High‐grade serous carcinoma of tubo‐ovarian origin: recent developments

Extra‐uterine high‐grade serous carcinoma (HGSC) accounts for most of the morbidity and mortality associated with ovarian carcinoma, and is one of the leading causes of cancer death in women. Until recently our understanding of HGSC was very limited compared to other common cancers, and it has only been during the last 15 years that we have learned how to diagnose this ovarian carcinoma histotype accurately. Since then, however, there has been rapid progress, with identification of a precursor lesion in the fallopian tube, development of prevention strategies for both those with inherited susceptibility (hereditary breast and ovarian cancer syndrome) and without the syndrome, and elucidation of the molecular events important in oncogenesis. This molecular understanding has led to new treatment strategies for HGSC, with the promise of more to come in the near future. In this review we focus on these recent changes, including diagnostic criteria/differential diagnosis, primary site assignment, precursor lesions and the molecular pathology of HGSC.     

Application of the ISTH bleeding score in hemophilia

Background

Hemophilia is an inherited bleeding disorder. With proper treatment and self-care, persons with hemophilia can maintain an active, productive lifestyle. Hemophilia can be mild, moderate, or severe, depending on the degree of plasma clotting factor deficiency. The aim of the study was to assess the utility of ISTH-BAT in diagnosis, determining severity of the bleeding condition in newly diagnosed and known hemophilia patients, compare the bleeding score (BS) in adult and pediatric groups and investigate its association with plasma factor levels.

Synthesis of diagnostic quality cancer pathology images by generative adversarial networks

Deep learning-based computer vision methods have recently made remarkable breakthroughs in the analysis and classification of cancer pathology images. However, there has been relatively little investigation of the utility of deep neural networks to synthesize medical images. In this study, we evaluated the efficacy of generative adversarial networks to synthesize high-resolution pathology images of 10 histological types of cancer, including five cancer types from The Cancer Genome Atlas and the five major histological subtypes of ovarian carcinoma. The quality of these images was assessed using a comprehensive survey of board-certified pathologists (n = 9) and pathology trainees (n = 6). Our results show that the real and synthetic images are classified by histotype with comparable accuracies and the synthetic images are visually indistinguishable from real images. Furthermore, we trained deep convolutional neural networks to diagnose the different cancer types and determined that the synthetic images perform as well as additional real images when used to supplement a small training set. These findings have important applications in proficiency testing of medical practitioners and quality assurance in clinical laboratories. Furthermore, training of computer-aided diagnostic systems can benefit from synthetic images where labeled datasets are limited (e.g. rare cancers). We have created a publicly available website where clinicians and researchers can attempt questions from the image survey ( http://gan.aimlab.ca/ ). © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Predicting clinical outcome in patients diagnosed with synchronous ovarian and endometrial cancer

PURPOSE: Patients with synchronous ovarian and endometrial cancers may represent cases of a single primary tumor with metastasis (SPM) or dual primary tumors (DP). The diagnosis given will influence the patient's treatment and prognosis. Currently, a diagnosis of SPM or DP is made using histologic criteria, which are frequently unable to make a definitive diagnosis. EXPERIMENTAL DESIGN: In this study, we used genetic profiling to make a genetic diagnosis of SPM or DP in 90 patients with synchronous ovarian/endometrial cancers. We compared genetic diagnoses in these patients with the original histologic diagnoses and evaluated the clinical outcome in this series of patients based on their diagnoses. RESULTS: Combining genetic and histologic approaches, we were able make a diagnosis in 88 of 90 cases, whereas histology alone was able to make a diagnosis in only 64 cases. Patients diagnosed with SPM had a significantly worse survival than patients with DP (P = 0.002). Patients in which both tumors were of endometrioid histology survived longer than patients of other histologic subtypes (P = 0.025), and patients diagnosed with SPM had a worse survival if the mode of spread was from ovary to endometrium rather than from endometrium to ovary (P = 0.019). CONCLUSIONS: Genetic analysis may represent a powerful tool for use in clinical practice for distinguishing between SPM and DP in patients with synchronous ovarian/endometrial cancer and predicting disease outcome. The data also suggest a hitherto uncharacterized level of heterogeneity in these cases, which, if accurately defined, could lead to improved treatment and survival.     

Clinical Value of Immunohistochemically Detected Lymphovascular Space Invasion in Early Stage Cervical Carcinoma

Background  This study investigates the clinical significance of lymphovascular space invasion (LVSI) as detected by hematoxylin and eosin (LVSI-H&E) and immunohistochemistry (LVSI-IHC) in early stage cervical carcinoma. Methods  Single representative sections from 97 patients with early stage squamous cell cervical cancer were immunostained with pancytokeratin and CD31 endothelial cell marker antibodies. The H&E sections and their corresponding immunostained sections were reexamined to identify LVSI. Associations between LVSI with clinicopathological factors were sought. Results  Overall, LVSI was present in 29 (29.9%) and absent in 68 (70.1%) by IHC, as compared with 18 cases (18.6%) and 79 cases (81.4%), respectively, by H&E. Statistical analysis revealed a significant association between LVSI-H&E and nodal metastasis (P = .004). Follow-up data were available for 76 patients. The median follow-up period was 64 months. During follow-up, 7 of 24 patients with recurrent disease had evidence of LVSI-H&E as opposed to 3 of 52 cases with no recurrence. There was a significant association between tumor recurrence and LVSI-H&E (P = .009). The 5-year recurrence-free survival was 30% for the group with LVSI-H&E compared with 73% without. There was a significant difference in the recurrence-free survival between the two groups (P = .002). In contrast LVSI-IHC was found to be associated with no pathological factors, and survival analysis revealed no statistically significant association with recurrence or survival. Conclusion  LVSI-H&E in early stage cervical cancer remains an important predictive factor of recurrent disease and reduced disease-free interval. Immunohistochemically detected LVSI is a common event and seems to be of no clinical value.     

Biodiesel versus diesel exposure: Enhanced pulmonary inflammation,oxidative stress,and differential morphological changes in the mouse lung

The use of biodiesel (BD) or its blends with petroleum diesel (D) is considered to be a viable approach to reduce occupational and environmental exposures to particulate matter (PM). Due to its lower particulate mass emissions compared to D, use of BD is thought to alleviate adverse health effects. Considering BD fuel is mainly composed of unsaturated fatty acids, we hypothesize that BD exhaust particles could induce pronounced adverse outcomes, due to their ability to readily oxidize. The main objective of this study was to compare the effects of particles generated by engine fueled with neat BD and neat petroleum-based D. Biomarkers of tissue damage and inflammation were significantly elevated in lungs of mice exposed to BD particulates. Additionally, BD particulates caused a significant accumulation of oxidatively modified proteins and an increase in 4-hydroxynonenal. The up-regulation of inflammatory cytokines/chemokines/growth factors was higher in lungs upon BD particulate exposure. Histological evaluation of lung sections indicated presence of lymphocytic infiltrate and impaired clearance with prolonged retention of BD particulate in pigment laden macrophages. Taken together, these results clearly indicate that BD exhaust particles could exert more toxic effects compared to D.