A Modern Approach to Endometrial Carcinoma: Will Molecular Classification Improve Precision Medicine in the Future?

Simple Summary The scientific community widely agrees that molecular classification will be key to endometrial carcinoma therapeutic strategies in the future. Retrospective analyses of large endometrial carcinoma patient cohorts gave rise to a new understanding of one of the most relevant gynecologic malignancies. Potentially replacing the current type I and type II terminology, four molecular subtypes have been established, each of them reflecting underlying molecular aberrations and distinct clinical behavior. Future research will have to focus on how to integrate these new findings into clinical practice with the ultimate goal to drive personalized endometrial carcinoma patient care forward. Endometrial cancer has been histologically classified as either an estrogen-dependent cancer with a favorable outcome or an estrogen-independent cancer with a worse prognosis. These parameters, along with the clinical attributions, have been the basis for risk stratification. Recent molecular and histopathological findings have suggested a more complex approach to risk stratification. Findings from the Cancer Genome Atlas Research Network established four distinctive genomic groups: ultramutated, hypermutated, copy-number low and copy-number high prognostic subtypes. Subsequently, more molecular and histopathologic classifiers were evaluated for their prognostic and predictive value. The impact of molecular classification is evident and will be recognized by the upcoming WHO classification. Further research is needed to give rise to a new era of molecular-based endometrial carcinoma patient care

Transdiaphragmatic Mucormycosis

Mucormycosis is a life-threatening infection. This is the first report of transdiaphragmatic mucormycosis in a series of 3 patients. We observed this phenomenon in 11% of patients. Clinicians should be aware of this possibly underreported entity, and as a consequence we envision more comprehensive imaging studies in patients with mucormycosis

First description of hematogenously metastasized sclerosing epithelioid fibrosarcoma arising in the uterine cervix

• First Case of hematogenously metastasized sclerosing epithelioid fibrosarcoma arising primarily in the cervix uteri. • Tumor cells were strongly and diffusely positive for MUC4. • Tumor showed a rare EWSR1-CREB3L2 gene fusion

Prevalence of abnormal Pap smear results in inflammatory bowel disease: a prospective study

Purpose Development of malignancy is a pending threat for patients with inflammatory bowel disease (IBD). Aim of this study was to analyze cervical dysplasia and infection with human papilloma virus (HPV) in patients with IBD. Methods This was a prospective, single center cohort study in Germany. Consecutive IBD patients admitted to the Department of Gastroenterology were sent to Gynecology, where a questionnaire was answered and gynecological examinations including a smear for cytology and HPV were taken. Participants of a general screening program constituted controls. Descriptive statistics, 95% confidence intervals and odds ratios were calculated. Results A total of 101 patients were recruited of which 99 patients participated. Analysis showed a significant (p = 0.05) difference between the prevalence of abnormal smears in patients with (22%) and without (6%) immunosuppressive therapy, while the latter had cervical abnormalities comparable with healthy controls (5%). All immunosuppressants showed similarly high risks for abnormal smear results. Only 11/99 (11%) patients had positive high-risk HPV tests, which is comparable with general population. Conclusion The prevalence of abnormal cervical smears is higher in IBD patients compared to healthy individuals, but the difference is confined to patients with IBD and immunosuppressive therapy. Annual screening is advisable

Preoperative biopsies as predictor for the necessity of inguinal lymph node surgery in squamous cell carcinoma of the vulva-a retrospective tertiary center analysis

Purpose Squamous cell carcinoma of the vulva (SQCV) is the fifth common cancer in women. Necessity of inguinal lymph node surgery depends on the depth of stromal invasion, inducing lymph node surgery, if depth of invasion is more than 1 mm. In this study we tested the prediction of stromal infiltration depth by measurements in preoperative biopsies. Methods We analyzed whether a different operative strategy in respect to lymph node surgery would have been chosen based on the pre- or postoperative depth of stromal invasion for each patient. Examination of infiltration depth in preoperative biopsies and surgical specimen were compared. Results In total 77 patients were included in this study. Of those 89.6% showed different depths of stromal invasion comparing the pre- and postoperative specimen. Within seventeen patients (22.1%) preoperative depth was 1 mm or less and a postoperative depth was > 1 mm. Conclusion We pointed, that only in 77.9% of the patients who should have undergo lymph node surgery based on the postoperative depth of infiltration underwent this procedure. Consequentially in 22.1% of the cases a second operation could not be prevented with a preoperative taken biopsy as indicator for the necessity of lymph node surgery

Cervical Intraepithelial Neoplasia 3 (Cervical Intraepithelial Neoplasia 3/High-Grade Squamous Intraepithelial Lesion) in Human Papillomavirus-Vaccinated Women-Results From a Tertiary Referral Center

Objective: High-grade cervical intraepithelial neoplasia (CIN 3) still develops in some vaccinated women despite established effectiveness of prophylactic human papillomavirus (HPV) vaccination. The purpose of this study was to define characteristics of women with CIN 3 after HPV vaccination referred to a gynecological dysplasia unit. Materials and Methods: Retrospective analysis of HPV-vaccinated women with CIN 3 in a single German center. Between July 2018 and September 2020, 791 women were referred to our university hospital-based dysplasia unit for colposcopic evaluation of abnormal cytological findings. Human papillomavirus vaccination status was retrieved. Human papillomavirus typing was performed in lesional biopsies and cervical swabs. Results: Nine women were identified who had previously been vaccinated with the quadrivalentHPV vaccine (Q-HPV) andwere diagnosedwith histologically confirmed CIN 3/high-grade squamous intraepithelial lesion. The Q-HPV had been administered between 12 and 28 years of age and 1-13 years before CIN 3 diagnosis. Nine different high-risk (HR)-HPV types were found in the CIN 3 biopsies, 6 monoinfections (twice HPV 16, once HPV 18, HPV 31, HPV 52, HPV 58, respectively) and 3 dual infections (HPV 33 + 52, HPV 51 + 52, HPV 53 + 66). Seven of these 9 HR-HPV types are not covered by Q-HPV, but only 2 CIN 3 lesions carried HR-HPV types not included in the nonavalent HPV vaccine. Conclusions: It is important to implement vaccination recommendations and administer HPV vaccination as early as possible in HPV-naive individuals. Because not all HR-HPV types are covered by the available HPV vaccines, other types may still cause CIN 3/high-grade squamous intraepithelial lesion. This requires further screening after vaccination, especially in women who were previously vaccinated with the bivalent or the quadrivalent HPV vaccine

Incidental FOXL2 mutated adult granulosa cell tumour of the ovary with thecoma-like foci

We report on the incidental finding of a FOXL2 mutated adult granulosa cell tumour of the ovary with thecoma-like foci, a rare entity recently described by Jennifer N. Stall and Robert H. Young in a series of sixteen cases in 2019, displaying features differing from conventional adult granulosa cell tumour. Our aim is to specify the morphologic and molecular particularities of this presumably underrecognized finding, with a short presentation of the typical clinical context. Awareness of this rare and challenging neoplasm with indeterminate clinical course is crucial in routine diagnostics

Quality control stress test for deep learning-based diagnostic model in digital pathology

Digital pathology provides a possibility for computational analysis of histological slides and automatization of routine pathological tasks. Histological slides are very heterogeneous concerning staining, sections' thickness, and artifacts arising during tissue processing, cutting, staining, and digitization. In this study, we digitally reproduce major types of artifacts. Using six datasets from four different institutions digitized by different scanner systems, we systematically explore artifacts' influence on the accuracy of the pre-trained, validated, deep learning-based model for prostate cancer detection in histological slides. We provide evidence that any histological artifact dependent on severity can lead to a substantial loss in model performance. Strategies for the prevention of diagnostic model accuracy losses in the context of artifacts are warranted. Stress-testing of diagnostic models using synthetically generated artifacts might be an essential step during clinical validation of deep learning-based algorithms

Tumour area infiltration and cell count in endoscopic biopsies of therapy-naive upper GI tract carcinomas by QuPath analysis: implications for predictive biomarker testing

Abstract Guidelines regulate how many (tumour-bearing) tissue particles should be sampled during gastric cancer biopsy to obtain representative results in predictive biomarker testing. Little is known about how well these guidelines are applied, how the number of tissue particles correlates with the actual tumour-infiltrated area and how many absolute tumour cells are captured. The study included endoscopic biopsies of untreated carcinomas of the upper gastrointestinal (GI)-tract during the 2016–2020 review period. Archival (H&E)-stained histological sections were digitised and the tumour areas were manually annotated. The tumour-bearing tissue area and absolute carcinoma cell count per case were determined by image analysis and compared with a reference primary surgical specimen. Biopsies from 253 patients were analysed. The following mean values were determined: (a) tumour tissue particle number: 6.5 (range: 1–25, standard deviation (SD) = 3.33), (b) number of tumour-bearing tissue particles: 4.7 (range: 1–20, SD = 2.80), (c) tumour-infiltrated area: 7.5 mm2 (range: 0.18–59.46 mm2, SD = 6.67 mm2), (d) absolute tumour cell count: 13,492 (range: 193–92,834, SD = 14,185) and (e) tumour cell count in a primary surgical specimen (tumour size: 6.7 cm): 105,200,176. The guideline-recommended tissue particle count of 10 was not achieved in 208 patients (82.2%) and the required tumour-bearing tissue particle count of 5 was not achieved in 133 patients (52.6%). Tissue particle count, tumour-infiltrated area and tumour cell count were only weakly correlated. Most cases featured an infiltrated area ≥ 4.5 mm2 (156, 61.7%). Cases with more tissue particles showed only a moderate increase in infiltrated area and tumour cells compared to cases with fewer particles. Biopsies are often used to determine predictive biomarkers, particularly Her2/neu and PD-L1. Diagnostic standards to ensure representative material have been suggested in guidelines to reduce false-negative predictions. However, the real-world practice seems to substantially deviate from recommended standards. To the best of our knowledge, this is the first systematic study describing the relationships between endoscopic tissue fragment number, actual infiltrated tumour area and carcinoma cell number. The data question the tissue particle number as a quality assessment parameter. We advocate histopathological reports indicating on which basis statements on therapy-relevant biomarkers were made. Digital pathology has the potential to objectively quantify the tissue for documentation, quality assessment and future clinical studies