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lymphangioleiomyomatosis

Etiology: 1) tuberous sclerosis 2) idiopathic (premenopausal women) Epidemiology: 1) rare 2) women of child-bearing age (idiopathic) 3) either sex tuberous sclerosis Pathology: 1) multisystem neoplasm of smooth muscle cells a) nodular & diffuse interstitial proliferation of smooth muscle in the lungs, lymph nodes & thoracic duct b) hamartomatous proliferation of smooth muscle along bronchi into alveoli c) smooth muscle cells may be progesterone receptor + [6] 2) obliteration of airways 3) pulmonary cysts - spindle cells coexpressing smooth-muscle & melanocytic markers line the cyst walls [11] 4) generally progressive disorder 5) renal angiomyolipoma 6) death from respiratory failure * image (lung biopsy, gross pathology) [11] Genetics: - smooth muscle cells with inactivating tuberous sclerosis gene complex mutations infiltrate the lung - somatic mutations in TSC2 or germline mutations in TSC1 or TSC2 - upregulation in RHEB with constitutive activation of mTORC1 [6] Clinical manifestations: 1) dyspnea 2) cough (case report) [6] 3) hemoptysis 4) spontaneous pneumothorax resulting from cyst rupture [11] 5) chylous pleural effusion (2/3 of patients) 6) chylous ascites from obstruction of thoracic duct 7) rapidly progressive airway disease may occur 8) variable features of tuberous sclerosis Laboratory: - vascular endothelial growth factor D in serum >= 800 pg/mL Special laboratory: - pulmonary function testing: a) obstructive pattern b) decreased DLCO c) hypoxemia Radiology: 1) chest X-ray a) hyperinflated lungs b) diffuse nodular interstitial infiltrates c) multiple small cystic areas d) pleural effusion may be noted 2) high-resolution computed tomography (CT) of thorax - diffuse, thin-walled small pulmonary cysts - pleural effusion may be noted * image (chest CT) [11] Complications: - often fatal Management: - sirolimus - blocks mTOR activation of downstream kinases - attenuates decline in FEV1 - hormonal therapy - oophorectomy - pleurodesis for pneumothorax [11] - lung transplantation

General

hereditary neoplastic syndrome; cancer susceptibility syndrome lung disease

Database Correlations

OMIM 606690

References

  1. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 756-57
  2. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 17. American College of Physicians, Philadelphia 2009, 2012, 2015
  3. UniProt :accession P49815
  4. McCormack FX, Inoue Y, Moss J et al Efficacy and safety of sirolimus in lymphangioleiomyomatosis. N Engl J Med. 2011 Apr 28;364(17):1595-606 PMID: 21410393
  5. Meraj R, Wikenheiser-Brokamp KA, Young LR, McCormack FX. Lymphangioleiomyomatosis: new concepts in pathogenesis, diagnosis, and treatment. Semin Respir Crit Care Med. 2012 Oct;33(5):486-97. Review. PMID: 23001803
  6. Weinstock M, Vaidya A, El-Chemaly S, et al The Verge of Collapse. INTERACTIVE MEDICAL CASE N Engl J Med 2018;378:e18. March 29, 2018 PMID: 29590548
  7. Henske EP, McCormack FX Lymphangioleiomyomatosis - a wolf in sheep's clothing. J Clin Invest. 2012 Nov;122(11):3807-16. Review. PMID: 23114603 Free PMC Article
  8. McCormack FX, Travis WD, Colby TV, Henske EP, Moss J. Lymphangioleiomyomatosis: calling it what it is: a low-grade, destructive, metastasizing neoplasm. Am J Respir Crit Care Med. 2012 Dec 15;186(12):1210-2. PMID: 23250499 Free PMC Article
  9. Goldberg HJ, Harari S, Cottin V et al Everolimus for the treatment of lymphangioleiomyomatosis: a phase II study.wal S, Cheng Y, Khindri S, Kovarik JM, Ma S, McCormack FX, Henske EP. Eur Respir J. 2015 Sep;46(3):783-94. PMID: 26113676 Free Article
  10. McCormack FX, Gupta N, Finlay GR et al Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management. Am J Respir Crit Care Med. 2016 Sep 15;194(6):748-61. PMID: 27628078 Free PMC Article
  11. Sclafani A, VanderLaan P. Lymphangioleiomyomatosis. N Engl J Med 2018; 378:2224. June 7, 2018 PMID: 29874537 https://www.nejm.org/doi/full/10.1056/NEJMicm1712581