Skeletal Radiology

, Volume 32, Issue 12, pp 724–727

Subungual melanoma with osteocartilaginous differentiation


  • H. Giele
    • Nuffield Department of Orthopaedic Surgery, University of OxfordNuffield Orthopaedic Centre
  • K. Hollowood
    • Nuffield Department of Orthopaedic Surgery, University of OxfordNuffield Orthopaedic Centre
  • C. L. M. H. Gibbons
    • Nuffield Department of Orthopaedic Surgery, University of OxfordNuffield Orthopaedic Centre
  • D. J. Wilson
    • Department of Radiology, University of OxfordNuffield Orthopaedic Centre
    • Department of Pathology, University of OxfordNuffield Department of Orthopaedic Surgery, Nuffield Orthopaedic Centre
Case Report

DOI: 10.1007/s00256-003-0697-y

Cite this article as:
Giele, H., Hollowood, K., Gibbons, C.L.M.H. et al. Skeletal Radiol (2003) 32: 724. doi:10.1007/s00256-003-0697-y


Osteocartilaginous metaplasia is known to occur rarely in melanomas, particularly in subungual melanomas. We present a case of a calcified subungual soft tissue tumour in which biopsy of the lesion showed malignant round and spindle-shaped tumour cells, many of which were associated with the formation of cartilage and osteoid-like material. Subsequent resection showed clear histological evidence of a subungual melanoma. Tumour cells expressed S100, melan-A and neurone-specific enolase but were negative for HMB45. Diagnostic radiological and histological features and the nature of the osteocartilaginous differentiation within this lesion is discussed.


MelanomaSubungualBone and cartilage differentiation


Melanomas are known to be associated with stromal metaplasia, most commonly fibrous and mucinous stromal change [1, 2]. Osteocartilaginous metaplasia has rarely been reported in these tumours, most commonly in recurrent melanomas arising in a subungual location [3, 4].

In this report, we present radiological and histological findings of a case of subungual melanoma in which, on initial biopsy, malignant round and spindle-shaped tumour cells and the formation of cartilage and partly mineralised osteoid-like material predominated to the extent that the diagnosis of a malignant bone or cartilage-forming tumour was strongly considered. Radiological and histological aspects of this subtype of subungual melanoma, which is often amelanotic and negative for melanoma-associated antigen, are reviewed and the origin and nature of the osteocartilaginous component of this tumour discussed.

Case report

A 50-year-old man had a 4-year history of nail dystrophy of the right index finger. He developed a groove and a split in the nail, the nail becoming discoloured and partly detached from the nail bed. This problem was initially thought to be due to a fungal infection, but no organism was identified on fungal scrapings. In the 6 months prior to presentation, he noticed a mass growing on the radial aspect of the pulp of the finger.

Radiographs of this lesion showed a soft tissue swelling adjacent to the terminal phalanx with distortion of the region of the nail (Fig. 1). Within this mass there was a poorly defined area of increased density which was central and irregular in outline and texture. It was difficult to determine whether this area of increased density represented calcification or ossification. In the absence of other lesions, and with no joint involvement, possible diagnoses that were considered included an implantation granuloma with calcification, myositis ossificans, juxtacortical chondroma, chronic sepsis with secondary calcification, bizarre parosteal osteochondromatous proliferation, subungual exostosis, synovial chondromatosis, fibro-osseous pseudotumour of the digits, metastatic deposits and soft tissue osteosarcoma or chondrosarcoma.
Fig. 1.

Lateral and A-P radiographs of the index finger showing a calcified soft tissue swelling over the terminal phalanx

It was clear that imaging could not easily distinguish between these various benign and malignant entities and a biopsy of the lesion was undertaken. At operation, the lesion was seen to extend between the nail bed and the distal phalanx onto the pulp of the index finger. The lesion was deep to the overlying skin surface, which was not directly involved but was stretched over the lesion.

Histology of the biopsy showed that the tumour extended from the dermis into deep subcutaneous tissue. The overlying nail bed epithelium and skin were not in continuity with the tumour and there was no junctional activity. Tumour cells were widely scattered throughout the dermis and subcutaneous tissue with occasional clumps and cords of tumour cells being noted. The tumour cells were highly pleomorphic and were disposed mainly between collagen bundles in the dermis and subcutaneous tissue. Focal areas of cartilage formation and osteoid-like material were seen in association with tumour cells that had hyperchromatic or vesicular nuclei with prominent nucleoli (Figs. 2 and 3). Some of the tumour cells surrounding these focal areas of cartilage and partly mineralised osteoid-like material had a vacuolated cytoplasm. There was no organised pattern to the formation of bone and cartilage in the tumour, although to some extent the close association between tumour cells and the focal areas of cartilage and osteoid-like material was somewhat reminiscent of a mesenchymal chondrosarcoma.
Fig. 2.

Photomicrograph of the tumour biopsy showing clumps of plump round tumour cells. Some of the cells have vacuolated cytoplasm and are associated with the formation of osteoid-like material, which is partly mineralised (Haematoxylin-eosin ×400)

Fig. 3.

A collection of round and spindle-shaped tumour cells within dense connective tissue. There is a focus of cartilage formation (Haematoxylin-eosin ×200)

Tumour cells were strongly positive for S100 and vimentin as well as weakly positive for neurone-specific enolase (NSE). Tumour cells were negative for HMB45, cytokeratin intermediate filaments, epithelial membrane antigen, desmin, muscle/smooth muscle actin, CD34 and neurofilaments. As the nature of this lesion was uncertain, it was referred widely to specialist osteoarticular and skin pathologists who suggested a number of diagnostic possibilities including acral mesenchymal chondrosarcoma/osteosarcoma, malignant peripheral nerve sheath tumour with bone and cartilage elements and subungual melanoma with bone and cartilage metaplasia.

