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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front Med    2012, Vol. 6 Issue (4) : 395-405     DOI: 10.1007/s11684-012-0231-5
RESEARCH ARTICLE |
Utility of transbronchial biopsy in the diagnosis of lymphangioleiomyomatosis
Riffat Meraj1, Kathryn A. Wikenheiser-Brokamp2, Lisa R. Young3, Sue Byrnes4, Francis X. McCormack1()
1. Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, University of Cincinnati School of Medicine, Cincinnati, OH 45529, USA; 2. Pathology and Laboratory Medicine, Cincinnati Children’s Hospital Medical Center and University of Cincinnati School of Medicine, Cincinnati, OH 45529, USA; 3. Division of Pediatric Pulmonary Medicine, Department of Pediatrics, Vanderbilt University, Nashville, TN 37232, USA; 4. The LAM Foundation, Executive Drive, Cincinnati, OH 45241, USA
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Abstract  

Pulmonary lymphangioleiomyomatosis (LAM) is a rare cystic lung disease that targets women during their reproductive years. A confident diagnosis can often be based on clinical grounds, but diagnostic certainty requires pathological analysis. Although surgical lung biopsy is considered the gold standard for obtaining tissue in patients with diffuse lung disease, it is also associated with higher morbidity and mortality than alternative, less invasive techniques. The objective of our study was to examine the utility of transbronchial biopsy in the diagnosis of LAM. We conducted two online surveys of over 1 000 LAM patients registered with the LAM Foundation who were accessible by email. Transbronchial biopsy specimens were subsequently collected and reviewed by an expert pathologist to validate the diagnosis. We found that transbronchial biopsy has a yield of approximately 60% in patients with LAM. We conclude that transbronchial biopsy may be a safe and effective method for establishing the diagnosis of LAM, obviating the need for surgical lung biopsy in more than half of LAM patients.

Keywords lymphangioleiomyomatosis      lymphangiomyomatosis      multicystic lung disease      diffuse cystic lung disease      transbronchial biopsy      perivascular epithelioid cell tumor (PEComa)      HMB-45     
Corresponding Authors: McCormack Francis X.,Email:frank.mccormack@uc.edu   
Issue Date: 05 December 2012
URL:  
http://academic.hep.com.cn/fmd/EN/10.1007/s11684-012-0231-5     OR     http://academic.hep.com.cn/fmd/EN/Y2012/V6/I4/395
Fig.1  Study schema.
Patient IDAge (year)Clinical HxDiagnosticDiagnostic features
229Not providedYesLAM cells (+) cysts (+)Hemosiderin (+)IMH: HMB-45 (scattered cells+ )SMA (focally+ )
337Possible LAMNoLAM cells (-), Cysts (?)Hemosiderin (+)IMH: HMB-45 (-)SMA (focally+ ), PR (focally+ )
440Honeycomb lung rule out LAM, eosinophilic granulomaClinical diagnosis: LAMNoLAM cells (-), Cysts (-)Hemosiderin (+)IMH: None
735Not providedYesLAM cells (+), Cysts (+)Hemosiderin (+)IMH: None
839History of LAM s/p lung transplant with increased dypsnea and CT showing increased septal lines; ?Rejection, ?PTLD, ?LAMYesLAM cells (?), Cysts (-)Hemosiderin (+)IMH: HMB-45 (2 slides; 1 (-), 1 (rare+ ))Desmin (focally+ ), ER (focally+ ), PR (rare+ )
9508 years of progressive dyspnea, cysts on chest CT, PFTs showing obstruction. Patient is a non-smoker with normal alpha-1 antitrypsin levels; rule out LAMNoLAM cells (-), Cysts (-)Hemosiderin (+)IMH: None
1037Not providedYesLAM cells (+), Cysts (+)Hemosiderin (+)IMH: None
11##Cystic lung disease; rule out LAMYesLAM cells (+), Cysts (+)Hemosiderin (+)IMH: HMB-45 (scattered+ )SMA (+), Desmin (+)
1240Cystic lung disease; assess for LAMYesLAM cells (+), Cysts (+)Hemosiderin (+)IMH: HMB-45 (scattered+ )SMA (+), ER (focally+ )
1341Cystic lung disease concerning for LAMNoLAM cells (-), Cysts (-)Hemosiderin (not examined)IMH: None
Tab.1  Transbronchial biopsy results in patients with a confirmed diagnosis of LAM
Fig.2  Surgical lung wedge biopsy (A–D) and transbronchial biopsy (E–F) from a patient who underwent both procedures. Both biopsies have diagnostic histologic features of LAM including cysts (A–B, E) with LAM cell bundles at the periphery. The LAM cells are morphologically heterogeneous with a spectrum ranging from spindle-shaped cells (C) to larger round to oval epithelioid cells (D).
Fig.3  Diagnostic transbronchial biopsies from two LAM patients (A–C and D–F) showing haphazardly arranged LAM cell proliferations surrounding enlarged airspaces (A, D, E). The LAM cells are diffusely positive for the smooth muscle markers, actin and desmin (B), and a subpopulation of LAM cells are positive for HMB-45 (C, F) by immunohistochemical stains. Hemosiderin laden macrophages are frequently present within airspaces (D, E).
Fig.4  (A) Gross pathologic image of LAM lung. Grossly, LAM lungs are enlarged and diffusely cystic, with dilated airspaces as large as 2.0 cm in diameter. (B) HRCT showing diffuse thin walled cysts in a patient with LAM. Diagnosis confirmed with transbronchial biopsy.
Fig.5  Summary of pathologic review of received transbronchial biopsies from LAM patients.
Fig.6  Proposed diagnostic algorithm for females with cystic lung disease.
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