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 Journal Article


Authors: Chang, J. C.; Montecalvo, J.; Borsu, L.; Lu, S.; Larsen, B. T.; Wallace, W. D.; Sae-Ow, W.; Mackinnon, A. C.; Kim, H. R.; Bowman, A.; Sauter, J. L.; Arcila, M. E.; Ladanyi, M.; Travis, W. D.; Rekhtman, N.
Article Title: 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
Abstract: 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. © 2018 Wolters Kluwer Health, Inc. All rights reserved.
Keywords: braf; bilayered; bronchiolar adenoma; ciliated muconodular papillary tumor; cmpt
Journal Title: American Journal of Surgical Pathology
Volume: 42
Issue: 8
ISSN: 0147-5185
Publisher: Lippincott Williams & Wilkins  
Date Published: 2018-08-01
Start Page: 1010
End Page: 1026
Language: English
DOI: 10.1097/pas.0000000000001086
PROVIDER: scopus
PUBMED: 29846186
PMCID: PMC8063713
DOI/URL:
Notes: Article -- Export Date: 1 August 2018 -- Source: Scopus
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MSK Authors
  1. Natasha Rekhtman
    434 Rekhtman
  2. Marc Ladanyi
    1332 Ladanyi
  3. William D Travis
    749 Travis
  4. Maria Eugenia Arcila
    669 Arcila
  5. Jason Chih-Peng Chang
    141 Chang
  6. Hyunjae Ryan Kim
    7 Kim
  7. Jennifer Lynn Sauter
    129 Sauter
  8. Anita S Bowman
    44 Bowman