Multifocal micronodular pneumocyte hyperplasia in tuberous sclerosis

Ristagno RL, Biddinger P, Pina EM, Meyer CA(AQ1) uberous sclerosis complex (TSC) is a neurocutaneous syndrome that presents clinically with seizures, mental retardation, and adenoma sebaceum. This classic combination of features (Vogt’s triad) is seen in only one-third of patients. TSC is inherited in an autosomal dominant pattern with nearly 100% penetrance and is caused by a mutation in the TSC1 or TSC2 gene. The TSC1 gene encodes hamartin and the TSC2 gene encodes tuberin. Hamartin and tuberin are believed to be early regulatory steps in cellular protein synthesis and growth. TSC genes are hypothesized to function as tumor suppressor genes that require a “second hit” at the cellular level, leading to loss of functional hamartin or tuberin with subsequent development of hamartomas [1]. Hamartomas in TSC patients are frequently present in the skin, kidneys, brain, and heart. Less frequently, hamartomas involve the retina, gingiva, bones, gastrointestinal tract, and lungs [1]. Although most patients have renal angiomyolipomas, hamartomas in the lung are rare [2]. The association of pulmonary angiomyolipomas to TSC has not been established [3]. Until recently, lymphangioleiomyomatosis (LAM), a hamartomatous cystic lung disease, was the only reported pulmonary radiologic manifestation of TSC and was estimated to occur in 1–2.3% of TSC patients [4]. However, two recent studies found 27–39% of TSC patients without previous pulmonary disease to have LAM when screened with high-resolution CT [5, 6]. Multifocal micronodular pneumocyte hyperplasia (MMPH), another hamartomatous pulmonary lesion, has also been recently described in TSC patients [2, 7–13]. We review the imaging findings in a case of MMPH and provide pathologic correlation.