Diagnosis: Lymphangioleiomyomatosis (LAM)
The finding of multiple cystic spaces in the lung parenchyma at 30 weeks gestation is most consistent with lymphangioleiomyomatosis (LAM), a rare disease that predominantly affects women of reproductive age and is characterized by diffuse thin-walled cysts throughout both lungs. 1
Diagnostic Confirmation Required
Proceed immediately to high-resolution CT (HRCT) of the chest using thin collimation (1 mm) with high spatial reconstruction algorithm to definitively characterize the cystic lesions. 1, 2 While imaging during pregnancy requires careful consideration, HRCT remains the gold standard for diagnosing cystic lung diseases and is essential for accurate diagnosis and management planning. 2
Key HRCT Features Supporting LAM Diagnosis
- Multiple (>10) thin-walled, round, well-defined air-filled cysts with preserved or increased lung volume strongly suggests LAM 1, 2
- Cysts typically range from 2-5 mm in diameter but can reach up to 30 mm 1, 2
- Cyst wall thickness ranges from barely perceptible to 2-4 mm 1, 2
- Even distribution throughout both lungs with normal intervening parenchyma is characteristic 1, 2
- Absence of other interstitial lung disease (except possible multifocal micronodular pneumocyte hyperplasia if tuberous sclerosis complex is present) 1
Essential Additional Workup
All patients with suspected LAM require abdominal-pelvic CT with contrast (>3 mm collimation, before and after IV contrast) to identify angiomyolipomas and lymphangioleiomyomas. 1, 3 The presence of renal angiomyolipomas in combination with characteristic HRCT findings can establish a clinical diagnosis of LAM without requiring tissue biopsy. 3
Serum VEGF-D Testing
Obtain serum VEGF-D level, as levels ≥800 pg/mL have 73% sensitivity and 100% specificity for diagnosing LAM and can obviate the need for lung biopsy. 3 A lower threshold of 600 pg/mL increases sensitivity to 84% with 98% specificity. 3
Critical Clinical Context
Assess for Tuberous Sclerosis Complex (TSC)
- Screen for TSC features, as LAM occurs in 30-40% of women with TSC 1
- The presence of TSC with characteristic HRCT findings is virtually diagnostic of LAM 3
- Consider brain MRI to evaluate for TSC-associated lesions 1
Pregnancy-Specific Considerations
- LAM predominantly affects women of reproductive age, making this diagnosis particularly relevant in a 30-week pregnant patient 3, 4
- Pregnancy may exacerbate LAM symptoms due to hormonal influences 1
- Document history of spontaneous pneumothorax, as this is a common presenting feature of LAM 2
When Tissue Diagnosis Is Needed
If HRCT findings are atypical, VEGF-D is <800 pg/mL, and no angiomyolipomas are present, lung biopsy may be necessary after delivery. 3 All pathology samples must be reviewed by a pathologist experienced in LAM, with immunohistochemistry for α-smooth muscle actin and HMB45 performed. 1, 3
Alternative Diagnoses to Consider (Less Likely)
While LAM is the most likely diagnosis, other diffuse cystic lung diseases should be briefly considered:
- Birt-Hogg-Dubé syndrome: Typically presents with basilar-predominant irregular cysts, often in a perivascular distribution 4, 5, 6
- Pulmonary Langerhans cell histiocytosis: Associated with smoking history, features nodules in addition to cysts, and has upper/mid-lung predominance 4, 7, 5
- Lymphoid interstitial pneumonia: Associated with ground-glass opacities and autoimmune conditions 5, 6
Critical Pitfalls to Avoid
- Do not confuse cysts with cavities, bullae, or emphysema - true cysts have thin, well-defined walls and are air-filled spaces within lung parenchyma 5, 6
- Do not delay HRCT imaging - chest X-ray alone is insufficient and misses significant pathology in up to 62% of cases 2
- Do not assume benign functional ovarian cysts explain the finding - the question specifically states cystic spaces are in the lung parenchyma, not adnexal structures 1