Neuroendocrine Marker Expression in Primary Non-neuroendocrine Epithelial Tumors of the Ovary: A Study of 551 Cases.

Expression of neuroendocrine (NE) markers in primary ovarian non-NE epithelial tumors has rarely been evaluated. The aim of our study was to evaluate the expression of the most widely used NE markers in these neoplasms and to determine any prognostic significance of NE marker expression. The cohort consisted of 551 primary ovarian tumors, including serous borderline tumors, low-grade serous carcinomas, high-grade serous carcinomas (HGSC), clear cell carcinomas, endometroid carcinomas, mucinous borderline tumors, and mucinous carcinomas. Immunohistochemical analysis was performed using antibodies against INSM1, synaptophysin, chromogranin, and CD56 on tissue microarray. Positivity for INSM1, synaptophysin, chromogranin, and CD56 was most frequently observed in mucinous tumors (48.7%, 26.0%, 41.5%, and 100%, respectively). The positivity for these NE markers was mostly restricted to nonmucinous elements distributed throughout the tumor. The mucinous borderline tumor and mucinous carcinomas groups had similar proportions of positivity (mucinous borderline tumor: 53%, mucinous carcinomas: 39%). In the other tumor types, except for HGSC, there was only focal expression (5%-10%) or negativity for NE markers. HGSC showed high CD56 expression (in 26% of cases). Survival analysis was only performed for CD56 in HGSC as this was the only group with sufficient positive cases, and it showed no prognostic significance. Except for mucinous tumors, expression of NE markers in non-NE ovarian epithelial tumors is low. CD56 expression in HGSC occurs frequently but is without diagnostic or prognostic value.

Role of fertility-sparing surgery and further prognostic factors in borderline tumors of the ovary.

OBJECTIVE: Borderline tumors of the ovary are a rare group of ovarian neoplasms with distinctive histological features. Considering their favorable prognosis and occurrence at a younger age, fertility-sparing surgery may be considered. Several risk factors have been identified as contributing to a higher recurrence rate, while the impact of pathohistological features varies in the literature. This study aimed to analyze risk factors for recurrence in patients with borderline tumors of the ovary. METHODS: Analysis included patients treated with first diagnosis of a borderline tumor at our center between January 1997 and December 2022 to analyze disease-free survival and to identify the role of fertility-sparing surgery, defined as preservation of at least one ovary, pathohistological features, and other prognostic factors for relapse. All stages classified according to the International Federation of Gynecology and Obstetrics (FIGO) were included. RESULTS: Among 507 patients, 26 patients (5.2%) had a recurrence, with 21 (4.1%) showing borderline histology and 5 (1%) with invasive relapses. Recurrence rate was higher following fertility-sparing surgery (p<0.0001). Median follow-up period was 49.2 (range 42.0-57.6) months. Among 153 patients (30.2%) who had fertility-sparing surgery, 21 (13.7%) experienced a recurrence (including one invasive relapse). Fertility-sparing surgery (HR 20; 95% CI 6.9 to 60; p<0.001), FIGO stage I with bilateral presence of tumor (HR 6.4; 95% CI 1.3 to 31; p=0.020), FIGO stage II (HR 15; 95% CI 3.4 to 68; p<0.001), FIGO stages III-IV (HR 38; 95% CI 10 to 140; p<0.001) in comparison with FIGO stage I with unilateral tumor, microinvasion (HR 8.6; 95% CI 2.7 to 28; p<0.001), and micropapillary growth patterns (HR 4.4; 95% CI 1.8 to 10; p=0.001) were identified as independent risk factors for recurrence in multivariate analysis. None of these factors were associated with an increased risk of disease-related death. CONCLUSIONS: Our study showed that although a fertility-preserving approach is associated with increased recurrence rates of a borderline tumor, it does not affect overall survival and can therefore be regarded as oncologically safe for patients desiring to preserve fertility. Additionally, presence of micropapillary patterns and microinvasion were identified as prognostic risk factors.

A combined computational and functional approach identifies IGF2BP2 as a driver of chemoresistance in a wide array of pre-clinical models of colorectal cancer.

