Clinicopathological analysis of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis in Japan

Background and objective: This study investigated the clinical and pathological findings of lung disease in tuberous sclerosis complex (TSC) as previously reported in Japan. Methods: The clinical and pathological findings in 15 patients diagnosed as having multifocal micronodular pneumocyte hyperplasia (MMPH) with TSC were analysed. Results: The majority of patients (80%) were women and the mean age was 37 years. Three patients had a family history of TSC. The radiological findings were small multiple nodular shadows with ground-glass opacity randomly distributed in the bilateral whole-lung fields in most patients. Differentiation from multiple atypical adenomatous hyperplasia or metastatic lung cancer was necessary in most patients. In 11 patients, the diagnostic method used to identify pulmonary lesions of MMPH with TSC was VAT. Among the complications of MMPH with TSC, lymphangioleiomyomatosis was recognized in 53% of patients. The prognosis was comparatively good because only one patient died of respiratory failure. The histological findings were papillary or tubular proliferation of type II pneumocytes without nuclear atypia lining the thickened alveolar septa and lymphocyte infiltration. Immunohistochemical staining for cytokeratin, and surfactant proteins A and B was positive in alveolar lining cells of all MMPH lesions. However, staining for HMB-45, alpha-smooth muscle actin, p53, carcinoembryonic antigen and hormonal receptor was negative in most patients. Conclusions: Surgical investigation and immunohistochemical staining for pathological markers are useful for diagnosing MMPH when the radiological findings indicate multiple micronodules with ground-glass opacity in patients with TSC.