CHEK2変異を有する外陰原発性顆粒細胞腫の転移症例：症例報告と分子学的考察

Granular cell tumors (GCTs) are rare neoplasms, typically of Schwannian origin, with generally a benign and indolent clinical behavior. However, a small subset exhibits malignant behavior, often without clear histologic features. We report a rare case of a vulvar granular cell tumor in a 21-yr-old woman with subsequent pulmonary metastasis. The patient presented with a slowly growing vulvar nodule and a subcutaneous lesion on the left flank. Imaging studies revealed residual disease in the vulva and a suspicious lung nodule, both of which were surgically resected. Histopathologic examination confirmed features consistent with granular cell tumor in both primary and metastatic sites, despite the absence of cytologic atypia, necrosis, or elevated mitotic activity. Immunohistochemistry revealed positivity for S100, CD68, NSE, and inhibin, with a low Ki-67 index (<1%). Next-generation sequencing identified a CHEK2 p.I200T mutation in both lesions, suggesting a shared clonal origin. This variant lies within the kinase domain of CHK2, a key mediator of the DNA damage response, and is of uncertain but potentially pathogenic significance. No microsatellite instability or homologous recombination deficiency was observed. This case highlights the diagnostic challenges in GCTs, particularly in distinguishing benign from malignant forms in the absence of classic histologic criteria. The presence of metastasis remains the most definitive indicator of malignancy. Our findings underscore the importance of integrating molecular profiling into the diagnostic and prognostic workup of GCTs and raise the question about the potential role of CHEK2 alterations as additional molecular determinants of aggressiveness beyond conventional histology. Long-term follow-up is warranted given the unpredictable clinical behavior of malignant GCTs.