Online Training and Self-assessment in the Histopathologic Classification of Endocervical Adenocarcinoma and Diagnosis of Pattern of Invasion: Evaluation of Participant Performance

Histopathologic classification of endocervical adenocarcinomas (EAC) has recently changed, with the new system based on human papillomavirus (HPV)-related morphologic features being incorporated into the 5th edition of the WHO Blue Book (Classification of Tumours of the Female Genital Tract). There has also been the introduction of a pattern-based classification system to assess invasion in HPV-associated (HPVA) endocervical adenocarcinomas that stratifies tumors into 3 groups with different prognoses. To facilitate the introduction of these changes into routine clinical practice, websites with training sets and test sets of scanned whole slide images were designed to improve diagnostic performance in histotype classification of endocervical adenocarcinoma based on the International Endocervical Adenocarcinoma Criteria and Classification (IECC) and assessment of Silva pattern of invasion in HPVA endocervical adenocarcinomas. We report on the diagnostic results of those who have participated thus far in these educational websites. Our goal was to identify areas where diagnostic performance was suboptimal and future educational efforts could be directed. There was very good ability to distinguish HPVA from HPV-independent adenocarcinomas within the WHO/IECC classification, with some challenges in the diagnosis of HPV-independent subtypes, especially mesonephric carcinoma. Diagnosis of HPVA subtypes was not consistent. For the Silva classification, the main challenge was related to distinction between pattern A and pattern B, with a tendency for participants to overdiagnose pattern B invasion. These observations can serve as the basis for more targeted efforts to improve diagnostic performance

Beyond Bacteria: A Study of the Enteric Microbial Consortium in Extremely Low Birth Weight Infants

Extremely low birth weight (ELBW) infants have high morbidity and mortality, frequently due to invasive infections from bacteria, fungi, and viruses. The microbial communities present in the gastrointestinal tracts of preterm infants may serve as a reservoir for invasive organisms and remain poorly characterized. We used deep pyrosequencing to examine the gut-associated microbiome of 11 ELBW infants in the first postnatal month, with a first time determination of the eukaryote microbiota such as fungi and nematodes, including bacteria and viruses that have not been previously described. Among the fungi observed, Candida sp. and Clavispora sp. dominated the sequences, but a range of environmental molds were also observed. Surprisingly, seventy-one percent of the infant fecal samples tested contained ribosomal sequences corresponding to the parasitic organism Trichinella. Ribosomal DNA sequences for the roundworm symbiont Xenorhabdus accompanied these sequences in the infant with the greatest proportion of Trichinella sequences. When examining ribosomal DNA sequences in aggregate, Enterobacteriales, Pseudomonas, Staphylococcus, and Enterococcus were the most abundant bacterial taxa in a low diversity bacterial community (mean Shannon-Weaver Index of 1.02±0.69), with relatively little change within individual infants through time. To supplement the ribosomal sequence data, shotgun sequencing was performed on DNA from multiple displacement amplification (MDA) of total fecal genomic DNA from two infants. In addition to the organisms mentioned previously, the metagenome also revealed sequences for gram positive and gram negative bacteriophages, as well as human adenovirus C. Together, these data reveal surprising eukaryotic and viral microbial diversity in ELBW enteric microbiota dominated bytypes of bacteria known to cause invasive disease in these infants

Vulvar leiomyosarcoma: A case report

Vulvar leiomyosarcoma is a rare malignant smooth muscle tumor and the most common type of vulvar sarcoma. It can mimic benign tumors, and misdiagnosis may delay appropriate treatment. A 35-year-old woman presented to the outpatient gynecology clinic at the Mirebalais Teaching Hospital for a right vulvar mass. A complete excision of the mass was performed. Histopathology with immunohistochemistry demonstrated leiomyosarcoma. We describe the contextual challenges that ultimately compromised her care, highlighting the challenges to safe delivery of cancer care in our setting

HPV-independent, p53-wild-type vulvar intraepithelial neoplasia: a review of nomenclature and the journey to characterize verruciform and acanthotic precursor lesions of the vulva

Vulvar squamous cell carcinomas and their precursors are currently classified by the World Health Organization based on their association with high-risk human papillomavirus (HPV). HPV independent lesions often harbor driver alterations in TP53, usually seen in the setting of chronic vulvar inflammation. However, a group of pre-invasive vulvar squamous lesions is independent from both HPV and mutant TP53. The lesions described within this category feature marked acanthosis, verruciform growth and altered squamous maturation, and over the last two decades several studies have added to their characterization. They have a documented association with verrucous carcinoma and conventional squamous cell carcinoma of the vulva, suggesting a precursor role. They also harbor recurrent genomic alterations in several oncogenes, mainly PIK3CA and HRAS, indicating a neoplastic nature. In this review, we provide a historical perspective and a comprehensive description of these lesions. We also offer an appraisal of the terminology used over the years, going from Vulvar Acanthosis with Altered Differentiation and Verruciform Lichen Simplex Chronicus to Differentiated Exophytic Vulvar Intraepithelial Lesion and Vulvar Aberrant Maturation, the latter term having been recently proposed by the International Society for the Study of Vulvovaginal Diseases. In line with the recognition of these lesions by the 2020 World Health Organization Classification of Tumours as a neoplastic precursor, we herein propose the term HPV-independent, p53-wild-type verruciform acanthotic Vulvar Intraepithelial Neoplasia (HPVi(p53wt) vaVIN), which better conveys not only the pathology but also the neoplastic nature and the biologic risk inherent to these uncommon and challenging lesions. We outline strict morphologic and immunohistochemical criteria for its diagnosis and distinction from mimickers. Immunohistochemistry for p16 and p53 should be performed routinely in the diagnostic work-up of these lesions, and the morphologic alternative term vaVIN should be reserved for instances in which p16/HPV/p53 status is unknown. We also discuss management considerations and the need to further explore precursors within and beyond the spectrum of verruciform acanthotic vulvar intraepithelial neoplasia

