Lymph nodal Merkel cell carcinoma: primary tumor or metastasis from unknown primary site?

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer with neuroendocrine differentiation (1-4). Most MCC affect the skin of the head and neck, often the periorbital region and the extremities; less than 10% affect the trunk or mucus membranes (1-5); regional lymph nodal metastases occur in 50 - 66% of the cases. In 1992, Eusebi et al (5) described eight cases of nodal MCC in the absence of primary skin tumours or any other localization. Afterwards other authors (3,4) reported cases of “primary” nodal MCC pointing out the question if it really exists or represents, instead, metastasis from an occult neoplasm (3,4). In these cases strict clinical and instrumental criteria should be applied to perform the diagnosis of primary nodal MCC (2); likewise it is difficult to diagnose these “ectopic” tumours as MCC due to their similarity to other poorly differentiated small cell neoplasms. Therefore a specific immunohistochemical (IHC) has to be demonstrated, namely coexistence of both neuroendocrine and epithelial features, this latter with typical dot-like pattern (1-5). We report a case of recurring MCC in two distinct lymph nodal sites in absence of any evidence of primary tumor. A 77-year-old male underwent to excision of a 35 X 27 mm large, right inguinal node. Histologically the node was replaced by diffuse infiltration of undifferentiated neoplasm. The tumor showed a roughly solid pattern, the cells were monomorphic, small and round with ovoid vesicular nuclei and scanty cytoplasm (fig. 1A); mitoses were frequent. ICC showed positivity for cytokeratin AE1/AE3 pattern, positivity for NSE, cromogranin and cytokeratin 20 with paranuclear-dots (fig. 1B) and negativity for LCA, cytokeratin 7 and TdT. Being negative all the clinical and instrumental investigations, including a PET-CT, a diagnosis of nodal MCC was performed. The patient received local radiotherapy (45 Gy) and was disease-free for 4 years when a routine ultrasound examination revealed a right axillary 35 x 28 mm node. The patient underwent to fine-needle cytology (FNC); the smears showed a dispersed cell population consisting of small cells with scanty and clear cytoplasm; the nuclei were round or polygonal with fine chromatin and inconspicuous nucleoli (fig. 1C). Immunocytochemistry, performed on cell block, showed a phenotype similar to that one observed in the former histological sample: NSE, CD56, CK AE1/AE3 and CK20 positivity, this latter with a dot-like pattern (Fig. 1D) and LCA, CK7 and TTF1 negativity; therefore a cytological diagnosis of nodal MCC was made. Again a careful investigation did not demonstrate any extra nodal site of origin; the patient underwent to the same former therapeutic procedure and after 8 months he is alive and free from disease. In conclusion, being Merkel cells or their precursors absent in normal lymph nodes (2), in case of primary nodal MCC the presence of an occult and/or regressed primary MCC is still the most reliable hypothesis. Nonetheless the peculiar clinico-pathological presentation of our case may support the existence of a subset of primary nodal MCC as suggested by Eusebi et al (5).