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The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements. The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
ABSTRACT
The first edition of ‘A Standardized Pathology Report for Gastric Cancer’ was initiated by the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists and published 17 years ago. Since then, significant advances have been made in the pathologic diagnosis, molecular genetics, and management of gastric cancer (GC). To reflect those changes, a committee for publishing a second edition of the report was formed within the Gastrointestinal Pathology Study Group of the Korean Society of Pathologists. This second edition consists of two parts: standard data elements and conditional data elements.The standard data elements contain the basic pathologic findings and items necessary to predict the prognosis of GC patients, and they are adequate for routine surgical pathology service. Other diagnostic and prognostic factors relevant to adjuvant therapy, including molecular biomarkers, are classified as conditional data elements to allow each pathologist to selectively choose items appropriate to the environment in their institution. We trust that the standardized pathology report will be helpful for GC diagnosis and facilitate large-scale multidisciplinary collaborative studies.
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Autoimmune hepatitis (AIH) is a chronic, autoimmune disease of the liver that occurs when the body’s immune system attacks liver cells, causing the liver to be inflamed. AIH is one of the manifestations of a coronavirus disease 2019 (COVID-19), as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Few cases of AIH have been described after vaccination with two messenger RNA (mRNA)-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of AIH occurring after Pfizer-BioNTech COVID-19 vaccine. A 27-year-old female presented with jaundice and hepatomegaly, appearing 14 days after receiving the second dose of Pfizer-BioNTech vaccine. Her laboratory results showed abnormal liver function with high total immunoglobulin G level. She was diagnosed with AIH with histologic finding and successfully treated with oral prednisolone. We report an AIH case after COVID-19 vaccination in Korea.
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Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
ABSTRACT
Although the understanding of appendiceal mucinous neoplasms (AMNs) and their relationship with disseminated peritoneal mucinous disease have advanced, the diagnosis, classification, and treatment of AMNs are still confusing for pathologists and clinicians. The Gastrointestinal Pathology Study Group of the Korean Society of Pathologists (GPSG-KSP) proposed a multicenter study and held a workshop for the “Standardization of the Pathologic Diagnosis of the Appendiceal Mucinous Neoplasm” to overcome the controversy and potential conflicts. The present article is focused on the diagnostic criteria, terminologies, tumor grading, pathologic staging, biologic behavior, treatment, and prognosis of AMNs and disseminated peritoneal mucinous disease. In addition, GPSG-KSP proposes a checklist of standard data elements of appendiceal epithelial neoplasms to standardize pathologic diagnosis. We hope the present article will provide pathologists with updated knowledge on how to handle and diagnose AMNs and disseminated peritoneal mucinous disease.
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Background@#Liver biopsy is the essential method to diagnose non-alcoholic steatohepatitis (NASH), but histological features of NASH are too subjective to achieve reproducible diagnoses in early stages of disease. We aimed to identify the key histological features of NASH and devise a scoring model for diagnosis. @*Methods@#Thirteen pathologists blindly assessed 12 histological factors and final histological diagnoses (‘not-NASH,’ ‘borderline,’ and ‘NASH’) of 31 liver biopsies that were diagnosed as non-alcoholic fatty liver disease (NAFLD) or NASH before and after consensus. The main histological parameters to diagnose NASH were selected based on histological diagnoses and the diagnostic accuracy and agreement of 12 scoring models were compared for final diagnosis and the NAFLD Activity Score (NAS) system. @*Results@#Inter-observer agreement of final diagnosis was fair (κ = 0.25) before consensus and slightly improved after consensus (κ = 0.33). Steatosis at more than 5% was the essential parameter for diagnosis. Major diagnostic factors for diagnosis were fibrosis except 1C grade and presence of ballooned cells. Minor diagnostic factors were lobular inflammation ( ≥ 2 foci/ × 200 field), microgranuloma, and glycogenated nuclei. All 12 models showed higher inter-observer agreement rates than NAS and post-consensus diagnosis (κ = 0.52–0.69 vs. 0.33). Considering the reproducibility of factors and practicability of the model, summation of the scores of major (× 2) and minor factors may be used for the practical diagnosis of NASH. @*Conclusions@#A scoring system for the diagnosis of NAFLD would be helpful as guidelines for pathologists and clinicians by improving the reproducibility of histological diagnosis of NAFLD.
