Transbronchial lung cryobiopsy in the diagnosis of fibrotic interstitial lung diseases

Abstract

Background: Histology is a key element for the multidisciplinary diagnosis of fibrotic diffuse parenchymal lung diseases (f-DPLD) when the clinical-radiological picture is nondiagnostic. Transbronchial lung cryobiopsy (TBLC) have been shown to be useful for obtaining large and well-preserved biopsies of lung parenchyma, but experience with TBLC in f-DPLD is limited.

Objectives: To evaluate safety, feasibility and diagnostic yield of TBLC in f-DPLD.

Method: Prospective study of 69 cases of TBLC using flexible cryoprobe in the clinical-radiological setting of f-DPLD with nondiagnostic high resolution computed tomography (HRCT) features.

Safety: pneumothorax occurred in 19 patients (28%). One patient (1.4%) died of acute exacerbation. Feasibility: adequate cryobiopsies were obtained in 68 cases (99%). The median size of cryobiopsies was 43.11 mm(2) (range, 11.94-76.25). Diagnostic yield: among adequate TBLC the pathologists were confident ("high confidence") that histopathologic criteria sufficient to define a specific pattern in 52 patients (76%), including 36 of 47 with UIP (77%) and 9 nonspecific interstitial pneumonia (6 fibrosing and 3 cellular), 2 desquamative interstitial pneumonia/respiratory bronchiolitis-interstitial lung disease, 1 organizing pneumonia, 1 eosinophilic pneumonia, 1 diffuse alveolar damage, 1 hypersensitivity pneumonitis and 1 follicular bronchiolitis. In 11 diagnoses of UIP the pathologists were less confident ("low confidence"). Agreement between pathologists in the detection of UIP was very good with a Kappa coefficient of 0.83 (95% CI, 0.69-0.97). Using the current consensus guidelines for clinical-radiologic-pathologic correlation 32% (20/63) of cases were classified as Idiopathic Pulmonary Fibrosis (IPF), 30% (19/63) as possible IPF, 25% (16/63) as other f-DPLDs and 13% (8/63) were unclassifiable.

Conclusions: TBLC in the diagnosis of f-DPLD appears safe and feasible. TBLC has a good diagnostic yield in the clinical-radiological setting of f-DPLD without diagnostic HRCT features of usual interstitial pneumonia. Future studies should consider TBLC as a potential alternative to SLBx in f-DPLD.

Figure 1. Different Examples of Cryobiopsy Showing UIP pattern.

A) A low-magnification image showing dense scarring obliterating the alveolar architecture and abruptly alternating with relatively normal lung (patchy fibrosis). Some fibroblastic foci are visible even at this magnification for their pale-gray color. B) Fibroblastic focus better visualized at higher magnification. C) An area of honeycombing.

Figure 2. NSIP pattern.

Lower lobe transbronchial cryobiopsy. A temporally homogeneous alveolar septal fibrosis is evident.

Figure 3. Freezing Artifacts.

Artifactual acute lung injury probably related to tissue damage from cold consisting in edema, intra-alveolar fibrin and blood. The lesion is seen in the lower left corner, consisting in an area of patchy fibrosis with some chronic inflammation and a fibroblastic focus (UIP with high confidence).

Figure 4. Description of Pathologic Interpretations.

Abbreviations: EOS-PMN, Eosinophilic Pneumonia; FB, Follicular Bronchiolitis; HP, Hypersensitivity Pneumonitis; OP, Organizing pneumonia; DAD, diffuse alveolar damage.

Figure 5. Correlations between Pathologic Interpretations of UIP cases and Final Diagnosis.

Report of pathologic interpretations and final diagnosis of 47 cases with UIP histologic features on cryobiopsy. TBLC column shows pathologic interpretations. HRCT column report radiologic characteristics of cases based on high resolution tomography findings. Last column summarises the final diagnosis achieved according to current ATS/ERS criteria.