Primary Merkel Cell Carcinoma of Lymph Node: A Distinct Entity Has Lower Association with Merkel Cell Polyomavirus (MCPyV) Than Its Cutaneous Counterpart
Zenggang Pan, Yuanyuan Chen, Xiaojun Wu, Vijay Trisal, Sharon Wilczynski, Qin Huang, Peiguo Chu, Huiqing Wu. University of Colorado Medical Center, Aurora, CO; City of Hope, Duarte, CA; Memorial Sloan-Kettering Cancer Center, New York, NY
Background: Rare cases of neuroendocrine tumor have been encountered in lymph node with no skin primary. They show similar morphologic and immunophenotypic features to those in skin Merkel cell carcinoma (MCC). It is not clear whether the "nodal MCC" is a primary tumor of lymph node or represents a metastasis from an occult tumor elsewhere. Moreover, making an accurate diagnosis of these nodal tumors can be difficult.
Design: Twenty-two cases of nodal MCC with unknown primary were selected based on strict criteria. Immunohistochemistry (IHC) stains were performed, including chromogranin A, CK AE1/AE3, CK7, CK20, PAX5, synaptophysin, TdT, and TTF1. MCPyV infection was studied by IHC and PCR assay. The clinicopathologic features of our cases were also compared with 526 cases of skin MCC from the literature (Table 1).
Results: The nodal MCCs mostly occurred in old patients (mean 65.2 years) with a male predominance (M:F=18:4) from the lymph nodes in head/neck (9 cases), inguina (8) and axilla (5). The tumor cells had nested, organoid or diffuse growth pattern with high N/C ratio, fine chromatin and inconspicuous nucleoli. All our cases were positive for cytokeratin, 20 of which expressed CK20 with characteristic perinuclear “dot-like” staining. The nodal and skin MCCs generally had similar immunohistochemical profiles statistically; however, the nodal cases had much lower MCPyV infection (P = 0.001), which was confirmed by PCR assays. Most of our cases had at least focal expression of PAX5 and TdT, which may mimic hematologic malignancies particularly in cases with a diffuse growth pattern. None of the 19 patients with follow-up developed any skin MCC with an average interval of 23.2 months (2-116 months). Four patients died, 2 of disease and 2 of other causes.
Conclusions: Despite sharing similar morphologic and immunophenotypic features, nodal MCCs had significantly lower association with MCPyV than skin MCCs. Therefore, these two entities may arise from overlapping but not identical biological pathways.
|Nodal MCC||Cutaneous MCC||P-Value|
|Gender (M:F)||18:4 (4.5:1)||326:229 (1.42:1)|
|Mean age (years)||65.2 (N=22)||71.7 (N=526)|
|CK7||3/22 (14%)||10/68 (15%)||1.00|
|CK20||20/22 (91%)||93/114 (82%)||0.37|
|Synaptophysin||19/19 (100%)||106/114 (93%)||0.60|
|Chromogranin A||13/19 (68%)||94/113 (83%)||0.20|
|TTF1||0/21 (0%)||4/114 (3.5%)||1.00|
|PAX5||8/13 (62%)||76/91 (84%)||0.12|
|TdT||10/13 (77%)||55/81 (63%)||0.75|
|MCPyV||3/13 (23%)||196/261 (75%)||0.001|