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The first edition of the ‘Standardized Pathology Report for Colorectal Cancer,’ which was developed by the Gastrointestinal Pathology Study Group (GIP) of the Korean Society of Pathologists, was published 13 years ago. Meanwhile, there have been many changes in the pathologic diagnosis of colorectal cancer (CRC), pathologic findings included in the pathology report, and immunohistochemical and molecular pathology required for the diagnosis and treatment of colorectal cancer. In order to reflect these changes, we (GIP) decided to make the second edition of the report. The purpose of this standardized pathology report is to provide a practical protocol for Korean pathologists, which could help diagnose and treat CRC patients. This report consists of “standard data elements” and “conditional data elements.” Basic pathologic findings and parts necessary for prognostication of CRC patients are classified as “standard data elements,” while other prognostic factors and factors related to adjuvant therapy are classified as “conditional data elements” so that each institution could select the contents according to the characteristics of the institution. The Korean version is also provided separately so that Korean pathologists can easily understand and use this report. We hope that this report will be helpful in the daily practice of CRC diagnosis.
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Purpose@#The most recent 2017 World Health Organization (WHO) classification of pancreatic neuroendocrine neoplasms (PanNENs) has refined the three-tiered 2010 scheme by separating grade 3 pancreatic neuroendocrine tumors (G3 PanNETs) from poorly differentiated pancreatic neuroendocrine carcinomas (PanNECs). However, differentiating between G3 Pan- NETs and PanNECs is difficult in clinical practice. @*Materials and Methods@#Eighty-two surgically resected PanNENs were collected from 16 institutions and reclassified according to the 2017 WHO classification based on the histological features and proliferation index (mitosis and Ki-67). Immunohistochemical stains for ATRX, DAXX, retinoblastoma, p53, Smad4, p16, and MUC1 were performed for 15 high-grade PanNENs. @*Results@#Re-classification resulted in 20 G1 PanNETs (24%), 47 G2 PanNETs (57%), eight G3 well-differentiated PanNETs (10%), and seven poorly differentiated PanNECs (9%). PanNECs showed more frequent diffuse nuclear atypia, solid growth patterns and apoptosis, less frequent organoid growth and regular vascular patterns, and absence of low-grade PanNET components than PanNETs. The Ki-67 index was significantly higher in PanNEC (58.2%± 15.1%) compared to G3 PanNET (22.6%±6.1%, p < 0.001). Abnormal expression of any two of p53, p16, MUC1, and Smad4 could discriminate PanNECs from G3 PanNETs with 100% specificity and 87.5% sensitivity. @*Conclusion@#Histological features supporting the diagnosis of PanNECs over G3 PanNETs were the absence of a low-grade PanNET component in the tumor, the presence of diffuse marked nuclear atypia, solid growth pattern, frequent apoptosis and markedly increased proliferative activity with homogeneous Ki-67 labeling. Immunohistochemical stains for p53, p16, MUC1, and Smad4 may be helpful in distinguishing PanNECs from G3 PanNETs in histologically ambiguous cases, especially in diagnostic practice when only small biopsied tissues are available.
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Background@#Immunohistochemistry (IHC) has played an essential role in the diagnosis of hematolymphoid neoplasms. However, IHC interpretations can be challenging in daily practice, and exponentially expanding volumes of IHC data are making the task increasingly difficult. We therefore developed a machine-learning expert-supporting system for diagnosing lymphoid neoplasms. @*Methods@#A probabilistic decision-tree algorithm based on the Bayesian theorem was used to develop mobile application software for iOS and Android platforms. We tested the software with real data from 602 training and 392 validation cases of lymphoid neoplasms and compared the precision hit rates between the training and validation datasets. @*Results@#IHC expression data for 150 lymphoid neoplasms and 584 antibodies was gathered. The precision hit rates of 94.7% in the training data and 95.7% in the validation data for lymphomas were not statistically significant. Results in most B-cell lymphomas were excellent, and generally equivalent performance was seen in T-cell lymphomas. The primary reasons for lack of precision were atypical IHC profiles for certain cases (e.g., CD15-negative Hodgkin lymphoma), a lack of disease-specific markers, and overlapping IHC profiles of similar diseases. @*Conclusions@#Application of the machine-learning algorithm to diagnosis precision produced acceptable hit rates in training and validation datasets. Because of the lack of origin- or disease- specific markers in differential diagnosis, contextual information such as clinical and histological features should be taken into account to make proper use of this system in the pathologic decision-making process.
