- Author: Joel Moss, MD, PhD; Chief Editor: Zab Mosenifar, MD, FACP, FCCP more...
Vascular endothelial growth factor-D (VEGF-D) levels, above a certain threshold, are found in lymphangioleiomyomatosis (LAM) but not other cystic lung diseases. Hence, a serologic test for VEGF-D may be useful for diagnosis or follow-up.[14, 15] A prior study has shown that high levels of VEGF-D are associated with lymphatic involvement (eg, lymphangioleiomyomas, adenopathy) in LAM.
Chest radiographs in lymphangioleiomyomatosis (LAM) may be normal. Fine reticular or reticulonodular interstitial infiltrate with preserved lung volumes is the most commonly observed abnormality. Pleural effusions may be present. Patients may present with pneumothorax.
CT scan and high-resolution CT scan findings include the following:
- Diffuse thin-walled cysts - The defining appearance in LAM
- Adenopathy and thoracic duct dilatation
- Pleural effusion
- Ground-glass opacities - May be present, perhaps representing alveolar hemorrhage or interstitial disease
- Pericardial effusion
- Multifocal multinodular pneumocyte hyperplasia (MMPH) - Can be seen in patients with tuberous sclerosus complex (TSC), but the pathology is distinct from LAM
Abdominal imaging by either ultrasound or CT scan may demonstrate the following:
- Angiomyolipoma (AML) - Benign tumors (kidney, liver, spleen) containing smooth muscle, abnormal blood vessels, and mature adipose tissue
- Retroperitoneal or mediastinal lymphangioleiomyomas
CT or MRI scanning of the head may reveal an incidental or symptomatic meningioma, which occurs with increased frequency in patients with LAM .
On bone densitometry, patients with LAM exhibit accelerated osteoporosis.
Pulmonary function testing, decreased diffusing capacity for carbon monoxide is the most common abnormality seen, and it is often markedly reduced.[9, 19] Hypoxemia at rest, worsening with exercise, is a common finding.
On spirometry, airflow obstruction is the most frequent abnormality; restriction or mixed obstruction and restriction can also be seen.
Lung volumes may show an increased ratio of residual volume to total lung capacity.
Histologic diagnosis can be made by performing an open lung, video-assisted thoracoscopic, or transbronchial biopsy (TBB) ; the amount of tissue obtained from TBB may be insufficient to confirm a diagnosis. Lymphangioleiomyomatosis (LAM) cells react with human melanoma black (HMB)–45, an antibody generated against an extract of melanoma. HMB-45 staining is used for the identification of LAM cells in biopsy specimans.
With classic high-resolution CT scans of the lung and associated findings of LAM (eg, tuberous sclerosis complex, angiomyolipoma, lymphangioleiomyomas), histologic confirmation may be unnecessary, especially if vascular endothelial growth factor D (VEGF-D) levels are elevated.
Cysts are evenly distributed in all lung fields. Lymph nodes (retroperitoneal and pelvic) may appear pale and spongy; large chyle-filled cysts can be found within the axial lymphatic system. The thoracic duct may be large, spongy, and sausagelike.
In histological sections of the lung, the following are observed :
- Proliferation of lymphangioleiomyomatosis (LAM) cells (spindle-shaped cells with small nuclei, larger epithelioid cells with clear cytoplasm and round nuclei) having a smooth muscle cell phenotype
- Loss of alveoli with cyst formation
- Aggregates of LAM cells abutting cystic spaces
- Distal airway narrowing, thickened arterial walls with venous occlusion, and hemosiderosis
In involved lymph nodes and the thoracic duct, there are interlacing bundles of LAM cells, which may invade the walls of the lymphatics.
Immunohistochemical staining of LAM lesions demonstrates the following:
- Reactivity with anti–alpha-smooth actin antibodies, which is consistent with smooth-muscle differentiation
- Estrogen and progesterone receptors
- Immunoreactivity with the monoclonal antibody HMB-45, which recognizes LAM cells with epithelioid features; rarely, spindle cells are also HMB-45 positive
- Renal and hepatic AMLs, as well as lymphangioleiomyomas, can also be detected with HMB-45 antibody
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