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.
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.1-3 Several terms have been used as synonyms for CUP, including unknown primary tumor, occult primary tumor, carcinoma of unknown primary, and metastasis of unknown origin. But carcinoma of unknown primary is the most widely accepted term.