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Biomedical subjects

M H Stoler

Publications and source records attributed to M H Stoler.

At least 55 records · Page 3Linked to original sources
PubMed1998

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 aim of the present study was to determine whether genital warts from individuals with or without human immunodeficiency virus (HIV) contain high-risk HPV types or areas of dysplasia. The study design was a nonrandomized analysis of genital warts removed by excision biopsy from 15 HIV-infected patients and 15 HIV-negative patients. The tissue was analyzed for HPV DNA by hybrid capture, and microscopic sections of each biopsy were examined for areas of dysplasia. Genital warts from HIV-infected patients contained cancer-associated ("high risk") HPV types in 9 of 15 cases, including 1 that contained only a high-risk type. High-grade dysplastic abnormalities were present in 2 of the 15 lesions from this group, both of which contained high-risk HPV types. Four genital warts removed from HIV-negative patients contained high-risk HPV types, but none contained dysplastic abnormalities. It is concluded that genital warts from HIV-infected patients often contain high-risk HPV types. Such lesions may exhibit dysplastic changes. The frequency of dysplastic changes in genital warts from HIV-infected patients is not known. Biopsy of genital warts may be indicated prior to additional therapy in HIV-infected patients, and surgical removal should be considered as a preferred treatment option in these patients.

Anus Diseases↗
PubMed1998

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. Tumors were semiquantitatively assessed for the number of positive cells. Immunopositivity was obtained in 18 (78%) of 23 adrenal cortical adenomas, 12 (80%) of 15 adrenal cortical carcinomas, 2 (11%) of 19 pheochromocytomas, 0 of 5 extra-adrenal paragangliomas, and 0 of 30 renal cell carcinomas. Immunoreactivity was strong in 7 (78%) of 9 adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. In contrast, only 4 (14%) of 29 tumors that were clinically nonfunctioning or associated with hyperaldosteronism demonstrated strong staining (P < .001). In clinically nonfunctioning tumors, there was a tendency for increased immunopositivity in tumors from patients with elevated levels of cortisol, androgen, or their precursors, with four of six tumors having at least moderate immunopositivity. Similar reactivity was present in only one of eight tumors from patients with normal laboratory values (P=.091). Moderate or strong immunopositivity was present in 9 (60%) of 15 adrenal cortical carcinomas, whereas of the pheochromocytomas, extra-adrenal paragangliomas, and renal cell carcinomas, only 1 (1.9%) of 54 showed moderate-to-strong reactivity. We conclude that moderate or strong immunoreactivity for the alpha subunit of inhibin occurs in adrenal cortical tumors from patients with Cushing's-related or virilizing symptoms. Immunolabeling for the inhibin alpha subunit is potentially useful in the differential diagnosis of neoplasms that include adrenal cortical carcinomas.

Adenoma↗
PubMed1998

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 (70.3%) of 192 women diagnosed as having squamous epithelial lesions or a higher grade in the independent review, whereas locally read smears detected 91 (47.4%) of these patients (P < .001). In hospital-based cytology laboratories, thin-layer cytology detected 308 (86.3%) of 357 women diagnosed with SILs or a higher grade in the independent review, compared with 283 (79.3%) diagnosed with smears (P = .011). Cancer-associated types of HPV DNA were detected in a slightly higher proportion of women with smears diagnosed as SILs than in women with thin-layer cytology diagnosed as SILs, whereas the overall number of HPV-associated SILs diagnosed was higher with thin-layer cytology. These data suggest that the ThinPrep method detects a higher percentage of SILs as defined in a masked, independent review than do concurrently prepared smears and that diagnoses of SILs rendered with ThinPrep correlate with the detection of cancer-associated types of HPV.

Cytological Techniques↗
PubMed1997

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. RESULTS: Forty-five cytology specimens with Aspergillus fungal forms, from 36 patients, were identified. Twenty-six patients had concurrent specimens sent for culture in whom II grew Aspergillus species (10 Aspergillus fumigatus), eight grew organisms other than Aspergillus, and seven were no growth. A total of 16 patients (44%) were treated with antifungal treatment (Amphotericin B). Treatment with Amphotericin B was significantly associated with a concurrent growth of Aspergillus species (9/11 patients with Aspergillus culture positive vs. 7/25 patients without a positive culture for Aspergillus, P value = 0.004 (ODDS ratio = 11, 95% confidence interval:#1.6-104, 2-tailed Fisher exact test.) CONCLUSIONS: The presence of fungal forms consistent with Aspergillus in cytology specimens is neither specific nor sensitive for significant infection due to Aspergillus. Treatment with Amphotericin B is more likely to be instituted when a concurrent clinical specimen grows Aspergillus species in culture.

