Prominent mononuclear cell infiltrate is characteristic of herpes esophagitis.

Diagnosis of herpes esophagitis is often difficult since the characteristic nuclear inclusions and/or multinucleate giant cells of herpes virus infection may be absent in endoscopic biopsy specimens. We have noted aggregates of large mononuclear cells with convoluted nuclei adjacent to infected epithelium in the exudates of herpetic esophagitis, and postulate that this is a characteristic inflammatory response to the virus. To test this hypothesis, we reviewed biopsies from 22 cases of ulcerative herpetic esophagitis and from 44 control cases of nonherpetic esophageal ulcers (including nine cases of candidal and five cases of bacterial esophagitis) that contained a quantifiable amount of exudate. The estimated percentage of mononuclear cells present in the specimens was ranked independently by two reviewers using coded photomicrographs of exudate. Wilcoxon's rank sum analysis demonstrated significant correlation between presence of herpes and increased mononuclear cells (P less than .0001). Only one of the 22 herpes cases did not show a prominent mononuclear cell infiltrate. Immunoperoxidase studies performed on Hollande-Bouin's-fixed paraffin-embedded material from 11 herpes cases showed strong staining of the mononuclear cells for KP-1 (CD68), indicating that the majority of these cells are macrophages. These findings suggest strongly that aggregates of macrophages are characteristic of the inflammatory response in ulcerative herpetic esophagitis. The presence of these mononuclear cells in a biopsy specimen that initially does not show herpetic inclusions warrants additional studies to rule out herpes virus infection.     

Herpes simplex esophagitis--a study in autopsy series

Autopsy cases were reviewed in order to determine the incidence and underlying diseases of herpes esophagitis. Review of both autopsy records and the preserved viscera of 145 cases disclosed 9 cases (6%) of herpes esophagitis. Herpes simplex virus type I specific antigen was detected in all of these nine cases by immunohistochemical method. Eight of nine cases had malignant diseases. Review only of autopsy records of other 254 cases disclosed 5 cases (2%) of herpes esophagitis. Thus, herpes esophagitis is thought to be more common than has previously been appreciated and may be overlooked at autopsy. Although antemortem diagnosis of this condition has been very rare, clinicians should have an accurate knowledge of this disease because herpetic esophageal ulcer may act as a portal of entry for generalized dissemination of virus and other pathogens, and effective antiviral agents are becoming available.     

Virological diagnosis of herpes simplex virus 1 esophagitis by quantitative real-time PCR assay

Herpes simplex virus 1 (HSV-1) esophagitis diagnosis is routinely based on the endoscopic findings confirmed by histopathological examination of the esophagitis lesions. Virological diagnosis is not systematically performed and restricted to viral culture or to qualitative PCR assay from esophagitis biopsy specimens. The aim of this study was to assess the interest of quantitative real-time PCR assay in HSV-1 esophagitis diagnosis by comparing the results obtained to those of histological examination associated with immunohistochemical staining, which is considered the "gold standard." From 53 esophagitis biopsy specimens, the PCR assay detected HSV-1 in 18 of 19 histologically proven to have herpetic esophagitis and in 9 of 34 that had esophagitis related to other causes, demonstrating sensitivity, specificity, positive predictive value, and negative predictive value of 94.7%, 73%, 66.7%, and 96%, respectively. Interestingly, HSV-1 was not detected in 16 specimens without the histological aspect of esophagitis. The viral loads normalized per μg of total extracted DNA in each biopsy specimen detected positive by HSV PCR were then compared and appeared to be significantly higher in histopathologically positive herpetic esophagitis (median = 2.9 × 10(6) ± 1.1 × 10(8)) than in histopathologically negative herpetic esophagitis (median = 3.1 × 10(3) ± 6.2 × 10(3)) (P = 0.0009). Moreover, a receiver operating characteristics analysis revealed that a viral load threshold greater than 2.5 × 10(4) copies would allow an HSV-1 esophagitis diagnosis with a sensitivity and specificity of 83.3% and 100%, respectively. In conclusion, this work demonstrated that HSV quantitative PCR results for paraffin-embedded esophageal tissue was well correlated to histopathological findings for an HSV-1 esophagitis diagnosis and could be diagnostic through viral load assessment when histopathological results are missing or uncertain.     

Diffuse esophageal intramural pseudodiverticulosis and nutcracker esophagus in a 54-year-old man

Summary Esophageal intramural pseudodiverticulosis, which was first described by Mendl et al. in 1960, is characterized by multiple small flaskshaped outpouchings in the esophageal wall. The pseudodiverticula represent dilated excretory ducts of deep mucous glands in the esophagus. The etiology of this rare condition is unknown. Hiatal hernias, gastroesophageal reflux, esophageal strictures, Candida esophagitis, herpes esophagitis, diabetes mellitus, and chronic alcoholism have been found associated with intramural pseudodiverticulosis. We report the second case of esophageal hypermotility in intramural pseudodiverticulosis.Abbreviations cm centimeter - kg kilogram - LES lower esophageal sphincter - ml/min milliliter per minute - mm millimeter - mmHg millimeter of mercury - U/l unit per liter     

食管鳞癌和反流性食管炎中p16和hMLH1基因甲基化的探讨

目的 探讨食管下段鳞癌和反流性食管炎组织中p16基因和hMLH1基因启动子区的甲基化状况,及与其临床病理特征之间的关系.方法 根据胃镜检查及病理学检查确诊正常食管上皮标本12例,食管下段鳞癌13例,反流性食管炎64例(其中基底细胞增生43例、不典型增生21例).提取各个组织的基因组DNA,用甲基化特异性聚合酶链反应法检测p16基因启动子区的甲基化状态;用亚硫酸氢钠-酶切法检测hMLH1基因启动子区的甲基化状态.用免疫组织化学SP法检测蛋白表达情况.结果 正常食管上皮、反流性食管炎中的基底细胞增生和不典型增生,以及食管下段鳞癌组织中p16基因启动子区甲基化率分别为:0/12、14.0%(6/43)、38.1%(8/21)、6/13;并且p16基因启动子区甲基化率随食管病变程度的进展呈逐渐升高趋势;p16蛋白在正常食管上皮组织中均正常表达,基底细胞增生、不典型增生和食管下段鳞癌组织中的阴性表达率分别为:25.6%(11/43)、76.2%(16/21)、11/13;在正常食管上皮和反流性食管炎组织里均未检测出hMLH1基因启动子区甲基化;在食管下段鳞癌组织中1例检测hMLH1基因启动子区甲基化.p16基因启动子区甲基化与蛋白阴性表达密切相关(P＜0.01),而hMLH1基因启动子区甲基化与蛋白表达无显著相关性(P=0.590).结论 p16基因动子区甲基化可能是食管下段鳞癌发生的早期分子事件之一;反流性食管炎的基底细胞增生可能与食管下段鳞癌相关;hMLH1基因启动子区甲基化可能不直接参与食管下段鳞癌的发生.

Abstract：

Objective To study the promoter methylation pattern of p16 and hMLH1 genes in esophageal squamous cell carcinoma and reflux esophagitis, and to correlate the results with clinical and pathologic findings. Methods Twelve cases of normal esophagus, 13 cases of esophageal squamous cell carcinoma, 43 cases of reflux esophagitis with basal cell hyperplasia and 21 cases of reflux esophagitis with dysplasia, as confirmed by endoscopic and pathologic examination, were enrolled into the study. Genomic DNA was extracted. The promoter methylation status of p16 was measured by methylation-specific polymerase chain reaction. The promoter methylation status of hMLH1 was measured by sodium bisulfite-restriction enzyme digestion. Immunohistochemical study for p16 and hMLH1 proteins was also carried out. Results The rates of p16 methylation in normal esophageal epithelium, basal cell hyperplasia, dysplasia and esophageal squamous cell carcinoma were 0/12, 14.0% (6/43), 38.1% (8/21) and 6/13, respectively.The p16 methylation correlated with the progress of esophageal lesions. On the other hand, the hMLH1 methylation was not observed in the normal esophageal epithelium and reflux esophagitis. One case of esophageal squamous cell carcinoma showed the presence of hMLH1 methylation. The hMLH1 promoter hypermethylation did not correlate with the clinical and pathologic features. Conclusions The p16 methylation may be one of the earliest events in the pathogenesis of esophageal squamous cell carcinoma and is also observed in reflux esophagitis. Reflux esophagitis may be related to the development of esophageal squamous cell carcinoma in Chinese population. In contrast, hMLH1 methylation may not be directly involved in the tumorigenesis of esophageal squamous cell carcinoma.     

Herpes simplex in gynecology and obstetrics.

The problems of herpes simplex in gynecology and obstetrics are reviewed. There were 40 patients showing the characteristic cellular changes of herpetic infection among the 79,357 Papanicolaou smears taken. Four patients, with cytologic evidence of herpes virus, also had cervical dysplasia. The relationship between herpes virus and dysplasia, carcinoma in situ, and invasive carcinoma is discussed. The use of a properly timed Papanicolaou smear to alert the physician to the danger of an infected birth canal is described. Three cases of neonatal herpes are cited.     

Herpes simplex lymphadenitis

Localized herpetic lymphadenitis is an extremely uncommon complication of herpes simplex virus (HSV) infection. The authors report two cases of localized herpetic lymphadenitis, both showing well-circumscribed areas of necrosis containing cells with diagnostic intranuclear inclusions. Electron microscopic studies in both cases revealed characteristic viral particles, and in situ hybridization studies using a herpes simplex genomic probe demonstrated HSV DNA in both specimens. Immunohistochemical studies demonstrated that the cells containing the inclusions were stromal, not lymphoid, cells. Combining the current two cases with the six well-documented cases previously reported in the literature, seven of the eight cases of HSV lymphadenitis have developed in inguinal lymph nodes, with four occurring in patients with previously or subsequently diagnosed hematopoietic malignancies, including both patients in the current series.     

食管炎与食管癌组织计量关系的探讨

４例正常食管粘膜、８例食管炎和５例食管癌的组织学标本在ＪＥＭ－１００Ｘ透射电镜８０００倍下观察，采用体视学线密度测量法测定了食管鳞状细胞表面积密度（ＳＶａ）和上皮细胞间桥面积密度（ＳＶａ）．其结果显示：Ｓｖａ在食管癌组与正常组、食管炎组间差异显著，而后两者间无显著性差异。同时发现三组间的集中趋势有一定的移行关系，这表明食管炎可能是诱发食管癌的因素之一；ＳＶａ在三组间无显著性差异，可能与例数较少及观察方法有关。     

Effect of the herpes simplex virus antigen on E rosette formation by the lymphocytes of patients with ocular herpes

Herpes simplex virus antigen was demonstrated to inhibit E-rosette formation in most cases of herpetic eye infection in contrast to those of adenovirus eye infection or healthy donors in whom inhibition of spontaneous E-rosette formation in the presence of herpes virus antigen is observed much more rarely. It is suggested that inhibition of E-rosette formation is associated with specific sensitivity of lymphocytes of the subjects under study to herpes antigen. It is also suggested that spontaneous E-rosette formation may be used to determine the degree of T-lymphocyte response to herpes virus antigen.     

Levels of T lymphocytes, but not specific antibodies, reflect clinical presentation in human herpes simplex keratitis

Total erythrocyte Rosette-forming cells (ERFC) have been found to be decreased in 44 patients with recurrent ocular herpes but normal in 26 patients with the primary form of the disease. Active ERFC have been found to be decreased in 27 patients with herpetic keratouveitis and normal in 43 patients with superficial herpetic keratitis. Antibodies to herpes simplex virus could not be used to distinguish the various clinical presentations of the disease.     

Modeling and characteristics of liver damage in herpes infection]

An experimental model of herpetic hepatitis is developed, levels and time course of changes in transaminases, the main indicators of lipid metabolism, are characterized, and morphologic features of hepatocyte injury by herpes simplex virus are shown. Liver involvement in herpetic infection is described in detail.     

Sequential Changes in T and B Lymphocyte Responses to Herpes Simplex Virus in Man

Lymphocytes of seven patients with primary herpetic infection, twenty-three patients with recurrent herpes labialis and of nineteen control subjects were separated into T and B enriched cells by the use of nylon wool columns. In the absence of a herpetic infection the thymidine incorporation and macrophage migration inhibition responses to herpes simplex virus (HSV), Candida albicans and PPD, and the thymidine incorporation induced by PHA were functions of T cells. When a herpetic infection was present, the unfractionated lymphocyte response to HSV was increased, as measured by thymidine incorporation, but the T cell response was unchanged. However, T cells did show an increased response to HSV when prepared by elimination of cells forming rosettes with zymosan-complement. T cells of some patients were stimulated by contact with zymosan, and this correlated with the response to C. albicans. It is suggested that lymphocyte responses to HSV in man are mediated by T cells, but that these cells are specifically retained by nylon wool columns at the time of a herpetic infection. This may be associated with acquisition of an Fc receptor by the sensitized T cells.     

Pathological anatomy of herpetic brain lesions in infants

Results of morphological examination of brain herpetic lesions in 29 children are presented. There were 5 observations of necrotic meningo-encephalitis, among children with generalized intrauterine herpes, less severe changes were found in other cases. 14 children suffered from acute necrotic meningo-encephalitis developed after birth. Changes typical for herpes are described in neural, glial and ependymal cells; the type of response in different forms of lesions is shown. The correlation between the gangliosides content in the brain tissue and the surviving neural cells and a specific increase of ganglioside GD1b fraction in brain tissue were demonstrated by biochemical and morphological studies.     

Chronic esophagitis dissecans presenting with esophageal strictures: a case report

Chronic esophagitis dissecans superficialis is a rare form of chronic esophagitis producing esophageal cast. Its clinical and histopathologic features have recently been defined. We present a 78-year-old patient with chronic esophagitis dissecans associated with esophageal strictures. The clinical and pathologic features of chronic esophagitis dissecans superficialis are reviewed. The association of chronic esophagitis dissecans superficialis with strictures has not been previously reported.     

Herpetic infection of the oral cavity in guinea pigs]

A convenient experimental model for serial studies of herpes simplex of the buccal mucosa has been developed in guinea pigs by application of fresh isolates of herpes simplex virus type 1 from a patient with primary herpetic gingivo-stomatitis on prescarified buccal mucosa. The herpetic nature of the eruptions in the oral cavity was confirmed by virus isolations and serologically. The possibility of exogenous reinfection of the buccal mucosa in convalescent animals against the background of humoral virus-neutralizing antibody has been demonstrated. No virus was isolated from the blood, brain, regional lymph nodes, oesophagus, trachea, lungs or liver of the animals with primary herpes simplex of the buccal mucosa. The model is recommended for experimental investigations of herpetic infections of the buccal mucosa.     

Alendronate-associated esophageal injury: pathologic and endoscopic features.

Ingestion of alendronate sodium (Fosamax) by osteoporotic patients can be associated with esophagitis and esophageal ulcer. Alendronate can damage the esophagus both by toxicity from the medication itself and by nonspecific irritation secondary to contact between the pill and the esophageal mucosa, similar to other cases of "pill esophagitis." Despite its wide use, the histologic appearances of alendronate-associated esophageal ulceration have not been previously described in detail, nor is this type of medication-induced injury commonly appreciated by pathologists when evaluating biopsies from ulcer sites. We report a series of 10 patients who experienced erosive/ulcerative esophagitis while ingesting alendronate, and describe the associated endoscopic and pathologic features. Biopsies from all patients showed inflammatory exudate and inflamed granulation tissue as characteristic of any ulcer site. Polarizable crystalline foreign material was present in six of 10 biopsies (60%). Multinucleated giant cells within the inflammatory exudate were present near this crystalline foreign material in three of 10 biopsies (30%). Adjacent squamous epithelium typically showed active inflammation and a reactive appearance with enlarged, hyperchromatic nuclei. Multinucleated squamous epithelial giant cells were present in two of 10 cases (20%). Microorganisms were unusual; scattered fungi and/or viral inclusions were present in only two of 10 biopsies (20%). Recognition of alendronate-associated erosive or ulcerative esophagitis, particularly in postmenopausal women, and communication of this possibility to the clinician can improve patient care.     

Localized herpes simplex lymphadenitis

Despite the marked immunocompromised status of most affected patients, visceral herpes simplex virus (HSV) infections in adults remain localized to the esophagus, with only rare examples of dissemination. Lymph node involvement with herpes simplex has been noted in three reported cases, but only in the context of a widespread fatal infection. This report describes two patients who presented with localized herpetic lymphadenitis documented by light microscopy, immunohistochemistry, and DNA hybridization technics.     

Acute hepatitis due to Herpes simplex virus in an adult

A case is described of herpetic hepatitis in a pregnant woman with primary herpetic stomatitis. Intranuclear inclusion bodies and virus particles were found in hepatocytes, and herpes virus was isolated from a liver biopsy and from oral swabs but not from blood. From rising titres of neutralizing and complement-fixing antibody it is concluded that the oral infection was a primary one. Factors predisposing to the hepatitis are discussed.     

IgM, IgG and IgG subclass antibodies to herpes simplex virus in persons of different ages

IgM, IgG antibodies to herpes simplex virus and their subclases were investigated in 565 subjects of different age tested at virological laboratories of St. Petersburg in 1996-1997. The majority of these subjects had a history of herpes infection and 21.5% had IgM antibodies to herpes simplex virus (HSV), marker of acute herpetic infection. Besides IgM, IgG1 antibodies can be referred to early antibodies appearing during the acute stage of herpetic infection. The predominant subclass was HSV IgG3 antibodies. As for IgG4, they were completely absent in infants aged under 1 year, were detected in 6.2% children aged under 14 years, and were present in 12.2-12.5% adults.     

Modern aspects in the treatment of ophthalmic herpes

The author report about study results conducted in Russia during the recent 30 years and dedicated to the treatment of ocular pathologies caused by the virus of herpes simplex. Three high-efficiency directions took shape during the mentioned period: 1. Non-specific antiviral therapy based on the local and systemic administration of interferon inductors (poludan--complexes of poly A, poly U etc.) possessing an extensive spectrum of the antiviral and immune-modeling actions; 2. Antirecurrent therapy, including the application of herpetic vaccine against the virus of herpes simplex, types I and II, combined with immune-modeling agents. A focal allergic test with herpetic vaccine was offered, it made it possible, for the first time, a non-invasive diagnostics of intraocular herpes. 3. A system of sparing microsurgical methods adapted to the treatment of an active herpetic keratitis and its outcomes. A synergistic effect of interferon inductors and acyclovir was proven both experimentally and clinically; a method of local autocytokinotherapy (based on poludan), which turned out to be most effective in the treatment of severe lesions at the cornea and of intraocular herpes, was worked out. The authors believe that the methods and means offered for the treatment of ophthalmoherpes contribute, to a great extent, to handling with the ocular herpes viral infection.