Algorithm for the diagnosis of lymphangioleiomyomatosis

LAM: lymphangioleiomyomatosis; PFTs: pulmonary function tests; DLCO: diffusing capacity carbon monoxide; HRCT: high resolution computed tomography; TSC: tuberous sclerosis; VEGF-D: vascular endothelial growth factor-D; AML: angiomyolipoma; VATS: video-assisted thoracoscopic surgery.
* PFTs may be normal in early LAM.
¶ Additional features on HRCT that may be helpful diagnostically include: Pleural effusion, pneumothorax, adenopathy, lymphangiomyoma, ground glass opacity (may suggest chylous congestion), or multifocal micronodules (suggestive of multifocal micronodular pneumocyte hyperplasia [MMPH] as seen in TSC-LAM). In some patients, LAM cysts are atypical.
Δ Refer to UpToDate text regarding diagnosis of TSC. Diagnosis of TSC often requires referral to TSC specialist. Features that may suggest TSC include:

• Family history of TSC
• Subungual fibromas
• Facial angiofibromas
• Hypomelanotic macules
• Confetti lesions
• Shagreen patches
• Seizures, cognitive impairment
• Autism
• Cortical dysplasias, subependymal nodules, and/or features of subependymal giant cell astrocytoma on brain imaging

◊ Refer to UpToDate text regarding patients who present with a low cyst burden (<10) or atypical cysts (eg, nonuniform or irregular shape).
§ In the United States, VEGF-D is ONLY available through the Translational Trials Laboratory at Cincinnati Children's Hospital Medical Center (www.cincinnatichildrens.org/ttdsl).
¥ Pleural fluid should be assessed for chyle and LAM cells. If no evidence of chylous pleural fluid and abdominal-pelvic HRCT shows ascites, perform paracentesis with assessment for chyle and LAM cells.
‡ The diagnosis of renal AML and cystic lymphangioleiomyomas is based on radiographic appearance. Of note, cystic lymphangioleiomyomas should not be aspirated or biopsied due to the risk of prolonged chyle leak.
† Chylous effusion: Triglycerides >110 mg/dL; cholesterol <200 mg/dL.
** For patients with lymphadenopathy (typically retroperitoneal or pelvic and less commonly thoracic), some experts perform lymph node aspiration before resorting to lung biopsy. Diagnostic lung tissue can often be obtained via transbronchial biopsy. Occasionally, biopsy may be deferred based on mild or nonprogressive disease or patient preference.
¶¶ A pathologist with experience in the diagnosis of LAM is essential.