A woman in her 30s, who was clinically diagnosed with tuberous sclerosis complex, underwent lung transplantation due to lymphangioleiomyomatosis with concomitant multifocal micronodular pneumocyte hyperplasia (MMPH). Histologically, MMPH lesions demonstrated variety in histology; some showed homogenous cells with mild nuclear atypia and elastic fibers proliferation, and the others showed enlarged nuclei without elastic fibers. Because the natural history of MMPH is not well characterized, we used next-generation sequencing to perform a comprehensive genetic analysis for the MMPH lesions to explore their malignant potential. Regardless of their histological variety, three of four lesions had BRAF missense mutations, especially the types frequently detected in atypical adenomatous hyperplasia that is considered to be benign rather than a precursor of adenocarcinoma. None of them had major driver mutations of lung adenocarcinoma, except for BRAF mutations. In conclusion, our study of the lesions from this patient indicated the benign characteristic of MMPH.

一名 30 多岁的女性，临床诊断为结节性硬化症，因淋巴管肌瘤病合并多灶性微结节性肺细胞增生 (MMPH) 而接受肺移植。组织学上，MMPH 病变表现出组织学上的多样性；有的细胞均质，核轻度异型，弹力纤维增生，有的细胞核增大，无弹力纤维。由于 MMPH 的自然病程未得到很好的表征，我们使用二代测序对 MMPH 病变进行全面的遗传分析，以探索其恶性潜能。无论其组织学类型如何，四个病变中有三个具有BRAF错义突变，尤其是在被认为是良性而非腺癌前兆的非典型腺瘤性增生中经常检测到的类型。除了BRAF突变外，他们都没有肺腺癌的主要驱动突变。总之，我们对该患者病变的研究表明 MMPH 的良性特征。