No abstract

No abstract

Vulvar intraepithelial neoplasia (VIN) is classified into 2 clinicopathologic subtypes, classic, related to human papillomavirus (HPV) infection and affecting relatively young women, and simplex (differentiated), negative for HPV and affecting elderly women. Histologically, classic VIN may be basaloid and characterized by a replacement of the whole epidermis by a homogeneous population of small, "undifferentiated" keratinocytes, which are diffusely positive for p16(INK4a) and negative for p53. Simplex VIN is characterized by atypia of the basal layer with high degree of cellular differentiation and shows negative staining for p16(INK4a) and frequent positivity for p53. Simplex VIN is frequently associated with squamous cell hyperplasia and lichen sclerosus. From a series of 110 invasive squamous cell carcinomas of the vulva negative for HPV by highly sensitive polymerase chain reaction, 51 had VIN lesions located at least 1 cm away from the tumor. In 4 (7.8%) cases, the VIN had basaloid histologic features. All cases showed obvious architectural disorganization with a homogeneous population of basaloid, undifferentiated keratinocytes with scanty cytoplasm replacing the whole epidermis. Immunohistochemically, all cases were negative for p16(INK4a) and strongly positive for p53 with suprabasilar extension of positive cells. All patients were postmenopausal (median age 61.0 y; range, 45-76). Squamous cell hyperplasia was identified in 1 case and lichen sclerosus in 1 case. The invasive squamous cell carcinoma was of keratinizing type in 3 cases and basaloid in 1 case. In conclusion, simplex, HPV-negative VIN may occasionally have basaloid morphology. Immunostaining for p16(INK4a) and p53 protein may be helpful in the identification of these lesions and the differential diagnosis with classic, HPV-positive basaloid VIN.

The distribution of acetylcholine receptors (AChRs) within and around the neuromuscular junction changes dramatically during the first postnatal weeks, a period during which polyneuronal innervation is eliminated. We reported previously that protein kinase C (PKC) activation accelerates postnatal synapse loss. Because of the close relationship between axonal retraction and AChR cluster dispersal, we hypothesize that PKC can modulate morphological maturation changes of the AChR clusters in the postsynaptic membrane during neonatal axonal reduction. We applied substances affecting PKC activity to the neonatal rat levator auris longus muscle in vivo. Muscles were then stained immunohistochemically to detect both AChRs and axons. We found that, during the first postnatal days of normal development, substantial axonal loss preceded the formation of areas in synaptic sites that were free of AChRs, implying that axonal loss could occur independently of changes in AChR cluster organization. Nevertheless, there was a close relationship between axonal loss and AChR organization; PKC modulates both, although differently. Block of PKC activity with calphostin C prevented both AChR loss and axonal loss between postnatal days 4 and 6. PKC may act primarily to influence AChR clusters and not axons, insofar as phorbol ester activation of PKC accelerated changes in receptor aggregates but produced relatively little axon loss.

No abstract

No abstract

No abstract

Objective To study colposcopic performance in diagnosing high-grade cervical intraepithelial neoplasia or cervical cancer (CIN2+ and CIN3+) using colposcopic characteristics and high-risk human papillomavirus (hrHPV) genotyping.Design Cross-sectional multicentre study.Setting Two colposcopy clinics in The Netherlands and Spain.Population Six hundred and ten women aged 17 years and older referred for colposcopy because of abnormal cytology.Methods A cervical smear was obtained. Colposcopists identified the worst lesion, graded their impression and scored the colposcopic characteristics of the lesions. Up to four biopsies were collected, including one biopsy from visually normal tissue.Main outcome measures CIN2+ and CIN3+, positive for HPV16 or other high-risk HPV types (non-16 hrHPV-positive).Results The mean age in HPV16-positive CIN2+ women was 35.1 years compared with 39.1 years in women with other hrHPV types (P = 0.002). Sensitivity for colposcopy to detect CIN2+ was 87.9% (95%CI 83.2-91.5), using colposcopic cut-off of 'any abnormality'. The remaining CIN2+ were found by a biopsy from visually normal tissue or endocervical curettage (ECC Conclusions In this population following European screening practice, HPV16-related CIN2+ lesions were detected at younger age and showed similar colposcopic impression as non-16 hrHPV high-grade lesions. There was no relationship between any of the colposcopic characteristics and HPV16 status.Keywords Cervical intraepithelial neoplasia, colposcopy, genotyping, HPV16, human papillomavirus.Please cite this paper as: van der Marel J, van Baars R, Quint WGV, Berkhof J, del Pino M, Torn e A, Ordi J, Wentzensen N, Schiffman M, van de Sandt MM, Lindeman J, Jenkins D, Helmerhorst TJM, Verheijen RHM, ter Harmsel B, Alonso I. The impact of human papillomavirus genotype on colposcopic appearance: a cross-sectional analysis.