Metastatic cervical carcinoma from an unknown primary: literature review

Carcinoma of an unknown primary (CUP) encompasses a heterogeneous group of tumors for which no primary site can be detected following a thorough history, physical examination, and noninvasive and invasive testing. CUP presenting with metastasis to the neck (metastatic cervical carcinoma from an unknown primary [MCCUP]) has been an enigma since von Volkmann first described it in 1882 as a cancer arising in a branchial cleft cyst. Genetic studies have shed some light on this unusual entity. In most cases, clinical features, imaging studies, and a meticulous assessment of the upper aerodigestive tract should assist in identifying the source of disease. Molecular testing of cytologic specimens for Epstein-Barr virus and human papillomavirus (HPV) can facilitate identification of the primary site in the nasopharynx and oropharynx. At least 25% of MCCUPs are directly attributable to HPV-related malignancies, and this number can be expected to increase. Minimally invasive transoral mucosal sampling can identify an otherwise clinically and radiologically occult cancer. We performed a literature review with the objective of discussing the history, epidemiology, clinical presentation, diagnostic workup, and management of MCCUP.