Adult↗
PubMed1997

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. HER-2/neu was detected by in situ hybridization and immunohistochemistry. Fisher's exact test was used to assess for statistical significance. RESULTS: Fifteen cases of adenocarcinoma in situ and invasive adenocarcinoma were analyzed. In situ hybridization detected HER-2/neu messenger ribonucleic acid in 8 cases, whereas immunohistochemistry detected protein in 5 cases. Overall, HER-2/neu activity was present in 10 cases (66.7%). HER-2/neu messenger ribonucleic acid was detected more commonly in lesions associated with human papillomavirus type 16 versus type 18 (85.7% vs 25.0%, p = 0.04). CONCLUSION: HER-2/neu is frequently expressed in human papillomavirus-infected glandular lesions of the cervix. In situ hybridization may provide a more sensitive indicator of HER-2/neu activity over immunohistochemistry. Preferential expression of HER-2/neu messenger ribonucleic acid was detected in human papillomavirus type 16 versus type 18 lesions. Further study is warranted to examine relationships between human papillomavirus infection and HER-2/neu expression.

Adenocarcinoma↗
PubMed1997

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. Systemic side- effects were modest in intensity and included fever, chills, myalgia, and headaches (flu-like symptoms). During the first 2 weeks of therapy, they were more common in the high dose group than in the low dose group (P = 0.02). Using survival analysis, there was no significant difference between the two groups in rates of resolution of warts present at baseline (P = 0.62). However, the rate of new lesion formation during the study was significantly lower in the high dose group (P = 0.04).

Adult↗
PubMed1997

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. GHRH-R was specifically localized in somatotroph cells in the normal pituitary. In the adenomas, all GH-producing adenomas originating from acromegalic patients demonstrated up-regulation of GHRH-R mRNA when compared with levels in the normal pituitary. Only one of five clinically nonfunctioning adenomas, a gonadotroph luteinizing hormone/follicle-stimulating hormone-positive adenoma, exhibited up-regulation of this receptor message. Adrenocorticotrophic hormone-secreting and prolactin-secreting adenomas did not express GHRH-R message. In summary, GHRH-R is specifically expressed in somatotrophs and GH-producing adenomas, suggesting that GHRH-R may influence GH release in adenomas similar to this receptor's actions in the normal somatotrophs and may be involved in the growth of GH-secreting adenomas.

Acromegaly↗
PubMed1996

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. However, CD8+ T cells from A/Japan/57-infected transgenic animals were unable to express cytolytic activity against target cells expressing the A/Japan/57 HA. The CD8+ T cell tolerance was also extremely specific, since transgenics immunized with an influenza strain containing a single amino acid substitution in a dominant HA epitope were able to mount full cytolytic responses to that epitope, but not the wild-type epitope. Adoptive transfer of CD8+ T cell clones into transgenic animals resulted extensive interstitial pneumonitis that was antigen-specific and associated with significant morbidity and mortality. We conclude that a lung-specific transgene may lead to specific CD8+ T cell tolerance, with CD4+ T cell and B cell reactivity to the antigen, and that CD4+ T cell reactivity may remain intact to an antigen expressed in the thymus, even when CD8+ T cell tolerance exists. This observation may have profound implications concerning immune-mediated lung diseases, particularly those mediated by CD4+ T cells.

Amino Acid Sequence↗
PubMed1996

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. The molecular interactions of the HPV genome with its host cell suggest a plausible mechanism for its carcinogenic action. This presentation will succinctly review current knowledge of HPV biology to facilitate an understanding of the clinical significance of this virus.

