Time-efficient sparse analysis of histopathological Whole Slide Images

International audienceHistopathological examination is a powerful method for the prognosis of critical diseases. But, despite significant advances in high-speed and high-resolution scanning devices or in virtual exploration capabilities, the clinical analysis of Whole Slide Images (WSI) largely remains the work of human experts. We propose an innovative platform in which multi-scale computer vision algorithms perform fast analysis of a histopathological WSI. It relies on specific high and generic low resolution image analysis algorithms embedded in a multi-scale framework to rapidly identify the high power fields of interest used by the pathologist to assess a global grading. GPU technologies as well speed up the global time-efficiency of the system. In a sense, sparse coding and sampling is the keystone of our approach. In terms of validation, we are designing a computer-aided breast biopsy analysis application based on histopathology images and designed in collaboration with a pathology department. The current ground truth slides correspond to about 36,000 high magnification (40X) high power fields. The time processing to achieve automatic WSI analysis is on a par with the pathologist's performance (about ten minutes a WSI), which constitutes by itself a major contribution of the proposed methodology

Retrospective study of infiltrating lobular carcinoma of breast with assessment of utility of p120 catenin /E-cadherin double immunostaining in the diagnosis

INTRODUCTION: It is important to differentiate between ductal and lobular carcinoma of breast, especially in the in-situ stage where it has therapeutic implications. E-cadherin helps to differentiate between these two types because neoplastic lobular proliferations show loss of E-cadherin. However, 15-19% cases of Infiltrating lobular carcinoma shows aberrant E-cadherin positivity. P120 is a relatively new antibody which has been found to be useful in this differential, cytoplasmic localisation of which indicates a lobular phenotype. AIMS AND OBJECTIVES: This study aims to study in detail the clinical and histomorphological features of invasive lobular carcinoma. We also compared the utility of p120/E-cadherin double immunostaining versus E-cadherin immunohistochemistry. MATERIALS AND METHODS: Cases diagnosed as lobular carcinoma (both in situ and invasive) (n=71) over the period from January 2012 to September 2016 were included in this study. Clinicopathologic parameters were assessed for each case. E-cadherin was available in 50 cases. Double immunolabelling by p120/E-cadherin was done on 37 cases and staining patterns, localisation, intensity, and proportion of positive cells were recorded. The utility of both the methods were compared. RESULTS: We have seen that 30% of lobular carcinoma cases showed aberrant immunostaining for E-Cadherin. All cases of ILC and LCIS showed cytoplasmic positivity for p120 on double immunostaining, indicating high sensitivity of the antibody. More importantly, p120 was positive in all cases with aberrant E-cadherin positivity: CONCLUSION: Double immunostaining helps to diagnose invasive and in situ lobular carcinoma more accurately than using E-cadherin alone. In case of core biopsies where tissue is very less double immunostaining is helpful

Avian Papilloma and Squamous Cell Carcinoma: a Histopathological, Immunohistochemical and Virological study

In this retrospective study, we describe the histopathological findings in seven papillomas and 45 squamous cell carcinomas (SCCs) from psittacine birds, raptors and domestic fowl. The age of affected birds ranged from 3 to 40 years, with median age significantly higher in psittacines (P = 0.014). The majority of tumours were located in the skin (24/52, 46.2%) or uropygial gland (10/52, 19.2%). Thirty of the SCCs (66.7%) were well differentiated and 15 (33.3%) were poorly-differentiated. SCCs exhibited a significantly higher degree of nuclear pleomorphism (P = 0.005) and a greater proportion were ulcerated (P = 0.001) compared with papillomas; however, there was no significant difference in mitotic count (MC) or inflammation score. The expression of cyclo-oxygenase (COX)-2 and E-cadherin was investigated by immunohistochemistry. The COX-2 total score (TS) was significantly higher in SCCs compared with papillomas (P = 0.002), but the difference between COX-2 TS of well- and poorly-differentiated SCCs was not significant. COX-2 labelling was predominantly cytoplasmic, but some tumours had concurrent membranous and/or perinuclear labelling. SCCs with membranous labelling had a significantly higher MC (P = 0.028). A significantly higher proportion of SCCs were negative for E-cadherin compared with papillomas (P = 0.042), but there was no significant difference between well- and poorly-differentiated SCCs. Fourteen papillomas and SCCs from psittacines were also tested by polymerase chain reaction for the presence of Psittacus erithacus papillomavirus 1 and Psittacid herpesvirus 1, but all samples tested negative. We demonstrate for the first time the expression of COX-2 and E-cadherin in avian tissues, and suggest that these markers may be useful in differentiating papillomas from SCCs, particularly when sample size is small

BRAF V600E Mutations Are Common in Pleomorphic Xanthoastrocytoma: Diagnostic and Therapeutic Implications

Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs

BRAF V600E Mutations Are Common in Pleomorphic Xanthoastrocytoma: Diagnostic and Therapeutic Implications

Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs

Expression and Clinicopathologic Correlation of Basal Cytokeratins in Breast Cancer

INTRODUCTION: Treatment for breast cancer is based on the expression of the immunomarkers such as ER, PR and HER2/neu. Cases which are negative to all the three immunomarkers, are called Triple Negative Breast Cancers (TNBC) and they have a poor prognosis. Recent studies have shown that some of the TNBCs express cytokeratins CK 5/6 (subcategorizing them as basal-like breast cancers) and these respond well to anthracycline-based chemotherapy. AIM AND OBJECTIVES: To study the expression of basal cytokeratins CK 5/6 in breast carcinomas reported in our centre and to correlate with histological type, grade, size, clinical features and ER, PR and HER2/neu status. METHODS: Tissues of 44 cases of breast carcinoma diagnosed between June 2009 and May 2014 were retrieved. Immunohistochemical staining for CK 5/6 was done and it was correlated with parameters such as histopathological type, grade, size, invasion and ER, PR and HER2/neu status. RESULTS: Eight of the breast carcinomas (18%) were categorized as Triple Negative Breast Cancers (TNBC) as they were negative for ER, PR and HER2/neu. Four of the TNBCs (50%), were positive for CK 5/6. Significant statistical correlation was observed between the size of the tumour and positive CK 5/6 expression. All CK 5/6 positive cases were of high grade. CONCLUSION: The routine use of CK 5/6 is recommended in all cases of TNBCs, as 50% of them are positive for these markers. Patients in this subcategory could benefit from anthracycline-based chemotherapy