p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma

Abstract

Morphologic distinction of high-grade adenoid cystic carcinoma from basaloid squamous cell carcinoma can be difficult. Equivocal diagnoses can mislead treatment. We have investigated the possibility that immunohistochemical staining for the presence of p63, a novel epithelial stem-cell regulatory protein, could be a useful means of distinguishing these two neoplasms. Archival, routinely processed slides were subjected to citrate-based antigen retrieval, exposure to anti-p63 monoclonal 4A4, and developed with a streptavidinbiotin kit and diaminobenzidine as chromogen. p63 was detected in 100% of the adenoid cystic carcinomas (n ¼ 14) and 100% of basaloid squamous cell carcinomas (n ¼ 16). Basaloid squamous cell carcinomas consistently displayed diffuse p63 positivity, with staining of nearly 100% of tumor cells. In contrast, adenoid cystic carcinoma displayed a consistently compartmentalized pattern within tumor nests. Compartmentalization was manifested in two patterns: (1) selective staining of a single peripheral layer of p63-positive cells surrounding centrally located tumor cells that were p63-negative and (2) tumor nests consisting of multiple contiguous glandular/cribriform-like units of p63-positive cells surrounding or interspersed with p63-negative cells. p63 immunostaining constitutes a specific and accurate means of distinguishing adenoid cystic carcinoma from basaloid squamous cell carcinoma. p63 positivity in adenoid cystic carcinoma appears to be homologous to that seen in the basal and/or myoepithelial compartments of salivary gland and other epithelia, and may signify a stem-cell-like role for these peripheral cells. Diffuse p63 positivity in basaloid squamous cell carcinoma suggests dysregulation of p63-positive stem cells in poorly differentiated squamous carcinoma.

Detection of human papilloma virus and p16 expression in high-grade adenoid cystic carcinoma of the head and neck

“…Although both tumors are positive, basaloid squamous cell carcinomas typically show strong and diffuse positivity throughout, whereas adenoid cystic carcinomas typically show positivity in only a subset of cells, frequently located at the periphery of the tumor cells nests, or sometimes within the tumor cell nests mixed with a p63-negative cell population. 20,21 This characteristic pattern of p63 positivity was seen in our two cases of high-grade adenoid cystic carcinoma that were positive for HPV, supporting our morphological impression. Both of these cases occurred in the nasal cavity of young to middle-aged men (aged 43 and 49 years).…”

Large Cell Neuroendocrine Carcinoma of the Larynx: Definition of an Entity

“…The nuclei lack nucleoli and are generally regular, but can have some pleomorphism and sometimes have significant apoptosis and mitotic activity [19,20]. Immunohistochemistry is positive for p63, but only in a patchy distribution which occurs characteristically at the periphery of the nests, presumably in cells with myoepithelial differentiation [21]. Immunohistochemistry in ACC is negative for neuroendocrine markers [18].…”

Sinonasal Squamous Cell Carcinoma: A Review with Emphasis on Emerging Histologic Subtypes and the Role of Human Papillomavirus

“…Solid adenoid cystic carcinoma and the newly described HPVrelated adenoid cystic-like carcinoma both lack diffuse p63/p40 expression. Solid adenoid cystic carcinoma classically shows patchy p63 expression that is usually limited to the focal myoepithelial differentiation at the periphery of the nests [19]. HPV-related adenoid cystic-like carcinoma has focal ductal differentiation, expresses p63 in its abluminal cells only, and expresses myoepithelial markers such as smooth muscle actin, S-100, and calponin [7], features not seen in basaloid or NKSCC.…”