Fine needle aspiration cytology from this mass yielded highly cellular smears with presence of predominantly dispersed cell population and few cohesive clusters of round to polygonal to plasmacytoid cells. These cells had moderate amount of pale basophilic cytoplasm, round to oval monotonous-looking nuclei with inconspicuous nucleoli. Few cells showed prominent nucleoli and some mitotic figures were also seen (Figure 1). A cell block prepared from the aspirated material showed polygonal to round cells with a moderate amount of pink cytoplasm and a single nucleus with prominent nucleoli in some cells. Considering the site and morphology, a diagnosis of malignant myoepithelioma was considered and an urgent excision was advised.
Meanwhile CT scan of the head and neck was done which revealed that the mass extended to the tail of the parotid while the submandibular salivary gland was unremarkable. The patient was taken up for surgery and intraoperatively the mass was found to be infiltrating the muscle and reaching the tail of the parotid. However, the submandibular salivary gland was not related to the mass. The mass was excised and sent for histopathological examination. It measured 6.5×5×4 cm with a bosselated outer surface and the cut surface showed large areas of haemorrhage and necrosis (Figure 2). H&E stained sections from the tumor showed tumor cells arranged in the form of nests and lobules (Figure 3). Cell morphology was the same as seen in the cell block (Figure 4). Few areas revealed brown- to blackcolored pigment that stained positive for Masson's Fontana, thus confirming that this pigment was melanin. Extensive sampling showed intracytoplasmic pigment in many cells. In view of these findings, a differential diagnosis of malignant melanoma and myoepithelial carcinoma with melanocytic differentiation was considered and immunohistochemistry was used to differentiate the two. The tumor was strongly positive for S100 and HMB 45. It was negative for Calponin, Smooth muscle actin and Cytokeratin thus ruling out myoepithelial carcinoma. More sections were taken to look for presence of salivary gland or lymph node. No lymphoid tissue could be delineated and the adherent salivary gland was unremarkable (Figure 4). A detailed history was taken and complete clinical examination of the patient was carried out including all mucosal sites, skin and ocular examination to look for a possible primary site. The complete systemic examination was unremarkable, thus giving a final diagnosis of malignant melanoma metastatic to subcutaneous tissue with unknown primary site.
Figure 2: Mass measuring 6.5x5x4 cm with large areas of haemorrhage and necrosis.
Figure 3: H&E stained section showing low magnification (x100).
Figure 4: H&E stained section showing prominent nucleoli and occasional binucleated cells (x400).
This problem becomes more complex when it presents at unusual sites with unknown primary sites (MUP). Lymph nodes have been found to be the most common site of MUP in most studies. Axillary lymph nodes are the most common followed by inguinal and cervical nodes[4]. Schlagenhauff et al found cutaneous/subcutaneous metastases to be more frequent, accounting for more than half of all MUPs in a series including 3258 melanoma patients[2]. The prevalence of solitary lesions of melanoma confined to dermal or subcutaneous tissue has been reported to be 0.51%, 0.63% and 0.92% in three large series[2,4,5]. The sites included the head and neck, upper extremity, lower extremity, and trunk.
These tumors were extensively investigated for the first time by Das Gupta et al in a series of 47 patients. The criteria proposed by this group for the diagnosis of melanoma of unknown primary have been universally applied till now. According to these criteria, history of previous orbital exenteration and presence of a mole, birth mark, freckle, chronic paronychia, or other skin lesions previously excised, cauterized or desiccated has to be excluded for a diagnosis of MUP. The authors also proposed to examine patients thoroughly including ophthalmoscopy and examination of the anogenital region[1].
Several studies have reported worse prognosis for patients with MUPs[10], while others have reported better[2,6,11] or similar survival rates[3,7]. With regard to isolated subcutaneous masses, Schlagenhauff et al reported a 5 year survival of 83%[2]. Anbari et al described 3 patients with isolated subcutaneous nodules, all 3 of which were alive after 8 years[4], Bowen et al reported an 8-year survival rate of 83%[5] which is higher than expected for Stage III (13-50%) or Stage IV disease (5-17.9%). Our patient is well after 15 months of follow-up.
Several etiologies for MUP have been proposed including 1) an antecedent unrecognized, spontaneously regressed melanoma[12] 2) a previously excised clinically and/or histologically misdiagnosed melanoma, 3) a concurrent clinically unrecognized melanoma, and 4) de novo malignant transformation of an errant melanocyte at a lymph node or visceral site or melanocytes associated with deeper appendageal structures[1].
In conclusion, malignant melanoma is a difficult diagnosis to make particularly when the primary site is not known. Since it is an aggressive tumor, the importance of timely diagnosis is unquestionable. A high index of suspicion, extensive sampling to look for melanin pigment and appropriate immunohistochemistry are the keys to accurate diagnosis.
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