Primary cutaneous rhabdomyosarcoma with EWSR1/FUS::TFCP2 fusion: four new cases with distinctive morphology, immunophenotypic, and genetic profile.

EWSR1/FUS::TFCP2-rearranged rhabdomyosarcoma (RMS) is a rare tumor with an aggressive clinical course, a predilection for craniofacial bones, spindled and/or epithelioid histomorphology, and positive immunohistochemistry (IHC) for epithelial and myogenic markers, along with variable ALK expression. Herein, we present four additional cases of primary cutaneous TFCP2-rearranged RMS. Notably, one tumor (case 1) displayed a varied pathological spectrum, initially presenting as a low-grade spindle cell neoplasm, but progressed into a high-grade spindle/epithelioid tumor.

Oral administration of bromelain and acetylcysteine in pseudomyxoma peritonei (PMP) caused by low-grade appendiceal mucinous neoplasm (LAMN): a case report.

Background: Pseudomyxoma Peritonei (PMP) is a severe neoplastic clinical syndrome characterised by secretion of mucin from tumors often originating in the appendix. The standard treatment includes cytoreductive surgery (CRS) combined with heated intraperitoneal chemotherapy (HIPEC). A new perspective in PMP treatment aims at the mucins themselves as a therapeutic target.

[Automation and the use of robots in the pathology laboratory : A journey through time and a consideration of efficiency].

In the past 20 years, numerous technical innovations were introduced to the histopathology laboratory, providing tools for improved standardization and occupational safety. Digital tracking serves as a backbone accompanying the workflow from the labeling of cassettes and slides to the final steps of preparing whole slide images and archiving blocks and sections. Multifunctional devices eliminated time consuming manual work prone to mistakes and loss of materials.

[Automation and application of robotics in the pathology laboratory].

Over the last 20 years, numerous technical innovations have been introduced to the histopathology laboratory, providing tools for improved standardization and occupational safety. Digital tracking serves as a backbone accompanying the workflow from labeling cassettes and slides to the final steps of preparation of whole slide images and archiving blocks and sections. Multifunctional devices eliminated time consuming manual work prone to mistakes and loss of materials.

Common variants in breast cancer risk loci predispose to distinct tumor subtypes.

Background: Genome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.

Methods: Among 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.

Germline variants and breast cancer survival in patients with distant metastases at primary breast cancer diagnosis.

Breast cancer metastasis accounts for most of the deaths from breast cancer. Identification of germline variants associated with survival in aggressive types of breast cancer may inform understanding of breast cancer progression and assist treatment. In this analysis, we studied the associations between germline variants and breast cancer survival for patients with distant metastases at primary breast cancer diagnosis.

Double adenomas of the pituitary reveal distinct lineage markers, copy number alterations, and epigenetic profiles.

Purpose: Pituitary adenoma (PA) constitutes the third most common intracranial neoplasm. The mostly benign endocrine lesions express no hormone (null cell PA) or the pituitary hormone(s) of the cell lineage of origin. In 0.

Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.

A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), and 42 (signal 3) credible causal variants at these loci. We used publicly available in silico DNase I and ChIP-seq data with in vitro reporter gene and CRISPR assays to annotate signals 2 and 3.

Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.

Background: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

Methods: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes.

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.

Consumer behaviour survey for assessing exposure from consumer products: a feasibility study.

Evaluating chemical exposures from consumer products is an essential part of chemical safety assessments under REACH and may also be important to demonstrate compliance with consumer product legislation. Modelling of consumer exposure needs input information on the substance (e.g.

Molecularly defined diffuse leptomeningeal glioneuronal tumor (DLGNT) comprises two subgroups with distinct clinical and genetic features.

Diffuse leptomeningeal glioneuronal tumors (DLGNT) represent rare CNS neoplasms which have been included in the 2016 update of the WHO classification. The wide spectrum of histopathological and radiological features can make this enigmatic tumor entity difficult to diagnose. In recent years, large-scale genomic and epigenomic analyses have afforded insight into key genetic alterations occurring in multiple types of brain tumors and provide unbiased, complementary tools to improve diagnostic accuracy.

Histopathological changes resulting from selective internal radiotherapy (SIRT).

Background: Selective internal radiotherapy (SIRT) has emerged as an effective therapy for patients with liver malignancies. Here, we report our analysis of histopathological changes in tumors and healthy liver tissue after SIRT and liver resection. Our main intent was to determine if specific histopathological changes occur in tumor and normal liver tissues.

Body mass index and breast cancer survival: a Mendelian randomization analysis.

Background: There is increasing evidence that elevated body mass index (BMI) is associated with reduced survival for women with breast cancer. However, the underlying reasons remain unclear. We conducted a Mendelian randomization analysis to investigate a possible causal role of BMI in survival from breast cancer.

Association analysis identifies 65 new breast cancer risk loci.

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry.

PALB2, CHEK2 and ATM rare variants and cancer risk: data from COGS.

Background: The rarity of mutations in PALB2, CHEK2 and ATM make it difficult to estimate precisely associated cancer risks. Population-based family studies have provided evidence that at least some of these mutations are associated with breast cancer risk as high as those associated with rare BRCA2 mutations. We aimed to estimate the relative risks associated with specific rare variants in PALB2, CHEK2 and ATM via a multicentre case-control study.

Genes associated with histopathologic features of triple negative breast tumors predict molecular subtypes.

Distinct subtypes of triple negative (TN) breast cancer have been identified by tumor expression profiling. However, little is known about the relationship between histopathologic features of TN tumors, which reflect aspects of both tumor behavior and tumor microenvironment, and molecular TN subtypes. The histopathologic features of TN tumors were assessed by central review and 593 TN tumors were subjected to whole genome expression profiling using the Illumina Whole Genome DASL array.

Multi-center evaluation of the novel fully-automated PCR-based Idylla™ BRAF Mutation Test on formalin-fixed paraffin-embedded tissue of malignant melanoma.

The advent of BRAF-targeted therapies led to increased survival in patients with metastatic melanomas harboring a BRAF V600 mutation (implicated in 46-48% of malignant melanomas). The Idylla(™) System (Idylla(™)), i.e.

Liver resection after selective internal radiotherapy (SIRT): Proof of concept, initial survival, and safety.

Background And Objectives: Extent of liver resections are restricted by the volume of the future liver remnant. Different strategies have been developed to increase the frequency of curative resections. Selective internal radiation therapy (SIRT) has emerged as an effective therapy for patients with primary non-resectable malignancies of the liver.

Clear cell papillary renal cell carcinoma and renal angiomyoadenomatous tumor: two variants of a morphologic, immunohistochemical, and genetic distinct entity of renal cell carcinoma.

Clear cell papillary renal cell carcinoma (ccpRCC) and renal angiomyoadenomatous tumor (RAT) share morphologic similarities with clear cell (ccRCC) and papillary RCC (pRCC). It is a matter of controversy whether their morphologic, immunophenotypic, and molecular features allow the definition of a separate renal carcinoma entity. The aim of our project was to investigate specific renal immunohistochemical biomarkers involved in the hypoxia-inducible factor pathway and mutations in the VHL gene to clarify the relationship between ccpRCC and RAT.

Common germline polymorphisms associated with breast cancer-specific survival.

Introduction: Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium.