Endometrial carcinoma, grossing and processing issues: recommendations of the International Society of Gynecologic Pathologists.

Endometrial cancer is the most common gynecologic neoplasm in developed countries; however, updated universal guidelines are currently not available to handle specimens obtained during the surgical treatment of patients affected by this disease. This article presents recommendations on how to gross and submit sections for microscopic examination of hysterectomy specimens and other tissues removed during the surgical management of endometrial cancer such as salpingo-oophorectomy, omentectomy, and lymph node dissection-including sentinel lymph nodes. In addition, the intraoperative assessment of some of these specimens is addressed. These recommendations are based on a review of the literature, grossing manuals from various institutions, and a collaborative effort by a subgroup of the Endometrial Cancer Task Force of the International Society of Gynecological Pathologists. The aim of these recommendations is to standardize the processing of endometrial cancer specimens which is vital for adequate pathological reporting and will ultimately improve our understanding of this disease

Pathologic Prognostic Factors in Endometrial Carcinoma (Other Than Tumor Type and Grade)

Although endometrial carcinoma (EC) is generally considered to have a good prognosis, over 20% of women with EC die of their disease, with a projected increase in both incidence and mortality over the next few decades. The aim of accurate prognostication is to ensure that patients receive optimal treatment and are neither overtreated nor undertreated, thereby improving patient outcomes overall. Patients with EC can be categorized into prognostic risk groups based on clinicopathologic findings. Other than tumor type and grade, groupings and recommended management algorithms may take into account age, body mass index, stage, and presence of lymphovascular space invasion. The molecular classification of EC that has emerged from the Cancer Genome Atlas (TCGA) study provides additional, potentially superior, prognostic information to traditional histologic typing and grading. This classifier does not, however, replace clinicopathologic risk assessment based on parameters other than histotype and grade. It is envisaged that molecular and clinicopathologic prognostic grouping systems will work better together than either alone. Thus, while tumor typing and grading may be superseded by a classification based on underlying genomic abnormalities, accurate assessment of other pathologic parameters will continue to be key to patient management. These include those factors related to staging, such as depth of myometrial invasion, cervical, vaginal, serosal surface, adnexal and parametrial invasion, and those independent of stage such as lymphovascular space invasion. Other prognostic parameters will also be discussed. These recommendations were developed from the International Society of Gynecological Pathologists Endometrial Carcinoma project

A pharmaco-economic analysis of second-line treatment with imatinib or sunitinib in patients with advanced gastrointestinal stromal tumours

Second-line treatments recommended by the National Cancer Center Network to manage advanced-stage gastrointestinal stromal tumours (GIST) were evaluated to determine the cost and cost-effectiveness of each intervention in the Mexican insurance system, the Instituto Mexicano del Seguro Social (IMSS). Treatments examined over a 5-year temporal horizon to estimate long-term costs included 800 mg day−1 of imatinib mesylate, 50 mg day−1 of sunitinib malate (administered in a 4 week on/2 week rest schedule), and palliative care. The mean cost (MC), cost-effectiveness, and benefit of each intervention were compared to determine the best GIST treatment from the institutional perspective of the IMSS. As sunitinib was not reimbursed at the time of the study, a Markov model and sensitivity analysis were conducted to predict the MC and likelihood of reimbursement. Patients taking 800 mg day−1 of imatinib had the highest MC (±s.d.) of treatment at $35 225.61 USD (±1253.65 USD); while sunitinib incurred a median MC of$17 805.87 USD (±694.83 USD); and palliative care had the least MC over treatment duration as the cost was $2071.86 USD (±472.88 USD). In comparison to palliative care, sunitinib is cost-effective for 38.9% of patients; however, sunitinib delivered the greatest survival benefit as 5.64 progression-free months (PFM) and 1.4 life-years gained (LYG) were obtained in the economic model. Conversely, patients on imatinib and palliative care saw a lower PFM of 5.28 months and 2.58 months and also fewer LYG (only 1.31 and 1.08 years, respectively). Therefore, economic modeling predicts that reimbursing sunitinib over high dose imatinib in the second-line GIST indication would deliver cost savings to the IMSS and greater survival benefits to patients

Primary fallopian tube carcinoma: review of MR imaging findings

Objectives To review the epidemiological and clinical features of primary fallopian tube carcinoma (PFTC), and to illustrate the spectrum of MRI findings, with pathological confirmation. Methods This article reviews the relevant literature on the epidemiological, clinical, and imaging features of primary fallopian tube carcinoma, with pathological confirmation, using illustrations from the authors' teaching files. Results Primary fallopian tube carcinoma came under focus over the last few years due to its possible role on the pathogenesis of high-grade serous epithelial ovarian and peritoneal cancers. Typical symptoms, together with the presence of some of the most characteristic MRI signs, such as a "sausage-shaped" pelvic mass, hydrosalpinx, and hydrometra, may signal the presence of primary fallopian cancer, and allow the radiologist to report it as a differential diagnosis. Conclusions Primary fallopian tube carcinoma has a constellation of clinical symptoms and magnetic resonance imaging features, which may be diagnostic. Although these findings are not present together in the majority of cases, radiologists who are aware of them may include the diagnosis of primary fallopian tube cancer in their report more frequently and with more confidence. Teaching Points PFTC may be more frequent than previously thought PFTC has specific clinical and MRI characteristics Knowledge of typical PFTC signs enables its inclusion in the differential diagnosis PFTC is currently staged under the 2013 FIGO system PFTC is staged collectively with ovarian and peritoneal neoplasmsinfo:eu-repo/remantics/publishedVersio

