Lung adenocarcinoma in a case of tuberous sclerosis complex with multifocal micronodular pneumocyte hyperplasia

Tuberous sclerosis complex (TSC) is an autosomal dominant disease with two causative genes, TSC1 and TSC2. This disease causes tumors in all organs, including skin, brain, kidneys, heart, and lungs. TSC is complicated by respiratory pathological conditions, including multifocal micronodular pneumocyte hyperplasia (MMPH) and pulmonary lymphangioleiomyomatosis (LAM). We present a case of lung adenocarcinoma in a patient with TSC complicated by MMPH, along with a brief literature review. A 75-year-old woman was diagnosed with TSC at 50 years, with MMPH simultaneously detected in both lung fields. Since then, she had been followed-up for MMPH by chest radiography. In 2021, a mass opacity, 2.5 cm in diameter, was detected in the right upper lobe for the first time. Since her serum carcinoembryonic antigen (CEA) level was also elevated to 7.0 ng/mL, adenocarcinoma was suspected. Video-assisted thoracoscopic wedge resection was performed in the right upper lobe. Pathological examination showed adenocarcinoma measuring 2.8 cm in maximum diameter. The wedge-resected specimen contained four pulmonary metastatic lesions and many ground-glass nodules. These nodules required pathological differentiation between MMPH and atypical adenomatous hyperplasia (AAH) or adenocarcinoma in situ (AIS). In the nodules, the cytoplasms and nuclei of epithelial cells were more prominently enlarged than those in AAH or AIS, and elastic fibers proliferated in the interstitium. Thus, MMPH was pathologically diagnosed. The patient is still alive 15 months after surgery, and her CEA level has decreased to 2.4 ng/mL. A literature search yielded only a few previously reported cases of lung carcinoma in patients with TSC complicated by MMPH in Japan.