Lymphangiomyomatosis (LAM)

Epidemiology and Etiology:

• Women ( almost exclusively)
• Men with tuberous sclerosis complex rarely
• Childbearing years (almost exclusively)

Common sites:

•  Lungs
• mediastinal and retroperitoneal lymph nodes and lymphatics

Gross features:

• numerous cysts throughout the lungs with relatively thick septa

Histologic features:

• cystic changes
• LAM cell infiltrates:
• lacy pattern of round and spindled smooth muscle proliferation within the interstitium and around bronchi, bronchioles, veins, and lymphatics
• in early cases, found in nests at edges of cysts and along pulmonary lymphatics
• appear to “spin off” the muscle coat of the above structures
• extend into walls of adjacent alveolar ducts and alveoli
• haphazard arrangement or whorled pattern
• infiltrate walls of vessels and small airways
• often papillary clusters in lymph nodes
• more diffuse than benign metastasizing leiomyoma
• muscle cells:
• round, oval, or spindle shaped cells, morphologically heterogenous
• moderate amount of eosinophilic cytoplasm
• nuclei with fine or veicular chromatin
• rare mitoses
• rare atypical cells
• often have a clear cytoplasm (abundant intracellular glycogen)
• multifocal micronodular pneumocyte hyperplasia (MMNPH) can be seen in tuberous sclerosis patients, and is virtually pathognomonic for TSC

Immunophenotype:

Marker:	Sensitivity:	Specificity:
HMB45 (cytoplasmic granules, not all cells)		Good
ER / PR	Some
SMA
Desmin

Molecular features:

• allelic loss of TSC2 gene (most)

Other features:

• Pecoma
• Most occur outside of tuberous sclerosis
• familial syndromes:
• tuberous sclerosis (1-3% have full-blown LAM)
• may be associated with simlar smooth-muscle proliferations of the abdominal or thoracic lymphatic ducts and lymph nodes
• some may respond to antiestrogen therapy
• may recur in donor lung tissue (recipient smooth muscle)
• complications:
• repeated pneumothorax often
• hemoptysis
• chylous pleural effusions
• prognosis:
• progressive with poor prognosis
• pathogenesis:
• bronchiolar obstruction causes air trapping and overdistention leading to cystic blebs
• venous and lymphatic obstruction

References:

• Sternberg 2004
• Rosai 2004
• Non-Neoplastic Disorders of the Lower Respiratory Tract (AFIP) 2002