Graft-vs-host disease (GVHD) is a potentially treatable cause of progressive neurologic decline after bone marrow transplantation (BMT). The authors present histologic confirmation of CNS granulomatous angiitis in a child with chronic GVHD after BMT. Since cranial MRI showed only nonspecific findings, CNS vasculitis associated with GVHD after BMT may be underdiagnosed.

Nineteen cases of mucinous carcinoma of the breast were studied. Twelve tumours were of the pure type, and seven were mixed. All had abundant neutral and acidic mucin, and stained strongly with CAM 5.2. Of the 12 pure mucinous tumours, six were devoid of argyrophilic granules and were S-100 negative, and only one was CEA positive. All six patients are alive with no evidence of recurrence (mean follow-up 42 months). The other six pure mucinous tumours were rich in argyrophilic granules. Five of these showed S-100 positivity and all were CEA positive. One patient developed local recurrence and one died of myocardial infarction with no evidence of tumour recurrence (mean follow-up 80 months). Of the seven mixed tumours, only one contained an occasional cell with argyrophilic granules and four had variable degrees of CEA positivity. Two patients died and one developed bony metastasis (mean follow-up 40 months). Our findings emphasise the microscopic and prognostic differences between the three subtypes of mucinous carcinoma of the breast, and support the concept of dividing pure mucinous tumours into two distinct subtypes. We suggest that the latter subtyping can be qualitatively made on the basis of the presence or absence of argyrophilic granules in the tumour cells.

not available at time of publication. Abstract not available at time of publication. Retrospective studies on male breast cancer (MBC) have suff ered from small numbers of cases available from any one centre; thus a signifi cant problem in eff ectively studying this disease is accruing suffi ciently large numbers to allow comparative analysis of biomarkers associated with response. Using a coordinated multicentre approach, we present the fi rst large-scale study to address the relevance of the expression of hormone receptors in MBC and female breast cancer (FBC) using immunohistochemistry combined with a novel bioinformatics approach. Following ethical approval, 523 archival blocks (260 MBCs and 263 matched FBCs) were obtained retrospectively. Tissue microarrays were constructed and sections stained for ERα, ERβ1, ERβ2, ERβ5, total PR, PRA, PRB and AR and typed using CK5/6, CK14, CK18 and CK19 by immunohistochemistry. Following scoring, a range of ordination techniques were conducted on the datasets including hierarchical clustering and principal component analysis (PCA) + ) were infrequent in both. Hierarchical clustering revealed common clusters between MBC and FBC including total PR-PRA-PRB and ERβ1/2 clusters. ERα occurred on distinct clusters between males and females. AR, ERβ1, ERβ2 and ERβ5 all existed on the same cluster but with a diff erent substructure, particularly around the positioning of AR. ERα associated with this cluster in the male but not the female group. PCA confi rmed that in both groups strong infl uences came from PR-PRA-PRB. In MBC strong infl uences additionally came from AR and ERβ1, ERβ2 and ERβ5, whereas in FBC strong infl uences came from ERα alone. Our data support the hypothesis that breast cancer is biologically diff erent in male and females, which could have implications for therapy. Introduction The response rarely sustains long among the responders for Herceptin (trastuzumab) monotherapy treatment. It is still poorly understood how Herceptin exerts its mechanism of action and how the acquired resistance to this drug occurs. Materials and methods We used a multidisciplinary approach including fl uorescence resonance energy transfer and biochemical methods to assess the eff ects of Herceptin on various signalling pathways and to determine the acquired resistance mechanisms of Herceptin in various HER2-positive breast cell lines and a BT474 xenograft model. Results We have shown that Herceptin does not decrease HER2 phosphorylation despite the eff ect on HER2 receptor downregulation. HER2 phosphorylation is maintained by the activation of EGFR, HER3 and HER4 via their dimerisation with HER2 in breast cancer cells. The activation of EGFR, HER3 and HER4 is induced by HER ligand release, including heregulin and betacellulin. The release of HER ligands is mediated by ADAM proteases including ADAM17/TACE. Furthermore, we demonstrated that the feedback loop involving HER ligands and ADAM proteases is activated due to a decrease in PKB phosphorylation induced by Herceptin t...