CONTEXT: Lymphangioleiomyomatosis (LAM) is a cystic lung disease that can be 
included in the wide group of proliferative lesions named PEComas (perivascular 
epithelioid cell tumors). These proliferative tumors are characterized by the 
coexpression of myogenic and melanogenesis-related markers. In all these 
lesions, genetic alterations related to the tuberous sclerosis complex (TSC) 
have been demonstrated. Striking improvements in the understanding of the 
genetic basis of this autosomal dominant genetic disease are coupled to the 
understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 
(16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. These data 
have opened a new era in the comprehension of the pathogenesis of LAM and have 
also suggested new therapeutic strategies for this potentially lethal disease.
OBJECTIVE: To present and discuss the pathologic and molecular features of LAM 
within the spectrum of PEComas, providing a rational approach to their 
diagnosis.
DATA SOURCES: The published literature and personal experience.
CONCLUSIONS: The inclusion of LAM within the PEComa category is supported by a 
variety of biologic data and can significantly help in providing a comprehensive 
view of this interesting and clinically relevant group of lesions. The 
demonstration of molecular alterations of the mTOR pathway in LAM and other 
PEComas represents a rational basis for innovative therapeutic approaches with 
inhibitors of mTOR signaling.