Letter to the Editor
Diffuse TTF-1 expression in a case of Merkel cell carcinoma

Dear Editor,

We herein report an unusual case of a cytokeratin-20 positive/cytokeratin-7 negative (CK20+/CK7–) Merkel cell carcinoma (MCC) that also showed immunoreactivity to two different thyroid transcription factor-1 (TTF-1) clones. An 88-year-old woman with no known history of a non-cutaneous neuroendocrine neoplasm presented with a 1.1 cm tumour located in the upper lip, allegedly having noticed it 2 months previously. The lesion was excised with negative margins. Lymph nodes were negative according to clinical examination (no pathological node examination was performed).
Histologically, the presence of a fairly circumscribed neoplasm was observed with neuroendocrine cell tumour morphology, compatible with MCC. It consisted of intermediate size, roundish cells, in groups or trabeculae, with minimal cytoplasm, a coarse chromatin pattern and increased mitotic activity (Fig. 1). In between neoplastic buds extending to the subcutaneous fatty tissue, multiple vessels and areas of necrosis were observed, but no lymphovascular invasion and no skin ulceration. Immunohistochemically, nuclear TTF-1 positivity was observed in a substantial amount of tumour cells. Two different clones raised against TTF-1 were used, namely SPT24 [Novocastra, UK, 1/80 dilution] (Fig. 1B) and 8G7G1/1 [DAKO, Denmark, 1/50 dilution] (Fig. 1C). The rest of the marker panel immunophenotype, namely chromogranin A+, CD56+, NF+, CK20+ (dot-like/crescentic) (Fig. 1D), and CK7- confirmed initial histological diagnosis of MCC. MCC polyomavirus antigen presence could not be investigated.
The neoplasm was staged as IB (T1cN0M0). The patient was clinically evaluated with no other relevant finding. The presence of a primary extra-cutaneous neuroendocrine carcinoma was excluded. During a 2-year follow-up period the patient did not show recurrence.
Merkel cell carcinoma is a rare, clinically aggressive, primary neuroendocrine skin neoplasm with variable prognosis. Adverse histopathological prognostic factors include lymphovascular invasion, large tumour size, small cell size and high mitotic rate [1]. Merkel cell carcinoma should be distinguished from a metastatic small cell carcinoma (SCC), mostly of the lung. Expression of TTF-1, especially when combined with immunostaining with CK20 and certain neuroendocrine markers, holds great differential-diagnostic value in the distinction between an MCC and a skin metastasis of an SCC (pulmonary or extra-pulmonary). Although...


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