Prevalence and genotype distribution of human papillomavirus in cervical adenocarcinoma (usual type and variants): A systematic review and meta-analysis.

Cervical glandular neoplasms represent a heterogeneous group of tumors for which a comprehensive overview of the involvement of high-risk human papillomaviruses (HPV) in pathogenesis is still lacking. We first searched MEDLINE (PubMed), Embase, and Scopus databases (until October 2022), and systematically reviewed available literature. We then quantitatively estimated both pooled and genotype-specific prevalence of HPV DNA as well as the influence of various factors (e.g., geographical region, histological subtype, tissue/sample type) on computed effect size by means of random effects meta-analysis. In total, 379 studies comprising 17 129 cases of cervical adenocarcinoma were identified. The pooled HPV prevalence was 78.4% (95% confidence interval [95% CI]: 76.2-80.3) with a significant between-study heterogeneity (I2 = 79.4%, Q test p < 0.0001). Subgroup analyses indicated that the effect size differed substantially by geographical region (from 72.5% [95% CI: 68.7-76.1] in Asia to 86.8% [95% CI: 82.2-90.3] in Oceania) (p < 0.0001) and histological subtype of cancer (from 9.8% [95% CI: 5.5-17] in gastric-type to 85% [95% CI: 79.6-89.2] in usual-type cervical adenocarcinoma) (p < 0.0001). HPV16 and HPV18 were by far the most frequently detected viral strains with specific prevalence of 49.8% (95% CI: 46.9-52.6) and 45.3% (95% CI: 42.8-47.8), respectively. When stratified by continent or histologic variant, these genotype-specific results varied in a relatively limited manner. Altogether, these findings support that all histological subtypes of cervical adenocarcinoma are etiologically linked to high-risk HPV but to varying degrees. Therefore, a dual-criteria classification taking into account accurately both morphological and virological aspects could be an interesting evolution of the current binary World Health Organization classification, better reflecting the pathogenic diversity of the disease.

Genomic catastrophe, the peritoneal cavity and ovarian cancer prevention.

The current theory of carcinogenesis for the deadliest of 'ovarian' cancers-high-grade serous carcinoma (HGSC)-holds that the malignancy develops first in the fallopian tube and spreads to the ovaries, peritoneum, and/or regional lymph nodes. This is based primarily on the observation of early forms of serous neoplasia (serous tubal intraepithelial lesions [STILs], and serous tubal intraepithelial carcinomas [STICS]) in the fimbria of women undergoing risk reduction surgery. However, these lesions are uncommon in the general population, confer a low risk (5%) of HGSC following their removal in at-risk women with germ-line BRCA1/2 mutations, and require 4 or more years to recur as intraperitoneal HGSC. These features suggest that isolated STILs and STICs behave as precursors, with uncertain cancer risk rather than carcinomas. Their evolution to HGSC within, or after, escape from the tube could proceed stepwise with multiple biologic events; however, it is unclear whether tubal or ovarian HGSCs encountered in the setting of advanced disease evolved in the same fashion. The latter scenario could also be explained by a 'catastrophic' model in which STICs suddenly develop with invasive and metastatic potential, overwhelming or obscuring the site of origin. Moreover, a similar model might explain the sudden emergence of HGSC in the peritoneal cavity following escape of precursor cells years before. Long-term follow-up data from opportunistic or prophylactic salpingectomy should shed light on where malignant transformation occurs, as well as the timeline from precursor to metastatic HGSC. © 2022 The Pathological Society of Great Britain and Ireland.

Uterine Sarcoma With FGFR1-TACC1 Gene Fusion: A Case Report and Review of the Literature.

