Observer agreement comparing the use of virtual slides with glass slides in the pathology review component of the POSH breast cancer cohort study.

AIMS: (1) To compare the use of scanned virtual slide images (virtual microscopy) with glass slides (conventional microscopy) in the assessment of morphological characteristics of breast cancers within the setting of the Prospective study of Outcomes in Sporadic versus Hereditary breast cancer (POSH), involving a cohort of women under 40 years of age, presenting with breast cancer. (2) To assess the acceptability to histopathologists of the use of virtual slide images. METHODS: 13 histopathologists from the UK and Australia participated in the POSH pathology review. The observers were asked to assess multiple morphological features such as tumour grade and type. Comparisons were made for a single observer using both virtual images and glass slides. Intra- and inter-observer variability was calculated using the κ statistic and a comparison was made between the use of each image modality. RESULTS: Diagnostic performance with virtual slides was comparable to conventional microscopic assessment, with the measurement of agreement best for vascular invasion, necrosis and the presence of a central scar (κ=0.37-0.78), and poor for more subjective parameters such as pleomorphism, stroma, the nature of the tumour border and the degree of lymphocytic infiltrate (κ=0.1). CONCLUSION: Virtual slides represent an acceptable methodology for central review of breast cancer histopathology and can circumvent the need for either travel to view material, or the potential problems of sending it by post.

Expression of calretinin by breast carcinoma and the potential for misdiagnosis of mesothelioma.

AIMS: Calretinin and cytokeratin (CK)5/6 are frequently used to differentiate between metastatic breast cancer and primary malignant mesothelioma in pleural biopsies, but both tumours may express these markers. This study was aimed at evaluating the frequency of calretinin expression in primary breast carcinomas, and assessing the characteristics of the calretinin-positive tumours. METHODS AND RESULTS: Fifty-three primary breast adenocarcinomas were analysed for immunohistochemical expression of calretinin. CK5/6 and epidermal growth factor receptor (EGFR) immunostaining were performed on the calretinin-positive subset. Tumours were classified as basal-like if they met standard morphological and immunohistochemical criteria. Fifteen per cent (8/53) of the breast tumours were positive for calretinin. Eighty-eight per cent (7/8) of the calretinin-positive tumours were grade 3, as compared with 20% (9/45) of the calretinin-negative tumours (P<0.001). Only 13% (1/8) of the calretinin-positive tumours were also oestrogen receptor (ER)-positive, as compared with 87% (39/45) of the calretinin-negative tumours (P<0.001). Eleven per cent (6/53) of the tumours were classified as basal-like. Of these, four were positive for calretinin and two were negative (P=0.003). CONCLUSIONS: Fifteen per cent of breast carcinomas stain with calretinin. These tumours are more likely to be high-grade, ER-negative, and display a basal-like phenotype. These tumours may be misdiagnosed as malignant mesothelioma when they metastasize to the pleura.

Problems in mesothelioma diagnosis.

Many centres are now seeing increasing numbers of patients with malignant mesothelioma. This presents pathologists involved in making the diagnosis with a number of problems, which can be divided into those encountered in making the distinction between mesothelioma and benign changes and those experienced in separating mesotheliomas from other types of epithelial and connective tissue tumours. Immunohistochemistry plays a major role in helping to make the diagnosis, but it should be interpreted with due regard to the clinical setting and radiological features, and with a knowledge of the wide morphological variations seen in mesothelioma. This review identifies some of these problems and addresses the uses and limitations of immunohistochemistry in different situations. It includes a discussion of some of the less common variants of mesothelioma and other pleural-based tumours that enter into the differential diagnosis.