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Observer variability in histopathological reporting of cervical biopsy specimens.

Sections from 100 cervical biopsy specimens were studied by 12 consultant histopathologists to determine the robustness of the existing pathology terminology and classification. Analysis by kappa statistics showed good agreement in the diagnosis of CIN 3 and squamous carcinoma but an inability to distinguish accurately between the lesser grades of CIN. It is recommended that the classification be changed to low grade (present CIN 1 and 2) and high grade (present CIN 3) categories alone. There was very poor agreement in the identification of cellular changes associated with human papilloma virus (HPV) infection.

Biopsy↗

An unusual case of peripheral T-cell lymphoma with CD56 positivity and angiocentric, angiodestructive morphology arising in the ileum.

Natural killer cell and cytotoxic T-cell lymphomas are frequently difficult to distinguish because they share many common features, and yet it is important to make an accurate diagnosis because their prognoses differ. We report an unusual case of a white man with a CD56-positive T-cell lymphoma in the ileum. The histologic pattern was characterized by angioinvasion and angiodestruction. Immunohistochemical staining showed positive reactions to CD3, CD8, CD43, CD45RO, CD56, and T-cell intracellular antigen-1, but negative reactions to CD4, CD5, CD20, CD23, and CD57. Epstein-Barr virus (EBV) was not detected by EBV-latent membrane protein staining and EBV polymerase chain reaction technique. The T-cell receptor gamma chain gene was rearranged. According to the World Health Organization classification, the absence of EBV excludes the diagnosis of extranodal natural killer/T-cell lymphoma, nasal type. However, the association of EBV with this lymphoma in white patients is not clear. Therefore, absence of EBV alone does not necessarily exclude nasal-type natural killer/T-cell lymphoma, particularly because the histologic pattern in this case is highly characteristic of this tumor.

Aged↗

Anal neoplasia and its precursors: facts and controversies.

The normal anal mucosa shows a complex histology, and a large variety of tumors and lesions with more or less malignant potential may arise in this region. Several of these seem to be related to venereal diseases, homosexual behavior, and anal intercourse, and to immunosuppression. Human papilloma virus (HPV) has been identified in many cases, but the relation to the histological picture is not constant and the significance is unclear. However, these observations have helped us to identify risk groups. Histological classification is often difficult and it is likely that the reproducibility is limited. This may, in part, explain different observations with regard to frequency and biological behavior. A reliable diagnosis still largely depends on exact clinical information on location and appearance, detailed knowledge of the normal histology, and careful handling of the specimen. The revised World Health Organization (WHO) classification represents an improvement, but more variants are still identified and a classification based on conventional histology alone seems in many cases unsatisfactory. Immunohistochemistry and hybridization and other techniques hopefully will provide us with improved typing of these lesions.

Adenocarcinoma↗

[Cytostatic pneumonitis in children. Pathogenetic and morphologic aspects].

Pulmonary complications of cytostatic treatment have been reported with increasing frequency in children treated for leukaemia. A report is given of the morphology of biopsy specimens of children receiving combined cytostatic treatment complicated by fatal pneumonitis. Histology showed fibrosing interstitial changes with variable phases of proliferation. In addition, unusual proliferation of epithelium and massive increase and activation of the monocyte-macrophage system were observed. Histochemical analysis permitted histogenetic classification of proliferating, and in part atypical, cell forms. Knowledge of the relevant clinical data is essential otherwise the findings cannot be differentiated with certainty from paraneoplastic epithelial anomalies or atypical cells induced by virus infection. The prognosis of cytostatic pneumonitis decisively depends on early correct diagnosis. Complete restitution without typical pulmonary fibrosis can be expected only under ideal conditions, i.e. timely exclusion of the detrimental cytostatics.

Antineoplastic Agents↗

Lymphomas of the oral cavity: histology, immunologic type, and incidence of Epstein-Barr virus infection.