Imunohistochemické a vybrané genetické reflexní testy pro všechny děložní leiomyosarkomy a STUMP pro genové přeskupení ALK mohou poskytovat účinný screeningový nástroj pro identifikaci mezenchymálních nádorů s přeskupeným ALK

Zkoumali jsme hodnotu cíleného molekulárního screeningu pro identifikaci mezenchymálních nádorů s přesmykem děložního anaplastického lymfomu (ALK), včetně imunohistochemie ALK následované molekulárně genetickým testováním, u všech děložních leiomyosarkomů a STUMP (nádory hladkého svalstva s nejistým maligním potenciálem). Všechny případy leiomyosarkomu a STUMP diagnostikované v 10letém období (2006–2016) na LF UK v Plzni byly získány a přezkoumány. Z 23 případů byl jeden případ (LMS [leiomyosarkom]) pozitivní na přeskupení ALK, a to fúzní gen PPP1CB – ALK. V tomto případě nebyly pozorovány žádné specifické histologické znaky (tj. Lymfocytární infiltrát a stromální edém). To naznačuje, že histologické rysy podobné zánětlivým myofibroblastickým nádorům (IMT) nemusí být počátečním spolehlivým screeningovým nástrojem při identifikaci děložních IMT případů. Navrhli jsme tedy dvoustupňové IHC a molekulární genetické testování (jako reflexní test) na IMT ve všech případech LMS a STUMP dělohy. To zlepší správnou detekci nádorů tohoto typu v populaci a tím se vytvoří možnost pro dostupnou a cílenou terapii.In a recent paper in Electron. J. Combin. 23 (2016) Estélyi and Pisanski raised a question whether there exist vertex-transitive Haar graphs that are not Cayley graphs. In this note we construct an infinite family of trivalent Haar graphs that are vertex-transitive but non-Cayley. The smallest example has 40 vertices and is the well-known Kronecker cover over the dodecahedron graph G(10,2), occurring as the graph ‘40’ in the Foster census of connected symmetric trivalent graphs

The role of adjuvant therapy in stage IA serous and clear cell uterine cancer: A multi-institutional pooled analysis.

OBJECTIVE: As the optimal adjuvant management of stage IA serous or clear cell endometrial cancer is controversial, a multi-institutional review was conducted with the objective of evaluating the appropriateness of various strategies including observation. METHODS: Retrospective chart reviews for 414 consecutive patients who underwent hysterectomy for FIGO stage IA endometrial cancer with serous, clear cell or mixed histology between 2004 and 2015 were conducted in 6 North American centers. Time-to-event outcomes were analyzed by Kaplan-Meier estimates, log-rank test, univariable and multivariable cox proportional hazard regression models. RESULTS: Post-operative management included observation (50%), chemotherapy and radiotherapy (RT) (27%), RT only (16%) and chemotherapy only (7%). The 178 RT patients received external beam (EBRT, 16%), vaginal vault brachytherapy (VVB, 56%) or both (28%). Among patients without any adjuvant treatment, 5-year local control (LC), disease free survival (DFS) and cancer-specific survival (CSS) were 82% (95% confidence interval: 74-88), 70% (62-78) and 90% (82-94), respectively. CSS in patients without adjuvant treatment was improved with adequate surgical staging (100% vs. 87% (77-92), log-rank p=0.022). Adjuvant VVB was associated with improved LC (5-year 96% (91-99) vs. 84% (76-89), log-rank p=0.007) and DFS (5-year 79% (66-88) vs. 71% (63-77), log-rank p=0.033). Adjuvant chemotherapy was associated with better LC (5-year 96% (90-98) vs. 84% (77-89), log-rank p=0.014) and DFS (5-year 84% (74-91) vs. 69% (61-76), log-rank p=0.009). On multivariable analysis, adjuvant chemotherapy and VVB were associated with improved LC while adjuvant chemotherapy and age were significant for DFS. CONCLUSIONS: In stage IA serous or clear cell uterine cancer, adjuvant RT and chemotherapy were associated with better LC and DFS. Observation may be appropriate in patients who have had adequate surgical staging