Western Pathologists Research Articles

Unravelling interobserver variability in gastrointestinal glandular neoplasia: a contemporary study of US and Korean pathologists

AimsInterobserver variability in the assessment of gastric neoplasia biopsies between most Western and Eastern (predominantly represented by Japanese in the literature) pathologists has been documented. It is unknown if such...

Different Threshold of Malignancy for RAS-like Thyroid Tumors Causes Significant Differences in Thyroid Nodule Practice.

Simple SummaryHistopathological diagnosis is prone to significant observer variation in the diagnosis of papillary thyroid carcinomas (PTCs) due to different thresholds of malignancy for RAS-like nuclear features (worrisome nuclear features of PTC). RAS-like PTCs in Western practice are differently classified by most Asian pathologists into follicular adenomas when they are not invasive, follicular carcinomas when they are invasive, and follicular variant PTCs when they have fully developed nuclear features. This commentary emphasizes that this observer variation in diagnosing RAS-like thyroid tumors among practices underlies several issues in thyroid nodule practice.Histopathological diagnosis of papillary thyroid carcinomas (PTCs) is prone to significant observer variation due to different thresholds of RAS-like nuclear changes among pathologists. This gap recently widened due to a defensive attitude by Western pathologists where malpractice litigation is significant. Cases with delicate RAS-like nuclear changes are follicular adenomas when they are noninvasive, follicular carcinomas when invasive, and follicular variant PTCs when they have fully developed PTC-type nuclear features in Asian practice. The different diagnostic threshold of PTC nuclear features resulted in a high (50–90%) incidence of BRAFV600E mutation of PTCs in most Asian countries, whereas it was low (35–50%) in most Western patient cohorts. The contamination of indolent RAS-like tumors in the malignant PTC category in Western patient cohorts explains why the BRAFV600E gene test identifies aggressive PTCs. However, the BRAFV600E test has no prognostic value for Asian PTC patients because most biologically benign or low-risk RAS-like tumors are excluded from PTC. All prognostic analyses of thyroid carcinomas before 2017 must be re-evaluated because most clinical guidelines were established based on data obtained from Western patient cohorts where a significant number of indolent RAS-like tumors were misclassified in the malignant category.

Clinicopathologic correlations of superficial esophageal adenocarcinoma in endoscopic submucosal dissection specimens

BackgroundEndoscopic submucosal dissection (ESD) is a novel endoscopic treatment for early esophageal adenocarcinoma (EAC). The western pathologists’ experience with ESD specimens remains limited. This study aimed to correlate histopathologic features of Barrett’s esophagus (BE)-associated adenocarcinoma in ESD resections with clinical outcomes to determine whether they aid future management decisions.MethodsWe retrospectively evaluated 49 consecutive ESD resection specimens from 42 patients with BE-associated adenocarcinoma (24 intramucosal and 18 submucosal EAC) at a single tertiary referral center. Pathologic evaluation included presence of dysplasia, invasive adenocarcinoma, peritumoral inflammation, desmoplasia, lymphovascular and perineural invasion; tumor differentiation, depth of invasion, morphology, and budding; and margin status for dysplasia or carcinoma. Follow up data included endoscopic biopsies in 35 patients and pathology reports of esophagectomies in 11 patients. Poor outcomes were defined as recurrence or residual invasive adenocarcinoma at esophagectomy, metastasis on imaging, or R1 resection in patients undergoing ESD for tumor debulking.ResultsTwo patients (8%) with intramucosal adenocarcinoma and 9 patients (50%) with submucosal adenocarcinoma had poor outcomes. Histopathologic features associated with poor outcomes included poor differentiation, lymphovascular invasion, submucosal invasion > 500 μm, tumor budding, and tubuloinfiltrative histologic pattern. Four patients had positive deep margin away from the deepest tumor invasion and did not show residual tumor on follow up.ConclusionsOur results validated European Society of Gastroenterology (ESGE) guidelines of high-risk pathologic features for additional therapy in esophageal adenocarcinoma and identified tumor budding frequently in association with other high-risk features. Positive deep margin distant from deepest tumor invasion could be procedural and warrants endoscopic correlation for management.

