These factors explain, at least partially, superior stage-specific survival rates after R2 compared with R1 resections, without a real survival benefit in individual patients.

Purpose: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8 þ T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve Results: Forty-three patients were assigned to either ISA101 with imiquimod (n ¼ 21) or ISA101 only (n ¼ 22). Imiquimod did not improve the outcomes of vaccination. However, vaccineinduced clinical responses were observed in 18 of 34 (53%; 95% CI, 35.1-70.2) patients at 3 months and in 15 of 29 (52%; 95% CI, 32.5-70.6) patients, 8 of whom displayed a complete histologic response, at 12 months after the last vaccination. All patients displayed vaccine-induced T-cell responses, which were significantly stronger in patients with complete responses. Importantly, viral clearance occurred in all but one of the patients with complete histologic clearance.Conclusions: This new study confirms that clinical efficacy of ISA101 vaccination is related to the strength of vaccine-induced HPV16-specific T-cell immunity and is an effective therapy for HPV16-induced high-grade VIN/VaIN.

The results of the present study provide further support for the follicle centre cell origin of both PCFCCL and PCLBCL-leg, and indicate that staining for Bcl-2, Bcl-6 and CD10 can serve as an important adjunct in the differential diagnosis of cutaneous B-cell lymphoproliferative disorders.

To evaluate the efficacy of cryocoagulation as a treatment for cervical intraepithelial neoplasia (C.I.N.), it is necessary to know the maximum depth of the glandular crypts, the maximum crypt involvement by C.I.N. and the extension of the cryolesion, obtained under standardized conditions. In a morphometric study on this subject, one has to take into account the shrinkage of the cervical tissue, caused by processing the tissue for histological examination. In the present study, tissue shrinkage of the cervix in different directions was measured in three separate steps. First shrinkage caused by formalin fixation was determined, second shrinkage caused by dehydration, clearing and paraffin wax embedding and finally that caused by section cutting and mounting. Shrinkage caused by formalin fixation, and by dehydration, clearing and paraffin wax embedding did not differ significantly in the different directions and resulted in an average shrinkage of respectively 2.7% and 12.6% of the original dimensions. The alterations of the dimensions by section cutting and mounting is not a process of shrinkage, but actually a deformation caused by pressure on the tissue during sectioning. Generally the dimension decreases in the cutting direction and increases in the direction perpendicular to it. In the calculation of the total shrinkage these alterations can be neglected, since the changes, although not consistent are small. It follows that in morphometric studies a total shrinkage of about 15% of the original dimensions has to be taken into consideration.

Malignant transformation of parathyroid tumours is rare. Nevertheless, this small subset of malignant tumours often creates diagnostic and therapeutic problems. In this work, the morphological characteristics of 26 primary parathyroid carcinomas and seven metastases have been studied. Furthermore, immunohistochemical expression profiles for the calcium sensing receptor (CASR), cyclin D1 (CCND1), and Ki-67 were determined for parathyroid carcinomas and compared with adenomas and hyperplasias using a tissue microarray. Loss of heterozygosity (LOH) of the chromosome 1q region containing the HRPT2 gene and chromosome 11q (MEN1) was determined in the carcinomas. In contrast to the adenomas and hyperplasias, 31% of carcinomas demonstrated down-regulation of CASR. A significant correlation was found between CASR expression and the Ki-67 proliferation index. Chromosome 1q and chromosome 11q LOH were found in 12 of 22 (55%) and 11 of 22 (50%) carcinomas tested, respectively. Combined 1q and 11q LOH was seen in 8 of 22 (36%) carcinomas, in contrast to the low percentage of LOH reported in both regions in adenomas. In conclusion, this study demonstrates that combined 1q and 11q LOH in parathyroid tumours is suggestive of malignant behaviour. Strong down-regulation of the CASR protein is seen in a proportion of parathyroid carcinomas with a high proliferation index.