CM-Path Molecular Diagnostics Forum-consensus statement on the development and implementation of molecular diagnostic tests in the United Kingdom.

Background: Pathology has evolved from a purely morphological description of cellular alterations in disease to our current ability to interrogate tissues with multiple 'omics' technologies. By utilising these techniques and others, 'molecular diagnostics' acts as the cornerstone of precision/personalised medicine by attempting to match the underlying disease mechanisms to the most appropriate targeted therapy.

Methods: Despite the promises of molecular diagnostics, significant barriers have impeded its widespread clinical adoption.

Targeted next generation sequencing of pancreatic solid pseudopapillary neoplasms show mutations in Wnt signaling pathway genes.

Solid pseudopapillary neoplasms of the pancreas are rare neoplasms that have been shown to harbor recurrent somatic pathogenic variants in the beta-catenin gene, CTNNB1. Here, we used targeted next generation sequencing to analyze these tumors for other associated mutations. Six cases of solid pseudopapillary neoplasms were studied.

Mesonephric adenocarcinoma of the vagina masquerading as a suburethral cyst.

Mesonephric adenocarcinoma (MA) of the vagina is an extremely rare tumour of the female genital tract. There are currently 22 reported cases in the published literature. Consequently, its pathophysiology and disease progression remain poorly understood.

Outcome of Appendicectomies at Surgery for Mucinous Ovarian Neoplasms: Report From A UK Center and Review of Literature.

Objective: This study aimed to determine the frequency of malignant pathology in a macroscopically normal appendix during surgery for a borderline or malignant mucinous ovarian tumor (MOT).

Methods: Women with borderline and malignant MOT were identified from the pathology database from 2000 to 2014. Women who had a benign MOT and had an appendicectomy were excluded from the study.

Endometriosis of Extra-Abdominal Soft Tissues: A Tertiary Center Experience.

While endometriosis, defined as the presence of endometrial tissue in extrauterine sites, is most frequently encountered within the peritoneal cavity, a small but significant proportion of cases occur at extra-abdominal soft tissue sites, particularly in relation to previous abdominal surgery. We reviewed the cases of endometriosis of soft tissue sites seen at a tertiary soft tissue center. All cases of extra-abdominal soft tissue endometriosis diagnosed at this institution over a 13-year period were reviewed, and clinical and pathologic findings were recorded.

Gross examination and reporting of soft tissue tumours: evaluation of compliance with the UK Royal College of Pathologists soft tissue sarcoma dataset.

Aims: Soft tissue tumours are a heterogeneous group of neoplasms that can arise at almost every anatomical site. As they often show similar clinical and radiological findings, histology is the definitive diagnostic method and it is crucial that the surgical pathology report contains accurate, useful information for management and prognostication. The soft tissue sarcoma minimum dataset produced by the Royal College of Pathologists in the UK outlines a structure for handling and reporting soft tissue tumours, including the core data required, and aiding pathologists in forming a consistent reporting approach.

The comparative utility of fluorescence in situ hybridization and reverse transcription-polymerase chain reaction in the diagnosis of alveolar rhabdomyosarcoma.

Fluorescence in situ hybridization (FISH) for FOXO1 gene rearrangement and reverse transcription-polymerase chain reaction (PCR) for PAX3/7-FOXO1 fusion transcripts have become routine ancillary tools for the diagnosis of alveolar rhabdomyosarcomas (ARMS). Here we summarize our experience of these adjunct diagnostic modalities at a tertiary center, presenting the largest comparative series of FISH and PCR for suspected or possible ARMS to date. All suspected or possible ARMS tested by FISH or PCR for FOXO1 rearrangement or PAX3/7-FOXO1 fusion transcripts over a 7-year period were included.

Fluorescence In Situ Hybridization for MDM2 Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center.

Background. The assessment of MDM2 gene amplification by fluorescence in situ hybridization (FISH) has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL) in specialist sarcoma units. We describe our experience of its utility at our tertiary institute.

A Unique Case of Extraovarian Sex-Cord Stromal Fibrosarcoma, With Subsequent Relapse of Differentiated Sex-Cord Tumor.

Primary fibrosarcoma arising from ovarian sex-cord stroma is a very rare neoplasm, with only a few reports in the literature. These tumors have been reported to express inhibin which allows their distinction from fibrosarcomas of soft tissue. Here, we report a case of a fibrosarcoma arising in the broad ligament.

Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity.

Clear cell sarcoma-like tumor of the gastrointestinal tract (CCSLGT) is a rare malignant neoplasm that occurs in the wall of the small bowel, stomach, or large bowel, predominantly in young adults. It is an aggressive neoplasm that frequently presents with metastatic disease and has a high mortality rate. Histologically, it is usually composed of medium-sized primitive ovoid or epithelioid cells with pale or clear cytoplasm that are arranged in sheets or in papillary or alveolar architectures.

Expression profile of mucins (MUC1, MUC2, MUC5AC, and MUC6) in ovarian mucinous tumours: changes in expression from benign to malignant tumours.

Aims: Mucins (MUCs) constitute a family of glycoproteins expressed by epithelial cells. They show specific tissue-type expression, and are useful for differentiating between different cancers. Studies have shown changes in MUC expression with tumour progression in a variety of cancers.

Histopathological diagnostic discrepancies in soft tissue tumours referred to a specialist centre: reassessment in the era of ancillary molecular diagnosis.

Introduction. Soft tissue tumour pathology is a highly specialised area of surgical pathology, but soft tissue neoplasms can occur at virtually all sites and are therefore encountered by a wide population of surgical pathologists. Potential sarcomas require referral to specialist centres for review by pathologists who see a large number of soft tissue lesions and where appropriate ancillary investigations can be performed.

