In light of lack of efficacy associated with current cancer vaccines, we aimed to develop a novel vaccine platform called DepoVax as a therapeutic vaccine for breast/ovarian cancer. This study was designed to examine the efficacy of this novel platform over conventional emulsion vaccine using human class I MHC transgenic mice. We have developed a water-free depot vaccine formulation (DPX-0907) with high immune activating potential. Naturally processed peptides bound to HLA-A2 molecules isolated from independent breast and ovarian tumor cell lines, but not normal cells, were isolated and used as antigens in DPX-0907 along with a proprietary adjuvant and a T helper peptide epitope. Efficacy of vaccine was tested in immunized HLA-A*0201/H2Dd transgenic mice by measuring the frequency of IFN-gamma secreting cells in the draining lymph nodes, and regulatory T-cell frequencies in the spleen. Compared with a water-in-oil emulsion vaccine, DPX-0907 enhanced IFN-gamma+CD8+ T cells in vaccine site-draining lymph nodes, as seen by immunofluorescence staining and increased the frequency of IFN-gamma+ lymph node cells as seen by enzyme-linked immunosorbent spot assay. Notably, while conventional vaccine formulations elicited elevated levels of splenic Foxp3+CD4+ and IL10-secreting T cells, this was not the case for DPX-0907-based vaccines, with treated animals exhibiting normal levels of regulatory T cells. These data support the unique capabilities of a vaccine formulation containing novel tumor peptides and DPX-0907 to elicit type-1 dominated, specific immunity that may represent a potent clinical therapeutic modality for patients with breast or ovarian carcinoma.

In pursuit of physician-specific performance data in cytology, we have been calculating the ASCUS/SIL (atypical squamous cells of undetermined significance/squamous intraepithelial lesion) ratio of cytopathologists (CPs) and providing confidential feedback every 6 months. At the same time, thin-layer technology was introduced as an alternative to conventional smears. Thus we analyzed factors that may influence the ASCUS/SIL ratio, particularly the effect of periodic feedback on outliers (defined by a professional benchmark). For 3 years, the mean ASCUS/SIL ratio for all CPs decreased significantly from 2.92 to 1.87. There was great variability in the mean ASCUS/SIL ratio among 12 CPs (range, 1.11-5.89). Of the 6 CPs who worked continuously during this time, 2 showed a statistically significant decrease in their ASCUS/SIL ratio, including the CP with the highest ratio; 1 showed a significant increase. The mean ASCUS/SIL ratio did not correlate well with years of CP experience or with individual annual case volume. The ASCUS/SIL ratio of some CPs can decrease significantly over time. Whether it was due to feedback or the introduction of thin-layer preparations could not be determined.

Conclusions: FNA was found to be significantly superior to NCB in obtaining material for FCI. However, NCB resulted in fewer indeterminate final diagnoses due to benefit of histologic correlation. In our opinion, NCB for histology combined with dedicated FNA material for FCI may yield the best results for a minimally invasive approach to the diagnosis of hematologic neoplasms. V C 2014 International Clinical Cytometry Society

Erdheim-Chester disease (ECD) is a rare xanthomatous non-Langerhans cell histiocytosis which involves the marrow space of the long bones. Extraosseous sites most commonly affected include the eyes, lungs, pituitary glands, and kidneys. We report the case of a 49-year-old woman who presented with palpable breast nodules, followed by progressive soft tissue and subcutaneous disease, and involvement of the long bones, dysarthria, and dysphagia. The histopathologic features and skeletal radiography findings are consistent with ECD. This case represents an unusual presentation, which led to delayed diagnosis, as ECD of the breast has been rarely reported. ECD should be considered in the differential diagnosis of histiocytoid breast lesions, including fat necrosis and histiocytoid invasive mammary carcinoma.