Answer: Pseudoephitheliomatous hyperplasia

Histology: Although the surface epithelium of this small mucosal biopsy is not overtly dysplastic, there are atypical nests of squamous cells budding off of the basilar layer and extending into the submucosa. The cells have a glassy pink cytoplasm and form keratin pearls. A most notable finding is in the nature of the stroma surrounding the atypical squamous cell nests. Instead of the fibrotic stroma of infiltrating carcinoma, the stroma is highly cellular and filled with cells having abundant pink and granular cytoplasm. Immunohistochemical studies were performed, and these “granular” cells were found to be strongly positive for S-100.

Discussion: If granular cell tumors are given consideration in the differential diagnosis of proliferative squamous lesions of the upper respiratory tract, they are fairly easy to recognize and diagnose. If they are not routinely included in the differential diagnosis, they are fated to be misdiagnosed as squamous cell carcinoma. This mistake can have profound treatment implications.

Granular cell tumors of the larynx, like those arising in other sites, are comprised of sheets and nests of large polygonal cells with abundant pink granular cytoplasm. About ten percent of lesions in the upper aerodigestive tract are associated with prominent pseudoepitheliomatous hyperplasia of the overlying surface epithelium. This squamous proliferation may dominate the histologic picture and obscure the underlying granular cell tumor, especially in superficial biopsies. It would be unwise to make a diagnosis of invasive squamous cell carcinoma in the presence of a granular cell tumor.
The diagnosis of granular cell tumor can be confirmed using an S-100 immunostain. The granular cells are now known to be of Schwann cell derivation, and not a modified skeletal muscle cell as once believed.