Detection of the alpha-subunit of inhibin in trophoblastic neoplasia.

Placental trophoblasts are the primary source of serum inhibin during pregnancy. We sought to characterize inhibin immunolabeling in trophoblastic neoplasms and compare the results with those for established markers of trophoblastic differentiation. Formalin-fixed, paraffin-embedded tissues from three normal term placentas, 13 hydatidiform moles (HM), five choriocarcinomas (CC) (three gestational, one testicular, one mediastinal), and five placental site trophoblastic tumors (PSTT) were immunolabeled with antibodies to the alpha-subunit of inhibin, hPL, and beta-hCG.

Structural and functional consequences of alveolar cell recognition by CD8(+) T lymphocytes in experimental lung disease.

CD8(+) T cells infiltrate the lung in many clinical conditions, particularly in interstitial lung disease. The role(s) that CD8(+) T cells might be playing in the pathogenesis of inflammatory lung disease is unclear at present, as is the direct contribution of CD8(+) T cell effector activities to lung injury. This report describes a transgenic model used to evaluate the impact, on respiratory structure and function, of CD8(+) T lymphocyte recognition of a target antigen expressed endogenously in alveolar epithelial cells.

Papillary squamotransitional cell carcinoma of the vagina.

A case of papillary squamotransitional carcinoma of the vagina is reported. The immunohistochemical profiles (cytokeratin-7 and -20) and the detection of human papillomavirus 16 support its close relationship to conventional squamous cell carcinoma. The lesion is compared to previously reported cases of papillary transitional cell carcinoma of the vagina and papillary squamotransitional cell carcinoma of the cervix.

Human papillomavirus type 16 E7 protein sensitizes cervical keratinocytes to apoptosis and release of interleukin-1alpha.

Interleukin-1alpha (IL-1alpha) is a multifunctional cytokine that promotes inflammation, tissue remodeling and epithelial hyperplasia. Keratinocytes produce and sequester large amounts of biologically active IL-1alpha which can be released after injury or infection. We show that high level expression of human papillomavirus (HPV) type 16 E6 and E7 oncoproteins enhanced release of IL-1alpha from cultures of normal cervical keratinocytes (relative effectiveness E7 > E6/E7 >> E6 > control).

Performance of liquid-based, thin-layer cervical cytology: correlation with reference diagnoses and human papillomavirus testing.

The performance of thin-layer cervical cytology with the use of ThinPrep (Cytyc Corporation, Boxborough, MA) was assessed by comparing the original independent diagnosis of ThinPrep slides and conventional smears prepared from 1780 split samples with the most abnormal diagnosis per patient on the basis of an independent pathologist's masked review and with the detection of cancer-associated types of human papillomavirus (HPV) DNA. Cases were selected on the basis of the original diagnoses to include all discordant pairs (those diagnosed as atypical squamous cells of undetermined significance or higher grade, n = 1017), all concordant abnormal pairs (n = 444), and a random 5% of concordant normal pairs (n = 319). In screening centers, thin-layer cytology detected 135 (70.

A human papillomavirus related to human papillomavirus MM7/LVX82 produces distinct histological abnormalities in human foreskin implants grown as athymic mouse xenografts.

Studies of human papillomaviruses (HPVs) are hampered by the lack of a conventional culture system because HPV completes its life cycle only in fully differentiated human tissue. To overcome this obstacle, the athymic mouse xenograft system has been used to study the pathogenesis of HPV 11 and to develop neutralizing assays for vaccine development. Recently, HPV 40 has been produced in this system, and HPV 16 has been produced using mice with severe combined immune deficiency.

Atypical glandular cells of undetermined significance: a five-year retrospective histopathologic study.

Objective: Our purpose was to ascertain the types and frequency of pathologic conditions associated with atypical glandular cells of undetermined significance on Papanicolaou smears.

Study Design: A 5-year retrospective review of screening cervical cytologic examinations diagnosed as atypical glandular cells of undetermined significance was performed at the University of Virginia to determine pathologic findings associated with atypical glandular cells of undetermined significance on Papanicolaou smears stratified by subtype and overall.

Results: Pathologic findings for the respective Papanicolaou smears with the diagnosis of atypical glandular cells of undetermined significance not otherwise specified, favor benign, squamous intraepithelial lesions, and favor neoplasia through the follow-up interval were as follows: squamous intraepithelial lesions in 11%, 8%, 38%, and 20%; adenocarcinoma in situ in 3%, 0%, 0%, and 10%; endometrial hyperplasia in 3%, 5%, 1%, and 2%; and cancer in 8%, 3%, 1%, and 7%.

The alpha subunit of inhibin in adrenal cortical neoplasia.