Histological criteria for “intraepithelial squamous cell carcinoma” of the esophagus: continued dialogue between Ukrainian and Japanese pathologists

Patients with esophageal squamous cell carcinoma (SCC) have a poor prognosis mostly due to the late diagnosis. A morphological method is still the main diagnostic method for SCC. The aim of the study was to find out which histological criteria, namely Western or Japanese criteria, for early stage SCC are used by pathologists in Ukraine as compared with their Japanese colleagues. 14Ukrainian and 6Japanese pathologists have participated in this study. Virtual slides for research were provided by National Cancer Research Center (Tokyo, Japan) in 2018. Each of the pathologists has used these slides and presented the conclusion via the Internet. Essential diagnostic discrepancies were revealed: a number of biopsy specimens was diagnosed by Japanese pathologists as "noninvasive carcinoma", while Ukrainian pathologists classified the specimens as high-grade or low-grade dysplasia, indefinite for neoplasia, or reactive/regenerative lesions. The adoption of a unified concept of criteria for non-invasive (intraepithelial) carcinoma underlies early endoscopic/surgical treatment, which significantly increases the survival rate of patients with SCC. A solid common approach to the diagnosis between Western and Japanese pathologists, as well as endoscopists, is necessary to ensure timely treatment and increase survival rate of patients with SCC.

Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer.

Endoscopic Recognition and Management Strategies for Malignant Colorectal Polyps: Recommendations of the US Multi-Society Task Force on Colorectal Cancer.

Contributions from Japan to gastrointestinal endoscopy training and development: Special report.

Contributions from Japan to gastrointestinal endoscopy training and development: Special report.

Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented.

The importance of the concept and histological criteria of \u201cintraepithelial squamous cell carcinoma\u201d of the esophagus: in comparison between Western and Japanese criteria

BackgroundThere are differences in the histological diagnostic criteria for early stage gastrointestinal carcinoma between Western and Japanese pathologists. Western histological criteria of carcinoma are “presence of stromal invasion of neoplastic cells”, while Japanese criteria are “the degree of cytological and structural abnormality of neoplastic cells, regardless of stromal invasion”. The aim of the present study is to clarify and review the present status of the Western and Japanese histological criteria of early stage esophageal squamous cell carcinoma (SCC) and also to clarify their significance and accuracy.MethodsTwenty-nine Polish, German, and Japanese pathologists participated in this study. A total of 18 histological slides of biopsy, endoscopic submucosal dissection (ESD), and surgical resection of esophageal squamous lesions were diagnosed using a virtual slide system.ResultsMost of noninvasive (intraepithelial) carcinomas diagnosed by Japanese pathologists were diagnosed as high- or low-grade dysplasia (intraepithelial neoplasia) or reactive atypia by the majority of Polish and German pathologists. Diagnoses of not only high-grade dysplasia but also low-grade dysplasia or reactive lesion by Western criteria were given for many biopsy specimens of cases in which the corresponding ESD or surgical specimens showed definite stromal invasion.ConclusionThere still exist differences in the histological diagnostic criteria for early stage esophageal carcinoma between Western and Japanese pathologists. The Japanese diagnostic criteria could improve agreement of diagnoses between biopsy and resected specimens of esophageal SCC. Moreover, diagnostic approaches using Western criteria may cause delay in the early diagnosis and treatment of esophageal SCC.

Differences in the pathological diagnosis of colorectal neoplasia between the East and the West: Present status and future perspectives from Japan

It is well known that there are discrepancies in the diagnosis of gastrointestinal neoplasia between Western and Japanese pathologists. In the West, colorectal cancer (CRC) is defined by invasion through the muscularis mucosa into the submucosa, especially depending on the presence of desmoplasia. In Japan, however, CRC is defined based on a combination of nuclear and architectural abnormalities, regardless of invasion status. As a result, intramucosal carcinoma is diagnosed as high-grade dysplasia and even intramucosal carcinoma with poorly differentiated component is classified as 'Tis' in the West. It is logical and reasonable that the term 'T1' is used to currently describe intramucosal carcinoma. Use of the term 'high-grade dysplasia' for intramucosal CRC is outdated. In order to determine appropriate clinical treatment of CRC, the various risk factors of metastasis should be fully evaluated. With improved contributions and communication between pathologists and clinicians, overtreatment and inadequate follow up can be avoided. The discrepancies in the diagnosis of CRC between Western and Japanese pathologists may be addressed by an increase in East-West exchange. In addition, in the future, molecular analysis may also be useful for establishment of standardized diagnostic criteria of CRC.

Gastric high-grade dysplasia can be associated with submucosal invasion: evaluation of its prevalence in a series of 121 endoscopically resected specimens.

Gastric neoplasms classified as high-grade dysplasia (HGD) by Western pathologists are frequently diagnosed as tubular adenocarcinoma in Japan. Here, we evaluated the prevalence of submucosal and lymphovascular invasion in a series of 125 endoscopically resected gastric neoplasms. On the basis of Western criteria, the lesions were classified as poorly cohesive carcinomas (n=4) (excluded from further analysis), low-grade dysplasia (n=4), pure HGD (n=78), HGD with tubular adenocarcinoma (n=4), and pure tubular adenocarcinoma (n=35). Submucosal invasion was found in 3.8% of the 78 HGDs, 75.0% of the 4 HGDs combined with adenocarcinoma, and 11.4% of the 35 adenocarcinomas. Venous invasion was detected in 1.3% of the 78 HGDs, 75% of the 4 HGDs combined with adenocarcinoma, and none of the 35 tubular adenocarcinomas. Lymphatic invasion was absent in HGD but noted in 25% of the HGDs combined with adenocarcinoma, and 2.9% of the tubular adenocarcinomas. Thus, we demonstrated that lesions characterized as HGD on the basis of Western criteria can be associated with submucosal and lymphovascular invasion. Endoscopic therapy has made it less crucial to differentiate between HGD and intramucosal adenocarcinoma in biopsy samples of small tubular neoplasms. However, it is important to recognize that the criteria for dysplasia currently used in the West may understate the degree of malignant potential. To limit any diagnostic discrepancy between biopsy, endoscopic resection, and surgical specimens, it is suggested that the features of HGD and adenocarcinoma be reevaluated, which may result in some lesions being classified as mucosal adenocarcinoma.

Definition of Barrett's esophagus dysplasia: are we speaking the same language?

The definition of Barrett's esophagus (BE) is still a matter of debate. The diagnostic criteria adopted around the world for both BE and BE-related pre-cancerous lesions are inconsistent, particularly between Eastern and Western pathologists. From a clinical perspective, these different clinico-biological approaches may affect how the literature is interpreted, with detrimental effects on the clinical management of patients. The present review focuses on the major discrepancies in the field, covering both the non-neoplastic and the pre-cancerous lesions associated with Barrett's disease.

Endoscopic resection for gastric epithelial neoplasia: How to solve pathological discrepancy and achieve curative resection?

Endoscopic resection (ER) was introduced to China from Japan, while most pathologists are influenced by Western criteria. Japanese and Western pathologists have debated for decades how best to distinguish between gastric intraepithelial neoplasia (GIEN) and early gastric cancer (EGC). In this study we aimed to find out how to solve this pathological discrepancy and improve the curative resection of lesions based on our experiences. In total, 143 patients with GIEN or EGC were treated by ER in our hospital from April 2008 to April 2012. The risk factors related to the degree of malignancy of the lesions and the non-curability of ER were analyzed. Pathological discrepancy between forceps biopsies and ER specimens was also compared. According to the histological types of the ER specimens, there were 67 patients with low-grade intraepithelial neoplasia (LGIN), 35 with high-grade intraepithelial neoplasia (HGIN) and 41 with EGC. The ER histological type was significantly correlated with gender, ER method, macroscopic type, tumor size, ulcer and histological type of the forceps biopsy (P < 0.05). The discrepancy between forceps biopsy and ER specimens was 41.3% (59/143). Furthermore, the depth of tumor invasion and ER histological type were associated with the curative resection of HGIN and EGC (P < 0.05). The pathological discrepancy shows that patients with HGIN in forceps biopsy should be considered candidates for ER. The risk factors of lesion malignancy and ER curability indicate the great importance of pretreatment evaluation for ER.