Staging investigations were performed. Clinical examination showed no skin lesions or lymphadenopathy. An MRI of the upper limb showed no other lesions. A CT examination of the chest was normal. Bone scintigraphy revealed a focal area of increased radiopharmaceutical activity over the left sacro-lilac joint. A pelvic radiograph and CT revealed a 5-cm area of increased radio-opacity over the left sacro-iliac joint. Biopsy of this lesion showed features in keeping with those of fibrous dysplasia and no evidence of melanoma.

Amputation of the right index finger through the head of proximal phalanx was undertaken. This gave at least a 1-cm margin from the most proximal extent of the tumour. Pathological examination of the specimen showed that the tumour in the dermis and subcutaneous tissue was composed mainly of malignant spindle-shaped and round tumour cells, similar to those seen in the original biopsy. It was also noted that beneath the nail bed there were a few small nests of pleomorphic round and spindle-shaped tumour cells; this component of the tumour was continuous with an area of junctional activity in the overlying nail bed (Fig. 4a). Scattered tumour cells, some of which formed small cords and clumps (Fig. 4b), extended into the dermis and subcutaneous tissue where they merged with ill-defined collections of hyperchromatic round and spindle-shaped tumour cells that were associated with cartilage formation. These tumour cells were positive for S100 and NSE, but negative for HMB45. However, staining for the melanoma marker melan-A (on both the biopsy and the resection specimen) showed that the tumour cells reacted for this antigen (Fig. 4c). The tumour cells were also negative for CD99, CD68, leucocyte common antigen, c-kit, CD34, muscle/smooth muscle actin, epithelial membrane antigen and cytokeratin. No melanin pigment was identified in the biopsy or the resection specimen. On morphological and immunophenotypic grounds, this lesion was diagnosed as a subungual melanoma showing areas of osteocartilaginous differentiation.
Fig. 4a–c.

Histology of the resection specimen showing: focal junctional activity in the epithelium of the nail bed with scattered tumour cells in the underlying dermis; infiltrating clumps and cords of melanoma cells within the dermis. c Mekan-A staining of clumps of tumour cells. a, b Haematoxylin-eosin ×600, ×200, respectively. c Immunoperoxidase ×400


Osteocartilaginous change in malignant melanoma is very rare. Several large series of cases of acral cutaneous melanoma and subungual melanoma, including two recent series, did not identify any cases of melanoma with bone or cartilage differentiation [5, 6, 7, 8]. Fewer than 20 cases of this subtype of subungual melanoma have been reported in the literature to date [4, 9, 10, 11, 12, 13, 14]. Most are single case reports apart from a series of four cases presented by Lucas et al. [4].

In most of the reported cases, a histologically distinct melanoma component is seen in association with areas of osteoid or bone formation. In some tumours, both bone and cartilage differentiation may be noted; in one case, cartilaginous differentiation alone was seen. All these cases presented similarly with a long history of nail dystrophy or other nail problem sometimes followed, as in the present case, by the appearance of a hard nodule. Most of the reported cases, including the present one, arose in middle-aged adults. In the series reported by Lucas et al. [4], the tumours were acral lentiginous melanomas; three of the cases were subungual in location, the other involved the sole of the foot. Regional lymph node metastasis was seen in three of the four cases but was not present in our case.

Histological diagnosis on biopsy in our case was difficult as there was no clear-cut melanoma component and the lesion did not stain for HMB45. Examination of the amputation specimen readily permitted morphological identification of a malignant melanoma component, although this by no means formed the bulk of the lesion. The expression of S100 and melan-A by tumour cells is in keeping with the tumour being a subungual melanoma and would argue for these antibodies being routinely employed in this case. It should be noted that HMB45 staining was also absent in two of the three cases of subungual melanoma reported by Lucas et al. [4].

Metaplastic bone or cartilage formation can occur in several neoplastic and non-neoplastic soft tissue lesions such as tumours of neural and adipose differentiation as well as epithelial tumours such as breast or skin carcinomas [15]. It may be noted in melanocytic lesions such as the dermal naevus of Nanta and in congenital naevi [16, 17]. The cause of this metaplastic change is uncertain but it could be due to osteoid or cartilage formation as part of a reparative response to injury [18]; in this regard it is interesting to note that a history of previous trauma is often present in cases of subungual melanoma with osteocartilaginous differentiation. Invading melanoma cells could also induce sarcomatous proliferation of pluripotent connective tissue stroma with subsequent bone or cartilage formation. Alternatively, it is possible that melanoma cells may themselves be capable of differentiation into mesenchymal tumour cells. The latter is suggested in our case by the fact that the tumour cells in direct relation to the cartilage and osteoid-like matrix material being formed were S100 and melan-A positive. Malignant melanoma is a tumour of neural crest cell origin. Neural crest cells are now known to give rise to a wide range of tissue elements and the skeletogenic potential of neural crest cells is now well recognised [19, 20]. Differentiation to cells of bone and cartilage, odonoblasts, melanocytes, vascular smooth muscle cells, endocrine and neural cells has been demonstrated.

The differential diagnosis of subungual melanoma with osteocartilaginous differentiation from the radiological and histological point of view covers a number of different entities, both benign and malignant. This is, in fact, one of the few reports in which the radiological features of this lesion have been presented; they are clearly not distinctive and fall within the wide ambit of phalangeal/subungual soft tissue lesions that are associated with ossification or calcification. Clearly, however, this tumour should be borne in mind as a rare cause of acral subungual soft tissue calcification/ossification. It should also be noted that histological confirmation of the diagnosis of this subtype of melanoma can also be problematic, particularly as HMB45 may not be expressed by the tumour cells.


The authors thank Dr. Alan Darby for help in diagnosing this lesion.

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