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PubMed This is a summary of 15 peer-reviewed journal articles Updated
Pulmonology

The Path to a Clear Diagnosis

At a Glance

Lymphangioleiomyomatosis (LAM) is primarily diagnosed using a High-Resolution CT (HRCT) scan to look for uniform lung cysts, followed by a VEGF-D blood test. A VEGF-D level of 800 pg/mL or higher, combined with typical cysts, confirms LAM without the need for a lung biopsy.

The process of diagnosing LAM has changed significantly over the last decade. Modern guidelines, established by the American Thoracic Society (ATS) and the Japanese Respiratory Society (JRS), now prioritize a “non-invasive” approach—meaning many women can receive a definitive diagnosis through imaging and blood tests alone, avoiding the need for surgery [1][2].

The First Step: High-Resolution CT (HRCT)

The most important tool in diagnosing LAM is a specialized scan called a High-Resolution CT (HRCT) [3]. Unlike a standard chest X-ray, an HRCT provides detailed slices of the lung tissue.

  • What doctors look for: In LAM, the scan typically reveals multiple, round, thin-walled cysts [2].
  • Distribution: These cysts are usually spread uniformly (evenly) throughout both lungs, which helps distinguish LAM from other diseases where cysts might only appear in certain areas [4][5].

The Power of the VEGF-D Blood Test

If your CT scan shows these characteristic cysts, the next step is often a blood test for a protein called Vascular Endothelial Growth Factor-D (VEGF-D) [6].

  • The Threshold: A VEGF-D level of 800 pg/mL or higher is considered highly specific for LAM [7].
  • Why it Matters: If your level is at or above this “gold standard” threshold, and you have the characteristic cysts on your CT, you can be diagnosed with Definite LAM without needing a lung biopsy [8][6].

Criteria for a “Definite” Diagnosis

According to the latest guidelines, you have a Definite LAM diagnosis if you have characteristic HRCT cysts PLUS one of the following:

  1. VEGF-D ≥ 800 pg/mL [6].
  2. Tuberous Sclerosis Complex (TSC) [1].
  3. Renal Angiomyolipoma (a specific type of kidney tumor) [9].
  4. Chylous Effusion (milky fluid in the chest or abdomen) [10].
  5. Pathological Confirmation (positive results from a lung biopsy) [11].

If you only have the characteristic cysts on your CT but none of the other features yet, your diagnosis may be labeled as Probable LAM while further testing is completed [8]. Ensuring your workup includes these “corroborating” tests is an important way to advocate for an accurate and timely diagnosis.

When a Biopsy is Needed

If your VEGF-D level is lower than 800 pg/mL and you don’t have other signs (like kidney tumors or a history of TSC), your doctor may recommend a lung biopsy to confirm the diagnosis [8]. During a biopsy, a small piece of lung tissue is removed and examined by a pathologist under a microscope.

Specialized Stains (Immunohistochemistry)

LAM cells can be difficult to see with standard stains. Pathologists use specialized “tags” to make the LAM cells stand out:

  • HMB-45: This is a classic marker that identifies LAM cells. However, it can sometimes be “patchy” or negative even if LAM is present [12][13].
  • Cathepsin K: This is a newer, highly sensitive marker that is often more reliable than HMB-45 for identifying LAM cells in tissue samples [14][15].
  • Smooth Muscle Actin (SMA): This stains the muscle-like parts of the LAM cells to confirm their identity.

Common questions in this guide

What will a CT scan show if I have LAM?
A High-Resolution CT (HRCT) scan of a patient with LAM typically reveals multiple, round, thin-walled cysts. These cysts are usually spread evenly throughout both lungs, which helps doctors distinguish LAM from other lung diseases.
What is the VEGF-D blood test for LAM?
The VEGF-D test measures a specific protein in your blood. A level of 800 pg/mL or higher, along with characteristic lung cysts on an HRCT scan, can provide a definite LAM diagnosis without needing a surgical lung biopsy.
What are the criteria for a definite LAM diagnosis?
A definite diagnosis requires characteristic cysts on a CT scan plus one corroborating factor. These confirming factors include a high VEGF-D blood level, Tuberous Sclerosis Complex (TSC), specific kidney tumors, chylous effusion (milky fluid in the chest or abdomen), or a positive lung biopsy.
When is a lung biopsy needed to diagnose LAM?
A lung biopsy may be recommended if your VEGF-D levels are lower than 800 pg/mL and you do not have other confirming signs. During the biopsy, a pathologist will examine your lung tissue using specialized stains like HMB-45 and Cathepsin K to look for LAM cells.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What was my specific VEGF-D level, and does it meet the 800 pg/mL threshold for a definite diagnosis?
  2. 2.Does my HRCT show the 'uniform' cyst distribution that is typical for LAM?
  3. 3.Besides my lungs, have we checked for other signs like kidney tumors or fluid in my abdomen?
  4. 4.If we are doing a biopsy, will the pathologist be testing for both HMB-45 and Cathepsin K?
  5. 5.Are there any other conditions, like Birt-Hogg-Dubé, that you have ruled out?