AIM: Chemoresistance is a major cause of treatment failure in colorectal cancer (CRC) therapy. In this study, the impact of the IGF2BP family of RNA-binding proteins on CRC chemoresistance was investigated using in silico, in vitro, and in vivo approaches. METHODS: Gene expression data from a well-characterized cohort and publicly available cross-linking immunoprecipitation sequencing (CLIP-Seq) data were collected. Resistance to chemotherapeutics was assessed in patient-derived xenografts (PDXs) and patient-derived organoids (PDOs). Functional studies were performed in 2D and 3D cell culture models, including proliferation, spheroid growth, and mitochondrial respiration analyses. RESULTS: We identified IGF2BP2 as the most abundant IGF2BP in primary and metastastatic CRC, correlating with tumor stage in patient samples and tumor growth in PDXs. IGF2BP2 expression in primary tumor tissue was significantly associated with resistance to selumetinib, gefitinib, and regorafenib in PDOs and to 5-fluorouracil and oxaliplatin in PDX in vivo. IGF2BP2 knockout (KO) HCT116 cells were more susceptible to regorafenib in 2D and to oxaliplatin, selumitinib, and nintedanib in 3D cell culture. Further, a bioinformatic analysis using CLIP data suggested stabilization of target transcripts in primary and metastatic tumors. Measurement of oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) revealed a decreased basal OCR and an increase in glycolytic ATP production rate in IGF2BP2 KO. In addition, real-time reverse transcriptase polymerase chain reaction (qPCR) analysis confirmed decreased expression of genes of the respiratory chain complex I, complex IV, and the outer mitochondrial membrane in IGF2BP2 KO cells. CONCLUSIONS: IGF2BP2 correlates with CRC tumor growth in vivo and promotes chemoresistance by altering mitochondrial respiratory chain metabolism. As a druggable target, IGF2BP2 could be used in future CRC therapy to overcome CRC chemoresistance.

Primary Mucinous Tumors of the Ovary: An Interobserver Reproducibility and Detailed Molecular Study Reveals Significant Overlap Between Diagnostic Categories.

Primary ovarian mucinous tumors represent a heterogeneous group of neoplasms, and their diagnosis may be challenging. We analyzed 124 primary ovarian mucinous tumors originally diagnosed as mucinous borderline tumors (MBTs) or mucinous carcinomas (MCs), with an emphasis on interobserver diagnostic agreement and the potential for diagnostic support by molecular profiling using a next-generation sequencing targeted panel of 727 DNA and 147 RNA genes. Fourteen experienced pathologists independently assigned a diagnosis from preset options, based on a review of a single digitized slide from each tumor. After excluding 1 outlier participant, there was a moderate agreement in diagnosing the 124 cases when divided into 3 categories (κ = 0.524, for mucinous cystadenoma vs MBT vs MC). A perfect agreement for the distinction between mucinous cystadenoma/MBT as a combined category and MC was found in only 36.3% of the cases. Differentiating between MBTs and MCs with expansile invasion was particularly problematic. After a reclassification of the tumors into near-consensus diagnostic categories on the basis of the initial participant results, a comparison of molecular findings between the MBT and MC groups did not show major and unequivocal differences between MBTs and MCs or between MCs with expansile vs infiltrative pattern of invasion. In contrast, HER2 overexpression or amplification was found only in 5.3% of MBTs and in 35.3% of all MCs and in 45% of MCs with expansile invasion. Overall, HER2 alterations, including mutations, were found in 42.2% of MCs. KRAS mutations were found in 65.5% and PIK3CA mutations in 6% of MCs. In summary, although the diagnostic criteria are well-described, diagnostic agreement among our large group of experienced gynecologic pathologists was only moderate. Diagnostic categories showed a molecular overlap. Nonetheless, molecular profiling may prove to be therapeutically beneficial in advanced-stage, recurrent, or metastatic MCs.

ESTRO/ESGO/SIOPe Guidelines for the management of patients with vaginal cancer.

Primary vaginal malignancies are rare, comprising only 2% of all female genital tract malignancies in adults and 4.5% in children. As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) jointly with the European Society for Radiotherapy & Oncology (ESTRO) and the European Society of Pediatric Oncology (SIOPe) developed evidence-based guidelines in order to improve the management of patients with vaginal cancer within a multidisciplinary setting.ESTRO/ESGO/SIOPe nominated practicing clinicians who are involved in the management of vaginal cancer patients and have demonstrated leadership through their expertise in clinical care and research, their national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (13 experts across Europe comprising the international development group). To ensure that the statements were evidence based, the current literature was reviewed and critically appraised.In the case of absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 112 independent international practitionners in cancer care delivery and patient representatives and their comments and input were incorporated and addressed accordingly.These guidelines cover comprehensively the diagnostic pathways as well as the surgical, radiotherapeutical and systemic management and follow-up of adult patients (including those with rare histological subtypes) and pediatric patients (vaginal rhabdomyosarcoma and germ cell tumours) with vaginal tumours.

