Cynthia Heffron

Impact of positive margins on outcomes of oropharyngeal squamous cell carcinoma according to p16 status

Currently, positive surgical margins in head and neck cancer are considered to be an indicator for postoperative chemoradiotherapy (CRT) over radiotherapy (RT) alone. However, there are less data regarding the impact of margin status on human papillomavirus (HPV)‐related oropharyngeal squamous cell carcinoma (SCC).

High-throughput oncogene mutation profiling shows demographic differences in BRAF mutation rates among melanoma patients

Because of advances in targeted therapies, the clinical evaluation of cutaneous melanoma is increasingly based on a combination of traditional histopathology and molecular pathology. Therefore, it is necessary to expand our knowledge of the molecular events that accompany the development and progression of melanoma to optimize clinical management. The central objective of this study was to increase our knowledge of the mutational events that complement melanoma progression. High-throughput genotyping was adapted to query 159 known single nucleotide mutations in 33 cancer-related genes across two melanoma cohorts from Ireland (n=94) and Belgium (n=60). Results were correlated with various clinicopathological characteristics. A total of 23 mutations in 12 genes were identified, that is – BRAF, NRAS, MET, PHLPP2, PIK3R1, IDH1, KIT, STK11, CTNNB1, JAK2, ALK, and GNAS. Unexpectedly, we discovered significant differences in BRAF, MET, and PIK3R1 mutations between the cohorts. That is, cases from Ireland showed significantly lower (P<0.001) BRAFV600E mutation rates (19%) compared with the mutation frequency observed in Belgian patients (43%). Moreover, MET mutations were detected in 12% of Irish cases, whereas none of the Belgian patients harbored these mutations, and Irish patients significantly more often (P=0.027) had PIK3R1-mutant (33%) melanoma versus 17% of Belgian cases. The low incidence of BRAFV600E-mutant melanoma among Irish patients was confirmed in five independent Irish cohorts, and in total, only 165 of 689 (24%) Irish cases carried mutant BRAFV600E. Together, our data show that melanoma-driving mutations vary by demographic area, which has important implications for the clinical management of this disease.

Association of Extracapsular Spread With Survival According to Human Papillomavirus Status in Oropharynx Squamous Cell Carcinoma and Carcinoma of Unknown Primary Site

IMPORTANCEnThe presence of extracapsular spread (ECS) of metastatic nodes is considered a poor prognosticator in head and neck cancer, with postoperative chemoradiation therapy often recommended over radiation therapy alone in such cases. However, there is less clarity regarding the effect of ECS on human papillomavirus-associated oropharynx squamous cell carcinoma (OPSCC) or carcinoma of unknown primary site (CUP).nnnOBJECTIVEnTo investigate the association of ECS according to human papillomavirus status in OPSCC and CUP with survival.nnnDESIGN, SETTING, AND PARTICIPANTSnThis investigation was a retrospective cohort study performed between August 1998 and March 2015 at an academic teaching hospital. Participants were 83 patients with OPSCC (nu2009=u200962) or CUP (nu2009=u200921) undergoing neck dissection as part of initial treatment.nnnMAIN OUTCOME AND MEASURESnHuman papillomavirus status was determined by p16 immunohistochemistry. The presence of ECS was extrapolated from pathology reports, and the extent of ECS was determined by rereview of original pathology slides. Disease-specific survival (DSS) and recurrence-free survival (RFS) were assessed.nnnRESULTSnAmong 83 patients (71 male), there were 45 p16-positive and 38 p16-negative tumors. Fifty-one patients had ECS, which was graded as extensive in 43 cases. The median follow-up was 31 months for all patients and 50 months for surviving patients. Among the entire cohort, adverse predictors of RFS were p16-negative status (hazard ratio [HR], 9.4; 95% CI, 3.3-27.2) and ECS (HR, 6.5; 95% CI, 2.0-21.6). Adverse predictors of DSS were p16-negative status (HR, 16.8; 95% CI, 3.9-71.2) and ECS (HR, 8.3; 95% CI, 2.0-35.3). Among p16-negative patients, ECS was significantly associated with worse RFS (HR, 9.7; 95% CI, 1.3-72.3) and DSS (HR, 8.7; 95% CI, 1.1-62.7). In contrast, among p16-positive patients, ECS had no effect on RFS (HR, 1.1; 95% CI, 0.2-7.8) or DSS (HR, 1.2; 95% CI, 0.1-18.7).nnnCONCLUSIONS AND RELEVANCEnThe presence of ECS appears to be associated with survival in OPSCC and CUP according to p16 status. Our findings raise questions regarding the benefits of postoperative chemoradiation therapy in p16-positive patients with ECS.

