early metastasis. In the case of a metastatic melanoma, a primary lesion must be rapidly identified. Assessment should include a full dermatological examination and anorectal, genital and ophthalmological examination. The primary lesion commonly presents as skin, mucous membrane or ocular lesions. In some cases, it is not identified and is referred to as a melanoma of unknown primary (MUP) origin.\u003c/p\u003e \u003cp\u003eThe first entity of MUP was proposed by Das Gupta et al. in 1963 [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. It is defined by the presence of histologically confirmed melanoma in skin/subcutaneous tissue, lymph nodes or viscera, without manifestation of a primary lesion. MUP is rare, accounting for approximately 3% of diagnosed melanomas [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. It usually occurs in people in their 40s and 50s, with a male predominance.\u003c/p\u003e \u003cp\u003eThe pathophysiological mechanism of MUP is not fully understood. Two hypotheses have been suggested: complete spontaneous regression of the primary lesion after metastasis and primary origin from ectopic melanocytes in lymph nodes or viscera [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The spontaneous regression hypothesis is the most supported, secondary to an immunological response [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eMetastases from MUP may be subcutaneous, lymph node or visceral [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. Lymph node metastases are the most common, occurring in 60% of cases. Muscle metastases are rare and solitary forms occur in 0.8% of cases [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. This low incidence may be attributed to the hostile environment of the muscles for cancer progression. In small series and single case reports, muscle metastases from melanoma often manifest as a palpable and painful mass. The paravertebral and proximal limb muscles are most affected [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Some cases were initially misdiagnosed as a lipoma [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. However, the diagnosis of certainty is anatomopathological from a muscle or lymph node biopsy.\u003c/p\u003e \u003cp\u003eDue to the lack of precision in the American Joint Committee on Cancer staging system, the authors classified MUP as stage III or IV [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Patients with lymph node, skin/subcutaneous or soft tissue metastases are classified as stage III. Other forms are classified as stage IV. In our case, the melanoma was classified as stage III.\u003c/p\u003e \u003cp\u003eThe prognosis of MUP has been shown to be better than melanoma of known origin at the corresponding stage [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. In other studies, the clinical outcome is worse for patients with MUP [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. These results remain inconclusive as the data are contradictory. Furthermore, treatment depends on the staging of the lesion and is generally similar in both forms of melanoma.\u003c/p\u003e \u003cp\u003eThe diagnosis of melanoma is difficult in the absence of a skin lesion. MUP is thus evoked. Patients are diagnosed with subcutaneous, lymph node or visceral metastases. Invasion of striated muscles is rare in melanoma but also in cancer in general. Muscle metastases usually present as a painful mass and may suggest a benign pathology. Biopsy plays an important role in the diagnosis of certainty and should be performed systematically for any adenopathy or muscle mass.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMUP\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emelanoma of unknow primary\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWritten informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll data generated are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they do not have a grant from any specific organisation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eANOTF: patient follow-up, visualisation, critical revision. RRMF: patient follow-up, writing. NP, RMAC: patient follow-up, clinical data collection. VHMD, RF: validation, monitoring. All authors have read and approved the final version of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all the staff of the Oncology, Thoracic Surgery, Pathological Anatomy and Cytology and Medical Imaging departments of the Joseph Raseta Befelatanana Hospital, Antananarivo, Madagascar.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eO\u0026rsquo;Neill CH, Scoggins CR. Melanoma. J Surg Oncol 2019; 120(5):873-81. \u003cu\u003edoi:10.1002/jso.25604\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eWorld Health Organization. Melanoma of skin. Global Cancer Observatory 2020. [online]. Available on\u0026nbsp;: https://gco.iarc.fr/today/data/factsheets/cancers/16-Melanoma-of-skin-fact-sheet.pdf [Accessed 02/07/2022]\u003c/li\u003e\n\u003cli\u003eGershenwald JE, Scolyer RA, Hess KR, Sondak VK, Long GV, Ross MI, et al. Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin 2017; 67(6):472-92. \u003cu\u003edoi:10.3322/caac.21409\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eG\u0026oacute;mez-Le\u0026oacute;n N, Pacheco-Barcia V, Ballesteros AI, Fraga J, Colomer R, Friera A. Skeletal muscle and solitary bone metastases from malignant melanoma: multimodality imaging and oncological outcome. Melanoma Res 2018; 28(6):562-70. \u003cu\u003edoi:10.1097/CMR.0000000000000466\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eDas Gupta T, Bowden L, Berg JW. Malignant melanoma of unknown primary origin. Surg Gynecol Obstet 1963; 117:341-45.