Lymphangiomyomatosis

For patient information, click here. Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Varun Kumar, M.B.B.S. [2] Ammu Susheela, M.D. [3]

Synonyms and keywords: Lymphangioleiomyomatosis; LAM; Pulmonary lymphangioleiomyomatosis; Pulmonary lymphangiomyomatosis

Overview

Lymphangiomyocytosis is defined as a multifocal neoplasm with differentiation of the perivascular epithelioid cell and has a female prepondrance, especially females of child-bearing age. On microscopic histopathological analysis, smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels are characteristic findings of lmphangiomyomatosis. Lymphangiomyomatosis must be differentiated from other diseases that cause similar clinical features, such as asthma, spontaneous pneumothorax, emphysema, interstitial pulmonary fibrosis, eosinophilic granuloma (EG), Birt-Hogg-Dube syndrome, lymphangiomas, pulmonary lymphangiectasis, and leiomyosarcoma. Symptoms of lymphangiomyomatosis may include constipation, dyspnea, and cough. The mainstay of therapy for lymphangiomyomatosisis include sirolimus, medroxyprogesterone, gonadotropin-releasing hormone agonists, and tamoxifen.

Pathophysiology

• Lymphangiomyocytosis is defined as a multifocal neoplasm with differentiation of the perivascular epithelioid cell and has a female prepondrance, especially females of child-bearing age.
• Lymphangiomyomatosis is the result of disorderly smooth muscle proliferation throughout the bronchioles, alveolar septa, perivascular spaces, and lymphatics, resulting in the obstruction of small airways (leading to pulmonary cyst formation and pneumothorax) and lymphatics (leading to chylous pleural effusion). LAM occurs in a sporadic form, which only affects females, who are usually of childbearing age. Lymphangiomyocytosis also occurs in patients who have tuberous sclerosis.
• The tuberous sclerosis complex (TSC) gene mutation has been associated with the development of lymphangiomyomatosis.
• On microscopic histopathological analysis, smooth muscle and epithelioid cells and by the proliferation of lymphatic vessels are characteristic findings of lmphangiomyomatosis.

Causes

• There are no established causes for lymphangiomyomatosis.

Differentiating Lymphangiomyomatosis from other Diseases

• Lymphangiomyomatosis must be differentiated from other diseases that cause similar clinical features, such as:

• Asthma
• Spontaneous pneumothorax
• Emphysema
• Interstitial pulmonary fibrosis
• Eosinophilic granuloma (EG)
• Birt-Hogg-Dube syndrome
• Lymphangiomas
• Pulmonary lymphangiectasis
• Leiomyosarcoma

Epidemiology and Demographics

• Till date, 1500 cases of sporadic cases of lymphangiomyomatosis was estimated to be in United States.

Age

• Lymphangiomyomatosis is more commonly observed among femele patients aged 15-45 years old.

Gender

• Lymphangiomyomatosis affects women exclusively who are of reproductive age group.

Race

• There is no racial predilection for lymphangiomyomatosis.

Natural History, Complications and Prognosis

• Common complications of lymphangiomyomatosis include ascitis, chylous pleural effusion, pneumothorax, hemoptysis, chyloptysis, chyluria, hematuria, pericardial effusion, pneumoperitoneum, lymphedema, respiratory failure, osteoporosis, and meningioma.

Diagnosis

Symptoms

• Symptoms of lymphangiomyomatosis may include the following:

• Constipation
• Dyspnea
• Cough

Physical Examination

• Physical examination may be remarkable for:

• Crackles
• Wheezes
• Pleural effusion
• Pneumothorax
• Ascites
• Facial angiofibromas
• Periungual fibromas
• Hypomelanotic macules, ash-leaf spots
• Shagreen patch
• Forehead plaque
• Retinal hamartoma

Laboratory Findings

• There are no specific laboratory findings associated with lymphangiomyomatosis.

Imaging Findings

• High-resolution CT of the chest is both more specific than chest x ray for the diagnosis, as well as better able to assess the degree of pulmonary involvement.

• 

• With lmphangiomyomatosis, there is diffuse replacement of the pulmonary parenchyma by thin-walled cysts measuring 2-20 mm in diameter, with equal involvement of upper and lower lung zones. On chest X-rays, superimposition of the cysts gives a reticulonodular pattern of interstitial lung disease.

Other Diagnostic Studies

• Lymphangiomyomatosis may also be diagnosed using immunohistochemistry.
• Findings on immunohistochemistry include Flt-4 (VEGFR-3).

Treatment

Medical Therapy

• The mainstay of therapy for lymphangiomyomatosisis include sirolimus, medroxyprogesterone, gonadotropin-releasing hormone agonists, and tamoxifen.

Surgery

• Surgical intervention can only be performed for patients with receuurent lymphangiomyomatosis resitant to medical therapy.