With the growing availability of RNA sequencing technology in the pathology laboratory, new gene fusion-associated malignancies are increasingly being characterized. In this article, we describe the second ever reported case of a uterine sarcoma harboring a FGFR1-TACC1 gene fusion. The patient, a 53-yr-old perimenopausal woman, was found to have a 6 cm mass spanning the lower uterine segment and endocervix. Histologically, this was a spindle cell neoplasm with coagulative necrosis, moderate cytologic atypia, and increased mitotic activity. By immunohistochemistry, the neoplastic cells coexpressed CD34 and S100, and lacked smooth muscle marker expression. RNA sequencing revealed the presence of a FGFR1-TACC1 gene fusion. This report provides further evidence to suggest that FGFR1-TACC1 may be a recurrent fusion in a subset of uterine sarcomas. RNA sequencing using a panel that includes FGFR-TACC family fusions should be considered for uterine sarcomas that do not fit conventional diagnostic criteria, particularly as tumors with these fusions may be amenable to targeted therapy.

BCOR Internal Tandem Duplication Associated Uterine Sarcoma: Expanding the Clinicopathologic Spectrum.

The diagnosis of high-grade endometrial stromal sarcoma has become more refined following molecular characterization of these tumors. Recently BCOR internal tandem duplications (ITD) have been identified in a small number of high-grade endometrial stromal sarcoma. Here we present an additional case of this rare entity in a young woman in her late teens. She presented with menorrhagia and underwent resection of 2 uterine lesions. The tumor was a spindle cell neoplasm composed of long fascicles with low to moderate cellularity, mild to moderate cytologic atypia, and up to 2 mitotic figures per 10 high power fields. Necrosis was not identified. Immunohistochemical stains showed the tumor to be positive for cyclin D1 in >50% of tumor cells, focally positive for CD10, and negative for SMA, desmin, h-caldesmon, and ALK1. BCOR ITD was confirmed by polymerase chain reaction with subsequent Sanger sequencing. Clues to the diagnosis of BCOR ITD uterine sarcoma include young patient age, uniform nuclear features, and diffuse positivity for cyclin D1. These features should prompt further molecular interrogation for definitive diagnosis, which is important for prognostication.

A Case of Synchronous Malignant and Benign Granular Cell Tumor of the Vulva.

Granular cell tumors (GCT) are rare soft tissue neoplasms, which seldom occur in the vulva. They are more commonly benign, but malignant GCT do occur. We report a case of a 50-yr-old postmenopausal woman who presented with a vulvar lesion that was diagnosed as GCT on biopsy. Imaging and clinical examination revealed an enlarged, likely positive lymph node. Pathology of the subsequently resected total deep vulvectomy specimen showed 2 histologically distinct GCTs. The larger lesion met criteria for malignancy and histologically corresponded to metastatic deposits seen in the pelvic lymph nodes. The separate smaller lesion was histologically benign. This case illustrates a malignant GCT with a synchronous, likely benign GCT both occurring in the vulva. Our case demonstrates the application of histologic criteria in the diagnosis of malignant and benign GCT with discussion on the diagnosis and treatment of this rare tumor.

Retrospective detection of isolated tumor cells by immunohistochemistry in sentinel lymph node biopsy performed for endometrial carcinoma: is there clinical significance?

INTRODUCTION: Several studies have reported optimizing ultrastaging protocols using immunohistochemistry for sentinel lymph node (SLN) biopsy in endometrial carcinoma; however, the clinical significance of isolated tumor cells (ITCs) detected by ultrastaging is unknown. This study aimed to: (1) determine the frequency of retrospective ITC detection in patients with endometrial carcinoma and reported negative SLNs determined by hematoxylin and eosin (H&E) examination only; and (2) determine the clinicopathological features and outcomes of patients with endometrial carcinoma and previously undetected ITCs. METHODS: 474 SLNs from 155 patients with endometrial carcinoma and reported negative SLNs were subjected to an immunohistochemistry protocol which included staining slides with cytokeratin at 1, 10, 20, and 50 µm levels, to examine for ITCs. Clinicopathological data of patients with ITCs detected by this method were analyzed to determine patient outcomes. RESULTS: Using immunohistochemistry, ITCs were detected in 5.7% (27/474) of SLNs and 13.5% (21/155) of patients with previously reported negative SLNs. In this patient cohort, 95.2% (20/21) had endometrioid histology, with the remaining case being carcinosarcoma. 38.1% (8/21) received adjuvant therapy (either brachytherapy alone (4/8) or chemotherapy and radiation (4/8)) based on other parameters, while 61.9% (13/21) had no adjuvant therapy. Of the patients who did not receive adjuvant therapy, all had endometrioid histology and 84.6% (11/13) were International Federation of Gynecology and Obstetrics (FIGO) stage IA. No patients (0/13) recurred after a median follow-up of 31.5 (range 2-84.4) months. DISCUSSION: In this study, 38.1% of patients with previously undetected ITCs had adjuvant treatment based on other high risk factors; as such, reporting ITCs would not have altered patient management for those who received adjuvant chemotherapy. To date, no patients with previously undetected ITCs without adjuvant treatment had a recurrence, suggesting that ITC detection may not be clinically relevant.

