Granular cell tumor a study of 42 cases and systemic review of the literature

Background: Granular cell tumor (GCT) remains a diagnostic clinicopathologic problem because the exact frequency of its detailed morphological and clinical characteristics is unknown as most observations are collected from small series or isolated cases. Herein, our aim is to highlight the frequency of all clinicopathological characteristics of this rare tumor based in our series and the available medical (PubMed) literature. Material and Methods: 42 cases were evaluated for: tissue layers involved by the tumor (in skin and mucosae), growth pattern, nuclear pleomorphism, mitotic index, necrosis, spindling, calcification, hyalinization, and pustule-ovoid bodies of Milian, as well as perineural and vascular invasion, and the presence of adjacent epithelium changes, and lymphocytes and eosinophils infiltration., Follow-up was analyzed. The tumors were subclassified into benign, atypical and malignant according to Fanburg-Smith criteria and into benign or GCT of uncertain malignant potential according to Nasser criteria. The same characteristics were analyzed for 1499 cases reviewed according to PRISMA guidelines. Results: In the current series, the mean age at diagnosis was 45.8 years (range 6-69 years). Most patients were females (60 %) and the involved organs were by descending frequency: skin and subcutaneous tissue, bronchus, esophagus, breast, tongue, larynx, pharynx, gingiva, trachea, right colon, vulva, and hypopharynx. No recur-rence or progression was seen, despite 32 cases were incompletely excised, with the exception of one malignant tumor. The growth pattern was either infiltrative (85.71 %) or well limited (7.14 %). Sixteen tumors had vesicular nuclei. Mitotic activity was found in two tumors. Lymphocytic infiltration was found in 14 tumors. Eosinophils were present in 6 cases. One GCT of the right colon showed extensive calcification and hyalinization. Perineural invasion was noted in 6 lesions. No vascular invasion was found. One tumor was clinically malignant and the patient died 2 years after diagnosis. Medical literature review showed similar results in terms of frequency of the reported clinical and morphological features. Among cases with available follow up, almost 20 % showed positive margins and of those 20 % developed local recurrence. According to the Fanburg-Smith criteria, 72 % would be benign, 17 % atypical and 11 % malignant tumors, while according to those of Nasser, 93 % would be benign and 7% of uncertain malignant potential. However, true malignancy, as affirmed by metastasis of GCT is found in almost 2.5 % of the cases. Conclusion: GCT is a usually benign tumor, affecting any anatomic location. Necrosis and mitotic activity seem to be the most effective histologic criteria for detecting aggressive tumors, but the presence of metastasis (2.5 % of the cases) remains the most accepted definitive criterion for diagnosis of malignant GCT.