Lymphangioleiomyomatosis — a wolf in sheep’s clothing
Elizabeth P. Henske, Francis X. McCormack
Elizabeth P. Henske, Francis X. McCormack
Published November 1, 2012
Citation Information: J Clin Invest. 2012;122(11):3807-3816. https://doi.org/10.1172/JCI58709.
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Science in Medicine

Lymphangioleiomyomatosis — a wolf in sheep’s clothing

Abstract

Lymphangioleiomyomatosis (LAM) is a rare progressive lung disease of women. LAM is caused by mutations in the tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network. Over the past 11 years, there has been remarkable progress in the understanding of LAM and rapid translation of this knowledge to an effective therapy. LAM pathogenic mechanisms mirror those of many forms of human cancer, including mutation, metabolic reprogramming, inappropriate growth and survival, metastasis via blood and lymphatic circulation, infiltration/invasion, sex steroid sensitivity, and local and remote tissue destruction. However, the smooth muscle cell that metastasizes, infiltrates, and destroys the lung in LAM arises from an unknown source and has an innocent histological appearance, with little evidence of proliferation. Thus, LAM is as an elegant, monogenic model of neoplasia, defying categorization as either benign or malignant.

Authors

Elizabeth P. Henske, Francis X. McCormack

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Figure 1

The clinical and pathologic features of LAM.

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The clinical and pathologic features of LAM. (A–D) Representative radiol...
(A–D) Representative radiologic features of LAM include (A) multiple thin-walled cysts and pneumothorax, (B) pleural effusions (arrowhead), (C) renal angiomyolipomas (arrow), and (D) retroperitoneal lymphadenopathy (arrow). (E) High-power view of cystic change with surrounding LAM in the lung. LAM cells express the melanocystic antigen, HMB-45, as well as estrogen receptor and the smooth muscle cell antigen, smooth muscle actin. An immunohistochemical stain for podoplanin highlights lymphatic channels within cystic lesions and LAM cells clusters within the lymphatic lumen. Original magnification, ×400 (left and middle columns); ×200 (right column). Histology and immunohistochemistry courtesy of Kathryn Wikenheiser-Brokamp, Cincinnati Children’s Hospital Medical Center and the University of Cincinnati.