European Society of Gynaecological Oncology Guidelines for the Management of Patients with Vulvar Cancer - Update 2023.

BACKGROUND: As part of its mission to improve the quality of care for women with gynecological cancers across Europe, the European Society of Gynaecological Oncology (ESGO) first published in 2017 evidence-based guidelines for the management of patients with vulvar cancer. OBJECTIVE: To update the ESGO guidelines based on the new evidence addressing the management of vulvar cancer and to cover new topics in order to provide comprehensive guidelines on all relevant issues of diagnosis and treatment of vulvar cancer. METHODS: The ESGO Council nominated an international development group comprised of practicing clinicians who provide care to vulvar cancer patients and have demonstrated leadership through their expertize in clinical care and research, national and international engagement and profile as well as dedication to the topics addressed to serve on the expert panel (18 experts across Europe). To ensure that the statements were evidence-based, new data identified from a systematic search were reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Prior to publication, the guidelines were reviewed by 206 international practitioners in cancer care delivery and patient representatives. RESULTS: The updated guidelines cover comprehensively diagnosis and referral, staging, pathology, pre-operative investigations, surgical management (local treatment, groin treatment, sentinel lymph node procedure, reconstructive surgery), (chemo)radiotherapy, systemic treatment, treatment of recurrent disease (vulvar, inguinal, pelvic, and distant recurrences), and follow-up. Management algorithms are also defined.

ESGO/ESTRO/ESP Guidelines for the management of patients with cervical cancer - Update 2023.

In 2018, the European Society of Gynecological Oncology (ESGO) jointly with the European Society for Radiotherapy and Oncology (ESTRO) and the European Society of Pathology (ESP) published evidence-based guidelines for the management of patients with cervical cancer. Given the large body of new evidence addressing the management of cervical cancer, the three sister societies jointly decided to update these evidence-based guidelines. The update includes new topics to provide comprehensive guidelines on all relevant issues of diagnosis and treatment in cervical cancer.To serve on the expert panel (27 experts across Europe) ESGO/ESTRO/ESP nominated practicing clinicians who are involved in managing patients with cervical cancer and have demonstrated leadership through their expertise in clinical care and research, national and international engagement, profile, and dedication to the topics addressed. To ensure the statements were evidence based, new data identified from a systematic search was reviewed and critically appraised. In the absence of any clear scientific evidence, judgment was based on the professional experience and consensus of the international development group. Before publication, the guidelines were reviewed by 155 independent international practitioners in cancer care delivery and patient representatives.These updated guidelines are comprehensive and cover staging, management, follow-up, long-term survivorship, quality of life and palliative care. Management includes fertility sparing treatment, early and locally advanced cervical cancer, invasive cervical cancer diagnosed on a simple hysterectomy specimen, cervical cancer in pregnancy, rare tumors, recurrent and metastatic diseases. The management algorithms and the principles of radiotherapy and pathological evaluation are also defined.

Tumor Microenvironment in Male Breast Carcinoma with Emphasis on Tumor Infiltrating Lymphocytes and PD-L1 Expression.

