Pathological characterization and clinical outcome of penile intraepithelial neoplasia variants: a North American series.

Penile intraepithelial neoplasia (PeIN) is classified as human papillomavirus (HPV)- and non-HPV-related. This classification is associated with distinct morphologic subtypes. The natural history and prognosis of PeIN subtypes are not well known. This study aims to evaluate clinicopathological features, HPV status, and outcome of PeIN subtypes. Eighty-two lesions from 64 patients with isolated PeIN were retrospectively reviewed. Mean age was 59 years. Lesions were multicentric in 34% of patients and affected glans (33%), shaft (26%), and foreskin (20%). Histologically, 22% of patients had coexisting lesions, classified as hybrid and mixed. HPV-related PeIN (97%) included basaloid (59%), warty (8%), warty-basaloid (8%), hybrid (19%) and mixed (3%) types. P16 and HPV positivity occurred in 99% and 82% of lesions, respectively. HPV 16 was more common in basaloid PeIN. Multiple genotypes were detected in 35%, more commonly in hybrid PeIN (P = 0.051). Positive margins occurred in 63% of excisions. PeIN recurred in 48% of excisions and 30% of overall repeated procedures, and progression to invasive carcinoma occurred in 2%. At follow-up, 86% of patients had no evidence of disease and 12% were alive with disease. Lichen sclerosus occurred in non-HPV and HPV-related PeIN (100% and 47%).In conclusion, HPV-related and, more specifically basaloid PeIN were the predominant types and preferentially associated with HPV 16. While PeIN had a high recurrence rate, there was a slow and infrequent progression to invasive or metastatic carcinoma with multimodal treatments. Additional studies are needed to understand biology and natural history of PeIN.

A comparative analysis of lymphatic vessel density in ovarian serous tumors of low malignant potential (borderline tumors) with and without lymph node involvement.

Lymph node involvement is seen in approximately one quarter of women with surgically staged ovarian serous tumors of low malignant potential (serous borderline tumors), and this finding apparently does not adversely impact their overall survival. To help illuminate some of the pathomechanisms underlying this novel phenomenon, in which a largely noninvasive epithelial neoplasm is able to exit its primary site and be transported to lymph nodes with such a substantial frequency, we investigated whether significant differences in lymphatic vessel density exist between ovarian serous borderline tumors that show lymph node involvement and those that do not. The lymphatic vessel density of 13 conventional ovarian serous borderline tumors (i.e. tumors without stromal microinvasion, micropapillary/cribriform areas, or invasive implants) with at least 1 positive lymph node (study group) was compared with the lymphatic vessel density of an age- and disease extent-matched control group of 13 similarly selected lymph node-negative ovarian serous borderline tumors. Lymphatic vessel density was determined by counting the total number of vascular spaces immunohistochemically stained by the lymphatic endothelium marker D2-40 in 5 consecutive microscopic fields (x20 objective, field area of 1 microscopic field, 0.95 mm) in the most vessel-dense areas and calculating the average value per microscopic field. The peritumoral lymphatic vessel density was significantly higher than the intratumoral lymphatic vessel density in both groups. However, no statistically significant differences were found between the study and control groups regarding intratumoral lymphatic vessel density (8.0 vs. 7.61; P=0.77), peritumoral lymphatic vessel density (20.33 vs. 21.0; P=0.79), or combined, that is, peritumoral plus intratumoral lymphatic vessel density (27.81 vs. 28.62; P=0.83). Our findings, in conjunction with others in the medical literature, do not support a role for tumor lymphatics in nodal metastasis in this neoplasm. We discuss the possibility that nodal deposits may represent metastatic disease from secondary tumor implants.