A 34-year-old woman suffers two spontaneous pneumothoraces in one year. HRCT shows numerous thin walled round cysts distributed diffusely through both lungs without zonal predominance. Immunohistochemistry on biopsy shows sheets of immature appearing spindle cells staining positively with HMB45. The underlying genetic abnormality may involve:

• A TSC2 gene encoding tuberin ✓
• B CFTR gene on chromosome 7
• C EGFR exon 19 deletion
• D SERPINA1 gene encoding alpha-1 antitrypsin

Explanation

Lymphangioleiomyomatosis affects women of childbearing age, producing diffuse thin walled cysts, chylothorax, and recurrent pneumothorax. It may be sporadic or occur in tuberous sclerosis complex, involving loss of function mutations in TSC1 or TSC2, leading to mTOR pathway activation. The lesional smooth muscle like cells characteristically express melanocytic markers including HMB45. CFTR defects cause cystic fibrosis, EGFR mutations drive lung adenocarcinoma, and SERPINA1 mutations cause panacinar emphysema, none of which produce HMB45 positive spindle cell proliferations.

Reference: Robbins and Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.