Questions For You

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References

References (15)
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    Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guidelines: Lymphangioleiomyomatosis Diagnosis and Management.

    McCormack FX, Gupta N, Finlay GR, et al.

    American journal of respiratory and critical care medicine 2016; (194(6)):748-61 doi:10.1164/rccm.201607-1384ST.

    PMID: 27628078
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    A rare lung disease diagnosed by CT in a young pregnant woman.

    Persad S, Dowlath N, Prasad M, Harry V

    Clinical case reports 2021; (9(11)):e05071 doi:10.1002/ccr3.5071.

    PMID: 34795900
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    Two most common diagnoses among myriads of cystic lung diseases.

    Swol J, Würflein D, Böhm J, Ficker JH

    Hippokratia 2021; (25(2)):83-86.

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    Effect of non-uniform cyst distribution in lymphangioleiomyomatosis on pulmonary function: a cross-sectional study.

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    The European respiratory journal 2021; (57(3)) doi:10.1183/13993003.03769-2020.

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    Uncommon radiologic computed tomography appearances of the chest in patients with lymphangioleiomyomatosis.

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    Scientific reports 2021; (11(1)):7170 doi:10.1038/s41598-021-85999-5.

    PMID: 33785773
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    Serum vascular endothelial growth factor-D as a diagnostic and therapeutic biomarker for lymphangioleiomyomatosis.

    Hirose M, Matsumuro A, Arai T, et al.

    PloS one 2019; (14(2)):e0212776 doi:10.1371/journal.pone.0212776.

    PMID: 30818375
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    Diagnostic Value of Serum VEGF-D in Lymphangioleiomyomatosis: Results of the First Prospective Study in the Russian Federation.

    Makarova M, Baimakanova G, Belevskiy A, et al.

    Diagnostics (Basel, Switzerland) 2026; (16(4)) doi:10.3390/diagnostics16040533.

    PMID: 41750682
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    Lymphangioleiomyomatosis Diagnosis and Management: High-Resolution Chest Computed Tomography, Transbronchial Lung Biopsy, and Pleural Disease Management. An Official American Thoracic Society/Japanese Respiratory Society Clinical Practice Guideline.

    Gupta N, Finlay GA, Kotloff RM, et al.

    American journal of respiratory and critical care medicine 2017; (196(10)):1337-1348 doi:10.1164/rccm.201709-1965ST.

    PMID: 29140122
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    Clinical features and outcomes of male patients with lymphangioleiomyomatosis: A review.

    Zhang H, Hu Z, Wang S, et al.

    Medicine 2022; (101(52)):e32492 doi:10.1097/MD.0000000000032492.

    PMID: 36596036
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    Chylous Ascites as a Presentation of Lymphangioleiomyomatosis.

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    ACG case reports journal 2021; (8(3)):e00517 doi:10.14309/crj.0000000000000517.

    PMID: 33681402
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    Emerging biomarkers of lymphangioleiomyomatosis.

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    PMID: 29171770
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    Pulmonary lymphangioleiomyomatosis (LAM): A literature overview and case report.

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    Radiology case reports 2022; (17(5)):1646-1655 doi:10.1016/j.radcr.2022.02.075.

    PMID: 35330669
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    Difficult diagnosis and rare morphology of lymphangioleiomyomatosis with giant cysts.

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    Cathepsin K is Superior to HMB45 for the Diagnosis of Pulmonary Lymphangioleiomyomatosis.

    Rolim I, Makupson M, Lovrenski A, Farver C

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    TSC2, cathepsin K, and β-catenin as immunohistochemical markers for lymphangioleiomyomatosis.

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    PMID: 42102978

This page is for informational purposes only and does not replace professional medical advice. Always discuss your diagnostic test results, including imaging and biopsies, directly with your pulmonologist or care team.

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