Male breast cancer (MBC) is rare and usually presents as a locally advanced disease. Stromal tumor-infiltrating lymphocytes (sTILs) are associated with a better response to neoadjuvant chemotherapy and improved prognosis in all molecular subtypes of female breast cancer, but their role in MBC is less clear. We studied sTILs and the expression of programmed cell death ligand 1 (PD-L1) and pan-TRK in MBC. We retrospectively studied 113 cases of MBC surgically treated between 1988 and 2015. The tumors were evaluated for histological type and grade, stage, intrinsic subtype and sTILs. We performed immunohistochemistry for PD-L1 (clone SP142) and pan-TRK (clone EPR17341) on tissue microarrays. Pan-TRK positive cases were further analyzed by next-generation sequencing. The median age was 69 years (range 60−77). Invasive carcinoma of no special type was found in 94.7% of cases, of which 53.1% were grade 2. Estrogen receptor was positive in 92% of the tumors, progesterone receptor in 85.8%, androgen receptor in 70.8%; 4.4% were human epidermal growth factor receptor 2 (HER2)-positive, and 55.8% HER2-low. 40.7% of tumors were luminal A and 51.3% luminal B, 4.4% HER2-enriched and 3.5% triple negative carcinoma. sTILs density was <50% in 96.4% of the tumors, >50% in 3.6% of the tumors. PD-L1 immune cell score >1% was found in 7.1% of the tumors (all of luminal subtype). A weak focal cytoplasmic pan-TRK staining was present in 8.8% but without NTRK fusion. Neither sTILs nor PD-L1 had statistically significant outcomes. Our findings suggest that a subset of MBC patients harbors an immunological environment characterized by increased sTILs with PD-L1 expression. These patients may potentially benefit from immune checkpoint inhibitor therapy. Frequent HER2-low may offer novel anti-HER2 treatment options.

Terminology for cone dimensions after local conservative treatment for cervical intraepithelial neoplasia and early invasive cervical cancer: 2022 consensus recommendations from ESGO, EFC, IFCPC, and ESP.

Local cervical treatment for squamous intraepithelial lesion (SIL) or cervical intraepithelial neoplasia (CIN) removes or ablates a cone-shaped or dome-shaped part of the cervix that contains abnormal cells. This Series paper introduces the 2022 terminology for cone dimensions after local conservative treatment for SIL, CIN, or early invasive cervical cancer. The terminology was prepared by the Nomenclature Committee of the European Society of Gynaecologic Oncology, the European Federation for Colposcopy, the International Federation of Cervical Pathology and Colposcopy, and the European Society of Pathology. Cone length should be tailored to the type of transformation zone. Treatment of SIL or CIN is associated with an increased risk of preterm birth, which escalates with increasing cone length. There is a lack of agreement regarding terms used to report excised specimen dimensions both intraoperatively and in the pathology laboratory. Consensus is needed to make studies addressing effectiveness and safety of SIL or CIN treatment comparable, and to facilitate their use to improve accuracy of antenatal surveillance and management. This Series paper summarises the current terminology through a review of existing literature, describes new terminology as agreed by a group of experts from international societies in the field of cervical cancer prevention and treatment, and recommends use of the new terminology that will facilitate communication between clinicians and foster more specific treatment guidelines that balance obstetrical harm against therapeutic effectiveness.

Data Set for the Reporting of Carcinomas of the Vagina: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Primary carcinomas of the vagina are uncommon and currently detailed recommendations for the reporting of resection specimens of these neoplasms are not widely available. The International Collaboration on Cancer Reporting (ICCR) is developing standardized, evidence-based reporting data sets for multiple cancer sites. We describe the development of a cancer data set by the ICCR expert panel for the reporting of primary vaginal carcinomas and present the core and noncore data elements with explanatory commentaries. This data set has incorporated the updates in the 2020 World Health Organization Classification of Female Genital Tumours, 5th edition. The data set addresses controversial issues such as tumor grading, margin assessment, and the role of ancillary studies. The adoption of this data set into clinical practice will help ensure standardized data collection across different countries, facilitate future research on vaginal carcinomas, and ultimately lead to improvements in patient care.

Data Set for the Reporting of Carcinomas of the Vulva: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

A cogent and comprehensive pathologic report is essential for optimal patient management, cancer staging, and prognostication. This article details the International Collaboration on Cancer Reporting (ICCR) process and the development of the vulval carcinoma reporting data set. It describes the "core" and "noncore" elements to be included in pathology reports for vulval carcinoma, inclusive of clinical, macroscopic, microscopic, and ancillary testing considerations. It provides definitions and commentary for the evidence and/or consensus-based deliberations for each element included in the data set. The commentary also discusses controversial issues, such as p16/human papillomavirus testing, tumor grading and measurements, as well as elements that show promise and warrant further evidence-based study. A summary and discussion of the updated vulval cancer staging system by the International Federation of Obstetricians and Gynaecologists (FIGO) in 2021 is also provided. We hope the widespread implementation of this data set will facilitate consistent and accurate reporting, data collection, comparison of epidemiological and pathologic parameters between different populations, facilitate research, and serve as a platform to improve patient outcomes.

