Transbronchial Cryobiopsies in the Evaluation of Lung Allografts Do the Benefits Outweigh the Risks? Anja C. Roden, MD; Ryan M. Kern, MD; Marie Christine Aubry, MD; Sarah M. Jenkins, MS; Eunhee S. Yi, MD; John P. Scott, MD; Fabien Maldonado, MD  Context.—Transbronchial cryobiopsy technique yields larger biopsies with enhanced quality. The benefits and safety of cryobiopsies have not been thoroughly studied in lung allografts. Objective.—To compare size, quality, reproducibility of interpretation of rejection and complications of cryo- biopsies with those of conventional biopsies from lung allografts. Design.—All cryobiopsies (March 2014–January 2015) of lung allografts performed at Mayo Clinic, Rochester, and medical records were reviewed. For comparison, conven- tional biopsies from the same patient or, if unavailable, from a random patient, were selected. Two pathologists blinded to outcome reviewed all biopsies. Specimen volume, number of alveoli, small airways, and pulmonary vessels were counted and statistically compared. Results.—Fifty-four biopsies (27 cryobiopsies) from 18 patients (11 men) were reviewed. A median of 3 (range, 2– 5) and 10 (range, 6–12) specimens were obtained with cryobiopsies and conventional biopsies, respectively. Cryo- biopsies were larger and contained more alveoli (P , .001, both) and small airways (P ¼ .04). Conventional biopsies showed more fresh alveolar hemorrhage (procedural) and crush artifact/atelectasis (P , .001, both). Cryobiopsies contained more pulmonary veins and venules (P , .001). There was no significant difference between the types of biopsies with respect to the reviewers’ agreement on grades of rejection. Complications were more frequent in the cryobiopsy group, though the difference was not statistically significant. Conclusions.—Cryobiopsies of lung allografts are larger and have less artifact. However, complications occur and should be considered. Three cryobiopsy specimens appear sufficient for histopathologic evaluation of lung allografts. (Arch Pathol Lab Med. 2016;140:303–311; doi: 10.5858/ arpa.2015-0294-OA) T ransbronchial biopsy evaluation is the gold standard to assess lung allografts for rejection and to distinguish rejection from its clinical mimickers such as aspiration, infection, abnormal drug reaction, or recurrent disease. Morphologic findings of allograft rejection might be patchy, raising the concern for sampling bias in small biopsies. In addition, bronchiolar tissue to assess for small airways rejection is not always present. Acute cellular and small airways rejection have been shown to be associated with chronic airways rejection and bronchiolitis obliterans syndrome (BOS), major complications and limiting factors for lung allograft survival. 1–3 Obliterative (constrictive) bronchiolitis, the histopathologic substrate of BOS, is rarely identified on conventional biopsies, at least in part owing to the relative paucity of small airways and sampling bias. Transbronchial cryobiopsies have recently become more popular, particularly for the diagnosis of interstitial lung diseases. 4 A few reports 5–10 describe the use of cryobiopsies in immunocompromised patients, lung allografts, and endobronchial tumors. Preliminary data suggest that this technique is safe and provides larger specimens with enhanced quality. 8,10–14 Cellular structures and microscopic architecture are reported to be preserved and immunohis- tochemical stains can be reliably performed. 14 Although pilot studies are encouraging, a detailed histologic compar- ison of cryobiopsies to conventional transbronchial biopsies has not been performed in lung allografts. Herein, we compare morphometric, architectural, and histopathologic characteristics of cryobiopsies with conven- tional biopsies of lung allografts. In addition, we study the reproducibility of the histopathologic interpretation of rejection and compare complications between cryobiopsies and conventional biopsies. Accepted for publication September 16, 2015. Published as an Early Online Release October 21, 2015. From the Department of Laboratory Medicine and Pathology (Drs Roden, Aubry, and Yi); the Division of Pulmonary & Critical Care Medicine (Drs Kern, Scott, and, Maldonado); and the Department of Health Sciences Research (Ms Jenkins), Mayo Clinic Rochester, Minnesota. The authors have no relevant financial interest in the products or companies described in this article. This manuscript was presented in part as an oral presentation at the 35th Annual Meeting & Scientific Sessions of the International Society for Heart and Lung Transplantation; April 17, 2015; Nice, France. Reprints: Anja C. Roden, MD, Division of Anatomic Pathology, Mayo Clinic Rochester, Hilton 11, 200 First St SW, Rochester, MN 55905 (email: Roden.anja@mayo.edu). Arch Pathol Lab Med—Vol 140, April 2016 Cryobiopsies for Lung Allografts—Roden et al 303