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High-quality histopathology is essential for the success of clinical trials. Histopathologists have a detailed understanding of tumour biology and mechanisms of disease, as well as practical knowledge of optimal tissue handling and logistical service requirements for study delivery, such as biomarker evaluation, tissue acquisition and turnaround times. As such, histopathologist input is essential throughout every stage of research and clinical trials, from concept development and study design to trial delivery, analysis and dissemination of results. Patient recruitment to trials takes place among all healthcare settings, meaning that histopathologists make an invaluable contribution to clinical trials as part of their routine day-to-day work that often goes unrecognised. More complex evaluation of surgical specimens in the neoadjuvant setting and ever-expanding minimum data sets add to the workload of every histopathologist, not just academic pathologists in tertiary centres. This is occurring against a backdrop of increasing workload pressures and a worldwide shortage of histopathologists and biomedical scientists. Providing essential histopathology support for trials at grassroots level requires funding for adequate resources including histopathologist time, education and training, biomedical scientist and administrative support and greater recognition of the contribution made by histopathology. This paper will discuss the many ways in which histopathologists are involved in clinical trials and the challenges faced in meeting the additional demands posed by trial participation and potential ways to address this, with a special emphasis on the UK model and the Cellular-Molecular Pathology Initiative (CM-Path).

© 2016 John Wiley & Sons Ltd Aims: PPARα agonists are in current clinical use as hypolipidaemic agents and show significant antineoplastic effects in human glioblastoma models. To date however, the expression of PPARα in large-scale glioblastoma datasets has not been examined. We aimed to investigate the expression of the transcription factor PPARα in primary glioblastoma, the relationship between PPARα expression and patients’ clinicopathological features and other molecular markers associated with gliomagenesis. Methods and results: With protein immunoblotting techniques and reverse transcription quantitative real-time PCR, PPARα was found to be significantly overexpressed in glioblastoma compared with control brain tissue (P = 0.032 and P = 0.005). PPARA gene expression was found to be enriched in the classical glioblastoma subtype within The Cancer Genome Atlas (TCGA) dataset. Although not associated with overall survival when assessed by immunohistochemistry, cross-validation with the TCGA dataset and multivariate analyses identified PPARA gene expression as an independent prognostic marker for overall survival (P = 0.042). Finally, hierarchical clustering revealed novel, significant associations between high PPARA expression and a putative set of glioblastoma molecular mediators including EMX2, AQP4, and NTRK2. Conclusions: PPARα is overexpressed in primary glioblastoma and high PPARA expression functions as an independent prognostic marker in the glioblastoma TCGA dataset. Further studies are required to explore genetic associations with high PPARA expression and to analyse the predictive role of PPARα expression in glioblastoma models in response to PPARα agonists.

Sarcomatoid/metaplastic carcinoma of the breast: a clinicopathological study of 12 cases Aims: To analyse the clinical and pathological features with long-term follow-up of a series of 12 cases of sarcomatoid carcinoma of the breast. Methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacent in-situ carcinoma/atypical epithelial proliferation. The mean age of the patients was 61 years with a median of 64 and range 46–82 years. The mean size of the tumour was 52 mm (range 22–100 mm). None of the patients had distant metastasis at presentation and only one case had local lymph node metastasis which had a carcinomatous appearance. Five women were still alive after a minimum 12-year follow-up period. Four patients died of their disease (three with lung metastasis only and one with lung and bone metastases), one died of carcinoma of the cervix and two patients were lost to follow-up. Pathologically, four cases (33.3%) had no or almost undetectable epithelial structures by light microscopy, i.e. ‘monophasic sarcomatoid carcinoma’. The remaining cases revealed varying proportions of both epithelial and mesenchymal elements, i.e. ‘biphasic sarcomatoid carcinoma’. Of the epithelial component, six (50%) tumours had predominantly carcinoma of no special type, one lobular and one tubular carcinoma. The mesenchymal component was fibromatosis/nodular fasciitis-like, malignant fibrous histiocytoma-like (MFH), osteosarcoma-like and fibrosarcoma-like in five (42%), four (33%), two (17%) and one (8%) tumours, respectively. In 3/4 monophasic tumours, the mesenchymal component was of a low-grade fibromatosis/nodular fasciitis type. In 6/12 (50%) of the cases there was associated in-situ atypical epithelial proliferation (five ductal carcinoma in situ (DCIS) and one atypical ductal hyperplasia). Conclusions: From this small series it appears that sarcomatoid carcinoma is an uncommon tumour, which is large in size and tends to lack local or distant metastasis at presentation. Pathologists should be alert to the presence of the bland monophasic sarcomatoid carcinoma which has a pure mesenchymal appearance on light microscopy, but epithelial components demonstrated by cytokeratin immunohistochemistry. These showed metastases on long-term follow-up, similar to other histological patterns of sarcomatoid carcinoma.

To analyse the clinical and pathological features with long-term follow-up of a series of 12 cases of sarcomatoid carcinoma of the breast. methods and results: The cases were selected from the surgical files of the Department of Pathology, University of Edinburgh, between 1977 and 1988. The following clinical parameters were recorded: the age of the patients, size of tumour, presence or absence of lymph node or distant metastases, and patient survival. Pathological assessment included: the type of epithelial and mesenchymal components, the proportion of monophasic to biphasic tumours and the presence of adjacent in-situ carcinoma/atypical epithelial proliferation. The mean age of the patients was 61 years with a median of 64 and range 46-82 years. The mean size of the tumour was 52 mm (range 22-100 mm). None of the patients had distant metastasis at presentation and only one case had local lymph node metastasis which had a carcinomatous appearance. Five women were still alive after a minimum 12-year follow-up period. Four patients died of their disease (three with lung metastasis only and one with lung and bone metastases), one died of carcinoma of the cervix and two patients were lost to follow-up. Pathologically, four cases (33.3%) had no or almost undetectable epithelial structures by light microscopy, i.e. "monophasic sarcomatoid carcinoma". The remaining cases revealed varying proportions of both epithelial and mesenchymal elements, i.e. "biphasic sarcomatoid carcinoma". Of the epithelial component, six (50%) tumours had predominantly carcinoma of no special type, one lobular and one tubular carcinoma. The mesenchymal component was fibromatosis/nodular fasciitis-like, malignant fibrous histiocytoma-like (MFH), osteosarcoma-like and fibrosarcoma-like in five (42%), four (33%), two (17%) and one (8%) tumours, respectively. In 3/4 monophasic tumours, the mesenchymal component was of a low-grade fibromatosis/nodular fasciitis type. In 6/12 (50%) of the cases there was associated in-situ atypical epithelial proliferation (five ductal carcinoma in situ (DCIS) and one atypical ductal hyperplasia).From this small series it appears that sarcomatoid carcinoma is an uncommon tumour, which is large in size and tends to lack local or distant metastasis at presentation. Pathologists should be alert to the presence of the bland monophasic sarcomatoid carcinoma which has a pure mesenchymal appearance on light microscopy, but epithelial components demonstrated by cytokeratin immunohistochemistry. These showed metastases on long-term follow-up, similar to other histological patterns of sarcomatoid carcinoma.