Background:
Sinonasal mucosal melanoma is a rare and highly aggressive malignant neoplasm with a very unfavorable prognosis. It can exhibit various histological patterns, potentially mimicking other diagnoses. Therefore, complementary immunohistochemical studies are crucial alongside morphological analysis.
We present an unusual case of locally advanced sinonasal melanoma, negative for PS100 and displaying a plasmacytoid morphology with focal aberrant expression of CD138.

A 74-year-old patient experienced epistaxis, decreased visual acuity, and treatment-resistant headaches in August 2022. A brain scan revealed a large tumor in the left nasal fossa. Initial biopsy suggested nasal plasmacytoma based on the presence of disorganized, plasmacytoid cells, CD138 positivity, and PS100 negativity. Radiotherapy was administered, but symptoms worsened. A subsequent scan showed an extensively advanced maxillo-ethmoido-sphenoidal left-sided tissue mass with distant metastases. An initial bone marrow biopsy, cervical adenectomy, and another mass biopsy were performed.

Results:
Received tissue fragments appeared brownish-black.
Histologically, the tumor proliferation comprised large, markedly atypical cells arranged in diffuse sheets, with nuclei exhibiting eccentricity, dense or vesicular chromatin, and prominent nucleoli. Melanin pigments were diffusely present in the cytoplasm.
Immunohistochemical analysis revealed diffuse positive staining for two melanocytic markers, HMB45 and MelanA. PS100 was initially very focally positive on the second biopsy, contrasting with its complete negativity in the medullary and nodal areas. CD138 was negative, avoiding confusion with melanin pigments.
Based on these findings, a diagnosis of melanoma was established.

Discussion and Conclusion:
Mucosal melanoma constitutes 0.3% to 2% of melanomas. Tumors displaying focally melanin pigments with unique histomorphology pose diagnostic challenges. Key melanocytic markers are PS100, HMB45, and MelanA.
In this case, initial and metastatic biopsies were entirely PS100-negative, except for a weak, focal positivity in the later biopsy. Such immunohistochemical profile variations underscore intratumoral immunophenotypic heterogeneity.
The absence of PS100 expression and focal CD138 expression should not lead to diagnostic errors. A comprehensive panel, including at least two plasmacytic and two melanocytic markers, is mandatory for a conclusive diagnosis.