Architectural patterns of ovarian/pelvic high-grade serous carcinoma.

We describe the architectural patterns of advanced ovarian/pelvic high-grade serous carcinomas that have been treated with upfront surgery, followed by adjuvant chemotherapy or neoadjuvant chemotherapy, followed by interval debulking to explore the association with the chemotherapeutic response. For 70 cases of advanced (i.e. stage III/IV) high-grade serous carcinomas (33 platinum resistant/intermediate, 37 platinum sensitive; 24 neoadjuvantly treated, 44 primary surgery), all tumor-containing histologic slides were reviewed by 1 of 3 pathologists. Histologic type was confirmed and the following features were assessed: major architectural pattern and the presence of any of 8 predefined minor architectural patterns (papillary, transitional cell carcinoma-like, micropapillary, microcystic, nested papillary, slit-like, glandular, solid). A semiquantitative assessment of psammoma bodies, histiocytic response, necrosis, nuclear atypia, and single-cell invasion was performed. Mitotic count was performed in 10 HPF and 1 HPF was counted for intraepithelial lymphocytes. The morphologic features were tested for an association with previous neoadjuvant chemotherapy and response to chemotherapy (resistant/intermediate versus chemotherapy-sensitive cases stratified by neoadjuvant chemotherapy), which was carried out using χ tests for categorical variables and analysis of variance for continuous data. Combinations of features were analyzed using unsupervised clustering (Wald). Although 8 of 18 features were significantly different when samples from neoadjuvantly treated patients were compared with those not previously treated, no individual histomorphologic feature or a combination of features was associated with response to chemotherapy. Further subtyping of high-grade serous carcinomas will likely need ancillary molecular markers that may have a greater potential to identify cases that will not respond to platinum-based chemotherapy.

Fluoroquinolone-Associated Type A Aortic Dissection in Alpha-1 Anti-Trypsin Deficiency.

Fluroquinolone antibiotics have come under increased scrutiny given their recent association with aortic events. Although judicious use has been urged in select patient populations, such as those with Marfan and Ehlers-Danlos syndromes, that have a known predisposition for aortopathy, other at-risk patient populations may remain. We describe the atypical delayed-presentation of a type A aortic dissection in a patient with alpha-1 anti-trypsin (A1AT) deficiency and longstanding FQ exposure. This case suggests that caution in prescribing fluroquinolone antibiotics should be extended to include those with A1AT deficiency.

A refined experimental model of fusiform aneurysms in a rabbit carotid artery.

OBJECTIVE: Reliable animal models are an important aspect of translational research, especially for relatively uncommon clinical entities such as fusiform aneurysms. While several animal models exist, very few are tailored to cerebral fusiform aneurysms, which have unique attributes compared to abdominal fusiform aneurysms. The authors aimed to build from previous models to create a cerebral fusiform aneurysm model that is simple to use and reliable. METHODS: Twelve female New Zealand White rabbits were assigned to 3 groups: group E, elastase only; group C, CaCl2 only; group EC, elastase + CaCl2. All rabbits underwent surgical exposure of the right common carotid artery (CCA) and 20 minutes of peri-carotid incubation with their respective chemicals. Angiography was performed 6 weeks later for arterial dilation measurements, with 50% increase in diameter being defined as fusiform aneurysm formation. The arterial segments, along with the contralateral CCAs, were harvested and assessed histologically for wall component measurements and elastin semiquantification. A separate rabbit underwent aneurysm creation per the group EC protocol and was treated with an endovascular flow-diversion device. RESULTS: All of the group EC rabbits developed fusiform aneurysms (mean dilation of 88%), while none of the group E or group C rabbits developed aneurysms (p = 0.001). Histological analysis revealed increased internal elastic lamina fragmentation in the group EC aneurysms, which also had less tunica intima hyperplasia. All aneurysms exhibited thinning of the tunica media and reduction in elastin content. The use of an endovascular flow-diverting stent was successful, with complete parent vessel remodeling, as expected, 4 weeks after deployment. CONCLUSIONS: The peri-arterial application of combined elastase and CaCl2 to the CCA appears sufficient to reliably produce fusiform aneurysms after 6 weeks. Exposure to elastase or CaCl2 individually appears insufficient, despite the observed histological changes to the arterial wall. The proposed fusiform aneurysm model is able to accommodate endovascular devices, simulating the tortuous pathway experienced in using such devices in human cerebral aneurysms and thus is a satisfactory model to use in translational research.

Immunohistochemistry utilization in autopsy pathology: a Canadian experience.

Immunohistochemistry (IHC) is an important part of the diagnostic work-up in surgical pathology, but the use of IHC in autopsy pathology is poorly defined. We measured IHC utilization by pathologists performing 609 consecutive non-medicolegal, hospital-based, adult autopsies over a three-year period. IHC requests on non-neurologic and neurologic material were analyzed separately. Total stains, number of tissue blocks, specific antibody requests, resident trainee involvement, and ordering pathologist were recorded. For all autopsies on which IHC was requested, the final autopsy report was reviewed. IHC was requested on 345 cases (57%), and a total of 4612 stains were performed (mean 13.5 per autopsy). For non-neurologic autopsy tissues, IHC was used most commonly for the accurate diagnosis of malignancy. For neuropathologic autopsy examinations, IHC was employed most commonly to exclude neurodegenerative conditions and correlate ante-mortem clinical neurologic findings. Resident involvement did not significantly impact utilization. Individual pathologists demonstrated a wide variation in IHC utilization. We conclude that IHC is used extensively in Canadian non-medicolegal autopsy pathology reflecting the complexity, extent, and severity of disease in patients dying in a tertiary-care, academic hospital setting. Utilization is strongly influenced by the neuropathology component of these autopsies. The results provide a point of reference for IHC utilization in autopsy pathology.