Diagnosis and management of a recurrent polymerase-epsilon (POLE)-mutated endometrial cancer.

Polymerase-epsilon (POLE)-mutated carcinomas are a rare, but well-known subtype of endometrial cancer. While typically associated with good prognosis, recurrences are documented. Here we present a case of recurrent POLE-mutated endometrial cancer, discuss pathologic features, current methods of molecular classification, and explore therapeutic implications for the POLE-mutation phenotype.

Insufficient and Scant Endometrial Samples: Determining Clinicopathologic Outcomes and Consistency in Reporting.

There are no widely accepted pathologic criteria for reporting endometrial samples with limited tissue and no consensus on the clinical follow-up of patients with these samples. Our study compares clinicopathologic outcomes and determines reporting consistency for these samples. This was done in 3 parts: (1) retrospective chart review of all patients with reported insufficient or scant endometrial samples from 2010 to 2013 at our center to determine repeat sampling and final pathologic diagnosis; (2) survey of gynecologists about their practice for managing patients with these samples; (3) blind review of 99 cases of previously reported scant or insufficient samples in which 4 reviewers separately reassigned cases as scant, insufficient, or diagnostic. Agreement was determined across reviewers. For part (1): 1149 patients had insufficient (49%) or scant (51%) samples with no significant difference in repeat biopsy rate (33% vs. 31%; P=0.33). Final diagnosis of uterine malignancy was higher in patients with a previous insufficient sample than with scant (19% and 9%, respectively), but this was not statistically significant. For part (2): among gynecologists surveyed, 4 of 5 reported managing patients with insufficient or scant samples similarly. For part (3): complete consensus across raters occurred in 57% of cases (Fleiss κ, 0.4891). Similar repeat biopsy rates between scant and insufficient samples suggest that our clinicians choose similar management for both terminologies. As such, distinction between insufficient and scant samples may not be necessary in pathologic reporting. Given the malignancy outcomes, both groups merit repeat sampling in the appropriate context.

Pimping in Residency: The Emotional Roller-Coaster of a Pedagogical Method - A Qualitative Study Using Interviews and Rich Picture Drawings.

Phenomenon: Pimping has become a well-known and distinct form of questioning in medical education, and as a pedagogical method it has both proponents and detractors. Pimping occurs when a teacher (pimper) asks difficult questions of the learner (pimpee), usually in rapid succession. There is a paucity of literature formally studying this technique and its effects on teachers and learners. Our study examines the use of and attitudes toward pimping in a pathology residency program to better understand its perceived value and effectiveness. Approach: Using a qualitative approach, we conducted semistructured interviews with 8 pathology trainees and 9 pathologists. As part of the interview process, we asked participants to draw a rich picture of a pimping encounter. Consistent with this qualitative method, we analyzed data iteratively using constant comparison. Findings: Negative emotions including anxiety and self-doubt dominated among the learners during pimping encounters. For some, these resulted in motivation to study, and for others this was a futile, nonmotivating experience. Most trainees felt that they were being judged during pimping; however, they perceived that the intentions of pimping were not malicious and in their best interests. This was supported by pathologists, who stated that their motivation for pimping was to identify knowledge gaps, thus benefiting the trainee. Insights: Pimping created a dichotomy of emotions within the majority of learners in this study. Negative emotions occurred during pimping encounters; however, following the encounter, pimping was perceived in a more positive light. Recognizing when and how pimping can create negative emotions that may interfere with learning may enable educators to create more consistently meaningful interactions.