Dataset for the Reporting of Gestational Trophoblastic Neoplasia: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Comprehensive pathology reporting of cancers is important for patient management, tumor staging, and prognostication. Standardized cancer datasets are essential in guiding pathology reporting in a consistent and concise manner and this facilitates effective global cancer information exchange and comparison. The International Collaboration on Cancer Reporting (ICCR) is an alliance of several national and international pathology societies in many countries as well as bodies which are involved in tumor classification and staging. One function of the ICCR is to develop evidence-based, standardized reporting datasets for each cancer site. Herein, we report the development of an evidence-based cancer dataset by an ICCR panel of international experts for the reporting of primary uterine gestational trophoblastic neoplasia. We present the core elements that should be included and noncore elements that are recommended for inclusion in pathology reports. Lists of the response values are provided for each element, along with explanatory commentaries. The dataset also discusses controversial issues in the reporting of gestational trophoblastic neoplasia. Such evidence-based and structured pathology datasets developed through an international effort will facilitate consistent and accurate exchange and comparison of epidemiological and pathologic parameters among different populations and countries. This will ultimately improve gestational trophoblastic neoplasia patient care and facilitate future research.

Data Set for the Reporting of Ovarian, Fallopian Tube and Primary Peritoneal Carcinoma: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

The move toward consistent and comprehensive surgical pathology reports for cancer resection specimens has been a key development in supporting evidence-based patient management and consistent cancer staging. The International Collaboration on Cancer Reporting (ICCR) previously developed a data set for reporting of the ovarian, fallopian tube and primary peritoneal carcinomas which was published in 2015. In this paper, we provide an update on this data set, as a second edition, that reflects changes in the 2020 World Health Organization (WHO) Classification of Female Genital Tumours as well as some other minor modifications. The data set has been developed by a panel of internationally recognized expert pathologists and a clinician and consists of "core" and "noncore" elements to be included in surgical pathology reports, with detailed commentary to guide users, including references. This data set replaces the widely used first edition, and will facilitate consistent and accurate case reporting, data collection for quality assurance and research, and allow for comparison of epidemiological and pathologic parameters between different populations.

Data Set for Reporting of Uterine Malignant and Potentially Malignant Mesenchymal Tumors: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

The International Collaboration on Cancer Reporting (ICCR) seeks to produce standardized, evidence-based protocols for the reporting of tumors with the aim of ensuring that all cancer reports generated worldwide will be of similar high quality and record the same elements. Herein, we describe the development of the data set for the reporting of uterine malignant and potentially malignant mesenchymal tumors by a panel of expert pathologists and a single clinician and provide the commentary and rationale for the inclusion of core and noncore elements. This data set, which incorporates the recent updates from the 5th edition of the World Health Organization Classification of Female Genital Tumors, addresses several subjects of debate including which mesenchymal tumors should be graded, how to document extent of invasion, mitotic counts, and the role of ancillary testing in tumor diagnosis and patient management. The inclusion of elements is evidence-based or based on consensus of the expert panel with clinical relevance being the guiding standard.

Dataset for the Reporting of Carcinoma of the Cervix: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Cervical carcinoma remains one of the most common cancers affecting women worldwide, despite effective screening programs being implemented in many countries for several decades. The International Collaboration on Cancer Reporting (ICCR) dataset for cervical carcinoma was first developed in 2017 with the aim of developing evidence-based standardized, consistent and comprehensive surgical pathology reports for resection specimens. This 4th edition update to the ICCR dataset on cervical cancer was undertaken to incorporate major changes based upon the updated International Federation of Obstetricians and Gynecologists (FIGO) staging for carcinoma of the cervix published in 2018 and the 5th Edition World Health Organization (WHO) Classification of Female Genital Tumors published in 2020 and other significant developments in pathologic aspects of cervical cancer. This updated dataset was developed by a panel of expert gynecological pathologists and an expert gynecological oncologist, with a period of open consultation. The revised dataset includes "core" and "noncore" elements to be reported; these are accompanied by detailed explanatory notes and references providing the rationale for the updates. Standardized reporting using datasets such as this helps facilitate consistency and accuracy, data collection across different sites and comparison of epidemiological and pathologic parameters for quality and research purposes.

Data Set for the Reporting of Endometrial Cancer: Recommendations From the International Collaboration on Cancer Reporting (ICCR).

