[Tuberous sclerosis complex-associated multifocal micronodular pneumocyte hyperplasia: a clinicopathological features and TSC1/TSC2 gene mutation analysis of eight cases].
Summary
This retrospective study investigated eight cases of multifocal micronodular pneumocyte hyperplasia (MMPH) associated with tuberous sclerosis complex (TSC), a rare benign pulmonary lesion. Patients typically presented with multiple ground-glass nodules in the lungs on CT scans and various clinical manifestations of TSC. A significant diagnostic challenge was highlighted, as intraoperative frozen sections were often misdiagnosed as early-stage lung adenocarcinoma. Next-generation sequencing revealed TSC1 or TSC2 gene mutations in most patients, confirming the association with TSC. All followed-up patients showed a favorable overall survival.
Analysis
Clinique: This retrospective study of 8 cases highlights the clinical and pathological features of MMPH, a rare benign pulmonary lesion often associated with tuberous sclerosis complex. The most critical clinical finding is the diagnostic challenge posed by its resemblance to early-stage lung adenocarcinoma, as evidenced by six cases initially misdiagnosed on frozen sections. This underscores the necessity for a multidisciplinary diagnostic approach integrating clinical data (TSC history), imaging (ground-glass nodules), and molecular pathology. Although a small study, it enhances the understanding of this entity and could inform guidelines for a more thorough evaluation of pulmonary nodules in TSC patients, potentially preventing unnecessary surgeries or inappropriate treatments. Clinical impact could be medium-term (3-5 years) to refine diagnostic protocols. Biomol: Next-generation sequencing (NGS) played a crucial role in confirming the diagnosis of MMPH by identifying mutations in TSC1 (6 cases) and TSC2 (1 case) genes, with an overall detection rate of 7 out of 8. This technological approach allowed for the differentiation of these benign lesions from adenocarcinomas. The concurrent detection of a class III BRAF G466E missense mutation in one TSC2-mutated case is an interesting discovery, though its significance in the context of MMPH requires further investigation. The application of NGS on surgical resection samples or cryobiopsies demonstrates its analytical validity for detecting these mutations, providing a valuable tool for differential diagnosis and understanding the molecular mechanisms underlying MMPH in TSC.