Grading of Total Mesorectal Excision Specimens: Assessment of Interrater Agreement.

BACKGROUND: Total mesorectal excision is the standard of care for patients with rectal cancer. Pathological evaluation of the quality of the total mesorectal excision specimen is an important prognostic factor that correlates with local recurrence, but is potentially subjective. OBJECTIVE: This study aimed to determine the degree of variation in grading, both between assessors and between fresh and formalin-fixed specimens. DESIGN: Raters included surgeons, pathologists, pathology residents, pathologists' assistants, and pathologists' assistant trainees. Specimens were assessed by up to 6 raters in the fresh state and by 2 raters postfixation. Four parameters were evaluated: mesorectal bulk, surface regularity, defects, and coning. Interrater agreement was measured using ordinal α-values. SETTING: The study was conducted at a single academic center. MAIN OUTCOME MEASURES: The primary outcome was agreement between individuals when grading total mesorectal excision specimens. RESULTS: A total of 37 total mesorectal excision specimens were assessed. Reliability between all raters for fresh specimens for mesorectal bulk, surface regularity, defects, coning, and overall grade were 0.85, 0.85, 0.92, 0.84, and 0.91. When compared with all raters, pathologists and residents had higher agreement and pathologists and surgeons had lower agreement. Ordinal α-values comparing pathologist and pathologist's assistant agreement for overall grade were similar pre- and postfixation (0.78 vs 0.80), but agreement for assessing defects decreased postfixation. Among pathologists' assistants, agreement was higher when grading specimens postfixation than when grading fresh specimens. LIMITATIONS: Assessment bias may have occurred because of the greater number of pathologists' assistants participating than the number of residents and pathologists. CONCLUSIONS: The results indicate good interrater agreement for the assessment of overall grade, with defects showing the best interrater agreement in fresh specimens. Although total mesorectal excision specimens may be consistently graded postfixation, the assessment of defects postfixation may be less reliable. This study highlights the need for additional knowledge-transfer activities to ensure consistency and accurate grading of total mesorectal excision specimens. See Video Abstract at http://links.lww.com/DCR/A497.

Mitotically Active Sclerosing Stromal Tumor of the Ovary: Report of a Case Series With Parallels to Mitotically Active Cellular Fibroma.

Sclerosing stromal tumor of the ovary is a rare neoplasm that typically occurs in the second and third decades of life. To date, all reported cases have behaved in a benign manner. In their usual form, these neoplasms exhibit scant, if any, mitotic activity. Herein, we report a case series of 6 sclerosing stromal tumors with increased mitotic activity (between 7 and 12 mitoses per 10 high-power fields in the most mitotically active areas). Follow-up is available in 4 of 6 cases (ranging from 3 wk to 68 mo) and 1 tumor recurred within the pelvis. We suggest that the term mitotically active sclerosing stromal tumor is used for such neoplasms and draw parallels with mitotically active cellular fibroma, another benign ovarian stromal neoplasm which occasionally recurs locally, but which does not metastasize.

Malignant Phyllodes Tumors of the Breast With Rhabdomyosarcomatous Differentiation: A Case Report and Literature Review.

