Metastatic Cancer of Unknown Primary to Cervical Lymph Nodes

Metastatic cancers of unknown primary (CUP) site to cervical lymph nodes are a common non-gynecologic sample in cytology. Often, the site of origin is identified after FNA; however, a small subset of cases remains of unknown primary origin despite extensive diagnostic workup. A broad range of tumors can metastasize to cervical lymph nodes, but some are much more common than others. Metastatic squamous cell carcinoma (SCC) is by far the most frequently encountered CUP in the head and neck, and the differential diagnosis includes HPV-independent SCC, HPV-associated SCC, and EBV-associated nasopharyngeal carcinoma. Cutaneous cancer metastases (e.g. SCC, melanoma, Merkel cell carcinoma) are a second common type of CUP. Among cervical lymph node compartments, those in levels II–III are most often involved by metastatic cancers of unknown primary followed by levels I and IV–V. Having material for ancillary studies is important to help identify the site of origin and subtype of cancer to allow for the best patient management.