Year : 2010 | Volume
: 53 | Issue : 1 | Page : 130--132
Malignant melanoma with osteocartilaginous differentiation
Shirley Sundersingh, Urmila Majhi, Kanchan Murhekar, Radha Krishnamurthy
Department of Pathology, Cancer Institute (W.I.A.), 38, Sardar Patel Road, Chennai-600 036, India
New No.23, Jambulingam Street, Nungambakkam, Chennai-600 034
We report a case of acral lentiginous melanoma on the plantar aspect of foot in a 50-year-old male that exhibited a prominent osteo-cartilaginous differentiation in the metastatic inguinal lymph node. The ability of melanomas to undergo multidirectional differentiation leads to a variety of histological appearances that can be misleading. Although the true nature of the tumor is most often recognized at the primary cutaneous site, metastatic tumors may closely mimic other malignant mesenchymal or neuro-ectodermal tumors. Hence awareness of this unusual phenomenon occurring in malignant melanoma is essential to avoid misdiagnosis.
|How to cite this article:|
Sundersingh S, Majhi U, Murhekar K, Krishnamurthy R. Malignant melanoma with osteocartilaginous differentiation.Indian J Pathol Microbiol 2010;53:130-132
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Sundersingh S, Majhi U, Murhekar K, Krishnamurthy R. Malignant melanoma with osteocartilaginous differentiation. Indian J Pathol Microbiol [serial online] 2010 [cited 2020 Aug 12 ];53:130-132
Available from: http://www.ijpmonline.org/text.asp?2010/53/1/130/59204
Malignant melanoma may exhibit divergent differentiation.  This uncommon phenomenon characterized by the development of non-melanocytic tissues frequently manifests as fibroblastic/myofibroblastic, Schwannian or perineurial differentiation in desmoplastic or neurotropic melanoma.  Osteocartilaginous differentiation is rare. Cartilaginous differentiation was first described by Wahlstrom and Saxen  while Urmacher  was the first to describe bone and osteoid formation in malignant melanomas. We report a case of predominantly amelanotic type of acral lentiginous melanoma involving the plantar aspect of the left foot in a 50-year-old male. The melanoma exhibited a prominent osteo-cartilaginous differentiation in the metastatic left inguinal lymph nodes. The clinico-pathological features, brief review of literature and proposed mechanisms by which divergent differentiation occurs are presented.
A 50-year-old man presented to our institute with history of a pigmented lesion in the plantar aspect of the left foot (of one year duration) and swelling in the left groin of two months duration. Examination showed a pigmented area with a 2x1cm, elevated, nodule in the left sole. No satellite nodules were seen. Multiple enlarged lymph nodes were palpable in the left groin with the largest node measuring about 4x3cms. Wedge biopsy of the plantar lesion showed markedly hyperkeratotic epidermis with the dermis showing a tumor composed predominantly of sheets of small round oval cells with moderate eosinophilic cytoplasm and hyperchromatic nuclei with nucleoli separated by myxoid stroma [Figure 1].
Pseudo-glandular and pseudo-angiomatous pattern with lobules and nests of better differentiated large polygonal cells with abundant cytoplasm and vesicular nuclei with prominent nucleoli were seen towards the deep dermis and subcutaneous fat. Mitoses were one to three/hpf. There was lentiginous proliferation of atypical melanocytes at the dermoepidermal junction. Intracytoplasmic melanin pigment was identified focally at the dermoepidermal junction and deep dermal and subcutaneous aspect of tumor. Immunohistochemistry showed positivity of the tumor cells for vimentin, S-100 protein, HMB 45 and Melan A with increasing intensity towards the better differentiated deeper aspect of the tumor. A diagnosis of malignant melanoma, Clark's level V was made.