Phyllodes tumor (PT) is a rare fibroepithelial breast neoplasm that is typically graded histopathologically as benign, borderline, and malignant. Malignant PTs (MPTs) exhibit marked stromal cellularity, atypia, overgrowth, increased mitotic activity, and the propensity to metastasize. MPTs represent 10%-15% of all PT cases and often have a notably aggressive disease course. Infrequently, these tumors contain heterologous histological elements, including liposarcoma and fibrosarcoma, among others. Rhabdomyosarcomatous differentiation is an exceptionally rare example of such variation. This report documents the clinical presentation and disease course of a 62-year-old woman diagnosed with MPT with rhabdomyosarcomatous differentiation, just the seventh such confirmed case in the English literature. The patient experienced an arduous disease course, developing metastases to her lungs and axial skeleton just months after her initial diagnosis. Palliative radiation and chemotherapy were initiated, but the patient unfortunately succumbed to her disease just 10 months after the initial diagnosis. This case adds to the scarce literature surrounding the rare development of a heterologous rhabdomyosarcomatous element in an MPT, as well as the decision-making process surrounding the use of radiation to treat such lesions. The details discussed in this paper may inform future approaches for patients diagnosed with this disease.

Assessment of Pathology Domain-Specific Knowledge of ChatGPT and Comparison to Human Performance.

CONTEXT.­: Artificial intelligence algorithms hold the potential to fundamentally change many aspects of society. Application of these tools, including the publicly available ChatGPT, has demonstrated impressive domain-specific knowledge in many areas, including medicine. OBJECTIVES.­: To understand the level of pathology domain-specific knowledge for ChatGPT using different underlying large language models, GPT-3.5 and the updated GPT-4. DESIGN.­: An international group of pathologists (n = 15) was recruited to generate pathology-specific questions at a similar level to those that could be seen on licensing (board) examinations. The questions (n = 15) were answered by GPT-3.5, GPT-4, and a staff pathologist that recently passed their Canadian pathology licensing exams. Participants were instructed to score answers on a 5-point scale and to predict which answer was written by ChatGPT. RESULTS.­: GPT-3.5 performed at a similar level to the staff pathologist, while GPT-4 outperformed both. The overall score for both GPT-3.5 and GPT-4 was within the range of meeting expectations for a trainee writing licensing examinations. In all but one question, the reviewers were able to correctly identify the answers generated by GPT-3.5. CONCLUSIONS.­: By demonstrating the ability of ChatGPT to answer pathology-specific questions at a level similar to (GPT-3.5) or exceeding (GPT-4) a trained pathologist, this study highlights the potential of large language models to be transformative in this space. In the future, more advanced iterations of these algorithms with increased domain-specific knowledge may have the potential to assist pathologists and enhance pathology resident training.

Body composition and endometrial cancer outcomes.

BACKGROUND: Obesity is a known risk factor for developing endometrial cancer. However, the association of obesity with endometrial cancer (EC) outcomes has not been clearly established. This study examined how outcomes in women with early stage EC vary with body composition measured via computed tomography (CT). METHODS: In this retrospective study, patients diagnosed with EC international Federation of Gynecology and Obstetrics stages I-III and available CT scans were included. Automatica software was used to assess the areas of visceral adipose tissue, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) and skeletal muscle area. RESULTS: Of 293 patient charts assessed, 199 met eligibility criteria. Median body mass index (BMI) was 32.8 kg/m2 (interquartile range [IQ] = 26.8-38.9); 61.8% had histologic subtype endometrioid carcinoma. Adjusted for age, international Federation of Gynecology and Obstetrics stage, and histologic subtype, a BMI of at least 30 vs less than 30 kg/m2 was associated with lower endometrial cancer-specific survival (ECSS) (hazard ratio [HR] = 2.32, 95% confidence interval [CI] = 1.27 to 4.25) and overall survival (OS) (HR = 2.7, 95% CI = 1.35 to 5.39). Higher IMAT 75th vs 25th percentile and SAT of at least 225.6 vs less than 225.6 cm2 were associated with lower ECSS (HR = 1.53, 95% CI = 1.1 to 2.13, and HR = 2.57, 95% CI = 1.13 to 5.88) and OS (HR = 1.50, 95% CI = 1.11 to 2.02, and HR = 2.46, 95% CI = 1.2 to 5.01), respectively. The association of visceral adipose tissue (75th vs 25th percentile) with ECSS and OS was not statistically significant (HR = 1.42, 95% CI = 0.91 to 2.22, and HR = 1.24, 95% CI = 0.81 to 1.89). CONCLUSION: Higher BMI, IMAT, and SAT were associated with higher mortality from EC and lower OS. A better understanding of the mechanisms underlying these relationships could inform strategies to improve patient outcomes.

