Objective:To investigate the variations and co-alteration of KRAS and HER-family genes in the patients with ampullary carcinoma.Methods:A total of 37 formalin-fixed paraffin-embedded primary ampullary carcinoma specimens, which were collected at Peking Union Medical College Hospital from April 2019 to October 2024 were analyzed for KRAS and HER-family gene mutations using next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed for HER2 protein expression in HER2 mutation cases and fluorescence in situ hybridization (FISH) for further gene status in HER2 IHC 2+cases.Results:In our cohort (22 males, 15 females; 31-82 years old), KRAS gene mutations were detected in 51.4% (19/37) of cases, with G12D being the most frequent abnormality (7/19), followed by G12V (5/19) and Q61R (3/19). Other variants of KRAS gene included G12C, A146T, N116H, and Q61H (each 1/19). In this cohort, 27.0% (10/37) of cases harbored HER-family gene alterations with most frequently in HER2 (6/10) and HER3 genes (missense mutations mainly). Notably, 3 cases (8.1%, 3/37) with coexistence of KRAS and HER-family genes mutations were recognized in our series, including KRAS p.G12D/HER2 p.V842I/HER2 p.V777L (c.2329 G>T)/HER3 p.Asp581Asn, KRAS p.Q61R/HER4 p.D1018H and KRAS p.G12C/HER2 p.R678Q. Additionally, a mutation of HER3 p.V104L (c.310 G>C) was identified in our population. Moreover, 4 novel mutations including HER3 p.V296E, HER3 p.V920L (c.2758 G>T), HER3 p.Asp581Asn, and HER4 p.D1018H were detected. In 6 tumors with HER2 gene changes (16.2%, 6/37), 5 variants with the high proportion of HER2 p.S310Y (3/6) were revealed. A tumor (HER2 IHC 2+) with HER2 p.S310Y presented HER2 gene amplification confirmed by NGS and FISH, and another one (also HER2 IHC 2+) with HER2 p.L755S possessed HER2 gene amplification determined by FISH assay.Conclusion:In ampullary carcinoma, co-alteration of KRAS and HER-family genes is observed, and HER2 gene mutations account for more than half of HER-family gene abnormities, which may be accompanied by gene amplification.

Objective:To investigate the diagnostic features of eosinophilic gastroenteritis (EGE) of the stomach and duodenum.Methods:A case-control study was conducted to retrospectively analyze 238 biopsy specimens of gastric and duodenal EGE (75 cases) and 133 biopsy specimens of chronic active gastroenteritis (97 cases) in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China from 2012 to 2023. The eosinophil count, infiltration site and other pathological features (e.g., infiltration of neutrophils into the epithelium, edema, and increase of background lymphocytes and plasma cells) were examined under a microscope. Chi-square test, chi-square multiple comparison ( Bonferroni method) and modified Poisson regression were used to analyze the data. Results:The results showed that there were significant differences in eosinophil count ( χ2=43.926, P<0.01), location ( χ2=31.391, P<0.01), neutrophilic infiltration of the epithelium ( χ2=5.199, P=0.023), edema ( χ2=3.934, P=0.047), and lymphoplasmacytosis ( χ2=36.813, P<0.01) between the EGE and control cases. The results of Chi-square multiple comparisons showed that eosinophils distributed in clusters or sheets (versus other grades of eosinophil presence) were statistically associated with EGE. When eosinophils infiltrated the epithelium (versus eosinophils in other locations of the mucosa), there was a statistically significant association with EGE. Modified Poisson regression also showed that EGE was more likely to have eosinophilic infiltration of epithelium [ RR=1.661, P=0.001,95% CI (1.397,1.973)] and that of muscularis mucosa [ RR=1.818, P<0.01,95% CI (1.491,2.216)]. Conclusions:The important pathological features for diagnosing EGE of the stomach and duodenum are that eosinophils are clustered or distributed in sheets with epithelial infiltration. However, epithelial infiltration by neutrophils, edema and background lymphoplasmacytosis are relatively rare.

A 15-year-old boy developed abdominal pain and melena two weeks after COVID-19 infection, which was followed by gross hematuria and proteinuria. Laboratory studies revealed significantly elevated inflammatory markers. Endoscopic examinations showed multiple jejunal and ileal ulcers. Renal biopsy suggested mesangial proliferative glomerulonephritis with crescent formation, necrosis of capillary loops, and mesangial IgA deposits. IgA vasculitis without purpura was considered as a possible diagnosis, and the treatment with prednisone led to remission of both gastrointestinal and renal diseases.

Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74％(36/38),and the excellent& good rate was 26.32％(10/38).The excellent & good rate of automated staining(41.12％,7/17)was significant-ly higher than that of manual staining(14.29％,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.

Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74％(36/38),and the excellent& good rate was 26.32％(10/38).The excellent & good rate of automated staining(41.12％,7/17)was significant-ly higher than that of manual staining(14.29％,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.