Towards the Standardization of Gastric Dysplasia and Early Gastric Cancer Histological Diagnosis

Copyright: © 2013 Saragoni L. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. As the history of the pathological diagnosis of Gastric Dysplasia (GD) and Early Gastric Cancer (EGC) clearly shows, Western pathologists and their Japanase counterparts have always differed over the classification of the two categories. What in the West is identified as GD is often considered as EGC in Japan.

Update on Precursor and Early Lesions of Hepatocellular Carcinomas

There is increasing evidence to support a multistep model of the process of human hepatocarcinogenesis. Precursor lesions are characterized by the appearance of dysplastic lesions in the form of microscopic dysplastic foci and macroscopic dysplastic nodules. There are 2 types of small hepatocellular carcinoma (HCC) (≤2 cm in diameter): (1) early HCC with an indistinct margin and (2) progressed HCC with a distinct margin. Pathologic diagnostic criteria for early HCC have recently been set up based on a consensus between Eastern and Western pathologists. To review the nomenclature, pathology, and biomarkers of precursor and early lesions of HCC. Literature review and illustrations from case materials were used. Dysplastic foci are composed of large and small cell changes. Small cell change is considered to be a more advanced precursor lesion than large cell change, and large cell change is a rather heterogeneous lesion that may represent both reactive change and true dysplasia. Dysplastic nodules can be categorized as low or high grade according to the degree of atypia. High-grade dysplastic nodules have been reported to show molecular changes similar to HCC and have a high risk of malignant transformation. Early HCC, which may correspond to microinvasive carcinomas of other organs, is a well-differentiated HCC, and differential diagnosis between early HCC and high-grade dysplastic nodule is difficult. Identification of stromal invasion and application of a panel of markers (glypican-3, heat shock protein 70, and glutamine synthetase) is helpful for diagnosis of early HCC. Detection of precursor lesions of HCC is important in recognizing patients with higher risk of developing HCC, and diagnosis of early HCC can improve patient survival by allowing for early and adequate treatment.

Update on precursor and early lesions of hepatocellular carcinomas.

Abstract Context.—There is increasing evidence to support a multistep model of the process of human hepatocarcinogenesis. Precursor lesions are characterized by the appearance of dysplastic lesions in the form of microscopic dysplastic foci and macroscopic dysplastic nodules. There are 2 types of small hepatocellular carcinoma (HCC) (≤2 cm in diameter): (1) early HCC with an indistinct margin and (2) progressed HCC with a distinct margin. Pathologic diagnostic criteria for early HCC have recently been set up based on a consensus between Eastern and Western pathologists. Objective.—To review the nomenclature, pathology, and biomarkers of precursor and early lesions of HCC. Data Sources.—Literature review and illustrations from case materials were used. Conclusions.—Dysplastic foci are composed of large and small cell changes. Small cell change is considered to be a more advanced precursor lesion than large cell change, and large cell change is a rather heterogeneous lesion that may represent both reactive ...

Diagnosis of gastric epithelial neoplasia: Dilemma for Korean pathologists

The histopathological diagnosis of gastric mucosal biopsy and endoscopic mucosal resection/endoscopic submucosal dissection specimens is important, but the diagnostic criteria, terminology, and grading system are not the same in the East and West. A structurally invasive focus is necessary to diagnose carcinoma for most Western pathologists, but Japanese pathologists make a diagnosis of cancer based on severe dysplastic cytologic atypia irrespective of the presence of invasion. Although the Vienna classification was introduced to reduce diagnostic discrepancies, it has been difficult to adopt due to different concepts for gastric epithelial neoplastic lesions. Korean pathologists experience much difficulty making a diagnosis because we are influenced by Japanese pathologists as well as Western medicine. Japan is geographically close to Korea, and academic exchanges are active. Additionally, Korean doctors are familiar with Western style medical terminology. As a result, the terminology, definitions, and diagnostic criteria for gastric intraepithelial neoplasia are very heterogeneous in Korea. To solve this problem, the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists has made an effort and has suggested guidelines for differential diagnosis: (1) a diagnosis of carcinoma is based on invasion; (2) the most important characteristic of low grade dysplasia is the architectural pattern such as regular distribution of crypts without severe branching, budding, or marked glandular crowding; (3) if nuclear pseudostratification occupies more than the basal half of the cryptal cells in three or more adjacent crypts, the lesion is considered high grade dysplasia; (4) if severe cytologic atypia is present, careful inspection for invasive foci is necessary, because the risk for invasion is very high; and (5) other structural or nuclear atypia should be evaluated to make a final decision such as cribriform pattern, papillae, ridges, vesicular nuclei, high nuclear/cytoplasmic ratio, loss of nuclear polarity, thick and irregular nuclear membrane, and nucleoli.

Italy-Japan agreement and discrepancies in diagnosis of superficial gastric lesions

The agreement between Italian and Japanese endoscopists and pathologists on endoscopic and histopathological diagnoses of superficial gastric lesions is verified with the use of Paris and Vienna classifications. The correlations between Paris endoscopic types and Vienna histopathological categories is high in both the independent Italian and Japanese evaluations. However, the agreement between Italian and Japanese endoscopists is moderate due to the difficult evaluation of the height of the lesions, in particular when they are mixed. The agreement on the size of the lesions is fairly good. The probability of the same allocation to the Vienna categories of a single case is 87 per cent, disagreements remaining in dysplasia grading, between dysplasia, not only high-grade but also low-grade, and in situ carcinoma, and on cancer invasion of the lamina propria. The results indicate that use of the Paris and Vienna classifications has reduced the discrepancies between Western and Japanese endoscopists and pathologists in the diagnosis of these lesions.

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.

Fabulous contributions of Japanese doctors to relevant gastrointestinal, especially esophageal, pathology in the United States as well as areas of contention

There are innumerable contributions of Japanese doctors, especially Japanese pathologists, to the practice of modern gastrointestinal pathology. Among these are the basic descriptions and definitions of the most important gastric polyps, the identification of the duplicated muscularis mucosae in Barrett’s esophagus, the discovery of the minute or seedling leiomyomas in both muscularis mucosae and propria, and the first recognition of the importance of the c-kit gene and its protein product in the evolution of gastrointestinal stromal tumors and in defining the cells that make up these tumors. There are also areas of disagreement between Japanese and Western pathologists, particularly about whether invasive growth is a requirement for the diagnosis of carcinoma in the gut. Regardless, each group of pathologists has successfully used its specific approach to the carcinoma diagnosis with appropriate response on the part of the involved clinicians. What works in Japan need not be what works in the West, and vice versa.

The Detection of Flat and Depressed Colorectal Lesions: Which Endoscopic Imaging Approach?

The secondary prevention of colorectal cancer (CRC) assumes that early detection and resection of precursor lesions disrupts the adenoma– carcinoma sequence and halts progression to invasive neoplastic disease. The adenoma– carcinoma sequence has until now formed the rationale for endoscopic therapies directed at reducing the incidence of CRC. The fact that snare polypectomy of exophytic lesions fails to prevent progression to carcinoma in up to 24% of cases has prompted reevaluation of the prevalence and clinicopathologic significance of flat and depressed colorectal lesions in Western population cohorts. Such lesions, although well-described in the Japanese literature, have only recently been reported in Western population cohorts. Debate has continued regarding their prevalence, anatomic localization, histopathologic characteristics, and proposed imaging modality of choice. Within this perspective, we summarize the key data pertinent to recently described endoscopic diagnostic modalities and detail their clinical applicability both for the detection of flat neoplastic lesions occurring in the “sporadic” patient cohort, familial polyposis syndromes, and chronic ulcerative colitis.