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1/8. Cervical adenoid cystic carcinoma coexisting with multiple human papillomavirus-associated genital lesions. A common etiology?

    Adenoid cystic carcinoma of the uterine cervix is a rare tumor with unknown etiology. We report a case of adenoid cystic carcinoma occurring in a young woman, associated with multiple human papillomavirus (HPV)-related lesions including condyloma acuminata, vulvar intraepithelial neoplasm, cervical intraepithelial neoplasm and invasive basaloid squamous cell carcinoma. While adenoid cystic carcinoma has previously been found to coexist with squamous cell carcinoma or cervical intraepithelial neoplasia, its association with such a variety of HPV-related lesions in our case has not been previously reported, and raises the speculation that HPV may also be the causative factor for adenoid cystic carcinoma. However, in situ DNA hybridization and polymerase chain reaction in our current study failed to demonstrate the existence of HPV DNA in adenoid cystic carcinoma.
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2/8. Synchronous CIN 3 and cervical lymphoma: a case report and review of the literature.

    Primary cervical lymphoma is rare, with less than 60 cases reported in the English literature, including a few cases of synchronous cervical intraepithelial neoplasia (CIN) with cervical lymphoma. We describe a 42-year-old woman with CIN 3 and malignant lymphoma of the cervix. The Papanicolaou cytology only revealed dysplastic cells of CIN 3, but not the malignant lymphoid cells. The histology of the cervix revealed diffuse infiltration of monotonous medium-sized lymphoid cells with dispersing tingible bodies, and a Burkitt's lymphoma in combination with a small CIN 3 lesion was diagnosed. Neither human papillomavirus nor Epstein-Barr virus was identified by polymerase chain reaction or in situ hybridization. The patient developed leukemic spreading and died soon after surgery.
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3/8. Superficial (early) endocervical adenocarcinoma in situ: a study of 12 cases and comparison to conventional AIS.

    Although established histologic criteria for the diagnosis of endocervical adenocarcinoma in situ (AIS) have been published, some lesions are not readily classified or present with more subtle degrees of epithelial atypia. Lesions confined to the surface mucosa may be particularly challenging, possibly because they represent early disease. Twelve cases of superficial AIS (SAIS) confined to the surface mucosa or crypt openings culled from the in-house and consultation practices were examined histologically, immunostained for MIB-1 and p16, and analyzed (when possible) for HPV nucleic acids by DNA-DNA in situ hybridization (INFORM). The mean age was 26.7 years for SAIS versus 37.0 years for 42 consecutive cases of conventional AIS from the same practice (P < 0.001). Seven and five were biopsies and conization specimens, respectively. Five coexisted with CIN, four arose in endocervical papillae, and two arose in endocervical polyps. Nuclear hyperchromasia was conspicuous in 10 and mitoses were present in all; however, apoptosis was rare or absent in four, and six exhibited only mild nuclear atypia. Mib-1 staining exceeded 40% in 5 of 7 cases tested, and all (8 of 8) were strongly positive for p16(ink4). Five of five were positive for HPV by ISH with an "integrated" dot-like pattern. SAIS is an early variant of AIS that 1) occurs at a younger mean age, 2) exhibits variable atypia, and 3) arises adjacent to morphologically normal columnar epithelium. Diffuse p16 expression and integrated HPV pattern are identical to that seen in more extensive forms of the disease. Superficial AIS should be suspected in endocervical columnar epithelium with segmental nuclear hyperchromasia with mitotic activity, and confirmed by biomarker staining (p16 and Mib-1) if the pathologist is uncertain of the diagnosis.
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4/8. Condyloma and cervical intraepithelial neoplasia of the endometrium.

    Many studies have shown the presence of squamous metaplasia, dysplasia, carcinoma in situ and squamous cell carcinoma of the endometrium, whether they arose de novo or from direct extension from the cervix. Condyloma associated with squamous metaplasia or dysplasia of the endometrium is rare. We report a case of cervical intraepithelial neoplasia (CIN I) and condyloma of the endometrium. A 58-year-old woman presented with high-grade dysplasia on two successive pap smears. A total vaginal hysterectomy showed extensive CIN I and condyloma involving the entire endometrium. DNA in situ hybridization and polymerase chain reaction documented the presence of condyloma.
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5/8. Squamous intraepithelial neoplasia in an ovarian cyst, cervical intraepithelial neoplasia, and human papillomavirus.

