Lateral neck cysts--the branchial theory revisited. A critical review and clinicopathological study of 97 cases with special emphasis on cytokeratin expression.

Theories regarding the origin of lateral neck cysts (LNC) range from congenital branchial pouch abnormalities to acquired salivary gland inclusions within lymph nodes. We analyzed 97 LNC histologically and evaluated their cytokeratin (CK) profile in a search for their derivation. 77/97 LNC were located in soft tissues, 20/97 within lymph nodes. LNC of young patients and of recent symptomatic presentation in older patients were lined by respiratory epithelium with scant lymphoid tissue, with expression of "simple epithelial" CK in ciliated cells and bimodal expression of "simple" and "stratified-epithelial-type" CK in basal cells. In longer standing symptomatic LNC, respiratory epithelium alternated with transitional-type pseudostratified epithelium with intraepithelial Langerhans cells and lymphoid hyperplasia, or consisted exclusively of squamous epithelium. We propose that respiratory epithelium is the "native" epithelium of LNC and squamous metaplasia results from inflammation induced stem cell hyperplasia in respiratory epithelium, evidenced by co-expression of "simple" and "stratified-epithelial-type" CK in all cells of transitional-type pseudostratified epithelium, the early stage in metaplastic transformation. Respiratory epithelium predominates in early LNC, lines pharyngeal tonsils and the recessus tonsillo-tubalis, and is a minor constituent of palatine tonsil but is not present in salivary glands. None of the LNC contained dysplasia, atypia, or carcinoma, or were associated with a primary carcinoma of tonsils or head and neck. We demonstrate that LNC arise from developmental remnants (congenital) of the 2nd branchial pouch, which may lie dormant for many years. Symptomatic enlargement, squamous metaplasia and lymphoid hyperplasia ensue as a consequence of immunologic stimulation a development reflected in hyperplastic palatine tonsils.