The purpose of this study was to determine the histologic class and immunologic phenotype of lymphomas presenting initially in the oral cavity and whether this correlated to a high incidence of Epstein-Barr virus (EBV) infection as has been reported with lymphomas in the nasal cavity. Seventy-one cases of oral lymphomas from the oral pathology referral service were analyzed retrospectively. They were classified according to the Revised European American Lymphoma (REAL) classification system using routine immunohistochemistry. EBV infection was determined by detection of early viral RNA sequences (EBER) and latent membrane protein (LMP-1) expression. Only non-Hodgkin's lymphomas were observed, with a female predominance of 2:1. They were primarily of B-cell origin and histologically classified mainly as large B-cell type (68%); T-cell lymphomas were rare (8%). EBV infection was observed in 14% of the B-cell lymphomas, an incidence rate higher than that reported in studies of B-cell lymphomas not located in the oral cavity but not as high as that observed in pleomorphic T-cell lymphomas (all sites, 36%) or nasal cavity T-cell lymphomas (nearly 100%). Interestingly, EBV proliferation did not correlate with expression of either Bcl-2 or p53.

Epstein-Barr Virus Infections↗

Hendra and Nipah viruses: different and dangerous.

Hendra virus and Nipah virus are highly pathogenic paramyxoviruses that have recently emerged from flying foxes to cause serious disease outbreaks in humans and livestock in Australia, Malaysia, Singapore and Bangladesh. Their unique genetic constitution, high virulence and wide host range set them apart from other paramyxoviruses. These features led to their classification into the new genus Henipavirus within the family Paramyxoviridae and to their designation as Biosafety Level 4 pathogens. This review provides an overview of henipaviruses and the types of infection they cause, and describes how studies on the structure and function of henipavirus proteins expressed from cloned genes have provided insights into the unique biological properties of these emerging human pathogens.

Animals↗

Molecular characterization of Pseudomonas aeruginosa bacteriophages: identification and characterization of the novel virus B86.

We have characterized a new phage, B86, of Pseudomonas aeruginosa isolated from nature. It is a temperate, uv-inducible, generalized transducing phage. To determine the relatedness of this phage to other characterized P. aeruginosa phages, DNA homology studies were carried out. P. aeruginosa phages have previously been grouped by immunological cross-reactivity. Our studies confirm this classification by demonstrating that phages of different class share little or no DNA homology. Based on homology studies as well as cross-immunity to superinfection, B86 is related to other class B phages and is most homologous with phage B39. The virion morphology of these two phages is quite different, however, as are the restriction enzyme digestion patterns of their genomes with several restriction enzymes. Wild-type B86 is subject to the host-controlled restriction-modification systems of P. aeruginosa PAO and PAT. Virulent mutants of this phage are not restricted by these same restriction-modification systems.

Bacteriophages↗

High prevalence of the hepatitis C virus infection among the inpatients of schizophrenia and psychoactive substance abuse in Japan.

Prevalence of anti-HCV antibody in 1193 hospitalized patients (848 males and 345 females) in psychiatric department was investigated. Overall prevalence ratio was 9.1%, indicating significantly higher than that of healthy blood donors. In the classification of ICD-10, the prevalence of the inpatients diagnosed in schizophrenia group and psychoactive substance use group accounted for 6.2% and 13.8%, respectively. However, adequate reasons such as sanitary issues were not found to account for the high prevalence. Only the age of the patients could account for the high prevalence in the schizophrenic group. In the psychoactive substance abuse group, the sanitary issues might be a major cause of the very high prevalence of anti-HCV antibody, while other factors such as dysfunction of the immune system might be considered to account for it.

Adult↗

Lymphoid changes suggesting escalation of immune response into malignant lymphoma.

The conditions in which the microscopic changes of the lymphoid organs, especially lymph nodes, render difficult the histologic decision of immune response or malignant lymphoma, are reviewed. The possibility that in certain circumstances, prolonged, pathologic immune response escalate to malignant lymphomas, as well as the new classifications of these diseases, in terms of this conception are discussed.

Diagnosis, Differential↗

Presence of herpes simplex DNA in surgical tissue from human epileptic seizure foci detected by polymerase chain reaction: preliminary study.

OBJECTIVES: To determine whether herpes simplex virus causes monofocal epilepsy and to assess the presence of herpes simplex virus 1 (HSV-1) and HSV-2 in surgical specimens from patients with epilepsy by using polymerase chain reaction and Southern blot analysis. BACKGROUND: Herpes simplex virus is a common neurotropic virus capable of latency within the central nervous system; it has a predilection for the temporal lobe. Central nervous system infection with HSV has been associated with seizure activity. DESIGN AND METHODS: Surgical specimens were removed from 50 patients as part of a treatment protocol for monofocal epilepsy. Neuropathological classification was done, and adjacent sections were screened for HSV by using polymerase chain reaction. Tissues obtained post mortem from the temporal lobe cortex of persons with Alzheimer disease (n=17), Parkinson disease (n=14), or nonneurological disease (n=17) served as controls. RESULTS: Twenty (40%) of the 50 epilepsy cases and 2 (4%) of the 48 control cases had at least one sample that tested positive for HSV (P<.001). Sixty-seven percent (8/12) of the epilepsy cases with heterotopia were positive for HSV. CONCLUSIONS: There was a statistically significant difference in the frequency of HSV-positive surgical specimens from monofocal seizure epicenters compared with nonepilepsy control specimens. These data suggest an association of the virus with seizure activity. All specimens positive for HSV (surgical specimens and control specimens) should be examined to determine the activity or latency state of the virus and cellular localization.

Adolescent↗

Nucleotide sequence of the 3'-terminal region of citrus tatter leaf virus RNA.

The 3'-terminal sequence of citrus tatter leaf virus lily isolate (CTLV-L) was determined from cloned cDNA. The sequence contains two open reading frames (ORFs). ORF1 encodes a protein that contains consensus sequences associated with the RNA-dependent RNA polymerase. ORF2, which is in a different reading frame within ORF1, can encode a 36 kD protein, putatively identified as a movement protein. CTLV-L coat protein (CP) was found to be located in the C-terminal region of the polyprotein encoded by ORF1. Evolutionary relationships and classification of capilloviruses is discussed.

Amino Acid Sequence↗

The impact of neurologic disease on hospitalizations related to human immunodeficiency virus infection in Maryland, 1991-1992.

OBJECTIVES: To determine the impact of neurologic disease on length of stay and total hospital charges for hospitalizations related to human immunodeficiency virus (HIV) infection. DESIGN: Review of all HIV-related hospitalizations from all acute nonfederal hospitals in Maryland in 1991 and 1992. Neurologic status and HIV disease status were determined by codes from the International Classification of Diseases, Ninth Revision Clinical Modification, in an administrative database. Total hospital charges and length of stay were also included in this database. RESULTS: Of 12 128 HIV-related hospitalizations (6013 patients with the acquired immunodeficiency syndrome [AIDS], 308 HIV-seropositive patients with symptoms without AIDS, and 5807 HIV-seropositive patients without symptoms), neurologic disease occurred in 1013 (8.4%), predominantly in patients with AIDS. In all HIV-seropositive patients, those with primary neurologic disease had a long mean (+/- SD) length of stay (16.4 +/- 16.5 days vs 9.3 +/- 11.3 days; P < .001) and higher mean (+/- SD) total charges ($12,733 +/- $12,009 vs $8069 +/- $11,247; P < .001) than those without neurologic disease. In patients with AIDS, those with primary neurologic disease also had a longer mean (+/- SD) length of stay (17.2 +/- 17.2 days vs 11.7 +/- 12.7 days; P < .001) and higher mean (+/- SD) total charges ($13,430 +/- $12,470 vs $10,794 +/- $13,537; P < .001) than those without neurologic disease. After adjustment for age, sex, race, and stage of HIV infection in all HIV-seropositive patients, our results indicated that neurologic disease increased the length of stay by 3.3 days (95% confidence interval [CI], 2.9-3.8) and total charges by $2552 (95% CI, $2111-$2993). After adjustment for age, sex, and race in discharged patients with AIDS, the results showed that neurologic disease increased length of stay by 2.24 days (95% CI, 0.73-3.77) and total charges by $1512 (95% CI, $40-$2894). CONCLUSION: Neurologic disease increases the length of stay and total hospital charges of HIV-infected patients.

Acquired Immunodeficiency Syndrome↗

[Primary nasal natural killer/T-cell lymphomas: classification and clinicopathological features].

BACKGROUND: Nasal NK/T-cell lymphomas are rare malignancies in Europe or North America. Histological diagnosis is difficult, because tumors imbedded in large necrotic areas and neoplastic infiltrates may be admixed with small lymphocytes, plasma cells, eosinophils, and histiocytes, and thus the process could be misdiagnosed as chronic inflammation. Progression of the disease leads to septal perforation and may also result in destruction of the hard palate, and if left untreated it ends fatally. This introduced the term "lethal midline granuloma", a term which should not be used any more. MATERIAL AND METHODS: Clinical features, pathohistology, and current classification of primary nasal NK/T-cell lymphomas are described against the background of the recent literature and a case report. RESULTS: Immunophenotyping is essential for the diagnosis. Tumor cells are uniformly infected by Epstein-Barr virus, which could be verified by EBER in situ hybridization. Immunohistochemically, tumor cells are positive for CD56, cytoplasmic CD3epsilon, and CD2 and they express cytotoxic molecules like granzyme B, TIA-1, GMP17, and perforin. Therapeutic options are radio- or radiochemotherapy. On average, 2- and 5-year survival rates of 50% are obtained in stages I and II. The prognosis of advanced tumor stages is very poor. CONCLUSIONS: Immunohistochemical and molecular genetic early diagnosis is of crucial prognostic relevance.

Adolescent↗

Nasopharyngeal carcinoma. Brief review.

Nasopharyngeal carcinoma has a well-defined geographic distribution, primarily affecting persons from southern China and Southeast Asia. Environmental factors are numerous and appear to have a secondary role, mainly in the promotion of the neoplastic process. Relationship with the Epstein-Barr virus is indicated by the identification of viral genome copies within the cells and by a persistent host antibody response with restricted specificity for nasopharyngeal malignancies. The World Health Organization has recently adopted a histologic classification categorized into three subtypes according to the degree of epithelial differentiation, keratinization, and stromal lymphocytic infiltration. The tumor expands locally to contiguous structures, spreads through the cervical lymphatics following the jugular chain, and eventually metastasizes to the skeleton and liver. Primary management consists of radiation therapy to cervicofacial fields and usually offers adequate palliation, with a five-year median survival of 67 percent for stage I and 17 percent for stage IV disease.

Antibodies, Viral↗

KSHV/HHV8-associated lymphoma simulating anaplastic large cell lymphoma.

We report a unique, previously undescribed case of KSHV/HHV8-associated lymphoma in a 49-year-old HIV-seropositive patient. The cervical lymph node-based lymphoma displayed distinctive characteristic features of preferential sinusoidal infiltrate and anaplastic cellular morphology, closely resembling classic anaplastic large cell lymphoma of the WHO classification both histologically and immunophenotypically. Paraffin immunohistochemical study showed that the lymphoma cells were strongly positive for KSHV/HHV8 latency-associated nuclear antigen, and PCR analysis confirmed the presence of KSHV/HHV8 infection. Epstein-Barr virus in situ hybridization was negative. Molecular study clearly demonstrated B-cell lineage with immunoglobulin heavy and kappa light chain gene rearrangements. This case may add to the spectrum of the heterogeneous category of KSHV/HHV8-associated B-cell lymphomas.

AIDS-Related Opportunistic Infections↗

Salivary gland tumors.

Salivary gland cancers continue to pose both diagnostic and treatment dilemmas. Over the past year, a great deal has been written concerning salivary gland tumors in children, fine needle aspiration for salivary gland neoplasms, prognostic factors, and pathologic evaluation and treatment. Some of the more important findings include imaging studies and approaches to the human immunodeficiency virus-positive patient with parotid enlargement, the molecular biology of salivary cancer, and the pitfalls of fine needle aspiration cytology. The necessity of facial nerve sacrifice in parotid surgery for malignancy is debated, and the classification of tumors is clarified.

Child↗