Answer: Metastatic cystic squamous cell carcinoma

Histology: The lesion consists of a cystic structure with prominent lymphoid reaction in the cyst wall. The surface epithelium lining the cyst is flattened squamous epithelium which appears basaloid given the high nuclear to cytoplasmic ratio. Although in some areas the epithelium appears relatively bland it lacks the abundant cytoplasm and small nuclei typical of totally benign squamous epithelium. In areas, the overlying epithelium has overt cytologic atypia. Beneath the cyst wall there are nests of squamous epithelium with individually keratinized epithelial cells. Some of these nests of cells also have more overt cytologic features of malignancy.

Discussion: The vast majority of cases with squamous cell carcinoma in what appear to be a branchial cleft cyst represent metastatic carcinoma with cystic degeneration. It is proposed that before one diagnoses carcinoma arising in a branchial cleft cyst one needs: 1) the correct anatomical location of branchial cleft cyst in the superior lateral neck ; 2) squamous cell carcinoma; 3) carcinoma lining the cyst wall; 4) transition from normal squamous epithelium of the cystic carcinoma; 5) and the absence of a primary malignant tumor after exhaustive evaluation of the patient including endoscopy, laryngoscopy, bronchoscopy, and esophagoscopy as well as radiographic examination of the head and neck. In the current case, while some of the features could be consistent with carcinoma arising in a branchial cleft cyst, it lacks areas of totally normal squamous epithelium with transition to carcinoma. Others have stressed that one needs at least a 5 year follow up after the diagnosis of a candidate for carcinoma in a branchial cleft cyst to rule out an occult primary. It is controversial whether carcinomas arising in a branchial cleft cyst even exist or all represent metastases from an unknown primary. In the current case, although there was no overt clinical primary, the patient underwent panendoscopy and random biopsies of the base of the tongue, nasopharynx, and bilateral tonsils Infiltrating HPV-related squamous cell carcinoma was found on the random biopsy of one of the tonsils proving that this lesion in the lateral neck was a cystic metastasis.