Impact of lymphocytic thyroiditis on incidence of pathological incidental thyroid carcinoma

The purpose of this study was to investigate the impact of lymphocytic thyroiditis on incidence of incidental thyroid cancers.

Pattern of invasion and lymphovascular invasion in squamous cell carcinoma of the floor of the mouth: an interobserver variability study.

Lymphovascular invasion (LVI) and the histological pattern of invasion (POI) at the invasive tumour front have been reported as adverse prognosticators in oral squamous cell carcinoma (SCC). However, assessment of these parameters is hampered by variation in the criteria used for their evaluation. Our objective was to evaluate interobserver variability in the assessment of the POI and LVI in SCC of the floor of the mouth (FOM), and to study the impact of the POI on clinical outcomes by using varying quantitative cut‐offs.

Sampling of wide local excision specimens in cutaneous malignant melanoma

Wide local excisions (WLEs) are frequently undertaken in the management of cutaneous melanoma; however, there is a considerable variability in their macroscopic sampling. The aim of our study was to establish evidence‐based guidelines for the macroscopic handling of these specimens with a subsequent review of the impact on our service.

Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma in a Warthin Tumor: Case Report and Literature Review:

Warthin tumor is the second most common salivary gland neoplasm. It occurs more commonly in males than in females. Malignant transformation in Warthin tumor is a rare but well-recognized phenomenon; however, the development or presentation of lymphoma in a Warthin tumor is rare. An 80-year-old man presented with painless mass of the right parotid gland of 2 years duration with recent ulceration of the overlying skin and right cervical lymphadenopathy underwent a surgical resection of parotid mass and biopsy of the periglandular lymph nodes. The histological diagnosis was malignant lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, present within the stroma of a Warthin tumor, and also present within the adjacent lymph node. This case is the third reported case describing a collision of Warthin tumor and chronic lymphocytic leukemia/small lymphocytic lymphoma. It also emphasizes the importance of careful examination of the lymphoid stroma of these tumors.

Nerve Infiltration by Benign Biliary Glands – A Diagnostic Dilemma

Perineural and intraneural infiltration is most often considered a diagnostic feature of malignancy but has been demonstrated in benign entities in a variety of organs. n nThis brief report describes benign glands apparently infiltrating nerves around bile ducts in a resected extra-hepatic biliary tree performed on a background of recurrent cholangitis and prior cholecystectomy. To our knowledge, benign glands infiltrating nerves within bile ducts has not been reported outside of the setting of end stage primary sclerosing cholangitis where one example has been described. n nWe identify several features which support the benign nature of this process including bland cytomorphology, identical appearance to adjacent glands and an exuberant neural rather than glandular proliferation supporting the probability of a reactive neural proliferation akin to traumatic neuroma. n nWe propose a pathogenesis that is somewhat analogous to traumatic neuroma of the biliary tree which, despite its rarity, is a documented complication of cholecystectomy, comprising a reactive proliferation of nerve tissue in response to injury. n nThis article is protected by copyright. All rights reserved.

BRAF V600 mutation detection in melanoma: a comparison of two laboratory testing methods

Aims The assessment of B-raf proto-oncogene, serine/threonine kinase (BRAF) gene status is now standard practice in patients diagnosed with metastatic melanoma with its presence predicting a clinical response to treatment with BRAF inhibitors. The gold standard in determining BRAF status is currently by DNA-based methods. More recently, a BRAF V600E antibody has been developed. We aim to investigate whether immunohistochemical detection of BRAF mutation is a suitable alternative to molecular testing by polymerase chain reaction (PCR). Methods We assessed the incidence of BRAF mutation in our cohort of 132 patients, as determined by PCR, as well as examining clinical and histopathological features. We investigated the sensitivity and specificity of the anti-BRAF V600E VE1 clone antibody in detecting the presence of the BRAF V600E mutation in 122 cases deemed suitable for testing. Results The incidence of BRAF mutation in our cohort was 28.8% (38/132). Patients with the BRAF mutation were found to be significantly younger at age of diagnosis. BRAF-mutated melanomas tended to be thinner and more mitotically active. The antibody showed a sensitivity of 86.1% with a specificity of 96.9%. The positive predictive value was 96.9%; the negative predictive value was 94.4%. The concordance rate between PCR and immunohistochemical BRAF status was 95.1% (116/122). Conclusions The rate of BRAF mutation in our cohort (28.8%) was lower than international published rates of 40%–60%. This may reflect ethnic or geographic differences within population cohorts. The high concordance rate of PCR and immunohistochemical methods in determining BRAF status suggests that immunohistochemistry is potentially a viable, cost-effective alternative to PCR testing and suitable as a screening test for the BRAF mutation.