A 23 year old male with right wrist mass
Nariman Atif Nawar, M.D .and H. James Williams M.D.
A 23 year old male patient presented with right wrist swelling. The swelling was initially noted 4 years ago and it is associated with pain and numbness. The patient stated that his condition was diagnosed as arthritis; however, despite the use of medications the pain did not improve. Physical examination showed a firm right wrist mass measuring 7.0 cm accompanied by atrophy of the thenar muscles. Radiological studies reveal a large lobular septated mass on the volar aspect of the right wrist with a mass effect on the adjacent flexor muscle. (Figure 1)
MRI shows a 6.0 x 5.4 x 3.1 cm mass on the volar aspect of the right wrist with septation (long arrow) and irregular borders (short arrow). The mass is compressing the flexor muscles (short arrow). These features are highly suggestive of malignancy.
Needle core biopsy of the wrist mass was performed. On low power there are nests of cuboidal cells with pale eosinophilic cytoplasm separated by bands of fibrous connective tissue and focal areas of brown pigmentation (Figure 2). On higher power, the tumor cells are seen to have hyperchromatic nuclei and prominent nucleoli with rare intranuclear inclusions and cytoplasmic melanin pigmentation (Figures 2 and 3). Immunohistochemical studies showed positive staining for MART-1, CD99 and negative staining for CD68 and CD45 (Figure 4).
The cells demonstrate positive staining for CD99 and MART-1 and negative staining for CD68 and CD45. The deep brown cytoplasmic pigmentation (black arrow) represents melanin, not to be misinterpreted as positive CD68 staining.
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The differential diagnosis for this case based on the clinical presentation and the histopathologic features is broad, including: malignant melanoma, lymphoma, giant cell tumor of tendon sheath, and clear cell sarcoma of tendons and aponeurosis (CCSTA). To narrow down the differential diagnosis ancillary studies using immunohistochemistry were performed including MART-1, CD45, CD68 and CD99. The negative staining pattern for CD45 and CD68 excluded lymphoma and giant cell tumor of tendon sheath respectively while the positivity for MART-1 and CD99 left malignant melanoma and CCSTA as the possible diagnosis. To solve this puzzle, testing for the classic translocation that identified CCSTA which is t (11; 22) (p13; q12) was performed and confirmed the diagnosis.
The CCSTA is a rare form of soft tissue tumor which was first described as malignant melanoma of soft parts in 1968. As the old name implies, this entity shares many features with malignant melanoma.
Clinically it manifests as a tender soft tissue mass in the extremities adjacent to a tendon or to an aponeurosis. It is more common in children and adolescents than in adults. The exact incidence of this disease is not known as it is believed it is overlooked and misdiagnosed as malignant melanoma quite often.
In gross examination CCSTA tends to form a well circumscribed mass with gray to dark brown discoloration. Microscopically the tumor consists mainly of cuboidal cells with melanin pigmentation as well as cytoplasmic melanosomes which can be visualized using electron microscopy.
As this tumor is actually derived from the neural crest cell, it stains positively for melanocytic markers such as MART-1, S-100, Melan-A, HMB-45 and for neuronal markers such as CD99 and neuron specific enolase. The immunophenotypic features for CCSTA are not specific and, hence, requires additional studies including molecular studies.
At the molecular level, CCSTA is characterized by t(12, 22) (q13:q12), which can be detected by using florescence in situ hybridization. Genes involved in this translocation are the Ewing sarcoma (EWSR1) gene on chromosome 22 and the activating transcription factor gene 1 (ATF 1) on chromosome 12 (Figure 5). Although the Ewing sarcoma gene is involved in the pathogenesis of a number of different types of tumors such as primitive neuroectodermal tumor, desmoplastic small round cell tumor, and extraskeletal myxoid chondrosarcoma, its fusion with the ATF1 gene is what characterizes CCSTA.
Treating CCSTA is quite challenging. It has a tendency to reoccur and metastasize despite aggressive surgical and medical treatment with chemotherapy and radiotherapy. The patient in this case was subsequent found to have a metastasis to a right axillary lymph node.
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