Expression profiling and significance of VEGF-A, VEGFR2, VEGFR3 and related proteins in endometrial carcinoma.

Background: Angiogenesis plays a key role in the progression of various tumors, including endometrial carcinomas. Several cytokines and their associated receptors are shown to be involved, particularly VEGF-A with VEGFR1, -2 and -3.

Methods: The expressions of VEGF-A, VEGFR2 and VEGFR3 were studied in by immunohistochemistry in 76 endometrial carcinoma specimens.

"Dominant" myelolipoma encasing adrenal cortical carcinoma: an unusual variation of myelolipoma occurring as a synchronous and predominant neoplasm.

Although myelolipomas of the adrenal glands are detected with increasing frequency with advances in imaging, the occurrence of myelolipoma with adrenal cortical carcinoma remains very rare. We present a case of combined myelolipoma with adrenal cortical carcinoma in a 47-year-old man. In previously reported cases of adrenal cortical carcinoma and myelolipoma, the latter occurred as incidental foci within or peripheral to the carcinoma, perhaps representing "myelolipomatous metaplasia" rather than true neoplasia.

Expression profile of mucins in ovarian mucinous tumors: distinguishing primary ovarian from metastatic tumors.

Ovarian mucinous tumors (OMTs) of the intestinal type share morphologic features with primary tumors of other sites, and it can often be difficult to distinguish primary ovarian from metastatic mucinous tumors. MUC1, MUC2, MUC5AC, and MUC6 expressions were studied by immunohistochemistry in 36 OMTs of intestinal type (17 malignant, 19 borderline), 18 pancreatic, 12 biliary, 15 esophageal, 9 gastric, and 7 colorectal/appendiceal adenocarcinomas. All samples were from primary sites, except for colorectal tumors which were from ovarian metastases.

Angiosarcoma of the Breast with Solitary Metastasis to the Ovary during Pregnancy: An Uncommon Pattern of Metastatic Disease.

Primary de novo angiosarcoma of the breast is an uncommon, aggressive neoplasm. Here, we present a case of a young woman who initially developed primary angiosarcoma of the breast, and subsequently angiosarcoma of the ovary during pregnancy two years later. Only two confirmed primary angiosarcomas of the breast metastasizing specifically to the ovary have been described in the literature.

Combined mesothelial cyst and lymphangioma of the small bowel: a distinct hybrid intra-abdominal cyst.

Intra-abdominal cysts have a variety of origins, of which lymphatic and mesothelial types are the most commonly encountered. Here we describe a combined mesothelial cyst and lymphangioma arising within the small bowel subserosa of an 80-year-old woman. This was found incidentally at laparotomy performed for an unrelated condition.

Expression Profiling of Proliferation and Apoptotic Markers along the Adenoma-Carcinoma Sequence in Familial Adenomatous Polyposis Patients.

Introduction. Familial adenomatous polyposis (FAP) patients have a germline mutation in the adenomatous polyposis coli (APC) gene. The APC protein interacts with beta-catenin, resulting in the activation of the Wnt signalling pathway.

Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo.

Nicastrin (NCT) is a crucial component of the γ-secretase (GS) enzyme, which prompted investigations into its biological role in cancer. We have previously shown that nicastrin is overexpressed in breast cancer (BC), conferring worse overall survival in invasive, ERα negative patients. Here, we used 2D and 3D Matrigel, anchorage-independent growth conditions and a breast cancer xenograft mouse model to assess the impact of nicastrin on breast cancer stem cell (BCSC) propagation and invasion in vitro and tumor growth in vivo.

Expression of EGFR, HER2, phosphorylated ERK and phosphorylated MEK in colonic neoplasms of familial adenomatous polyposis patients.

Purpose: The expression of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2) is associated with poor prognosis in sporadic colorectal carcinoma (CRC). EGFR inhibitors are approved for the treatment of refractory CRC. The aim of this study was to investigate the expression of EGFR and HER2 and downstream extracellular signal regulated kinase (ERK) and mitogen activated protein kinase (MAPK) in non-neoplastic colonic mucosa, adenomas and carcinomas from familial adenomatous polyposis coli (FAP) patients, exploring the expression along the adenoma-carcinoma sequence.

Pancreatobiliary and pancreatoduodenal fistulae in intraductal papillary mucinous neoplasm of the pancreas: report of a case.

Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas present more commonly in the elderly. This report describes a case of IPMN in a 36-year-old man who presented with obstructive jaundice and weight loss. The initial investigation by computed tomography scan revealed a cystic lesion in the head of pancreas fistulating into the duodenum and the common bile duct (CBD).

Biological and clinical implications of nicastrin expression in invasive breast cancer.

Nicastrin is an essential component of the gamma secretase (GS) enzyme complex, required for its synthesis and recognition of substrates for proteolytic cleavage. The purpose of this study was to investigate whether nicastrin has prognostic value or potential as a therapeutic target in breast cancer (BC). The suitability of nicastrin as a target in BC was assessed using BC tissue microarrays (TMAs) (n = 1050), and its biological role in vitro was evaluated in BC cell lines following gene silencing.

The expression of IL-8 and IL-8 receptors in pancreatic adenocarcinomas and pancreatic neuroendocrine tumours.

Background: Inflammatory mediators influence tumour progression. IL-8 has been shown to have pro-angiogenic, mitogenic and motogenic effects and several studies have demonstrated the expression of IL-8 by various human pancreatic cancer cell lines.

Methods: The expression of IL-8 and IL-8 receptors was studied in 52 pancreatic adenocarcinomas and 52 pancreatic neuroendocrine tumours using immunohistochemistry.