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Background@#Immunohistochemistry (IHC) has played an essential role in the diagnosis of hematolymphoid neoplasms. However, IHC interpretations can be challenging in daily practice, and exponentially expanding volumes of IHC data are making the task increasingly difficult. We therefore developed a machine-learning expert-supporting system for diagnosing lymphoid neoplasms. @*Methods@#A probabilistic decision-tree algorithm based on the Bayesian theorem was used to develop mobile application software for iOS and Android platforms. We tested the software with real data from 602 training and 392 validation cases of lymphoid neoplasms and compared the precision hit rates between the training and validation datasets. @*Results@#IHC expression data for 150 lymphoid neoplasms and 584 antibodies was gathered. The precision hit rates of 94.7% in the training data and 95.7% in the validation data for lymphomas were not statistically significant. Results in most B-cell lymphomas were excellent, and generally equivalent performance was seen in T-cell lymphomas. The primary reasons for lack of precision were atypical IHC profiles for certain cases (e.g., CD15-negative Hodgkin lymphoma), a lack of disease-specific markers, and overlapping IHC profiles of similar diseases. @*Conclusions@#Application of the machine-learning algorithm to diagnosis precision produced acceptable hit rates in training and validation datasets. Because of the lack of origin- or disease- specific markers in differential diagnosis, contextual information such as clinical and histological features should be taken into account to make proper use of this system in the pathologic decision-making process.
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PURPOSE: The diagnostic criteria of gastric intraepithelial neoplasia (IEN) are controversial across the world. We investigated how many discrepancies occur in the pathologic diagnosis of IEN and early gastric carcinoma in endoscopic submucosal dissection (ESD) specimens, and evaluated the reasons of the discordance. MATERIALS AND METHODS: We retrospectively reviewed 1,202 ESD specimens that were originally diagnosed as gastric IEN and early carcinoma at 12 institutions. RESULTS: The final consensus diagnosis of carcinoma were 756 cases, which were originally 692 carcinomas (91.5%), 43 high-grade dysplasias (5.7%), 20 low-grade dysplasias (2.6%), and 1 others (0.1%), respectively. High- and low-grade dysplasia were finally made in 63 and 342 cases, respectively. The diagnostic concordance with the consensus diagnosis was the highest for carcinoma (91.5%), followed by low-grade dysplasia (86.3%), others (63.4%) and high-grade dysplasia (50.8%). The general kappa value was 0.83, indicating excellent concordance. The kappa values of individual institutions ranged from 0.74 to 1 and correlated with the proportion of carcinoma cases. The cases revised to a final diagnosis of carcinoma exhibited both architectural abnormalities and cytologic atypia. The main differential points between low- and high-grade dysplasias were the glandular distribution and glandular shape. Additional features such as the glandular axis, surface maturation, nuclear stratification and nuclear polarity were also important. CONCLUSION: The overall concordance of the diagnosis of gastric IEN and early carcinoma in ESD specimens was excellent. It correlated with the proportion of carcinoma cases, demonstrating that the diagnostic criteria for carcinoma are more reproducible than those for dysplasia.
Subject(s)
Consensus , Diagnosis , Retrospective Studies , Stomach NeoplasmsABSTRACT
BACKGROUND/AIMS: Regulatory dendritic cells (rDCs), which can be induced by mesenchymal stem cells (MSCs), play an important role in inducing and maintaining homeostasis of regulatory T cells and exhibit anti-inflammatory functions. In this study, we investigated whether MSCs could differentiate DCs into rDCs and compared the therapeutic effects of rDCs and MSCs on dextran sodium sulfate (DSS)-induced chronic colitis mice. METHODS: Immature DCs (imDCs) and lipopolysaccharide (LPS)-treated mature DCs (mDCs) were co-cultured with MSCs for 48 hours, and then the profiles of surface markers and cytokines and regulatory roles of these DCs for primary splenocytes were analyzed. In addition, the therapeutic effects of MSCs and DCs co-cultured with MSCs were compared in chronic colitis mice. RESULTS: After co-culture of imDCs (MSC-DCs) or LPS-treated mDCs (LPS+MSC-DCs) with MSCs, the expression of CD11c, CD80, CD86, interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ), was decreased, but that of CD11b, IL-10, and transforming growth factor-β (TGF-β) was increased. Furthermore, MSC-DCs and LPS+MSC-DCs induced the expression of CD4, CD25, and Foxp3 in primary splenocytes isolated from mice. In DSS-induced colitis mice, MSCs and MSC-DCs increased colon length, body weight, and survival rate and induced histological improvement. Moreover, in the colon tissues, the expression of IL-6, TNF-α, and IFN-γ decreased, but that of IL-10, TGF-β, and Foxp3 increased in the MSC- and MSC-DC-injected groups. CONCLUSIONS: Our data suggest that MSCs differentiate DCs into rDCs, which ameliorate chronic colitis. Thus, rDCs stimulated by MSCs may be therapeutically useful for the treatment of chronic inflammatory diseases.
