Multifocal micronodular pneumocyte hyperplasia and lymphangioleiomyomatosis in tuberous sclerosis with a TSC2 gene

A 45-year-oldwoman with a long-standing diagnosis of tuberous sclerosis (TS C) is presented. She has multifocal micronodular pneumocyte hyperplasia (MM PH) and lymphangioleiomyomatosis (LAM) of the lung together with the detect ion of TSC2 gene mutation. During surgery for spontaneous pneumothorax, an open-lung biopsy was performed. Micronodules were well defined, measuring a pproximately 4 mm in diameter. These MMPHs were histologically composed of papillary proliferation of Type II pneumocytes, with positive immunoreactiv ity of keratin and surfactant apoprotein. The cystlike spaces, with dilatat ion and destruction of air spaces, were diffusely formed, and the walls wer e composed of the spindle cells. Such LAM showed positive immunoreactivity for HMB-45 (a monoclonal antibody specific for human melanoma) and tuberin (the gene product of TSC2). On germline mutation analysis using leukocytes of the present patient, a TSC2 gene mutation was confirmed as a deletion of G (or g) on Exon 9 by polymerase chain reaction-single-strand conformation al polymorphism. However, no mutation was detected in her son. With microdi ssection analysis using paraffin embedding lung tissues, LOH of the TSC2 ge ne preliminarily was detected in a LAM lesion but not in MMPH. It is sugges ted that MMPH, in addition to LAM, could be another pulmonary lesion in TSC patients and that the detection of TSC2 and/or TSC1 gene could essentially be useful for the pathogenesis of MMPH and LAM in TSC patients.