Malignant Melanoma Presenting as Multiple Lytic Bone Lesions Masquerading as Carcinoma of Unknown Primary on Clinical and Histopathological Examination
Correspondence Address :
Dr. Renu Sukumaran,
Associate Professor, Department of Pathology, Regional Cancer Centre, Thiruvananthapuram, Kerala, India.
E-mail: renu.sukumaran@gmail.com
Malignant melanoma presenting as multiple lytic bone lesions masquerading as carcinoma of unknown primary on clinical and histopathological examination. Malignant melanomas are aggressive tumours with frequent metastasis to lymph nodes and viscera. However, patients presenting with osseous metastasis of melanoma with no known primary source is relatively rare. The terminology “metastases of unknown origin” is used when the site of the primary neoplasm cannot be identified at the time of diagnosis despite a thorough history, physical examination, appropriate laboratory testing and imaging studies. Metastatic melanoma can have varied presentations. Herein, this is a case report of a 63-year-old female who presented with swelling in the occipital region of eight-month duration. Examination showed bony hard fixed swellings in the occipital and mastoid regions. Computerised Tomography scan (CT scan) showed lytic bone destruction in the occipital and mastoid part of right temporal bone, associated with soft tissue mass. With the differential diagnosis of metastatic carcinoma and myeloma, biopsy was taken which showed infiltrating neoplasm with plasmacytoid cells in cords and in vague nests surrounded by fibrosis. The neoplastic cells were Cytokeratin negative, Cluster of Differentiation (CD) 138 negative and showed patchy nuclear positivity for S100. On subsequent examination, the neoplastic cells showed diffuse strong positivity for HMB 45 (Human Melanoma Black) and patchy moderate positivity for Melan A confirming the diagnosis of malignant melanoma. Primary lesion could not be detected even after a detailed past medical and surgical history, physical examination and radiological investigations. The main causes of skull lytic lesions in adults are metastatic carcinoma and plasma cell myeloma. Possibility of metastatic melanoma should also be considered in cases of skull bone lesions as melanomas could exhibit varying cellular morphology mimicking carcinoma, sarcoma or haematolymphoid neoplasms.
Melanoma of unknown primary, Plasmacytoid cells, Skull lesions
A 63-year-old female presented to regional cancer centre with swelling in the occipital region of eight-month duration with rapid increase in size in past two months, associated with pain. She gave history of diffuse bone pain of two-year duration. Clinical examination showed bony hard, fixed, and tender swelling in the occipital and mastoid regions, measuring 11×10 cm and 5×4 cm respectively. CT scan showed lytic bone destruction in the occipital and mastoid part of right temporal bone with periosteal reaction, associated with soft tissue mass extending to extra-axial space inwards and to scalp outwards (Table/Fig 1). Lysis of pterygoid plate along with lytic lesion in manubrium sternum was also noted. Multiple lytic lesions pointed towards the differential diagnosis of metastatic carcinoma and plasma cell myeloma. Biopsy of the lesion was done. Microscopy showed infiltrating neoplasm composed of atypical cells in cords and in vague nests –surrounded by fibrosis. Individual cells were plasmacytoid with moderate amount of cytoplasm, eccentrically placed round/irregular nuclei with variably prominent nucleoli (Table/Fig 2)a-c. With morphological differential diagnosis of metastatic carcinoma and plasma cell myeloma, immunohistochemical examination was carried out. Cytokeratin and CD 138 were negative ruling out the two possibilities. Next panel included S100 with the differential diagnosis of malignant melanoma, which showed patchy nuclear positivity. On subsequent examination, the neoplastic cells showed diffuse strong positivity for HMB 45 and patchy moderate positivity for Melan A confirming the diagnosis of malignant melanoma (Table/Fig 3)a-c. Primary lesion could not be detected even after a detailed past medical and surgical history, physical examination and radiological investigations. Detailed history was taken regarding skin lesions, pigmentation at mucosal sites or any surgical interventions for skin lesions.
Melanoma of Unknown Primary (MUP) accounts for upto 3% of all melanomas and is defined as histologically confirmed melanoma metastasis to lymph nodes, subcutaneous tissue, or visceral sites without any evidence of a primary cutaneous, ocular, or mucosal melanoma (1),(2). Osseous metastases from malignant melanoma occur in patients with more advanced primary lesions. They are most frequently osteolytic and located in the axial skeleton (2),(3),(4). The wide range of clinical presentations and histopathological patterns of malignant melanoma create diagnostic challenges both for clinicians and pathologists. The clinical diagnosis can be difficult when the lesion occur in an unusual site, present in a metastatic site with an unknown primary or present as non pigmented lesion. Microscopically these tumour cells can show varied patterns (sheets, cords, trabeculae, pseudopapillary, cords) as well as a variety of histological cell types (spindle, epithelioid, signet-ring cell, pleomorphic, round cell) which may resemble a sarcoma, carcinoma or haematopoietic malignancy. Diagnosis will be more challenging in amelanotic lesions (5),(6),(7). In their study of MUP, Dasgupta TK and Brasfield RD used certain criteria for inclusion-1) absence of history of excision of any skin or anal lesion, 2) a negative ophthalmologic and dermatologic clinical examination, and 3) an absence of scars in the region of affected draining nodal basin (8). Proposed theories to explain the absence of a primary lesion in MUP include; 1) spontaneous regression of the primary lesion due to immune mechanisms, 2) de novo origin of melanomas in tissues lacking melanocytes and 3) unrecognised primary lesion (2),(3). The most commonly reported and most feasible explanation for the phenomenon of MUP is the spontaneous regression theory due to immune mechanisms. The same immune mechanisms may be responsible for the slightly better outcomes of patients with MUP, when compared to metastatic melanoma with a known primary of a similar stage (3),(6),(9),(10). Proper clinical history, physical examination, imaging studies are needed to diagnose MUP. Evaluation of patients suspected to have MUP includes imaging such as CT or 18-FDG-PET scanning to determine the extent of metastatic disease.
The problems encountered in the current case were the unusual presentation, absence of primary lesion, no known clinical or surgical history, amelanotic lesion histologically mimicking carcinoma.
When a patient presents with bone metastasis of an unknown primary site, the possibility of metastatic malignant melanoma should also be listed in the differential diagnosis. Melanomas could exhibit varying cellular morphology, mimicking poorly differentiated carcinoma, sarcoma or haematopoietic malignancies. Diagnosis of malignant melanoma may provide a challenge when the primary is unknown, when it occurs in an uncommon location or when exhibits unusual histomorphology, especially in amelanotic lesions.
DOI: 10.7860/JCDR/2022/55869.16570
Date of Submission: Feb 23, 2022
Date of Peer Review: Mar 30, 2022
Date of Acceptance: May 06, 2022
Date of Publishing: Jul 01, 2022
AUTHOR DECLARATION:
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? Yes
• For any images presented appropriate consent has been obtained from the subjects. No
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• iThenticate Software: Apr 26, 2022 (19%)
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