We analyzed 23 adrenal adenomas and 15 adrenal cortical carcinomas by immunolabeling for the alpha subunit of inhibin, and we then compared the results with the functional status of the neoplasms. We also studied 19 pheochromocytomas, 30 renal cell carcinomas, and 5 extra-adrenal paragangliomas, tumors posing differential diagnostic problems with adrenal cortical neoplasms. Immunolabeling was performed using automated immunohistochemical methods and an antibody directed against the alpha subunit.

The diagnostic utility of inhibin staining in ovarian neoplasms.

Previous immunohistologic studies have suggested that the antibody to the alpha subunit of inhibin is a sensitive marker of sex cord-stromal differentiation. However, detection has also been reported within both ovarian epithelial and germ cell tumors. To further study the normal tissue distribution of inhibin and the utility of its detection for the differential diagnosis of ovarian sex cord-stromal neoplasms, normal tissues and 225 lesions including sex cord-stromal lesions, ovarian epithelial and stromal cancers, ovarian and testicular germ cell tumors, metastases to the ovary, and non-ovarian cancers were analyzed using semi-automated immunohistochemistry.

Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells.

Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin.

Sebaceous carcinoma. Tumor progression through mutational inactivation of p53.

Background: Sebaceous carcinoma may masquerade for years as an inflammatory condition. In many cases, this may be because of the presence of longstanding intraepithelial disease (e.g.

Hypoxia induces type II NOS gene expression in pulmonary artery endothelial cells via HIF-1.

Type II nitric oxide synthase (NOS) is upregulated in the pulmonary vasculature in a chronic hypoxia model of pulmonary hypertension. In situ hybridization analysis demonstrates that type II NOS RNA is increased in the endothelium as well as in the vascular smooth muscle in the lung. The current studies examine the role of hypoxia-inducible factor (HIF)-1 in regulating type II NOS gene expression in response to hypoxia in pulmonary artery endothelial cells.

Interobserver variability in the classification of proliferative breast lesions by fine-needle aspiration: results of the Papanicolaou Society of Cytopathology Study.

This study evaluates the applicability of the published cytologic criteria in the categorization of proliferative breast lesions by assessing the diagnostic accuracy and interobserver reproducibility of a panel of experts. Twelve breast fine-needle aspiration (FNA) specimens of biopsy-proven nonproliferative breast lesion (NPL) (1 case), proliferative lesions without atypia (PL) (7 cases), proliferative lesion with atypia (PLA) (1 case), and low-nuclear grade ductal carcinoma in situ (DCIS) (3 cases) were selected. Six FNAs were Papanicolaou (PAP) and 6 were Diff-Quik-stained (DQ).

Human papillomavirus. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: Cervical squamous cell carcinomas, adenocarcinomas and their precursors are caused by the human papillomavirus (HPV). Although HPV appears to be essential to the transformation of these epithelial cells, it is not sufficient, and a variety of cofactors and molecular events must take place between when an HPV infection occurs and a cervical cancer or its precursor develops. This review examines the data supporting these contentions, briefly outlines the molecular events that occur, considers the epidemiology and natural history of the disease, and details the implications of using HPV detection and typing in both clinical management and population-based screening programs.

ASCUS and AGUS criteria. International Academy of Cytology Task Force summary. Diagnostic Cytology Towards the 21st Century: An International Expert Conference and Tutorial.

Issues: The conference participants addressed the following issues: (1) reporting of equivocal diagnoses, (2) strategies to minimize the use of such diagnoses, (3) morphologic criteria, and (4) management of women with equivocal diagnoses.

Consensus Position: Equivocal diagnoses should be minimized, to the extent possible, by emphasizing cytologist education and training, improved specimen collection and quality assurance monitoring of individual and laboratory diagnosis rates. Cases fulfilling criteria for other diagnostic entities should not be included in the equivocal category.

High-grade dysplasia in genital warts from two patients infected with the human immunodeficiency virus.

Cancer-associated human papillomavirus (HPV) types are detected in genital warts removed from immunosuppressed individuals more commonly than from those occurring in otherwise healthy individuals. The prognosis of genital warts containing cancer-associated HPV types is not known. Because it is assumed that genital warts are benign lesions, they are usually treated by destructive therapies without prior knowledge of histopathology.

The differential expression of the HER-2/neu oncogene among high-risk human papillomavirus-infected glandular lesions of the uterine cervix.

Objective: Our purpose was to examine the relationship between HER-2/neu expression and human papillomavirus infection in cervical glandular neoplasia.

Study Design: Cases of cervical adenocarcinoma in situ and invasive adenocarcinoma were selected for study. Human papillomavirus typing was performed by in situ hybridization.

A randomized, double-blind trial of parenteral low dose versus high dose interferon-beta in combination with cryotherapy for treatment of condyloma acuminatum.