Subject(s)
Animals , Mice , Body Weight , Coculture Techniques , Colitis , Colon , Cytokines , Dendritic Cells , Dextrans , Homeostasis , Inflammatory Bowel Diseases , Interleukin-10 , Interleukin-6 , Mesenchymal Stem Cells , Necrosis , Sodium , Survival Rate , T-Lymphocytes , T-Lymphocytes, Regulatory , Therapeutic UsesABSTRACT
With recent advances in molecular diagnostic methods and targeted cancer therapies, several molecular tests have been recommended for gastric cancer (GC) and colorectal cancer (CRC). Microsatellite instability analysis of gastrointestinal cancers is performed to screen for Lynch syndrome, predict favorable prognosis, and screen patients for immunotherapy. The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor has been approved in metastatic CRCs with wildtype RAS (KRAS and NRAS exon 2–4). A BRAF mutation is required for predicting poor prognosis. Additionally, amplification of human epidermal growth factor receptor 2 (HER2) and MET is also associated with resistance to EGFR inhibitor in metastatic CRC patients. The BRAF V600E mutation is found in sporadic microsatellite unstable CRCs, and thus is helpful for ruling out Lynch syndrome. In addition, the KRAS mutation is a prognostic biomarker and the PIK3CA mutation is a molecular biomarker predicting response to phosphoinositide 3-kinase/AKT/mammalian target of rapamycin inhibitors and response to aspirin therapy in CRC patients. Additionally, HER2 testing should be performed in all recurrent or metastatic GCs. If the results of HER2 immunohistochemistry are equivocal, HER2 silver or fluorescence in situ hybridization testing are essential for confirmative determination of HER2 status. Epstein-Barr virus–positive GCs have distinct characteristics, including heavy lymphoid stroma, hypermethylation phenotype, and high expression of immune modulators. Recent advances in next-generation sequencing technologies enable us to examine various genetic alterations using a single test. Pathologists play a crucial role in ensuring reliable molecular testing and they should also take an integral role between molecular laboratories and clinicians.
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BACKGROUND: Cancer stem cells have been investigated as new targets for colorectal cancer (CRC) treatment. We recently reported that CD133+ colon cancer cells showed chemoresistance to 5-fluorouracil through increased survivin expression and proposed the survivin inhibitor YM155 as an effective therapy for colon cancer in an in vitro study. Here, we investigate the relationship between survivin and CD133 expression in surgically resected CRC to identify whether the results obtained in our in vitro study are applicable to clinical samples. METHODS: We performed immunohistochemical staining for survivin and CD133 in surgically resected tissue from 187 stage II or III CRC patients. We also comparatively analyzed apoptosis according to survivin and CD133 expression using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling. RESULTS: The results of the Mantel-Haenszel test established a linear association between nuclear survivin and CD133 expression (p = .018), although neither had prognostic significance, according to immunohistochemical expression level. No correlation was found between survivin expression and the following pathological parameters: invasion depth, lymph node metastasis, or histologic differentiation (p > .05). The mean apoptotic index in survivin+ and CD133+ tumors was higher than that in negative tumors: 5.116 ± 4.894 in survivin+ versus 4.103 ± 3.691 in survivin– (p = .044); 5.165 ± 4.961 in CD133+ versus 4.231 ± 3.812 in CD133– (p = .034). CONCLUSIONS: As observed in our in vitro study, survivin expression is significantly related to CD133 expression. Survivin may be considered as a new therapeutic target for chemoresistant CRC.
Subject(s)
Humans , Apoptosis , Colonic Neoplasms , Colorectal Neoplasms , Deoxyuridine , Fluorouracil , In Vitro Techniques , Lymph Nodes , Neoplasm Metastasis , Neoplastic Stem CellsABSTRACT
PURPOSE: The molecular nature and the rate-limiting step of epigenetic field defects in the evolution of left-sided colorectal cancer (LCA) remain uncertain. MATERIALS AND METHODS: The methylation status of 27 candidate field defect markers, six classic CpG island methylator phenotype (CIMP) markers, and LINE-1 were determined in LCA and adjacent normal mucosas (ADJs) from 33 LCA patients and in left normal colorectal mucosa (LNM) from 33 age- and sex-matched controls. Hotspot mutation analyses in KRAS codons 12 and 13 and BRAF V600E were performed by genomic PCR and pyrosequencing using DNA extracted from endoscopically biopsied tissues. RESULTS: Among the 27 candidate genes tested, we confirmed 15 differentially methylated genes in cancer (15 DMGs; ER, SFRP1, MYOD1, MGMT, CD8a, SPOCK2, ABHD9, BNIP3, IGFBP3, WIF1, MAL, GDNF, ALX4, DOK5, and SLC16A12) in comparison to ADJ samples. We further compared the methylation status of 15 DMGs of ADJs to LNM and found only methylation levels of SLC16A12 in ADJs of LCA patients to be significantly higher than that in LNM (17.3% vs. 11.5%, p=0.002). Based on the CIMP, no significant differences in methylation levels of the 15 DMGs were found between ADJs in CIMP positive LCA cases and those without CIMP. In mutation analyses, no mutation was found in ADJs, while significant KRAS mutations (6/33, 18%) were noted in LCA samples. CONCLUSION: Epigenetic field defect marked by aberrant methylation is uncommon in normal-appearing ADJs of LCA, indicating the critical rate-limiting change of methylation is likely to occur with morphological alterations in the evolution of LCA.
