Answer: Atypical granular cell tumor

Histology: The lesion shows the classic features of a granular cell tumor with nests of cells containing abundant granular eosinophilic cytoplasm. There is moderate nuclear pleomorphism with prominent nucleoli. However, only rare mitotic figures are identified and the lesion lack necrosis.

Discussion: Although granular cell tumors are typically benign, rare examples of metastasizing granular cell tumor exist. These must be distinguished from multicentric benign granular cell tumor. In the largest series that examines criteria to examine benign from malignant granular cell tumor, six histological features were identified. These included: necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (greater than two mitoses per ten high power fields), high nuclear-to-cytoplasmic ratio, and pleomorphism. Neoplasms that have three or more of these criteria are classified as malignant, whereas lesions that have only one or two criteria present are diagnosed as atypical. If a granular cell tumor has only focal pleomorphism but has none of the other criteria, they are diagnosed as benign. In the current case, the lesion shows pleomorphism along with prominent nucleoli, yet lacks the other atypical features necessary for a diagnosis of malignancy.
Of the cases in this study that were diagnosed as malignant, 39% died of disease. An additional feature that may be helpful in identifying malignant granular cell tumor is that these tumors tend to have higher Ki-67 positivity (10-50% of the cells in about half of the tumors), whereas benign granular cell tumor typically show less than 1% Ki-67 positivity. p53 immunohistochemistry may also be useful in that in about 70% of malignant granular cell tumors, 50% of the cell population is positive, whereas p53 immunostaining is negative in benign granular cell tumors. Atypical granular cell tumors tend to have Ki-67 and p53 positivity at an intermediate level between benign and malignant tumors. Whereas CD68 is present in 100% of benign granular cell tumors, it tends to be less expressed in malignant variants. Otherwise, immunohistochemical staining of benign, atypical, and malignant granular cell tumors are identical, with strong expression of S-100 stain. A feature that may be seen in granular cell tumors that was not present in the current case is prominent pseudoepitheliomatous hyperplasia over the overlying squamous epithelium mimicking squamous cell carcinoma.

Reference(s):
– Am J Surg Pathol 22:779-794, 1998.