Forty-nine subjects were enrolled in a study comparing two dosages of parenterally administered interferon (IFN)-beta in combination with cryotherapy for the treatment of anogenital warts. Subjects were randomized to receive subcutaneous injections of either 2 x 10(6) or 4 x 10(6) IU/m2 of IFN-beta (Biogen) three times a week for a total of 6 weeks. Cryotherapy was administered concomitantly by aerosolization of liquid nitrogen at 10-day intervals.

Evaluation of PAPNET testing as an ancillary tool to clarify the status of the "atypical" cervical smear.

To assess the utility of the PAPNET system (Neuromedical Systems Inc., Suffern, NY) in clarifying the status of cervical smears showing borderline abnormalities, we analyzed the results of five cytotechnologists who reclassified 200 "atypical" smears by evaluating PAPNET images only. The interobserver agreement (reliability) of the PAPNET reviewers was computed, and their readings were compared with three standards: the consensus diagnosis of five pathologists who used light microscopy, the detection of cancer-associated human papillomavirus DNA by Southern analysis, and the correlation with diagnoses of biopsy specimens obtained during passive follow-up.

Growth hormone-releasing hormone receptor mRNA in acromegalic pituitary tumors.

The growth hormone (GH)-releasing hormone receptor (GHRH-R) has been recently cloned and found to be a member of a new family of seven transmembrane receptors that includes secretin, vasoactive intestinal peptide, calcitonin, and corticotropin-releasing factor. GHRH-R mRNA has been demonstrated by Northern blot analyses to be present specifically in the anterior pituitary gland. To determine the precise cellular localization of this receptor in normal anterior pituitary and pituitary adenomas, GHRH-R mRNA was analyzed in 2 normal human pituitary glands and 16 human pituitary adenomas using in situ hybridization.

Aspergillus in cytology specimens: a review of 45 specimens from 36 patients.

Objective: To assess the clinical significance associated with the identification of fungal elements consistent with Aspergillus in cytology specimens.

Materials And Methods: For all cytology specimens with reported fungal elements consistent with Aspergillus, reported over a 9 yr and 8 mo period at The Cleveland Clinic Foundation, the patient's medical charts were reviewed with particular attention to underlying disease, presentation, treatment, and clinical course. Cytology results were compared with available microbiologic cultures and tissue specimens in all of the patients.

A brief synopsis of the role of human papillomaviruses in cervical carcinogenesis.

The expansion of our knowledge in the realms of pathology, epidemiology, and molecular biology of human papillomaviruses (HPV) has defined them as the major and best understood class of true human tumor viruses. The interaction of the papillomavirus genome with its host cell produces the majority of cytologic abnormalities at which cervical cancer screening is directed. The epidemiologic pattern of HPV infection accounts for the established association of cervical neoplasia with sexual activity.

Human papillomavirus and Epstein-Barr virus in sinonasal Schneiderian papillomas. An in situ hybridization and polymerase chain reaction study.

Using the polymerase chain reaction (PCR), it has been recently reported that the Epstein-Barr virus (EBV) is present in the majority of Schneiderian sinonasal papillomas (SNP) of the inverted type and may play a role in the pathogenesis of these lesions. The reported prevalence rates of human papillomavirus (HPV) in different types of SNP is also controversial and in need of clarification. Twenty-eight SNP from 27 patients were histologically classified and evaluated for evidence of EBV using PCR and 2 different sensitive and specific in situ hybridization (ISH) procedures for EBER1.

A lung-specific neo-antigen elicits specific CD8+ T cell tolerance with preserved CD4+ T cell reactivity. Implications for immune-mediated lung disease.

The A/Japan/57 influenza hemagglutinin (HA) was expressed in BALB/c mice under the transcriptional control of the surfactant protein C (SP-C) promoter, resulting in expression of HA in type II alveolar epithelial cells, as well as low level variable expression in other tissues, including the thymus in some of the founder lines. Transgenic animals were able to recover from infection with A/Japan/57 influenza, and they were able to mount antibody responses to A/Japan/57 HA in titers similar to wild type. We therefore tested their CD4+ T lymphocyte responses to HA and found them to be similar to wild type responses.

Therapeutic efficacy and complications of excisional biopsy of condyloma acuminatum.

Background And Objectives: Among the various treatment modalities for condyloma acuminatum, excisional cold-blade surgery appears excellent but it has been little studied and little used, particularly for lesions not located in the perianal area.

Goals: To examine the efficacy and complications of scissors excision of single anogenital warts.

Study Design: Retrospective analysis of single warts completely excised with scissors for the purpose of biopsy before patient entry in a randomized, placebo-controlled study of the efficacy and safety of various parenteral interferons in combination with cryotherapy.