Subject(s)
Humans , Codon , Colorectal Neoplasms , CpG Islands , DNA , Epigenomics , Glial Cell Line-Derived Neurotrophic Factor , Methylation , Mucous Membrane , Phenotype , Polymerase Chain ReactionABSTRACT
BACKGROUND: The histomorphologic criteria for the pathological features of liver tissue from patients with non-alcoholic fatty liver disease (NAFLD) remain subjective, causing confusion among pathologists and clinicians. In this report, we studied interobserver agreement of NAFLD pathologic features and analyzed causes of disagreement. METHODS: Thirty-one cases of clinicopathologically diagnosed NAFLD from 10 hospitals were selected. One hematoxylin and eosin and one Masson's trichrome-stained virtual slide from each case were blindly reviewed with regard to 12 histological parameters by 13 pathologists in a gastrointestinal study group of the Korean Society of Pathologists. After the first review, we analyzed the causes of disagreement and defined detailed morphological criteria. The glass slides from each case were reviewed a second time after a consensus meeting. The degree of interobserver agreement was determined by multi-rater kappa statistics. RESULTS: Kappa values of the first review ranged from 0.0091-0.7618. Acidophilic bodies (k = 0.7618) and portal inflammation (k = 0.5914) showed high levels of agreement, whereas microgranuloma (k = 0.0984) and microvesicular fatty change (k = 0.0091) showed low levels of agreement. After the second review, the kappa values of the four major pathological features increased from 0.3830 to 0.5638 for steatosis grade, from 0.1398 to 0.2815 for lobular inflammation, from 0.1923 to 0.3362 for ballooning degeneration, and from 0.3303 to 0.4664 for fibrosis. CONCLUSIONS: More detailed histomorphological criteria must be defined for correct diagnosis and high interobserver agreement of NAFLD.
Subject(s)
Humans , Biopsy , Consensus , Diagnosis , Eosine Yellowish-(YS) , Fibrosis , Glass , Hematoxylin , Inflammation , Liver , Non-alcoholic Fatty Liver DiseaseABSTRACT
Gallbladder cancer (GBC) is the most common primary hepatobiliary carcinoma and the sixth most common gastrointestinal malignancy. Adenocarcinoma accounts for the vast majority of GBCs (80–95%), whereas squamous cell carcinoma constitutes only 0–3.3% of GBCs. A 69-year-old man was suspected to have GBC with a cholecystoduodenal fistula on an abdominal computed tomography scan. He underwent esophagogastroduodenoscopy, which revealed that the duodenum was obstructed by the mass. Duodenal and biliary stents were successfully placed using endoscopic retrograde cholangiopancreatography. Pathology obtained from the duodenum revealed the mass to be a squamous cell carcinoma.
Subject(s)
Aged , Humans , Adenocarcinoma , Carcinoma, Squamous Cell , Cholangiopancreatography, Endoscopic Retrograde , Duodenum , Endoscopy, Digestive System , Epithelial Cells , Gallbladder Neoplasms , Gallbladder , Intestinal Fistula , Pathology , StentsABSTRACT
Inflammatory pseudotumor of the liver is a benign disease which is histologically characterized by plasma cell infiltration and reactive fibrotic inflammation. Differentiating this disease from malignant tumor is not easy. The authors report a case of inflammatory pseudotumor mimicked as intrahepatic cholangiocarcinoma. A 74-year-old man visited the emergency department complaining of jaundice and myalgia which have lasted for 1 to 2 weeks. After computed tomography (CT) scan and magnetic resonance imaging of the liver, he was initially diagnosed with intrahepatic cholangiocarcinoma, but was ultimately found to be inflammatory pseudotumor after pathologic examination of the liver tissue. His symptoms improved after a course of antibiotic therapy and conservative treatment, and the lesion disappeared on follow-up CT scan.