DNA, Viral↗
PubMed1996

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. Similarly, two methods of ISH were also used for the detection of HPV, using biotinylated DNA probes sensitive for 14 different HPV types as well as more sensitive and specific radioactive RNA probes for HPV types 6, 11, and 16. Polymerase chain reaction was successful in 19 papillomas, including 12 of 19 inverted SNP, 1 of 1 inverted SNP with squamous cell carcinoma, 4 of 5 fungiform SNP, and 2 of 3 oncocytic lesions. Southern blot hybridization of PCR products showed the presence of EBV DNA in two lesions, including one inverted SNP and the single inverted SNP with squamous cell carcinoma. By both DNA- and RNA-mRNA ISH, positivity for EBER was detected in rare stomal lymphocytes but not the overlying epithelium in the inverted SNP with SCC. The remaining cases, including the other inverted SNP positive for EBV by PCR, were completely negative by both ISH techniques. Human papillomavirus was detected by ISH in 1 of 19 (5%) inverted, 1 of 1 (100%) inverted with squamous cancer, 5 of 5 (100%) fungiform, and 0 of 3 (0%) oncocytic SNP. Three SNP contained HPV 6 (all fungiform), three SNP labeled for HPV 11 (two fungiform and the inverted SNP with squamous cancer), and one inverted SNP contained HPV 16. Of the five fungiform SNP, four showed foci of koilocytosis. The results indicate that EBV is not present in sinonasal papillomas. The presence of EBV positive stromal lymphocytes in these lesions may account for a proportion of PCR-positive cases. Oncocytic SNP are unassociated with HPV, whereas inverted SNP contain HPV in a minority of cases. In contrast, fungiform SNP are consistently associated with HPV types 6 and 11 and usually show histologic evidence of viral infection.

Adolescent↗
PubMed1996

Cyclin D1 gene expression in human cervical neoplasia.

Amplification of chromosome 11q13 leads to overexpression of a G1 cyclin gene, cyclin D1 (PRAD-1, CCND-1), in many non-cervical human carcinomas. Homology between cyclin D1 and human papillomavirus oncoprotein E7 binding sites for the retinoblastoma tumor-suppressor protein suggests that human papillomavirus oncoproteins cyclin D1, and other cell cycle regulatory proteins may act through a common mechanism in the pathogenesis of human cervical squamous cell carcinoma. We have examined 48 cases of cervical neoplasia by RNA-mRNA in situ hybridization for human papillomavirus mRNA and cyclin D1 mRNA and by immunohistochemistry for cyclin D1 protein expression. Hybridization demonstrated human papillomavirus RNA in all 48 cases with types 6, 16, or 18 in 2, 26, and 20 cases, respectively. Immunohistochemical detection using anti-cyclin D1 rabbit polyclonal antibody 19 demonstrated appropriate cyclin D1 expression at constitutive low levels in normal squamous epithelium and low-grade intraepithelial lesions. Immunohistochemical staining failed to demonstrate significant protein expression in any of the high-grade or invasive lesions. In contrast to the immunohistochemical results, in situ hybridization demonstrated cyclin D1 mRNA overexpression in three of five cases of low-grade squamous intraepithelial lesion, one of eight cases of high-grade squamous intraepithelial lesion, 14 of 18 cases of invasive squamous cell carcinoma, two of five cases of adenocarcinoma in situ, one of seven cases of invasive adenocarcinoma, and two of five cases of small cell undifferentiated carcinoma. Transcriptional activation of cyclin D1 can occur in vivo in human papillomavirus-associated invasive cervical carcinoma, but it does not seem to result in a steady state, increased level of cyclin D1 protein expression. These data indicate a limited role for cyclin D1 protein in the pathogenesis of human papillomavirus-associated invasive cervical squamous carcinoma. They support a model in which human papillomavirus proteins can circumvent cellular requirements for cyclin D1 in human cervical neoplasia.

Carcinoma↗
PubMed1996

In situ hybridization analysis of glial fibrillary acidic protein mRNA reveals evidence of biphasic astrocyte activation during acute experimental autoimmune encephalomyelitis.

Reactive astrogliosis is a prominent pathological feature of multiple sclerosis and its animal model, experimental autoimmune encephalomyelitis. It is characterized by hypertrophy of astrocytes with increased content of glial fibrillary acidic protein (GFAP.) Studies of reactive astrocytes in acute experimental autoimmune encephalomyelitis have been complicated by the observation that the diffuse increase in GFAP immunohistochemical staining at the onset of central nervous system inflammation does not parallel the gradual increase in GFAP content probably because tissue edema enhances GFAP immunostaining. To characterize changes in GFAP expression, we performed in situ hybridization at 3- to 7-day intervals during the course of acute murine experimental autoimmune encephalomyelitis. We found a biphasic course of GFAP expression: an early phase of astrocyte reaction surrounding perivascular inflammatory cuffs and submeningeal infiltrates at the onset of central nervous system inflammation and clinical disease and a later phase of increased GFAP mRNA expression in regions of demyelination during resolution of inflammation and clinical improvement. IP-10, a member of a family of proinflammatory chemoattractant cytokines called chemokines, was expressed by astrocytes in a similar distribution as those expressing increased GFAP mRNA in the early phase of inflammation but was no detected in astrocytes in the later phase of activation. These results indicate that location and function of reactive astrocytes may vary during the course of immune-mediated demyelination.

