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Bronchiolar Adenoma: Expansion of the Concept of Ciliated Muconodular Papillary Tumors With Proposal for Revised Terminology Based on Morphologic, Immunophenotypic, and Genomic Analysis of 25 Cases

Chang, Jason C., MD*; Montecalvo, Joseph, MD*; Borsu, Laetitia, PhD*; Lu, Shaohua, MD; Larsen, Brandon T., MD, PhD; Wallace, William Dean, MD§; Sae-Ow, Wichit, MD; Mackinnon, Alexander C., MD, PhD; Kim, Hyunjae R., PhD*,#; Bowman, Anita, MSc*; Sauter, Jennifer L., MD*; Arcila, Maria E., MD*; Ladanyi, Marc, MD*; Travis, William D., MD*; Rekhtman, Natasha, MD, PhD*

The American Journal of Surgical Pathology: August 2018 - Volume 42 - Issue 8 - p 1010–1026
doi: 10.1097/PAS.0000000000001086
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We have identified 25 lesions involving alveolar lung parenchyma characterized by nodular proliferation of bland bilayered bronchiolar-type epithelium containing a continuous layer of basal cells. These lesions shared some histologic features with the recently described entity of ciliated muconodular papillary tumor (CMPT); however, the majority did not fit all diagnostic criteria in that they exhibited only focal or absent papillary architecture, and they had variable number of ciliated and mucinous cells, with some lesions entirely lacking 1 or both of these components. The morphologic and immunohistochemical features ranged from those resembling proximal bronchioles (proximal-type: moderate to abundant mucinous and ciliated cells; negative or weak TTF1 in luminal cells; n=8) to those resembling respiratory bronchioles (distal-type: scant or absent mucinous and ciliated cells; positive TTF1 in luminal cells; n=17). The hallmark of all lesions was a continuous layer of basal cells (p40 and CK5/6-positive). We provisionally designated these lesions as bronchiolar adenomas (BAs) and analyzed their clinicopathologic and molecular features. All BAs were discrete, sharply circumscribed lesions with a median size of 0.5 cm (range, 0.2 to 2.0 cm). Most lesions were either entirely flat (n=14) or contained focal papillary architecture (n=7); only 4 lesions, all proximal-type, were predominantly papillary, fitting the classic description of CMPT. Notably, of 9 lesions submitted for frozen section evaluation, 7 were diagnosed as adenocarcinoma. No postsurgical recurrences were observed for any lesions (median follow-up, 11 mo). Twenty-one BAs underwent next-generation sequencing and/or immunohistochemistry for BRAF V600E, revealing mutation profiles similar to those previously described for CMPTs, including BRAF V600E mutations (n=8, 38%), unusual EGFR exon 19 deletions (n=2, 10%), EGFR exon 20 insertions (n=2, 10%), KRAS mutations (n=5, 24%), and HRAS mutations (n=1, 5%). The mutation profiles were similar in proximal-type and distal-type lesions. In conclusion, we describe a family of putatively benign clonal proliferations with a spectrum of morphology recapitulating various levels of the bronchiolar tree, of which only a minor subset fits the classic description of CMPT. Comparable mutation profiles and partially overlapping morphologic features across the spectrum of these lesions support their nosological relationship. We propose designating this entire family of lesions as BAs, and that lesions currently designated CMPTs represent a subgroup of this family.

*Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY

Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, China

Department of Laboratory Medicine and Pathology, Mayo Clinic, Phoenix, AZ

§Department of Pathology, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA

Department of Pathology, the Queen’s Medical Center, Honolulu, HI

Department of Pathology, Medical College of Wisconsin, Milwaukee, WI

#Texas Children’s Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX

Conflicts of Interest and Source of Funding: Supported in part by a Memorial Sloan Kettering Cancer Center, Department of Pathology Research and Development grant (to N.R.). The MSK-IMPACT program is supported in part by NIH P01 CA129243 (M.L., L.B., N.R.), NIH P30 CA008748 (MSKCC), the Marie-Josée and Henry R. Kravis Center for Molecular Oncology at MSKCC, and Cycle for Survival. The authors have disclosed that they have no significant relationship with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Natasha Rekhtman, MD, PhD, Department of Pathology, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York, NY 10065 (e-mail: rekhtman@mskcc.org).

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