<b><i>V600E BRAF</i></b> versus Non-<b><i>V600E BRAF</i></b> 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.

<b><i>BRAF</i></b> Mutations in Lung Cancer

“…2) was less common (42.9 vs. 72%). In contrast to Salimian et al [1], who observed a more frequent occurrence of BRAF p.V600E mutations in female patients, in our series we did not observe any difference regarding gender. On the other hand, similarly to Salimian et al [1], the occurrence of BRAF non-p.V600E mutations was more frequent in male patients.…”

“…In contrast to Salimian et al [1], who observed a more frequent occurrence of BRAF p.V600E mutations in female patients, in our series we did not observe any difference regarding gender. On the other hand, similarly to Salimian et al [1], the occurrence of BRAF non-p.V600E mutations was more frequent in male patients. We also confirmed that BRAF non-p.V600E mutations may be associated with other oncogenic driver mutations; in fact, in 1 case, a non-p.V600E BRAF mutation was identified in association with a KRAS mutation (p.G12S).…”

“…With great interest we read the paper by Salimian et al [1], describing the distribution of different v-Raf murine sarcoma viral oncogene homolog B1 ( BRAF ) mutations in lung adenocarcinomas (ADCs), which has recently been published in Acta Cytologica . Their series was entirely composed of BRAF mutant cases, in order to investigate the relative prevalence of BRAF p.V600E versus BRAF non-p.V600E mutations.…”

“…This issue is of great clinical relevance, since only BRAF p.V600E can be targeted by dedicated treatment [2]. This study showed that p.V600E occurred in 10 (28%) of all 36 cases and it was more common in females [1]. …”

“…In Table 2 are detailed all the data derived from Salimian et al [1] and those generated in our series. In both studies, BRAF mutations were associated with ADC morphology and a median age ranging from 60 to 70 years.…”