TTF-1-Positive Merkel Cell Carcinoma in Situ

Merkel cell carcinoma in situ (MCCIS), especially when unaccompanied by invasive Merkel cell carcinoma, is exceptionally rare. Most reported cases of MCCIS without invasion demonstrate the typical immunophenotype of invasive MCC, including cytokeratin 20 (CK20) positivity and thyroid transcription factor-1 (TTF-1) negativity. Here we report a case of MCCIS without invasion exhibiting a phenotype not previously reported in MCCIS: CK20 negativity with diffuse nuclear TTF-1 positivity. Arising within a seborrheic (stucco) keratosis in a 78-year-old woman, the lesion demonstrated an entirely intraepidermal proliferation of atypical cells with neuroendocrine differentiation by histology (high nuclear-to-cytoplasmic ratio, crush artifact, and nuclear molding) and immunohistochemistry (positive synaptophysin, chromogranin, neuron-specific enolase, INSM1, and SATB2). The lesion was negative for squamous markers (cytokeratin 903, cytokeratin 5/6, p40, and p63), Merkel cell polyomavirus (MCPyV/CM2B4), and neurofilament. A review of the literature identified no prior TTF-1-positive MCCIS. To our knowledge, the present case represents the first reported TTF-1-positive MCCIS and only the second reported CK20-negative MCCIS. This unusual phenotype expands the recognized immunophenotypic spectrum of MCCIS and highlights a potential diagnostic pitfall.

Abstract from PubMed