Acute Disease↗
PubMed1995

Human papillomavirus type 11 E1--E4 and L1 proteins colocalize in the mouse xenograft system at multiple time points.

The most abundant viral mRNA species in HPV 11-infected tissue consists of two exons, joining a segment of open reading frame (ORF) E1 to ORF E4, potentially encoding the E1--E4 protein. The L1 ORF encodes the major capsid protein of HPV. Our previous studies demonstrated colocalization of the HPV 11 E1--E4 and L1 proteins within the same cells of HPV 11-infected human foreskin implants grown in athymic mice (the mouse xenograft system) and removed 12 weeks after implantation. Prior studies have demonstrated E1--E4 transcripts early in infection and throughout the HPV 11-infected epithelium, while L1 transcripts are detected later, and in a subset of E1--E4 mRNA-positive differentiated epithelial cells. Therefore, E1--E4 protein may be produced at an earlier time point or in less differentiated cells than the L1 protein. To study these questions, athymic mice were implanted with HPV 11-infected human foreskin fragments. Mice were sacrificed at 1-week intervals beginning 2 weeks after implantation of tissue. The E1--E4 and L1 proteins colocalized to the same differentiated epithelial cells or to tight clusters of cells in differentiated epithelial layers of HPV 11-infected implants. The E1--E4 and L1 proteins were first detected 4 weeks after implantation. E1--E4 protein was detected in the region of the cell membrane and cytoplasm, and never in the nucleus. L1 protein was only detected in the nucleus. Both proteins were detected in implants containing high viral copy numbers. No specific histologic changes were uniformly associated with detection of these proteins. The tight coupling of the E1-E4 and L1 proteins at multiple time points suggests that expression of both proteins is necessary to complete the virus life cycle.

Animals↗
PubMed1995

Cyclin D1 (PRAD1, CCND1) and glutathione-S-transferase pi gene expression in head and neck squamous cell carcinoma.

Chromosome 11q13 amplification has been identified in a subset of head and neck squamous cell carcinomas (H&N SCCs). This region contains several putative oncogenes, including cyclin D1 (PRAD1, CCND1), which encodes for an important cell cycle regulatory protein, and the locus encoding for the drug-detoxifying enzyme glutathione-S-transferase-pi (GST-pi). To determine the relationship of cyclin D1 and GST-pi gene amplification to expression of the encoded proteins, the authors examined 64 H&N SCCs by both Southern blot hybridization and immunohistochemistry, using a recently described, affinity-purified, anticyclin D1 polyclonal antibody no. 19 as well as a polyclonal antibody against GST-pi. Anticyclin D1 antibody no. 19 labeled the tumor cell nuclei in 28 (44%) of the H&N SCCs, whereas cytoplasmic immunoreactivity for GST-pi was noted in 55 (86%) neoplasms. By Southern blot 24 tumors (37.5%) showed twofold to tenfold amplification of 11q13 loci; only two of these were coamplified for GST-pi. Immunopositivity with anticyclin D1 antibody no. 19 but not anti-GST-pi significantly correlated with 11q13 amplification (P < .0001). Of the 28 tumors positive with anticyclin D1 antibody no. 19, however, only 18 (64%) were amplified for 11q13, and six amplified tumors did not react with the no. 19 antibody. A strong trend was noted between anticyclin D1 antibody no. 19 reactivity and a hypopharyngeal primary site (P = .053), but no correlations were observed between immunoreactivity and cytological grade, architectural pattern, pathological stage, and disease-free or overall survival. The inconsistent association of cyclin D1 immunoreactivity with 11q13 amplification indicates that other mechanisms may exist for protein overexpression. Immunoreactivity for the GST-pi protein is prevalent in H&N SCC but is clearly unassociated with amplification. In this series, the presence or extent of cyclin D1 and GST-pi immunoreactivity was of no proven prognostic benefit in H&N SCC.

Adult↗
PubMed1995

In situ hybridization detection of cyclin D1 mRNA in centrocytic/mantle cell lymphoma.

