Micronodular pneumocyte hyperplasia.

Abstract

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.