Subsequently the patient underwent a wide local excision of the sole lesion with left inguinal block dissection. Histo-pathological examination of the sole lesion confirmed the biopsy findings of malignant melanoma. However, microscopic examination of the inguinal block dissection showed many lymph nodes replaced by metastatic tumor composed predominantly of malignant oval to spindle cells merging with areas of osteoid and cartilaginous differentiation [Figure 2],[Figure 3]. Immunohistochemistry showed positivity of the tumor cells for S-100 protein, Melan A and HMB 45 [Figure 4]. A diagnosis of metastatic melanoma with osteocartilaginous differentiation was made.
Malignant melanoma possesses the ability to undergo multidirectional differentiation that includes fibroblastic/myofibroblastic, schwannian and perineurial, smooth muscle, rhabdomyoblastic, osteo-cartilaginous, ganglionic/ganglineuroblastic, neuroendocrine and probable epithelial components. This divergent differentiation may give rise to a variety of cyto-architectural and stromal patterns that may mimic carcinoma, sarcoma, neuroendocrine tumors, lymphoma or germ cell tumors.  Combined osteo-cartilaginous differentiation in malignant melanoma is rare. Melanomas with a predilection for osteo-cartilaginous differentiation include those at acral (particularly sub-ungual) location, tumors with high Breslow thickness, presence of lentiginous radial growth phase component and amelanotic phenotype. 
Since many of the melanomas with osteocartilaginous differentiation were either recurrences or previously biopsied/repeatedly traumatized tumors, it was believed that trauma initiated osteoid and bone formation as part of the reparative process. It was also suggested that mesenchymal metaplasia may have resulted in the production of osteocartilaginous components.  However, the term metaplasia is a misnomer in this case since metaplasia applies to a reversible change of one adult cell type to another adult cell type which lacks cellular features of malignancy. Considering the neural crest origin of melanoma and its skeletogenic potential, the most plausible mechanism for osteocartilaginous differentiation would be neo-differentiation of melanoma cells influenced by factors in the local milieu which lead to molecular cascades activating a series of downstream pathway. Alternatively, mutations of stem cells in the basal layer of epidermis which confers uncontrolled proliferative activity to tumor may also be responsible for divergent differentiation. 
In the absence of in-situ component, melanin pigmentation and absence of staining for HMB 45, diagnosis of melanoma may be difficult. However, in most of the reported cases a distinct melanoma component was seen in association with osteocartilaginous stroma. Malignant melanoma with osteo-cartilaginous differentiation may mimic different benign and malignant entities. Myositis ossificans can be distinguished by the presence of a zonal pattern of osseous maturation and lack of cellular anaplasia. The absence of primary bony involvement, presence of in situ component, regional lymphnode metastasis and positivity for markers like S-100 P and HMB-45 differentiates melanoma from osteosarcoma and chondrosarcoma.
The number of cases documented is too small to attribute prognostic implications to the osteo-cartilaginous component. However, most of the reported cases have behaved as conventional melanoma. Our patient developed pulmonary and splenic metastases and died 11 months after surgery.
|1||Banerjee SS, Eyden B. Divergent differentiation in malignant melanomas: a review. Histopathology 2008;52:119-29. |
|2||Lucas DR, Tazelaar HD, Unni KK, Wold LE, Okada K, Dimarzio DJ Jr, Rolfe B. Osteogenic melanoma. A rare variant of malignant melanoma. Am J Surg Pathol 1993;17:400-9.|
|3||Wahlström T, Saxén L. Malignant skin tumors of neural crest origin. Cancer 1976;38:2022-6.|
|4||Urmacher C. Unusual stromal patterns in truly recurrent and satellite metastatic lesions of malignant melanoma. Am J Dermatopathol 1984;6:331-5. |
|5||Banerjee SS, Harris M. Morphological and immunophenotypic variations in malignant melanoma. Histopathology 2000;36:387-402. |
|6||Cachia AR, Kedziora AM. Subungual malignant melanoma with cartilaginous differentiation. Am J Dermatopathol 1999;21:165-9. |
|7||Hoorweg JJ, Loftus BM, Hilgers FJ. Osteoid and bone formation in a nasal mucosal melanoma and its metastasis. Histopathology 1997;31:465-8.|