RET gene rearrangements occur in a subset of pancreatic acinar cell carcinomas.

Pancreatic acinar cell carcinoma is relatively rare (1 to 2% of pancreatic malignancies) but may be under-recognized. In contrast to pancreatic ductal adenocarcinoma, most acinar cell carcinomas lack mutations in KRAS, DPC, CDKN2A or TP53, but appear to have a high incidence of gene rearrangements, with up to 20% reported to be driven by BRAF fusions. With the development of a new class of RET-specific tyrosine kinase inhibitors, which appear to have particularly strong activity against RET gene rearranged tumours, there is now considerable interest in identifying RET gene rearrangements across a wide range of cancers. RET rearrangements have been reported to occur at a very low incidence (<1%) in all pancreatic carcinomas. We postulated that given its unique molecular profile, RET gene rearrangements may be common in acinar cell carcinomas. We performed fluorescent in-situ hybridization (FISH) studies on a cohort of 40 acinar cell spectrum tumours comprising 36 pure acinar cell carcinomas, three pancreatoblastomas and one mixed acinar-pancreatic neuroendocrine tumour. RET gene rearrangements were identified in 3 (7.5%) cases and BRAF gene rearrangements in 5 (12.5%). All gene rearranged tumours were pure acinar cell carcinomas. Our findings indicate that amongst all pancreatic carcinomas, acinar carcinomas are highly enriched for potentially actionable gene rearrangements in RET or BRAF. FISH testing is inexpensive and readily available in the routine clinical setting and may have a role in the assessment of all acinar cell carcinomas-at this stage to recruit patients for clinical trials of new targeted therapies, but perhaps in the near future as part of routine care.

Inflammatory Myofibroblastic Tumors of the Female Genital Tract Are Under-recognized: A Low Threshold for ALK Immunohistochemistry Is Required.

Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT. On review significant areas of all 4 tumors closely mimicked smooth muscle tumors morphologically, but all showed at least subtle/focal features suggesting IMT. Recognizing that the distinction between IMT and leiomyoma/leiomyosarcoma can be subtle, we then reviewed 1 hematoxylin and eosin slide from each patient undergoing surgery for "leiomyoma" from 2014 to 2017 and selected cases for ALK IHC with a low threshold. Of these, 30 of 571 (5.3%) underwent IHC. Two were confirmed to be IHC positive and FISH rearranged. Of the 6 IMTs, only 1 tumor with a previous diagnosis of leiomyosarcoma, an infiltrative margin and equivocal necrosis, metastasized. Of note it demonstrated a less aggressive clinical course compared with most metastatic leiomyosarcomas (alive with disease at 6 y). The patient was subsequently offered crizotinib to which she responded rapidly. In conclusion, IMTs may closely mimic gynecologic smooth muscle tumors. IMTs account for at least 5 of 1747 (0.3%) tumors previously diagnosed as leiomyoma and 1 of 44 (2.3%) as leiomyosarcoma. These tumors may be recognized prospectively with awareness of subtle/focal histologic clues, coupled with a low threshold for ALK IHC.

Implementation of an established algorithm and modifications for the identification of epilepsy patients in the veterans health administration.

Identification of epilepsy patients from administrative data in large managed healthcare organizations is a challenging task. The objectives of this report are to describe the implementation of an established algorithm and different modifications for the estimation of epilepsy prevalence in the Veterans Health Administration (VHA). For the prevalence estimation during a given time period patients prescribed anti-epileptic drugs and having seizure diagnoses on clinical encounters were identified. In contrast to the established algorithm, which required inclusion of diagnoses data from the time period of interest only, variants were tested by considering diagnoses data beyond prevalence period for improving sensitivity. One variant excluded data from diagnostic EEG and LTM clinics to improve specificity. Another modification also required documentation of seizures on the problem list (electronic list of patients' established diagnoses). Of the variants tested, the one excluding information from diagnostic clinics and extending time beyond base period of interest for clinical encounters was determined to be superior. It can be inferred that the number of patients receiving care for epilepsy in the VHA ranges between 74,000 and 87,000. In the wake of the recent implementation of ICD-10 codes in the VHA, minor tweaks are needed for future prevalence estimation due to significant efforts presented. This review is not only beneficial for researchers interested in VHA related data but can also be helpful for managed healthcare organizations involved in epilepsy care aiming at accurate identification of patients from large administrative databases.

Primary care utilization among veterans with chronic musculoskeletal pain: a retrospective chart review.

OBJECTIVE: Patients with chronic pain have been shown to be more frequent utilizers of primary care, a contributor to increased health care costs. This study aimed to clarify which patient factors predict primary care utilization among veterans with chronic pain. DESIGN: Data were gathered from the electronic medical records of veterans who used Veterans Affairs primary care services from 2003 to 2009 in upstate New York. Chronic pain cases (N = 792) were those veterans diagnosed with a musculoskeletal condition of the hip, knee, or lower back during two or more primary care encounters over a period ≥ 3 months. Cases were frequency matched by age to controls, or those veterans who did not have a chronic musculoskeletal condition of the hip, knee, or lower back. Demographic information, medical and psychiatric diagnoses, medication use, and other health-related factors were used in regression models to predict primary care utilization. RESULTS: Cases consistently accrued more primary care encounters than controls during each year of the observation period. Cases also accrued more encounters from specialty medicine clinics, chronic pain clinics, and behavioral health clinics co-located in primary care. The contribution of mental health factors to care utilization differed by case-control status. Diagnosis of depression and substance use disorders were predictors of care utilization only among controls, whereas anxiety disorders, use of anxiolytics, and adjustment disorders were predictors only among cases. Cases with a co-occurring anxiety disorder had a greater than twofold increased risk (odds ratio = 2.36, 95% confidence interval = 1.32-4.22) of being in the top 10% of the distribution of total primary care utilization. CONCLUSIONS: Mental health conditions that commonly co-occur with chronic musculoskeletal pain contribute to greater health care utilization. Improved screening and early intervention for these disorders in primary care may improve patient outcomes and stem high rates of care utilization of veterans.