Examining the Diagnostic Yield of Tumour Testing and Qualifying Germline Concordance for Hereditary Cancer Variants in Patients with High-Grade Serous Carcinoma.

Despite advances in treatment, prognosis for most patients with high-grade serous carcinoma (HGSC) remains poor. Genomic alterations in the homologous recombination (HR) pathway are used for cancer risk assessment and render tumours sensitive to platinum-based chemotherapy and poly (ADP-ribose) polymerase inhibitors (PARPi), which can be associated with more favourable outcomes. In addition to patients with tumours containing BRCA1 or BRCA2 pathologic variants, there is emerging evidence that patients with tumours harbouring pathologic variants in other HR genes may also benefit from PARPi therapy. The objective of this study is to assess the feasibility of primary-tumour testing by examining the concordance of variant detection between germline and tumour-variant status using a custom hereditary cancer gene panel (HCP). From April 2019 to November 2020, HCP variant testing was performed on 146 HGSC formalin-fixed, paraffin-embedded tissue samples using next-generation sequencing. Of those, 78 patients also underwent HCP germline testing using blood samples. A pathogenic variant was detected in 41.1% (60/146) of tumours tested, with 68.3% (41/60) having either a BRCA1 or BRCA2 variant (n = 36), or BRCA1/2 plus a second variant (n = 5), and 31.2% (19/60) carrying a pathogenic variant in another HCP gene. The overall variant rate among the paired germline and tumour samples was 43.6% (34/78), with the remaining 56% (44/78) having no pathogenic variant detected in the germline or tumour. The overall BRCA1/2 variant rate for paired samples was 33.3% (26/78), with germline variants detected in 11.5% (9/78). A non-BRCA1/2 germline variant in another HCP gene was detected in 9.0% (7/78). All germline variants were detected in the tumour, demonstrating 100% concordance. These data provide evidence supporting the feasibility of primary-tumour testing for detecting germline and somatic variants in HCP genes in patients with HGSC, which can be used to guide clinical decision-making, and may provide opportunity for improving patient triage and clinical genetic referral practices.

A Survey on Changes to the Canadian Anatomical Pathology Certification Examination Due to Coronavirus Disease 2019 and Implications for Competency-Based Medical Education.

The coronavirus disease 2019 pandemic resulted in a dramatic change in the Royal College of Physicians and Surgeons of Canada assessment process through elimination of the oral and practical components of the 2020 Anatomical Pathology examination. Our study sought to determine stakeholder opinions and experiences on these changes in the context of the 2019 implementation of competency-based medical education. Surveys were designed for residents and practicing pathologists. In total, 57 residents (estimated response rate 29%) and 185 pathologists (estimated response rate 19%) participated across Canada; 67% of pathologists disagreed with the 2020 Royal College examination changes, compared with 30% for residents (P = <.00001). When asked whether the Royal College examination should be eliminated, 95% of pathologists indicated they would be against this, compared to only 34% of residents (P = <.00001). Perceptions on changes to and importance of different components of assessment in competency-based medical education were similar between pathologists and residents, with participants perceiving assessment practices to have changed fairly little since its implementation, with the exception of more frequent feedback. Analysis of narrative comments identified several common themes around assessment, including the need for objectivity and standardization and the problem of failure-to-fail. However, residents identified numerous elements of their performance that can be assessed only through longitudinal evaluation. Pathologists, on the other hand, tended to view these aspects of performance as laden with bias. Our results will hopefully help guide future innovation in assessment by characterizing different stakeholder perspectives on key issues in medical education.

Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A Morphologic and Molecular Study of 26 Cases Confirms Recurrent NCOA1-3 Rearrangement.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare mesenchymal neoplasm, of uncertain biological potential, that was recently reported to exhibit recurrent gene fusions involving NCOA2-3. The purpose of this study was to, using a larger sample size, better characterize the histopathologic and molecular diversity of UTROSCT. Twenty-six cases of UTROSCT from 5 institutions were selected for further study. Fluorescence in situ hybridization for NCOA1, NCOA2, NCOA3, ESR1 and GREB1, and targeted RNA sequencing was performed on 17 and 8 UTROSCTs, respectively. Eight cases underwent massively parallel sequencing to detect single nucleotide variants (SNV), copy number variations, and structural variants using a targeted hybrid-capture based assay. NCOA1-3 rearrangement was identified in 81.8% (18/22) of cases. The most common fusion was ESR1-NCOA3, occurring in 40.9% (9/22). GREB1-NCOA1 (n=4), ESR1-NCOA2 (n=3), and GREB1-NCOA2 (n=1) rearrangements were also identified. No recurrent SNVs were identified and no tumor had SNVs in FOXL2, DICER1, STK11, or AKT1, which can be seen in ovarian sex cord-stromal tumors. Copy number variations were infrequent. Clinical follow-up was available for 11 cases with a mean follow-up interval of 94.4 (range, 1 to 319) months. Only one case had a recurrence 66 months after the initial diagnosis and this was the single case with a GREB1-NCOA2 fusion. This study reports the morphologic spectrum of UTROSCT and confirms the recently reported recurrent NCOA2-3 gene fusions, in addition to identifying novel rearrangements involving NCOA1 in these tumors.

Intradepartmental consultations in surgical pathology: Review of a standardized process and factors influencing consultation rates and practices in an academic and community hospital setting.

Intradepartmental consultations (ICs) are important for quality assurance (QA) and ensuring diagnostic accuracy in surgical pathology. Few studies have reviewed pathologist factors that influence IC rates. Our study reviews IC data and factors that influence both formal (written) and informal (verbal) consultation practices among pathologists in academic and community hospital settings. Formal IC records from the academic hospital were collected and academic and community pathologists were invited to complete a survey about their IC practices. All centers had a formalized process for documenting ICs; however, 92% of academic and 90% of community pathologists also requested informal IC. The top reasons for selecting a particular colleague for IC was perceived level of expertise; however, interpersonal relationships and office proximity had a greater impact on informal IC practice. Top reasons for requesting a formal IC were mandatory (subspecialty defined) consultation and uncertainty regarding pathological findings. Advice on wording was a common reason for informal IC. Written documentation of IC aids in QA and determination of IC metrics; however, informal, undocumented ICs still occur. Reasons for IC and choice of consulting pathologist are multifactorial, and identifying these can help target quality improvement initiatives.

The evolution of endometrial carcinoma classification through application of immunohistochemistry and molecular diagnostics: past, present and future.

Uterine cancer was first subclassified based on anatomic site, separating those tumours arising from the endometrium from cervical cancers. There was then further subclassification of endometrial cancers based on cell type, and this correlated with the Type I and Type II categories identified through the epidemiological studies of Bokhman, with endometrioid carcinoma corresponding (approximately) to Type I and serous carcinoma to Type II. These histotypes are not clearly separable in practice, however, with considerable interobserver variability in histotype diagnosis, especially for high-grade tumours. There followed studies of immunomarkers and then mutational studies of single genes, in attempts to improve subclassification. While these have revealed significant differences in protein expression and mutation profiles between endometrioid and serous carcinomas, there is also considerable overlap, so that there remain challenges in subclassification of endometrial carcinoma. Gene panel testing, using next-generation sequencing, was applied to endometrial cancers and highlighted that there are tumours that show genetic alterations intermediate between classic Type I/endometrioid and Type II/serous carcinomas. The Cancer Genome Atlas studies of endometrioid and serous carcinoma offered revolutionary insight into the subclassification of endometrial carcinoma, i.e. that there are four distinct categories of endometrial carcinoma, rather than two, based on genomic architecture. In this review, we provide an overview of immunohistochemical and molecular markers in endometrial carcinoma and comment on the important future directions in endometrial carcinoma subclassification arising from The Cancer Genome Atlas results.