\u003c/li\u003e\n\u003cli\u003eVerver D, van der Veldt A, van Akkooi A, Verhoef C, Gr\u0026uuml;nhagen DJ, Louwman WJ. Treatment of melanoma of unknown primary in the era of immunotherapy and targeted therapy: A Dutch population-based study. Int J Cancer 2020; 146(1):26-34. \u003cu\u003edoi:10.1002/ijc.32229\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eSong Y, Karakousis GC. Melanoma of unknown primary. J Surg Oncol 2019; 119(2):232-41. \u003cu\u003edoi:10.1002/jso.25302\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eCervinkova M, Kucerova P, Cizkova J. Spontaneous regression of malignant melanoma - is it based on the interplay between host immune system and melanoma antigens? Anticancer Drugs 2017; 28(8):819-30. \u003cu\u003edoi:10.1097/CAD.0000000000000526\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eGrech A, Mercieca N, Calleja-Agius J, Abela R. Metastatic malignant melanoma of unknown primary in temporalis muscle. J Surg Case Rep 2020; 2020(6):1-3. \u003cu\u003edoi:10.1093/jscr/rjaa202\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eBalch CM, Gershenwald JE, Soong SJ, Thompson JF, Atkins MB, Byrd DR, et al. Final version of 2009 AJCC melanoma staging and classification. J Clin Oncol 2009; 27(36):6199-206. \u003cu\u003edoi:10.1200/JCO.2009.23.4799\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eBae JM, Choi YY, Kim DS, Lee JH, Jang HS, Lee JH, et al. Metastatic melanomas of unknown primary show better prognosis than those of known primary: A systematic review and meta-analysis of observational studies. J Am Acad Dermatol 2015; 72(1):59-70. \u003cu\u003edoi:10.1016/j.jaad.2014.09.029\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003evan der Ploeg AP, Haydu LE, Spillane AJ, Scolyer RA, Quinn MJ, Saw RP, et al. Melanoma patients with an unknown primary tumor site have a better outcome than those with a known primary following therapeutic lymph node dissection for macroscopic (clinically palpable) nodal disease. Ann Surg Oncol 2014; 21(9):3108-16. \u003cu\u003edoi:10.1245/s10434-014-3679-5\u003c/u\u003e\u003c/li\u003e\n\u003cli\u003eMilton GW, Shaw HM, McCarthy WH. Occult primary malignant melanoma: factors influencing survival. Br J Surg 1977; 64(11):805-8. \u003cu\u003edoi:10.1002/bjs.1800641114\u003c/u\u003e\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":true,"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":"Biopsy, Melanoma, Melanoma of unknown primary, Muscle metastasis","lastPublishedDoi":"10.21203/rs.3.rs-1861692/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1861692/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBackground: Melanoma is usually discovered from an irregular skin patch or a modification of a pre-existing patch. Cutaneous and lymph node metastases are common. Muscle metastasis are rare. We report a case of melanoma with infiltration of the gluteus maximus, which had normal dermatological examination.\u003c/p\u003e\u003cp\u003eCase presentation: A 43-year-old man with no history of skin surgery was admitted with progressively worsening dyspnea. On admission, he presented with superior vena cava syndrome, painless cervical lymphadenopathy and a painful swelling in the right buttock. Skin and mucous membrane examination did not reveal any abnormal or suspicious lesions. The biology was limited to a C-reactive protein of 40 mg/L, \u0026nbsp;a white blood cell count of 23 G/L and a lactate dehydrogenase level of 1705 U/L. The computed tomography scan showed several lymphadenopathies, compression of the superior vena cava and a tissue mass at the expense of the gluteus maximus. Cervical lymph node biopsy and cytopuncture of the gluteus maximus were consistent with a secondary melanoma location. A stage III melanoma of unknown primary origin associated with lymph node metastases and extension to the right gluteus maximus was suggested.\u003c/p\u003e\u003cp\u003eConclusions: Melanoma of unknown primary accounts for 3% of diagnosed melanomas. Diagnosis is difficult in the absence of a skin lesion. Patients are diagnosed with multiple metastases. Muscle involvement is unusual and may suggest a benign pathology. In this context, biopsy remains essential for diagnosis.\u003c/p\u003e","manuscriptTitle":"Melanoma of unknown primary with skeletal muscle metastasis. A case report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-07-19 19:56:27","doi":"10.21203/rs.3.rs-1861692/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":"63c603bf-2684-46dd-8f16-8d303fdec4ae","owner":[],"postedDate":"July 19th, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2023-10-16T19:38:13+00:00","versionOfRecord":{"articleIdentity":"rs-1861692","link":"https://doi.org/10.1186/s13256-023-03813-4","journal":{"identity":"journal-of-medical-case-reports","isVorOnly":false,"title":"Journal of Medical Case Reports"},"publishedOn":"2023-03-12 19:31:40","publishedOnDateReadable":"March 12th, 2023"},"versionCreatedAt":"2022-07-19 19:56:27","video":"","vorDoi":"10.1186/s13256-023-03813-4","vorDoiUrl":"https://doi.org/10.1186/s13256-023-03813-4","workflowStages":[]},"version":"v1","identity":"rs-1861692","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1861692","identity":"rs-1861692","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}