Update for the practicing pathologist: The International Consultation On Urologic Disease-European association of urology consultation on bladder cancer

The International Consultations on Urological Diseases are international consensus meetings, supported by the World Health Organization and the Union Internationale Contre le Cancer, which have occurred since 1981. Each consultation has the goal of convening experts to review data and provide evidence-based recommendations to improve practice. In 2012, the selected subject was bladder cancer, a disease which remains a major public health problem with little improvement in many years. The proceedings of the 2nd International Consultation on Bladder Cancer, which included a 'Pathology of Bladder Cancer Work Group,' have recently been published; herein, we provide a summary of developments and consensus relevant to the practicing pathologist. Although the published proceedings have tackled a comprehensive set of issues regarding the pathology of bladder cancer, this update summarizes the recommendations regarding selected issues for the practicing pathologist. These include guidelines for classification and grading of urothelial neoplasia, with particular emphasis on the approach to inverted lesions, the handling of incipient papillary lesions frequently seen during surveillance of bladder cancer patients, descriptions of newer variants, and terminology for urine cytology reporting

Review of juxtaglomerular cell tumor with focus on pathobiological aspect

Juxtaglomerular cell tumor (JGCT) generally affects adolescents and young adults. The patients experience symptoms related to hypertension and hypokalemia due to renin-secretion by the tumor. Grossly, the tumor is well circumscribed with fibrous capsule and the cut surface shows yellow or gray-tan color with frequent hemorrhage. Histologically, the tumor is composed of monotonous polygonal cells with entrapped normal tubules. Immunohistochemically, tumor cells exhibit a positive reactivity for renin, vimentin and CD34. Ultrastructurally, neoplastic cells contain rhomboid-shaped renin protogranules. Genetically, losses of chromosomes 9 and 11 were frequently observed. Clinically, the majority of tumors showed a benign course, but rare tumors with vascular invasion or metastasis were reported. JGCT is a curable cause of hypertensive disease if it is discovered early and surgically removed, but may cause a fatal outcome usually by a cerebrovascular attack or may cause fetal demise in pregnancy. Additionally, pathologists and urologists need to recognize that this neoplasm in most cases pursues a benign course, but aggressive forms may develop in some cases

HIF-1 activation induces doxorubicin resistance in MCF7 3-D spheroids via P-glycoprotein expression: a potential model of the chemo-resistance of invasive micropapillary carcinoma of the breast

BACKGROUND: Invasive micropapillary carcinoma (IMPC) of the breast is a distinct and aggressive variant of luminal type B breast cancer that does not respond to neoadjuvant chemotherapy. It is characterized by small pseudopapillary clusters of cancer cells with inverted cell polarity. To investigate whether hypoxia-inducible factor-1 (HIF-1) activation may be related to the drug resistance described in this tumor, we used MCF7 cancer cells cultured as 3-D spheroids, which morphologically simulate IMPC cell clusters. METHODS: HIF-1 activation was measured by EMSA and ELISA in MCF7 3-D spheroids and MCF7 monolayers. Binding of HIF-1α to MDR-1 gene promoter and modulation of P-glycoprotein (Pgp) expression was evaluated by ChIP assay and FACS analysis, respectively. Intracellular doxorubicin retention was measured by spectrofluorimetric assay and drug cytotoxicity by annexin V-FITC measurement and caspase activity assay. RESULTS: In MCF7 3-D spheroids HIF-1 was activated and recruited to participate to the transcriptional activity of MDR-1 gene, coding for Pgp. In addition, Pgp expression on the surface of cells obtained from 3-D spheroids was increased. MCF7 3-D spheroids accumulate less doxorubicin and are less sensitive to its cytotoxic effects than MCF7 cells cultured as monolayer. Finally, HIF-1α inhibition either by incubating cells with 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (a widely used HIF-1α inhibitor) or by transfecting cells with specific siRNA for HIF-1α significantly decreased the expression of Pgp on the surface of cells and increased the intracellular doxorubicin accumulation in MCF7 3-D spheroids. CONCLUSIONS: MCF7 breast cancer cells cultured as 3-D spheroids are resistant to doxorubicin and this resistance is associated with an increased Pgp expression in the plasma membrane via activation of HIF-1. The same mechanism may be suggested for IMPC drug resistance

Pitfalls in machine learning-based assessment of tumor-infiltrating lymphocytes in breast cancer: a report of the international immuno-oncology biomarker working group

The clinical significance of the tumor-immune interaction in breast cancer is now established, and tumor-infiltrating lymphocytes (TILs) have emerged as predictive and prognostic biomarkers for patients with triple-negative (estrogen receptor, progesterone receptor, and HER2-negative) breast cancer and HER2-positive breast cancer. How computational assessments of TILs might complement manual TIL assessment in trial and daily practices is currently debated. Recent efforts to use machine learning (ML) to automatically evaluate TILs have shown promising results. We review state-of-the-art approaches and identify pitfalls and challenges of automated TIL evaluation by studying the root cause of ML discordances in comparison to manual TIL quantification. We categorize our findings into four main topics: (1) technical slide issues, (2) ML and image analysis aspects, (3) data challenges, and (4) validation issues. The main reason for discordant assessments is the inclusion of false-positive areas or cells identified by performance on certain tissue patterns or design choices in the computational implementation. To aid the adoption of ML for TIL assessment, we provide an in-depth discussion of ML and image analysis, including validation issues that need to be considered before reliable computational reporting of TILs can be incorporated into the trial and routine clinical management of patients with triple-negative breast cancer. © 2023 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland