The Vienna classification of gastrointestinal epithelial neoplasia

BACKGROUND: Use of the conventional Western and Japanese classification systems of gastrointestinal epithelial neoplasia results in large differences among pathologists in the diagnosis of oesophageal, gastric, and colorectal neoplastic lesions. AIM: To develop common worldwide terminology for gastrointestinal epithelial neoplasia. METHODS: Thirty one pathologists from 12 countries reviewed 35 gastric, 20 colorectal, and 21 oesophageal biopsy and resection specimens. The extent of diagnostic agreement between those with Western and Japanese viewpoints was assessed by kappa statistics. The pathologists met in Vienna to discuss the results and to develop a new consensus terminology. RESULTS: The large differences between the conventional Western and Japanese diagnoses were confirmed (percentage of specimens for which there was agreement and kappa values: 37% and 0.16 for gastric; 45% and 0.27 for colorectal; and 14% and 0.01 for oesophageal lesions). There was much better agreement among pathologists (71% and 0.55 for gastric; 65% and 0.47 for colorectal; and 62% and 0.31 for oesophageal lesions) when the original assessments of the specimens were regrouped into the categories of the proposed Vienna classification of gastrointestinal epithelial neoplasia: (1) negative for neoplasia/dysplasia, (2) indefinite for neoplasia/dysplasia, (3) non-invasive low grade neoplasia (low grade adenoma/dysplasia), (4) non-invasive high grade neoplasia (high grade adenoma/dysplasia, non-invasive carcinoma and suspicion of invasive carcinoma), and (5) invasive neoplasia (intramucosal carcinoma, submucosal carcinoma or beyond). CONCLUSION: The differences between Western and Japanese pathologists in the diagnostic classification of gastrointestinal epithelial neoplastic lesions can be resolved largely by adopting the proposed terminology, which is based on cytological and architectural severity and invasion status.     

Conclusions from the histological diagnosis of low-grade intraepithelial neoplasia in Barrett's oesophagus

OBJECTIVE: It is well known that low-grade intraepithelial neoplasia (LGIN) in Barrett's oesophagus (BE) might progress to high-grade intraepithelial neoplasia (HGIN) or carcinoma. Since accurate diagnosis of LGIN is difficult, general pathologists are frequently uncertain about the diagnosis of LGIN and its follow-up risks. The purpose of this study was to analyse the divergence between the diagnoses of general and specialized gastrointestinal pathologists. MATERIAL AND METHODS: Fifty consecutive patients with a previous diagnosis of LGIN in BE, made by a general pathologist, were included in our study. The histopathological slides of every patient were reassessed in a blinded fashion by two specialized gastrointestinal (GI) pathologists. Inter-observer variability was calculated using kappa statistics. RESULTS: LGIN was confirmed by specialized pathologists in only 25/50 patients (50%). Twenty-one patients (42%) had Barrett's metaplasia without intraepithelial neoplasia and in 4 patients (8%) HGIN or Barrett's carcinoma (BC) was revealed. Inter-observer agreement between the general and specialized pathologists for the diagnosis of LGIN was poor (kappa = - 0.17) and good between both of the specialized pathologists (kappa = 0.69). Patients with HGIN/BC were treated by endoscopic resection or surgery. In patients with LGIN, ablative therapy was performed. Complete response was achieved in 25 patients, but 3 patients developed HGIN and 1 patient developed BC after 10+/-3.6 months. CONCLUSIONS: BE with LGIN is difficult to diagnose. Inter-observer variability is unacceptable between general and specialized pathologists and therefore when diagnosing LGIN a second opinion should always be sought by a specialized GI pathologist. Ablation therapy seems to be effective in patients with LGIN, but follow-up endoscopies are necessary to detect metachronous neoplasia.     

Observer variation in the diagnosis of superficial oesophageal adenocarcinoma

BACKGROUND AND AIMS: When to perform oesophagectomy for neoplastic progression in Barrett's oesophagus is controversial. Some resect for high grade dysplasia whereas others defer treatment until intramucosal adenocarcinoma is diagnosed. Interobserver agreement for a diagnosis of high grade dysplasia or intramucosal adenocarcinoma remains unknown and may have therapeutic implications. METHODS: Histological slides from 75 oesophagectomy specimens with high grade dysplasia or T(1) adenocarcinoma were blindly reviewed by two gastrointestinal pathologists and one general surgical pathologist, and classified as high grade dysplasia, intramucosal adenocarcinoma, or submucosal adenocarcinoma. A subsequent re-review of all 75 cases by the same observers following establishment of uniform histological criteria was undertaken. Interobserver agreement was determined by kappa statistics. Coefficients <0.21, 0.21-0.40, 0.41-0.60, 0.61-0.80, and >0.80 were considered poor, fair, moderate, good, and very good agreement, respectively. RESULTS: Interobserver agreement among all pathologists and between gastrointestinal pathologists when comparing high grade dysplasia with intramucosal adenocarcinoma was only fair (k=0.42; 0.56, respectively) and did not substantially improve on subsequent re-evaluation following establishment of uniform histological criteria (K=0.50; 0.61, respectively). CONCLUSIONS: When evaluating resection specimens and after implementation of uniform histological criteria, even experienced gastrointestinal pathologists frequently disagree on a diagnosis of high grade dysplasia versus intramucosal adenocarcinoma. Treatment strategies based on the histological distinction of high grade dysplasia from intramucosal adenocarcinoma using limited biopsy specimens should be re-evaluated.     

Dysplasia in Barrett's esophagus--intra- and interobserver variability in histopathological diagnosis

BACKGROUND: Barrett's esophagus is a well-known pre-malignant condition. Pathologic interpretation of biopsy specimens guides endoscopic surveillance as well as the therapeutic approach that will be carried out. However, the predictive value of histopathologic diagnosis can be questioned due to its poor intra- and interobserver reproducibility. AIMS: To assess intra- and interobserver variability in the diagnosis of Barrett's dysplasia. MATERIAL AND METHODS: Three-micrometer thick sections from biopsy specimens from 42 patients with Barrett's esophagus were stained with hematoxylin-eosin and PAS-alcian blue. The reading of the slides was carried out blindly in a light microscope. Intra and interobserver variability in the interpretation of the slides was determined by kappa statistics. RESULTS: The number of tissue specimens was 229, with average of 5.45 (1 to 18) fragments for patient. Low grade dysplasia was diagnosed by pathologists in 21.4% to 52.4% of the cases. The intra-observer agreement for the diagnosis of low grade dysplasia was slight (kappa = 0.30). The interobserver agreement for the diagnosis of low grade dysplasia was poor, with kappa scores between 0.05 and 0.16. The diagnosis of dysplasia, with agreement for all pathologists examining the same set of slides, was 14.3%. CONCLUSIONS: Pathologic interpretation of Barrett's dysplasia may be subject to marked intra- and interobserver variabiliaty. Interpretation of low grade dysplasia, as high grade dysplasia, should also be considered for review by two or more pathologists.     

Postoperative Follow-Up of Anal Condylomata Acuminata in HIV-Positive Patients

PURPOSE: The purpose of this study was to analyze the postoperative follow-up of HIV-positive patients with anal condylomata acuminata, associating recurrence to the AIDS status. METHODS: Ninety-seven male, homosexual patients with anal condylomata were submitted to surgical treatment from August 1992 to December 1997. Specimens were obtained for histologic investigation of Ki-67 cell proliferation marker and for polymerase chain reaction to define the human papillomavirus type. The patients were advised to return weekly during the first month, and monthly up to the sixth month, to evaluate recurrence. Patients with high-grade anal intraepithelial neoplasia remain in follow-up. RESULTS: Histology revealed low-grade anal intraepithelial neoplasia in 81.44 percent of patients and high-grade lesions in 18.56 percent. The results showed that high-grade lesions were not more frequent in late-stage AIDS patients. Ki-67 expression, a cell proliferation marker, was greater in high-grade than in low-grade anal intraepithelial neoplasia, but had no association with AIDS status. Nononcogenic human papillomavirus 6 and 11 were the commonest types. Comparing papillomavirus types and anal intraepithelial grade, we noticed that both oncogenic and nononcogenic types were responsible for high-grade lesions. All patients healed and 51 (52.6 percent) had recurrence up to the sixth month. AIDS status and papillomavirus type were not associated with recurrence. However, high-grade anal intraepithelial neoplasia patients had more recurrence than those with low-grade lesions. Topical treatment failed in 20 patients (41.6 percent), and these were submitted to new surgical treatment. All of them were in the late stage of AIDS. Three who had high-grade lesions in the first operation had low-grade lesions in specimens from the second surgery. The same histologic pattern was observed in 17 patients who had low-grade lesions in warts removed in the first operation. Other patients with high-grade lesions had no recurrence or evolution to invasive carcinoma from five to ten years of follow-up. CONCLUSION: High-grade anal intraepithelial neoplasia and late-stage AIDS are risk factors for recurrence of anal condylomata.     

Human papillomavirus and anal intraepithelial neoplasia

PURPOSE OF REVIEW: A review of recent developments in the understanding of the natural history of anal squamous carcinoma arising from areas of high-grade anal intraepithelial neoplasia. RECENT FINDINGS: Anal intraepithelial neoplasia is a consequence of chronic human papillomavirus infection in the anal canal and appears to be driven by high viral loads of human papillomavirus. In men who have sex with men with multiple sexual partners prevalent human papillomavirus infection does not decline with age, in contrast to heterosexual patients. Anal intraepithelial neoplasia is equally prevalent in different age groups of men who have sex with men, but in other respects what is known of its natural history resembles that of cervical intraepithelial neoplasia. Low-grade lesions frequently resolve, but high-grade lesions are much more stable. HIV-positives who practise receptive anal intercourse are at highest risk of anal intraepithelial neoplasia. Screening is easy to perform using cytology; the limitations of anal cytology being similar to those of cervical cytology. Patients with any grade of cytological abnormality require further investigation, ideally with high-resolution anoscopy, every 6 months. Successful treatments for individual small to medium-sized high-grade lesions include trichloroacetic acid, infra-red coagulation and laser. In HIV-positive patients the development of new lesions elsewhere is very likely. Topical agents for multifocal disease include imiquimod and cidofovir. SUMMARY: There is a need for large prospective cohort studies in men who have sex with men and HIV-positive patients to further our understanding of this disease and to evaluate treatment strategies.     

Utilidad de la detección del virus del papiloma humano en el cribado de neoplasia intraepitelial anal en pacientes con conductas de riesgo

Introduction

The incidence of intraepithelial anal neoplasia is increasing in certain risk behaviour groups, and human papillomavirus (HPV) infection is involved in its pathogenesis. The systematic use of anal cytology, and more recently HPV detection by hybrid capture and genotyping, have been introduced into screening programs in recent decades.

Material and methods

A retrospective cohort study was carried out on individuals with risk behaviours of developing intraepithelial anal neoplasia and who attended Sexually Transmitted Infections clinics in the Dermatology area of the Hospital Costa del Sol from January 2010 to December 2012. The intraepithelial anal neoplasia screening was performed using anal cytology and HPV genotyping.

Results

Half (50%) of the study population were HIV positive. A high frequency of anal dysplasia and presence of HPV in cytology (82.1%) and genotype (79%) was found. A statistically significant association (P < .005) was obtained between the presence of high-risk HPV genotypes and the presence of high-grade dysplasia in the second directed cytology. HPV genotyping enabled 17 cases (22%) of severe dysplasia to be identified that were under-diagnosed in the first cytology.

Conclusion

Cases of high-grade dysplasia can be under-diagnosed by a first anal cytology. Detection of HPV can supplement this procedure, leading to the identification of those patients most at risk of developing high-grade anal dysplasia.     

Variable pathologic interpretation of columnar lined esophagus by general pathologists in community practice.

BACKGROUND: Pathologic interpretation of biopsy specimens of columnar lined esophagus guides subsequent endoscopic surveillance and/or surgical intervention. The aim of this study was to evaluate pathologic interpretation of columnar lined esophagus by general pathologists in community practice. METHODS: Five histologic slides representing different types of columnar lined esophagus were submitted for review by 20 randomly selected general pathologists in community practice. There were three cases with intestinal metaplasia (one with no dysplasia, one with low-grade dysplasia, and one with high-grade dysplasia) and two cases of gastric metaplasia (one fundic-type and one cardia-type). RESULTS: High-grade dysplasia was identified as such by 30% of pathologists and was called invasive adenocarcinoma by 20%, low-grade dysplasia by 30%, and moderate dysplasia by the remaining 20%. Low-grade dysplasia was identified as such by 35% of pathologists and was called high-grade dysplasia by 20%, moderate dysplasia by 20%, and no dysplasia by 25%. Specialized columnar epithelium with no dysplasia was identified as such by 35%, called low-grade dysplasia by 35%, moderate dysplasia by 15%, indeterminate for dysplasia by 10%, and invasive adenocarcinoma by 5%. Gastric metaplasia without specialized columnar epithelium was identified as Barrett's esophagus in 38% of cases. CONCLUSIONS:Pathologic interpretation of columnar lined esophagus by community pathologists may be subject to marked interobserver variation. The term Barrett's esophagus is often used to describe columnar lined esophagus without goblet cells. Because this finding is not clearly associated with an increased risk of cancer, these data support recent suggestions that the term Barrett's esophagus be abandoned. Interpretations of both high-grade and low-grade dysplasia should be considered for review by experts in esophageal pathology.     

Histological assessment of oesophageal columnar mucosa

This review presents the pathological features of Barrett's oesophagus, with an emphasis on the role of pathologists in the diagnosis, surveillance and treatment of the disease. The diagnosis of Barrett's oesophagus is based both on endoscopy and histology. The surveillance of patients relies on systematic biopsy sampling, looking for dysplasia - intraepithelial neoplasia. Well established classifications of dysplasia are now used by pathologists, but there remain problems with this marker. Therefore, many alternative biomarkers have been proposed, that remain of limited interest in daily practice, including DNA-ploidy, proliferation markers, and p53 abnormalities. Endoscopic improvements already allow a better selection of biopsies, and it may be that new technologies will allow 'virtual biopsies'. The role of pathologists is now extended to the evaluation of new therapeutic modalities of early neoplastic lesions in Barrett's oesophagus, especially endoscopic mucosal resection.     

Observer variability in the assessment of type and dysplasia of colorectal adenomas,analyzed using kappa statistics

PURPOSE: The aim of this study was to establish the intraobserver and interobserver variability in the assessment of histologic type (tubular, villous, and tubulovillous) and grade of cytologic dysplasia (mild, moderate, and severe) in colorectal adenomas. METHODS: One hundred eighty-seven slides of adenomas were assessed twice by three experienced pathologists, with an interval of two months. Results were analyzed using kappa statistics. RESULTS: For agreement between first and second assessment (both type and grade of dysplasia), kappa values for the three specialists were 0.5345, 0.9022, and 0.4100, respectively. Agreement was better for type than for dysplasia. The strength of agreement was moderate for Observers A and C and almost perfect for Observer B. Agreement between all three observers was seen in 35.2 percent for both type and dysplasia in 61 percent for type and in 47.8 percent for dysplasia. The kappa values for Observer A vs. B and Observer C vs. B were 0.3480 and 0.3770, respectively (both type and dysplasia). Values for type were better than for dysplasia, but agreement was only fair to moderate. CONCLUSION: The interobserver agreement was moderate to almost perfect, but the intraobserver agreement was only fair to moderate. A simpler classification system or a centralization of assessments would probably increase kappa values.Supported by grants from the Danish Cancer Society, Danish Medical Research Council (Grant 12-6355), Thomas Bartholin's Fund, Gundelach Meller's Fund, and Emmy Lange, born Kramp's Fund.     

Anal intraepithelial neoplasia and squamous cell carcinoma in HIV‐infected adults

Anal cancer is one of the most common non‐AIDS‐defining malignancies in the era of combination antiretroviral therapy. Its precursor lesion, anal intraepithelial neoplasia (AIN), is highly prevalent in HIV‐infected populations. More than 90% of anal squamous cell cancers are attributable to human papillomavirus (HPV). While the biology of HPV‐related intraepithelial neoplasia is consistent across lower anogenital sites, the natural history of AIN is not well established and cannot be assumed to be identical to that of cervical intraepithelial neoplasia. Screening strategies to prevent anal cancer should be developed based on robust natural history data in HIV‐infected and uninfected populations. Likewise, treatments need to be tested in randomized clinical trials, and reserved for those at significant risk of progression to cancer. This review covers the epidemiology, pathogenesis and immunology of HPV infection, AIN and anal cancer, and summarizes the current diagnosis, screening and treatment strategies in HIV‐infected adults.     

Biliary dysplasia as a marker of cholangiocarcinoma in primary sclerosing cholangitis

BACKGROUND/AIMS: Indentification of biliary dysplasia in a primary sclerosing cholangitis (PSC) liver biopsy may indicate developing cholangiocarcinoma. The objectives were to determine whether biliary dysplasia can be recognised reproducibly in PSC and to compare the frequency in cases with and without cholangiocarcinoma. METHODS: Liver biopsies from 26 PSC cases with concurrent or subsequent cholangiocarcinoma (within 2 years) were assessed for biliary dysplasia independently by three liver pathologists. This was done in two stages: initially, without agreement on criteria, and subsequently after such agreement. Liver biopsies from 60 PSC cases without cholangio-carcinoma were also assessed. RESULTS: Reproducibility for biliary dysplasia without prior agreement on criteria was only marginally better than random (kappa=0.129). In contrast, after prior agreement on criteria, reproducibility was moderate (kappa=0.44). Biliary dysplasia was agreed to be present by all three pathologists in 23% and 19% of biopsies in the first and second round, respectively, from patients with cholangiocarcinoma, but in none of the patients without cholangiocarcinoma. CONCLUSION: Criteria for biliary dysplasia can be agreed and the entity recognised in liver biopsies. The strong association of biliary dysplasia with cholangiocarcinoma in PSC suggests use of dysplasia as a marker for current or developing malignancy.     

Histologic inflammation is a risk factor for progression to colorectal neoplasia in ulcerative colitis: a cohort study

BACKGROUND & AIMS: Although inflammation is presumed to contribute to colonic neoplasia in ulcerative colitis (UC), few studies have directly examined this relationship. Our aim was to determine whether severity of microscopic inflammation over time is an independent risk factor for neoplastic progression in UC. METHODS: A cohort of patients with UC undergoing regular endoscopic surveillance for dysplasia was studied. Degree of inflammation at each biopsy site had been graded as part of routine clinical care using a highly reproducible histologic activity index. Progression to neoplasia was analyzed in proportional hazards models with inflammation summarized in 3 different ways and each included as a time-changing covariate: (1) mean inflammatory score (IS-mean), (2) binary inflammatory score (IS-bin), and (3) maximum inflammatory score (IS-max). Potential confounders were analyzed in univariate testing and, when significant, in a multivariable model. RESULTS: Of 418 patients who met inclusion criteria, 15 progressed to advanced neoplasia (high-grade dysplasia or colorectal cancer), and 65 progressed to any neoplasia (low-grade dysplasia, high-grade dysplasia, or colorectal cancer). Univariate analysis demonstrated significant relationships between histologic inflammation over time and progression to advanced neoplasia (hazard ration (HR), 3.0; 95% CI: 1.4-6.3 for IS-mean; HR, 3.4; 95% CI: 1.1-10.4 for IS-bin; and HR, 2.2; 95% CI: 1.2-4.2 for IS-max). This association was maintained in multivariable proportional hazards analysis. CONCLUSIONS: The severity of microscopic inflammation over time is an independent risk factor for developing advanced colorectal neoplasia among patients with long-standing UC.     

Squamous intraepithelial neoplasia of the esophagus: past, present, and future

With regard to the esophagus, the term “squamous dysplasia” has been used in European countries, the United States, and China, while its use is controversial in Japan. Recently, “low-grade intraepithelial neoplasia” and “high-grade intraepithelial neoplasia” have been used as inclusive terms for dysplasia and carcinoma in situ in the World Health Organization classification. Endoscopically, it is often difficult to identify squamous intraepithelial neoplasia by conventional endoscopy, but application of iodine is useful for the diagnosis of such a lesion. In addition, new types of endoscopic techniques, including magnifying endoscopy, narrow-band imaging (NBI), and endocytoscopy are helpful to detect squamous intraepithelial neoplasia. NBI is very useful for identifying the intrapapillary capillary loop pattern. Regarding the pathological criteria of squamous dysplasia and squamous cell carcinoma, the views of Japanese and Western pathologists have differed significantly. Before the term “intraepithelial neoplasia” was introduced, severe dysplasia as diagnosed by Western pathologists was in fact the same as squamous cell carcinoma in situ or noninvasive carcinoma as diagnosed by Japanese pathologists. This problem has been solved by the introduction of the Vienna classification; however, there are still some issues that need to be resolved. One of them is the presence of basal layer type squamous cell carcinoma in situ, which is often underdiagnosed as lowgrade intraepithelial neoplasia by Western pathologists. Endoscopic treatments such as endoscopic mucosal resection and endoscopic submucosal dissection have recently become possible choices for squamous intraepithelial neoplasia; however, these techniques are not in widespread use in the West. We believe that a consensus meeting between Japanese and Western pathologists as well as endoscopists should be held promptly to reach a common ground for the nomenclature.     

胃黏膜上皮内瘤变组织中COX-2表达及其临床意义

目的探讨胃黏膜上皮内瘤变组织中环氧合酶(COX)-2蛋白的表达情况及其临床意义。方法采用免疫组织化学技术,检测56例内镜活检病理证实为上皮内瘤变的标本中COX-2蛋白的表达情况。结果(1)经HE染色识别的胃黏膜组织上皮内瘤变56例中轻度不典型增生18例,中度不典型增生18例,重度不典型增生17例,原位癌3例。(2)COX-2蛋白表达在轻度不典型增生、中度不典型增生、重度不典型增生和原位癌的阳性率分别为33.33%(6/18)、50%(9/18)、70.59%(12/17)和100%(3/3),各组间比较差异显著(P0.05)。高级别上皮内瘤变的阳性表达率(75%)明显高于低级别上皮内瘤变者(41.67%),两者比较差异显著(P0.01)。结论检测胃黏膜上皮内瘤变组织中COX-2蛋白表达可以帮助临床识别胃黏膜上皮内瘤变组织,预测胃癌前病变的进展,为临床选择治疗方案(ESD、外科手术等)提供依据。     

Humanes Papillomavirus und Analkarzinom

The incidence of anal cancer is increasing worldwide, especially in male homosexual patients. The main risk factor for development of anal cancer is anal infection with the human papillomavirus (HPV). The prevalence of anal HPV infection in HIV-negative homosexual men is 50–60%, while in HIV-positive homosexual men the prevalence is nearly 100%. HPV-related anal intraepithelial neoplasia (AIN) is the putative precursor of anal cancer. AIN can be found in approximately 20% of HIV-negative homosexual men and 5–10% of these patients have high-grade dysplasia (AIN II–III). The prevalence of high-grade dysplasia in HIV-positive homosexual men is, however, significantly higher being up to 50%. Despite the prevalence of HPV-related anal dysplasia and the increasing number of patients with anal cancer, there is still a lack of consensus regarding screening, surveillance and therapy of patients with AIN. The standard treatment for anal cancer is still radiochemotherapy with 5-FU and mitomycin C independent of the HPV or HIV status.     

Sources of variability in histological scoring of chronic viral hepatitis

Inter-observer agreement on activity and fibrosis scores used in chronic viral hepatitis has only been studied under selected conditions. The aim of this study was to identify the sources of variability due to specimen characteristics and observers. This study included 254 liver specimens and 15 pathologists and used the Metavir score. In 44 specimens scored by 4 academic pathologists, agreement of Metavir score was good overall, but better for fibrosis (kappa = 0.59) than for activity (kappa = 0.43) and poor for lobular necrosis (kappa = 0.15). The mean agreement was better for senior (0.60 +/- 0.24) than junior pathologists (0.52 +/- 0.30, P < .05). Mean intrabserver agreement was better than inter-observer agreement (0.77 +/- 0.18 vs. 0.58 +/- 0.26, P < .01). In 157 specimens scored by 2 expert pathologists (one senior, one junior), agreement of Metavir score was only good but greatly improved after consensus reading (fibrosis: kappa = 0.48 and 0.77, activity: kappa = 0.44 and 0.70, respectively, before and after consensus). Several causes of disagreement were identified: specimen length, fibrosis class number, observer bias, and putative causes related to Metavir score or specimen. In an intercenter evaluation involving 59 specimens, 1 expert and 10 nonacademic pathologists, agreement was very poor and did not improve over 5 years for activity (kappa = 0.22-0.25) or fibrosis (kappa = 0.13-0.18). In conclusion, the level of experience (specialization, duration, and location of practice) has more influence on agreement than the characteristics of the specimen (length, fibrosis class number, miscellaneous factors). Agreement can be improved by experienced pathologist or consensus reading.     

EMR for Barrett's esophagus-related superficial neoplasms offers better diagnostic reproducibility than mucosal biopsy

BACKGROUND: EMR of Barrett's esophagus (BE)-related superficial neoplasms represents an efficacious staging modality. It also allows for better pathologic grading compared with mucosal biopsy specimens. However, the interobserver variation in the interpretation of EMR specimens has not been tested. OBJECTIVE: To evaluate consistency in the diagnosis of BE-related neoplasia on EMR specimens. DESIGN: Nine pathologists reviewed 25 esophageal EMR specimens and corresponding biopsy specimens independently. Each pathologist classified the cases as either non-neoplastic BE, low-grade dysplasia, high-grade dysplasia, intramucosal adenocarcinoma, or invasive adenocarcinoma. Interobserver concordance for both specimens from EMRs and biopsies was measured by intraclass correlation and Kendall's coefficient of concordance. The proportion of agreement was also calculated for each specimen and compared for EMR and biopsy by using the Wilcoxon signed rank test. SETTING: Teaching hospitals. PATIENTS: Twenty-five patients who underwent EMR for BE-related neoplasia. RESULTS: The intraclass correlation and the Kendall's coefficient for the 25 biopsy specimens was 0.938 (95% CI 0.880-0.965) and 0.677, respectively; for the 25 EMRs, these were significantly improved, at 0.977 (95% CI 0.957-0.987) and 0.831, respectively. In addition, the proportion of agreement for EMR specimens was significantly better compared with biopsy specimens (P = .015). CONCLUSIONS: Interobserver agreement of BE-related neoplasia on EMR specimens is significantly higher compared with biopsy specimens. The results may relate to the larger tissue sampling compared with biopsy specimens and the ability to evaluate mucosal landmarks, such as double muscularis mucosae. Thus, we suggest that EMRs, in addition to being a staging and therapeutic procedure, improve diagnostic consistency.     

High prevalence of anal squamous intraepithelial lesions and squamous-cell carcinoma in men who have sex with men as seen in a surgical practice

INTRODUCTION: Anal high-grade squamous intraepithelial lesions are probable invasive anal squamous-cell cancer precursors, and although unproved, treatment of high-grade squamous intraepithelial lesions may prevent progression to anal squamous-cell cancer. Men who have sex with men are often treated for benign anorectal disorders without consideration given to the possibility of concurrent high-grade squamous intraepithelial lesions or anal squamous-cell cancer. We determined the prevalence of anal high-grade squamous intraepithelial lesions and anal squamous-cell cancer in an urban surgical practice of men who have sex with men referred for treatment of anal condyloma and other benign noncondylomatous anal disorders. METHODS: One hundred thirty-one HIV-positive and 69 HIV-negative men who have sex with men referred for surgical treatment of presumed benign anorectal disease were evaluated by anal cytology, high-resolution anoscopy, and biopsy. Anal cytology and histology were reported with a modified Bethesda classification. RESULTS: One hundred fifty-seven patients (79 percent) were referred for condyloma, 4 (2 percent) for anal squamous intraepithelial lesions (anal high-grade squamous intraepithelial lesions) diagnosed by primary care providers, and 39 (19 percent) for other benign anorectal disorders. One hundred forty-three patients (93 percent) had abnormal anal cytology, with 107 (54 percent) having high-grade squamous intraepithelial lesions on cytology. Biopsy results revealed 120 patients (60.0 percent) with high-grade squamous intraepithelial lesions and 5 patients (3 percent) with invasive squamous-cell carcinoma. Four of five men with anal squamous-cell cancer were HIV positive. Fourteen men (36 percent) who have sex with men referred for noncondylomatous benign anal disorders had high-grade squamous intraepithelial lesions, and three (8 percent) had anal squamous-cell cancer. High-grade squamous intraepithelial lesions and anal squamous-cell cancer were seen most often at the squamocolumnar junction. CONCLUSIONS: Men who have sex with men referred for treatment of either condyloma or noncondylomatous benign anorectal disease had a high prevalence of anal high-grade squamous intraepithelial lesions and anal squamous-cell cancer. All men who have sex with men referred for treatment of benign anorectal disease should have high-resolution anoscopy and aggressive biopsy of all abnormal areas. Treatment of external lesions alone could miss high-grade squamous intraepithelial lesions or anal squamous-cell cancer.     

EU-USA pathology panel for uniform diagnosis in randomised controlled trials for HRCT screening in lung cancer.

Randomised controlled trials for lung cancer screening using high-resolution computed tomography are now underway. In order to allow effective future comparison of the different trials, as well as strengthening conclusions based upon the analysis of larger data sets, uniformity and consistency of pathology diagnosis are essential. The aim of the present study was to determine the effectiveness of the learning process in this difficult area of diagnostic pathology. Eight pathologists received two CD-ROMs, each with digital images of 30 cases. After diagnosing the first series, selected background reading was provided. Kappa (kappa) scores were calculated for each pathologist and category, and were compared to the consensus score. The readings of the first series showed a moderate agreement kappa score: mean+/-sd for category numbers 8 (all eight categories) and 2 were 0.53+/-0.05 and 0.65+/-0.04, respectively. The kappa 2 score distinguished between categories denoting benign and malignant lesions. The second series resulted in a good agreement kappa score: 0.65+/-0.06 for category number 8 and 0.81+/-0.02 for category number 2. In conclusion, this study demonstrates that screen-detected cases pose particular problems for pathologists and that a trained pathology panel serving randomised controlled trials is likely to lead to more consistent and accurate tissue diagnosis.