V600E BRAF versus Non-V600E BRAF Mutated Lung Adenocarcinomas: Cytomorphology, Histology, Coexistence of Other Driver Mutations and Patient Characteristics

Abstract

Objectives: We analyzed the morphologic features and clinical characteristics of lung adenocarcinomas (ACAs) harboring mutated BRAF.

Study design: A review of the histology/cytology of BRAF-mutated lung ACAs was performed at the Johns Hopkins Hospital from January 1, 2013, to January 1, 2015. Patient demographics, clinical history, and ACA morphology were assessed.

Results: Thirty-six cases were identified with a median age of 66 years (range 44-87), 58% (21/36) were female, and 94% (34/36) were current or former smokers. In total, 28% (10/36) had a BRAF-V600E mutation. Concurrent mutations were identified in KRAS in 4 cases (11%), PIK3CA in 2 cases (6%), and AKT1 in 2 cases (6%). No cases tested for ALK rearrangement were positive. The tumor grading varied from well to poorly differentiated, and the architecture assumed various patterns, including papillary, micropapillary, solid/cribriform, lepidic, and acinar. Of the cases with immunostains, 90% (18/20) were TTF-1 positive, 88% (14/16) were napsin-A positive, and 100% (8/8) were P63 negative.

Conclusion: Mutated-BRAF lung ACA arose on average in the seventh decade of life in patients who were current or former smokers and was infrequently found in combination with other common lung ACA driver mutations. The actionable V600E mutation was present in <30% of cases, more commonly in females. The histologic grade and architecture of these tumors varied significantly.

Keywords: BRAF; Cytology; Fine-needle aspiration; Lung adenocarcinoma; Next-generation sequencing.