Activating KRAS mutations in arteriovenous malformations of the brain: frequency and clinicopathologic correlation.

Arteriovenous malformations (AVM) of the brain are considered congenital. Most AVMs are presumably sporadic; however, rare familial cases occur and they may be observed in certain genetic disorders. We sought to determine the frequency of KRAS mutations and their association with clinicopathologic characteristics. We searched our neuropathology database from 2014-2017 for resected AVMs of the brain or dura mater. Twenty-one AVMs were tested (12 females, 9 males; average age: 32 years). KRAS mutations were found in 6/21 cases (28.5%). Five mutations were p.G12 V, and one p.G12C. The KRAS-mutant group contained 4 females and 2 males, with an average age of 28 years, compared to 34 years in the non-mutant group (P = .54). The average AVM size in the KRAS-mutant group was 3.9 cm, compared to 3.1 cm in the non-mutant group (P = .52). There were no histologic differences between KRAS-mutant and non-mutant cases. In summary, KRAS mutations occur in almost one-third of brain AVMs. KRAS p.G12 V was the most common mutation identified. We also demonstrate the first reported instance of a KRAS p.G12C mutation in a brain AVM. The mean age of patients with KRAS-mutant AVMs was lower than the non-mutant group, and the mean size larger. Histologic characteristics were equally distributed between KRAS-mutant and non-mutant groups.

Molecular Testing for EGFR Mutations and ALK Rearrangements in the Cytological Specimens From the Patients With Non-Small Cell Lung Cancer.

OBJECTIVE: The aim of this study was to investigate epidermal growth factor receptor (EGFR) gene mutations and anaplastic lymphoma kinase (ALK) gene rearrangements using cytological specimens from the patients with a diagnosis of primary or metastatic lung non-small cell carcinoma. MATERIALS AND METHODS: A total 307 cases were submitted for EGFR mutational analysis and 265 cases for ALK analysis. The cytological specimen sources included lung, lymph node, liver, bone, adrenal gland, mesentery mass, and body fluids/bronchial brushing. EGFR mutations in the exons 18 to 21 were analyzed with Qiagen EGFR Pyro Kits. Fluorescence in situ hybridization (FISH) studies for ALK rearrangement inv(2)(p21; p23) were performed on the paraffin-embedded cell block sections utilizing dual-color Vysis LSI ALK Break Apart Probe Kit. RESULTS: Among 307 fine needle aspirate cases for EGFR analysis, 302 cases (269 from cell blocks, 33 from direct smears) had sufficient material for EGFR test. Five cases failed due to inadequate cellularity. Twenty six of 302 (8.6%) cases were positive for EGFR mutations. A total of 265 cases submitted for ALK analysis included 240 cases of fine needle aspirate, 25 cases of pleural fluid/pericardial fluid/bronchial washings. Eight cases failed because of low cellularity, whereas 257 of 265 cases had sufficient material for ALK FISH study. Nine of 257 cases (3.5%) revealed ALK rearrangement by FISH. CONCLUSIONS: The current study demonstrates that cytological specimens can yield sufficient material for EGFR mutations and ALK rearrangement test. Our study reveals that 8.6% of EGFR mutation rate and 3.5% of ALK rearrangement rate in the cytology specimens from the patients with primary or metastatic lung non-small cell carcinoma.

Distinct clinicopathological features in metanephric adenoma harboring BRAF mutation.

BRAF mutation recently has been reported in metanephric adenoma. We sought to determine the clinical and morphologic features of BRAF-mutated metanephric adenoma and to correlate BRAF mutation with BRAF V600E immunohistochemical staining results. A series of 48 metanephric adenomas and 15 epithelial-predominant nephroblastomas were analyzed for the occurrence of BRAF mutation (BRAF V600E/V600E complex, BRAF V600D, BRAF V600K and BRAF V600R) using the BRAF RGQ PCR kit (Qiagen). Immunohistochemistry was performed using monoclonal mouse antibodies against p16INK4 and VE1 (Spring Bioscience), recognizing the BRAF V600E mutant protein. Forty-one of 48 cases (85%) showed BRAF V600E mutation; none of the other BRAF variants was detected. Of 41 BRAF-mutated metanephric adenomas, 33 showed positive VE1 immunostaining (sensitivity 80%, specificity 100%); in all cases we detected p16INK4 expression regardless of BRAF mutation status. All epithelial-predominant nephroblastomas were BRAF-wild-type and none expressed VE1. The following features were associated with BRAF V600E mutation: older patients (p=0.01), female predominance (p=0.005) and the presence of a predominantly acinar architecture (p=0.003). In summary, BRAF-mutated metanephric adenomas were associated with older age, female predominance, and the presence of a predominant acinar component. A subset (20%) of BRAF-mutated metanephric adenomas was not detected by VE1 immunostaining.