Lung

• Lung mesenchymal neoplasm that arises from abnormal smooth muscle cells around lymphatic vessels and causes parenchymal damage

• Mainly lungs; usually in a bilateral fashion
• Can be found in retroperitoneal lymph nodes (Am J Respir Crit Care Med 2006;173:105)

• Proliferation of smooth muscle-like cells due to activation of the mTOR signaling pathway as a result of biallelic inactivation, loss of heterozygosity or somatic mutations in TSC1 or TSC2 genes (Lymphat Res Biol 2010;8:33, Am J Hum Genet 1998;62:810, Proc Natl Acad Sci U S A 2000;97:6085)
• Estrogen (ER) and progesterone (PR) receptors may have a role in disease development (Endocr Relat Cancer 2016;23:265)

• Sporadic (Semin Respir Crit Care Med 2020;41:256)
• Associated with tuberous sclerosis complex (Semin Respir Crit Care Med 2020;41:256)

• Progressive exertional dyspnea is the most common symptom (Semin Respir Crit Care Med 2020;41:256)
• Pneumothorax (Semin Respir Crit Care Med 2020;41:256)
• Chylous pleural effusion (Am J Respir Crit Care Med 2016;194:748)
• Hemoptysis
• Extrapulmonary involvement of retroperitoneal lymph nodes or abdominal angiomyolipoma (AML) (Am J Respir Crit Care Med 2006;173:105)

• Usually a clinical diagnosis
• Multiple bilateral round lung cysts on high resolution computed tomography (CT) scan
• Screening CT scans are recommended for females with tuberous sclerosis complex (Am J Respir Crit Care Med 2006;173:105)

• Vascular endothelial growth factor (VEGF) D level of ≥ 800 pg/mL helps distinguish lymphangioleiomyomatosis from other cystic lung diseases (Semin Respir Crit Care Med 2020;41:256)

Images hosted on other servers:

Images hosted on other servers:

Contributed by Roseann I. Wu, M.D., M.P.H. and Yale Rosen, M.D.

Images hosted on other servers:

Images hosted on other servers:

• Lymphangioleiomyomatosis nodules are lined by type II pneumocytes with short microvilli and electron dense cytoplasmic lamellar bodies (Arch Pathol Lab Med 2000;124:1642)

Images hosted on other servers:

• See Pathophysiology

A 44 year old woman who is a nonsmoker presented to the emergency department with acute chest pain after several months of progressive dyspnea. Physical examination was notable for diminished breath sounds on the right side. Computed tomography of the chest revealed a large pneumothorax and diffuse, intraparenchymal pulmonary cysts. The patient underwent mechanical pleurodesis and a wedge biopsy was performed. The biopsy specimens contained numerous thin walled cysts lined with spindle cells; on immunohistochemistry, the spindle cells coexpressed smooth muscle and melanocytic markers. What is the most likely diagnosis?

1. Emphysema
2. Lymphangioleiomyomatosis
3. Metastasizing pulmonary leiomyoma
4. Sarcoidosis

B. Lymphangioleiomyomatosis. Answer A is incorrect because emphysema can present with pneumothorax and lung cysts on imaging but the process is usually more localized and most patients have a history of smoking. Additionally, cysts seen in emphysematous lung specimens represent lung parenchyma with cystic changes rather than lesional / neoplastic cells with the above mentioned immunophenotype. Answer D is incorrect because while sarcoidosis can present with shortness of breath and cystic changes in the lung, these changes are usually localized. Sarcoidosis patients usually have hilar adenopathy and fibrosis (not a finding in this patient). Answer C is incorrect because metastasizing leiomyoma is a diffuse process that can also be symptomatic and appear cystic; however, on immunohistochemistry, leiomyoma cells are not immunoreactive to melanocytic markers.

Comment Here

Reference: Lymphangioleiomyomatosis

A 44 year old woman who is a nonsmoker presented to the emergency department with acute chest pain after several months of progressive dyspnea. Physical examination was notable for diminished breath sounds on the right side. Computed tomography of the chest revealed a large pneumothorax and diffuse, intraparenchymal pulmonary cysts. The patient underwent mechanical pleurodesis and a wedge biopsy was performed. The biopsy specimens contained numerous thin walled cysts lined with spindle cells; on immunohistochemistry, the spindle cells coexpressed smooth muscle and melanocytic markers. What other findings may be seen on this patient's physical examination?

1. Characteristic skin changes
2. Fever
3. Lower extremity swelling
4. Tobacco stains

A. Characteristic skin changes. Most likely this patient also has TSC gene mutations as these contribute to the development of lymphangioleiomyomatosis (LAM). Skin changes / lesions such as angiofibromas or hypomelanotic macules are hallmarks / diagnostic features of tuberous sclerosis complex. Answer B is incorrect because fever has not been described for this disorder. Answer C is incorrect because lower extremity swelling and smoking history may raise suspicion for pulmonary embolism. Answer D is incorrect because tobacco stains would raise suspicion for complicated emphysema.

Comment Here

Reference: Lymphangioleiomyomatosis