BACKGROUND: Centrocytic/mantle cell lymphoma (MCL) is characterized by a specific chromosomal translocation, t(11;14)(q13;q32), which leads to deregulated expression of the G1 cyclin, cyclin D1 (PRAD1, CCND1, BCL1). Cyclin D1 overexpression has been demonstrated in MCL at the mRNA level by Northern blotting and at the protein level by both Western blotting and immunoperoxidase staining. PATIENTS AND METHODS: To assess the utility of in situ hybridization (ISH) to detect cyclin D1 mRNA expression in formalin-fixed, paraffin embedded tissue, five MCL specimens from three patients and two cases of B-cell small lymphocytic lymphoma (B-SLL) were studied. BCL1 major translocation cluster gene rearrangements had been previously documented in two MCL patients; the other MCL and the two B-SLL, showed no detectable BCL1 or cyclin D1 rearrangements. RESULTS: ISH was performed using anti-sense 3H-labeled RNA probes for the cyclin D1 3' untranslated region (pPL7) and partial cyclin D1 cDNA (pPL8). ISH experiments using an anti-sense actin RNA probe demonstrated adequate RNA preservation in all cases. Each of five specimens of MCL demonstrated increased cyclin D1 mRNA. In contrast, neither of the two cases of B-SLL demonstrated detectable levels. CONCLUSIONS: Overexpression of cyclin D1 mRNA can be detected in MCL by ISH using formalin fixed paraffin embedded tissue. The ISH technique may be useful in diagnosing and classifying low-grade B-cell lymphomas and should be applicable to the study of cyclin D1 mRNA expression in a broad spectrum of lymphoid proliferations and solid tumors.

Cyclin D1↗
PubMed1995

Vulvar vestibulitis. A histopathologic study of 36 cases, including human papillomavirus in situ hybridization analysis.

Vulvar vestibulitis is a recently described clinical condition of unknown etiology. Human papillomavirus (HPV) infection has been implicated as a causal pathogen by some investigators. Because reports on this entity are few, we studied the pathologic features of vestibulectomy specimens from 36 women with a clinical diagnosis of vulvar vestibulitis. The patients' ages ranged from 19 to 53 years (mean, 31 years). Bilateral excisions were performed in 34 patients and a unilateral excision in two. Minor vestibular glands or ducts were identified in 28 patients (78%). Chronic inflammation was present in all specimens. The inflammatory infiltrate consisted predominantly of T lymphocytes and plasma cells with smaller numbers of B lymphocytes. Lymphoid follicles were present in four patients, ulcers in two. The predominant site of inflammation was the squamous mucosa, especially the lamina propria, where the degree of inflammation was graded as mild in 11 patients, moderate in 21 patients, and severe in four patients. To a lesser degree, the inflammation also typically involved the periglandular/periductal connective tissue of the minor vestibular glands, where it was graded as mild in 25 patients and moderate in three patients. Foci of squamous metaplasia were observed in 27 of 28 patients with demonstrable vestibular ducts or glands. Nodular hyperplasia of a vestibular gland (so-called "adenoma") occurred in one patient. In six selected cases, fungi were not identified on silver stains. Morphologic findings of HPV infection, such as koilocytotic atypia or squamous dysplasia, were absent. In-situ hybridization studies for HPV types 6, 11, 16, 18, 31 and 35 were negative in all 36 cases. We conclude that (a) vestibulectomy specimens from patients with a clinical diagnosis of vulvar vestibulitis typically show a chronic inflammatory cell infiltrate that predominantly involves the mucosal lamina propria and periglandular/periductal connective tissue and (b) a pathogenetic role for HPV types 6, 11, 16, 18, 31 and 35 is not substantiated.

Adult↗
PubMed1995

Lymphocyte predominance Hodgkin's disease. Evidence for a kappa light chain-restricted monotypic B-cell neoplasm.

Over the last decade, it has been noted that nodular lymphocytic and/or histiocytic predominance Hodgkin's disease (NLPHD) has clinical, histological, and immunophenotypical differences from classical Hodgkin's disease, but it is not clear whether NLPHD represents a B-cell neoplasm or merely an unusual B-lineage reactive condition. We evaluated 36 cases of LPHD (31 nodular, 5 diffuse) for evidence of B-cell clonality by immunohistochemistry for light-chain protein using polyclonal antibodies and microwave antigen retrieval, and by a highly sensitive in situ hybridization technique for light-chain mRNA using 3H-labeled antisense RNA probes. We found monotypic light-chain restriction for kappa protein in 36% of cases, with no clear predominance for either light-chain protein in the other cases. By in situ hybridization, 80% of the evaluable cases showed clear evidence of light-chain monotypsim, with 96% of cases monotypic for kappa mRNA and one case monotypic for lambda mRNA. In virtually all of these cases, the L&H cells were found to be monotypic, consistent with monoclonality. In about one-half of these cases, a small lymphocytic component was also found to be monotypic. Our data support the hypothesis that NLPHD and its rare diffuse variant represent a monotypic B-cell neoplasm, almost always of kappa light-chain type. NLPHD represents a neoplasm distinct from classical Hodgkin's disease.

Adolescent↗