    A case of squamous intraepithelial neoplasia in an ovarian cyst in association with cervical intraepithelial neoplasia (CIN) III is described. In view of the association of human papillomavirus (HPV) and CIN, the possibility that HPV infection could be associated with similar changes in the ovary was postulated. The HPV genome was shown in formalin-fixed tissue of the cervical lesion by nonisotopic in situ hybridization (NISH) and by the polymerase chain reaction (PCR). However, HPV could not be shown in the ovarian lesion by NISH or PCR. On the basis of these findings there appears to be no association between HPV infection and squamous intraepithelial neoplasia in an ovarian cyst.
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6/8. cervical intraepithelial neoplasia 3, coinfected with HPV-16 and -18--case report.

    Recently, detection of human papillomavirus (HPV)mRNA expression was made possible by in situ hybridization. We described a patient with cervical intraepithelial neoplasia (CIN) 3, showing a distinctive and rare form of co-infection with HPV type 16 and 18. HPV-16 was detected in high grade squamous intraepithelial neoplastic lesion (CIN 3) and HPV-18 was in low grade lesion just adjacent to the HPV-16 infected area. This case suggests that HPV infection may be one of the most responsible causative agents producing malignant transformation and two distinctive HPV types can also simultaneously infect the squamous epithelium of the uterine cervix.
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7/8. Papillomavirus, p53 alteration, and primary carcinoma of the vulva.

    Twenty-nine samples from 28 cases of vulvar squamous cell carcinoma, of which 13 fulfilled the criteria of the bowenoid subtype (mean age 45 years, range 31-68) and 16 of the usual subtype of invasive squamous cell carcinoma (ISCC) (mean age 67.5 years, range 34-83) were investigated for human papillomavirus (HPV) DNA, TP53 alterations, and mdm2 and bcl-2 gene product deregulation. Microscopically all the bowenoid subtype cases (group I) showed a high-grade intraepithelial (VIN 3, carcinoma in situ) lesion associated with early invasive carcinoma in six cases and overt invasive carcinoma in one. By contrast, no evidence of early carcinoma was present in the ISCCs (group II). By in situ hybridization and/or Southern blot hybridization or polymerase chain reaction (PCR), HPV DNA was detected in all cases of group I and in four of 16 cases (25%) of group II, two only by Southern blot after PCR. By single-strand conformation polymorphism and immunocytochemistry only wild-type TP53 and absence of detectable p53 product, respectively, were found in all cases of group I, i.e., in high-risk HPV-positive carcinomas, whereas mutations and/or p53 overexpression accounted for 75% in group II, i.e., in mainly HPV-negative carcinomas. The TP53 gene mutations observed in invasive carcinomas were significantly related to node-positive cases (p = 0.04). Taken together and in agreement with in vitro data, these results support the view that an alteration of TP53, gained either by interaction with viral oncoproteins or by somatic mutations, is a crucial event in the pathogenesis of vulvar carcinomas, but that TP53 mutations are mainly associated with disease progression. Finally, a preliminary immunocytochemical analysis seems to speak against the possible involvement of both MDM2 and BCL-2 gene products in the development of vulvar carcinoma.
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8/8. Bilateral primary ovarian squamous cell carcinoma associated with human papilloma virus infection and vulvar and cervical intraepithelial neoplasia. A case report with review of the literature.

    Primary squamous cell carcinoma of the ovary is rare. Most cases represent malignant transformation of ovarian teratomas. Other cases are associated with preexisting brenner tumor or ovarian endometriosis. We report a primary ovarian squamous cell carcinoma in a 40-year-old woman. The patient had recurrent high-grade intraepithelial neoplasia of the vulva (VIN) and recurrent high-grade cervical intraepithelial neoplasia (CIN). Human papilloma virus (HPV) DNA 16/18 was identified in an in situ and invasive carcinoma in the left ovary; CIN and VIN were identified with in situ hybridization with biotinylated dna probes. review of the literature revealed nine cases of primary ovarian squamous cell carcinoma not associated with a preexisting ovarian lesion. Three cases were not associated with CIN and occurred in women who ranged in age from 64 to 90 years and did not have carcinoma in situ component. Six cases were associated with CIN, had a carcinoma in situ, and occurred in younger women ranging from 33 to 54 of age. Our case belonged to the latter category. This report raises the possible causal relationship of HPV with primary ovarian squamous carcinoma in the group of middle-aged patients with CIN.
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