Vulvar intraepithelial neoplasia (VIN) is the currently accepted generic designation for the spectrum of vulvar lesions with the histologic features of squamous dysplasia and squamous cell carcinoma in situ. Although several classifications of VIN have been espoused in the past 20 years, VIN can be readily classified into two principal clinicopathologic types: classic (bowenoid) VIN and simplex (differentiated) VIN. This manuscript summarizes the historical development and current status of our knowledge about VIN. Information on the clinical and pathologic aspects are detailed and illustrated, as are considerations of differential diagnosis.

This report is an analysis of 63 cases of metastatic cancers to the uterine corpus from extragenital neoplasms. The patients' ages ranged from 34–88 years (mean, 59.7 years). Twenty lesions were discovered in surgical specimens and 43 were detected at autopsy. The primary tumors arose in the breast (42.9%), colon (17.5%), stomach (11.1%), pancreas (11.1%), gallbladder (4.8%), lung (4.8%), cutaneous melanoma (3.2%), urinary bladder (3.2%), and thyroid (1.6%). In five (25%) of the surgical cases, uterine metastases were the first indication of the presence of an extragenital primary cancer. Metastases to leiomyomas were found in 13 instances. The myometrium was more often involved than the endometrium, but endometrial curettings contained the metastatic tumor in numerous cases. Metastases to the ovaries were detected in almost two thirds of cases. Although an infrequent event, abnormal uterine bleeding may result from secondary spread to the uterine corpus from an extragenital primary neoplasm.

Vulvar Paget's disease (VPD) is the most common type of extramammary Paget's disease; however, the frequency of dermal invasion and its clinical significance are unclear, as are the frequency and relationship of an associated regional internal cancer. Thus, we studied the clinicopathologic and immunohistochemical features of 19 patients with VPD. Patients ranged in age from 56 to 86 years (median 65). VPD was entirely intraepithelial (IE-VPD) in 13 patients. Three patients developed IE-VPD recurrence and one developed deeply invasive and metastatic VPD at 10.8 years. Five patients had invasive Paget's disease (INV-VPD) characterized by clinically occult microscopic foci of superficial dermal invasion, ranging in depth from 0.3 to 0.9 mm. All five patients were alive without disease after 12 months to 17 years (median 66 months). A regional internal cancer (CA ASSOC-VPD) occurred in one patient whose VPD was preceded by a deeply invasive grade 3 transitional cell carcinoma of the urinary bladder 9 months earlier. Immunophenotypes of 16 cases with IE-VPD or INV-VPD were CK7+/CK20-/GCDFP15+ in 14 cases and CK7+/CK20+/GCDFP15+ in two cases, with concordant immunophenotypes of the intraepithelial and invasive components in all cases studied. The patient with CA ASSOC-VPD had a CK7+/CK20+/GCDFP15- immunophenotype in the invasive TCC of the urinary bladder and the VPD. We conclude that the predominant form of VPD begins as a primary cutaneous intraepithelial neoplasm that is universally CK7+/GCDFP15+. Foci of unsuspected synchronous dermal invasion by Paget's cells can be expected in almost one third of cases. Subsequent progression into an invasive carcinoma occurs less often. Foci of "minimally invasive" carcinoma (<1 mm) probably do not adversely affect prognosis, whereas deeply invasive carcinoma behaves as a fully malignant adenocarcinoma. The rarer form of VPD appears to result from secondary intraepithelial spread from an associated regional internal carcinoma. The finding of Paget's cells that are CK20+/GCDFP15- suggests the presence of a regional internal carcinoma with a corresponding immunophenotype.

The concept and terminology of borderline epithelial tumors of the ovary have been controversial for over a century, in spite of the acceptance of a borderline category in almost all current classifications of ovarian tumors. Typically, borderline tumors are noninvasive neoplasms that have nuclear abnormalities and mitotic activity intermediate between benign and malignant tumors of similar cell type. Borderline tumors of all surface epithelial cell types have been studied. The most common and best understood are serous borderline tumors and mucinous borderline tumors of intestinal type, which are the subject of this review. Some of the most challenging issues for serous tumors include: the criteria and clinical behavior of stromal microinvasion; the high prevalence of synchronous extraovarian disease; the classification and histopathologic features of associated peritoneal tumor implants, especially invasive implants; and, the prognostic significance of micropapillary tumors. The mucinous borderline tumors of intestinal type have a different set of considerations, including: their frequently heterogeneous composition with coexisting benign, borderline and malignant elements; the classification and significance of accompanying noninvasive carcinoma; the recognition of stromal invasion, including microinvasion and expansile invasion; and, the historically misunderstood relationship to pseudomyxoma peritonei. All of these issues are discussed in this presentation, as are the important gross and microscopic features of serous and mucinous borderline tumors and pertinent information on their treatment and prognosis. Modern Pathology (2005) 18, S33-S50.