Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart

Abstract

Rare cases of Merkel cell carcinoma have been encountered in lymph nodes with unknown extranodal primary, which exhibit similar morphologic and immunophenotypic features to those in primary cutaneous Merkel cell carcinomas. However, it is uncertain whether the nodal Merkel cell carcinoma is a primary tumor of the lymph node or represents a metastasis from an occult or regressed extranodal lesion. To establish an accurate diagnosis of the nodal Merkel cell carcinoma can be challenging because of significant morphologic mimics, including lymphoblastic lymphoma and metastatic small cell carcinoma. Moreover, there is no consensus for a diagnostic term, and many different terms have been used, which can be confusing and may not fully reflect the nature of nodal Merkel cell carcinoma. In this study, we investigated the detailed clinicopathologic features of 22 nodal Merkel cell carcinomas, with comparison to 763 primary cutaneous cases retrieved from the literature. Overall, the nodal and cutaneous Merkel cell carcinomas shared similar clinical presentations, morphologic spectrum, and immunophenotype; both were mostly seen in elderly male with a typical neuroendocrine morphology. Most of cases expressed CK20, synaptophysin, and chromogranin A; and PAX5 and TdT were also positive in majority of cases. However, nodal Merkel cell carcinomas had a significantly lower association with Merkel cell polyomavirus than cutaneous cases (31% vs 76%, P ¼ 0.001). Therefore, these two entities may arise from overlapping but not identical biological pathways. We also recommend the use of the diagnostic term 'Merkel cell carcinoma of lymph node' to replace many other names used.

Neuroendocrine Merkel cell nodal carcinoma of unknown primary site: Management and outcomes of a rare entity

“…In serum of patients with MCC by enzyme-linked immunosorbent assay were found by Touze et al high antibody titers (>10,000) in 64.7% compared with 7.3% observed in the controls [34]. However, Pan and colleagues found a significantly lower association of MCV in MCCUP than in skin cases (31% vs 76%) [35]. Although, MCV can be detected in healthy individuals, it is profound that not all of them will develop MCC.…”

Oct2 and Bob1 are sensitive and specific markers in lineage determination of B cell lymphomas with no expression of conventional B cell markers

“…For example, PAX5 expression has been identified in a subset of AML cases, specifically in more than 30% of AMLs with t(8;21)(q22;q22) . In addition, PAX5 is expressed in certain types of non‐haematological malignancies, including most cases of Merkel cell carcinoma, small‐cell carcinoma of the lung, alveolar rhabdomyosarcoma and Wilms’ tumour, thus PAX5 might not be used solely for B cell lineage determination. Therefore, although CD20, CD79a and PAX5 are very useful markers for B cell lymphomas, especially in the initial work‐up, they have certain drawbacks in determining the lineage of poorly differentiated B cell neoplasms due to loss of expression in some unusual B cell lymphomas as discussed previously and aberrant expression in some non‐B cell neoplasms.…”

The expression of terminal deoxynucleotidyl transferase and paired box gene 5 in Merkel cell carcinomas and its relation to the presence of Merkel cell polyomavirus DNA

“…Expression of B‐lymphoid lineage markers in MCC is frequent (Table ), including TdT and PAX5. These markers are recurrent in MCC in both primary cutaneous tumors and metastatic lymph nodes . Nearly, 90% of the tumors reported express PAX5 and 65% express TdT .…”

“…These markers are recurrent in MCC in both primary cutaneous tumors and metastatic lymph nodes. 12,15,16,[27][28][29][30][31][32][33] Nearly, 90% of the tumors reported express PAX5 and 65% express TdT. 34 On the basis of the frequent expression of Blymphoid lineage markers, zur Hausen et al 31 proposed that the cell of origin of MCC might in fact not be the post-mitotic MC, but rather either a pro/pre-B cell or a pre-B cell.…”