title: 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=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.
authors.affiliation: 1] Department of Pathology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA [2] Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Zenggang
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Chen
authors.affiliation: Department of Pathology, New York University School of Medicine, Bellevue Hospital, New York, NY, USA.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Surgical Oncology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Vijay
authors.initials: V
authors.lastname: Trisal
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Sharon P
authors.initials: SP
authors.lastname: Wilczynski
authors.affiliation: Clarient Pathology Services, Aliso Viejo, CA, USA.
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Weiss
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Peiguo G
authors.initials: PG
authors.lastname: Chu
authors.affiliation: Department of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
authors.forename: Huiqing
authors.initials: H
authors.lastname: Wu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000957:Antigens, Viral, Tumor / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000378:metabolism; D015266:Carcinoma, Merkel Cell / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D004279:DNA, Viral / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008198:Lymph Nodes / Q000473:pathology; D008207:Lymphatic Metastasis; D008223:Lymphoma / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D008297:Male; D059965:Merkel cell polyomavirus / Q000235:genetics*; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D051757:PAX5 Transcription Factor / Q000378:metabolism; D016133:Polymerase Chain Reaction; D027601:Polyomavirus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology / Q000821:virology; D014412:Tumor Virus Infections / Q000378:metabolism / Q000473:pathology / Q000821:virology*
chemical_list: D000957:Antigens, Viral, Tumor; D014408:Biomarkers, Tumor; D004279:DNA, Viral; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D004253:DNA Nucleotidylexotransferase