Endometrial cancer is one of the most common cancers among women. The International Collaboration on Cancer Reporting (ICCR) developed a standardized endometrial cancer data set in 2011, which provided detailed recommendations for the reporting of resection specimens of these neoplasms. A new data set has been developed, which incorporates the updated 2020 World Health Organization Classification of Female Genital Tumors, the Cancer Genome Atlas (TCGA) molecular classification of endometrial cancers, and other major advances in endometrial cancer reporting, all of which necessitated a major revision of the data set. This updated data set has been produced by a panel of expert pathologists and an expert clinician and has been subject to international open consultation. The data set includes core elements which are unanimously agreed upon as essential for cancer diagnosis, clinical management, staging, or prognosis and noncore elements which are clinically important, but not essential. Explanatory notes are provided for each element. Adoption of this updated data set will result in improvements in endometrial cancer patient care.

Pathophysiological mechanisms of liver injury in COVID-19.

The recent outbreak of coronavirus disease 2019 (COVID-19), caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) has resulted in a world-wide pandemic. Disseminated lung injury with the development of acute respiratory distress syndrome (ARDS) is the main cause of mortality in COVID-19. Although liver failure does not seem to occur in the absence of pre-existing liver disease, hepatic involvement in COVID-19 may correlate with overall disease severity and serve as a prognostic factor for the development of ARDS. The spectrum of liver injury in COVID-19 may range from direct infection by SARS-CoV-2, indirect involvement by systemic inflammation, hypoxic changes, iatrogenic causes such as drugs and ventilation to exacerbation of underlying liver disease. This concise review discusses the potential pathophysiological mechanisms for SARS-CoV-2 hepatic tropism as well as acute and possibly long-term liver injury in COVID-19.

The Role of Predictive Biomarkers in Endocervical Adenocarcinoma: Recommendations From the International Society of Gynecological Pathologists.

To review the scientific evidence related to predictive biomarkers in cervical adenocarcinoma (ADC). The authors reviewed the literature regarding predictive biomarkers in cervical ADC. There were several limitations: (1) there is an overlap between predictive and prognostic biomarkers, as the vast majority of patients are treated with anticancer strategies; (2) in many studies and clinical trials, cervical ADC patients are included in a large series of patients predominantly composed of cervical squamous cell carcinomas; and (3) in most of the studies, and clinical trials, there is no distinction between human papillomavirus (HPV)-associated and HPV-independent cervical ADCs, or between various histologic subtypes. Results obtained from a small group of studies confirm that cervical ADCs exhibit distinct molecular features as compared with squamous carcinomas, and that there are different molecular features between different types of cervical ADCs. Promising areas of interest include ERBB2 (HER2) mutations and PD-L1 expression as predictive biomarkers for anti-HER2 treatment and immunotherapy, respectively. To date, no definitive data can be obtained from the literature regarding predictive biomarkers for cervical ADC. Clinical trials specifically designed for endocervical ADC patients are required to elucidate the predictive value of HER2 mutations and PD-L1 expression. The distinction between HPV-associated and HPV-independent cervical ADCs as well as early involvement of pathologists in the design of future clinical trials are needed to identify new predictive biomarkers in cervical ADC.

ESGO/ESTRO/ESP guidelines for the management of patients with endometrial carcinoma.

A European consensus conference on endometrial carcinoma was held in 2014 to produce multi-disciplinary evidence-based guidelines on selected questions. Given the large body of literature on the management of endometrial carcinoma published since 2014, the European Society of Gynaecological Oncology (ESGO), the European SocieTy for Radiotherapy and Oncology (ESTRO), and the European Society of Pathology (ESP) jointly decided to update these evidence-based guidelines and to cover new topics in order to improve the quality of care for women with endometrial carcinoma across Europe and worldwide.

Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome : Results From a Prospective, Single-Center, Clinicopathologic Case Series.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality. OBJECTIVE: To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes. DESIGN: Prospective autopsy study. SETTING: Single pathology department. PARTICIPANTS: 11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy). MEASUREMENTS: Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values. RESULTS: Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women). Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients. Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts. Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients. Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients. Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis. Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes. Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile. LIMITATION: The sample was small. CONCLUSION: COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency. Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation. Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory and imaging studies, and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism. PRIMARY FUNDING SOURCE: None.