Novel Mutations in Pilomatrixoma, CTNNB1 p.s45F, and FGFR2 p.s252L: A Report of Three Cases Diagnosed by Fine-Needle Aspiration Biopsy, with Review of the Literature

Pilomatrixoma (calcifying epithelioma of Malherbe) is an uncommon benign skin appendageal tumor that differentiates toward hair matrix cells. It is misdiagnosed in up to 75% of cases by nondermatologists. Although the histopathological findings are well recognized and characteristic, diagnosis by fine-needle aspiration biopsy may be quite challenging. Several reports have emphasized the challenges in cytodiagnosis of pilomatrixoma, leading to a false-positive diagnosis. The lesions may show avidity for fludeoxyglucose on positron emission tomography/computed tomography scan, raising concern of a possible malignant neoplasm. CTNNB1 mutations have been reported in a high percentage of pilomatrixomas. Expression of β-catenin, the protein encoded by CTNNB1, is also frequently observed. To determine if routine cytological specimens can be successfully used to perform additional investigation and support or confirm the diagnosis in three cases of pilomatrixoma, we performed molecular analysis and immunohistochemistry to search for CTNNB1 mutation and β-catenin, respectively. β-Catenin positivity by immunohistochemistry was observed in basaloid cells in all three cases. Exon 3 mutations in CTNNB1 were detected in all cases. In addition, we detected a fibroblast growth factor receptor 2 (FGFR2) mutation in one of the cases. We reviewed the literature and present the clinical and morphological characteristics that must be considered along with other findings to accurately achieve the correct diagnosis, in correlation with the results of the ancillary technique. In conclusion, routine cytological specimens can be successfully used to perform additional investigations and support cytodiagnosis in difficult cases.