The incidence of digestive system diseases is high. So digestive system pathology is widely concerned. In the past 10 years, Chinese pathologists insist on hard work and have made significant progress. This article reviews the research and practice progress in digestive system tumors and non-tumors in the past 10 years, including the establishment of diagnostic criteria for gastrointestinal tract, hepatobiliary and pancreatic diseases, the establishment and classification of new diseases with special morphology, the classification and standard update of gastrointestinal and pancreatic neuroendocrine tumors, the progress of molecular pathology, and non-tumor lesions of the digestive system. The future development trend of digestive system pathology is also prospected.

The incidence of digestive system diseases is high. So digestive system pathology is widely concerned. In the past 10 years, Chinese pathologists insist on hard work and have made significant progress. This article reviews the research and practice progress in digestive system tumors and non-tumors in the past 10 years, including the establishment of diagnostic criteria for gastrointestinal tract, hepatobiliary and pancreatic diseases, the establishment and classification of new diseases with special morphology, the classification and standard update of gastrointestinal and pancreatic neuroendocrine tumors, the progress of molecular pathology, and non-tumor lesions of the digestive system. The future development trend of digestive system pathology is also prospected.

Objective:To investigate the variations and co-alteration of KRAS and HER-family genes in the patients with ampullary carcinoma.Methods:A total of 37 formalin-fixed paraffin-embedded primary ampullary carcinoma specimens, which were collected at Peking Union Medical College Hospital from April 2019 to October 2024 were analyzed for KRAS and HER-family gene mutations using next-generation sequencing (NGS). Immunohistochemistry (IHC) was performed for HER2 protein expression in HER2 mutation cases and fluorescence in situ hybridization (FISH) for further gene status in HER2 IHC 2+cases.Results:In our cohort (22 males, 15 females; 31-82 years old), KRAS gene mutations were detected in 51.4% (19/37) of cases, with G12D being the most frequent abnormality (7/19), followed by G12V (5/19) and Q61R (3/19). Other variants of KRAS gene included G12C, A146T, N116H, and Q61H (each 1/19). In this cohort, 27.0% (10/37) of cases harbored HER-family gene alterations with most frequently in HER2 (6/10) and HER3 genes (missense mutations mainly). Notably, 3 cases (8.1%, 3/37) with coexistence of KRAS and HER-family genes mutations were recognized in our series, including KRAS p.G12D/HER2 p.V842I/HER2 p.V777L (c.2329 G>T)/HER3 p.Asp581Asn, KRAS p.Q61R/HER4 p.D1018H and KRAS p.G12C/HER2 p.R678Q. Additionally, a mutation of HER3 p.V104L (c.310 G>C) was identified in our population. Moreover, 4 novel mutations including HER3 p.V296E, HER3 p.V920L (c.2758 G>T), HER3 p.Asp581Asn, and HER4 p.D1018H were detected. In 6 tumors with HER2 gene changes (16.2%, 6/37), 5 variants with the high proportion of HER2 p.S310Y (3/6) were revealed. A tumor (HER2 IHC 2+) with HER2 p.S310Y presented HER2 gene amplification confirmed by NGS and FISH, and another one (also HER2 IHC 2+) with HER2 p.L755S possessed HER2 gene amplification determined by FISH assay.Conclusion:In ampullary carcinoma, co-alteration of KRAS and HER-family genes is observed, and HER2 gene mutations account for more than half of HER-family gene abnormities, which may be accompanied by gene amplification.

Objective:To investigate the diagnostic features of eosinophilic gastroenteritis (EGE) of the stomach and duodenum.Methods:A case-control study was conducted to retrospectively analyze 238 biopsy specimens of gastric and duodenal EGE (75 cases) and 133 biopsy specimens of chronic active gastroenteritis (97 cases) in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China from 2012 to 2023. The eosinophil count, infiltration site and other pathological features (e.g., infiltration of neutrophils into the epithelium, edema, and increase of background lymphocytes and plasma cells) were examined under a microscope. Chi-square test, chi-square multiple comparison ( Bonferroni method) and modified Poisson regression were used to analyze the data. Results:The results showed that there were significant differences in eosinophil count ( χ2=43.926, P<0.01), location ( χ2=31.391, P<0.01), neutrophilic infiltration of the epithelium ( χ2=5.199, P=0.023), edema ( χ2=3.934, P=0.047), and lymphoplasmacytosis ( χ2=36.813, P<0.01) between the EGE and control cases. The results of Chi-square multiple comparisons showed that eosinophils distributed in clusters or sheets (versus other grades of eosinophil presence) were statistically associated with EGE. When eosinophils infiltrated the epithelium (versus eosinophils in other locations of the mucosa), there was a statistically significant association with EGE. Modified Poisson regression also showed that EGE was more likely to have eosinophilic infiltration of epithelium [ RR=1.661, P=0.001,95% CI (1.397,1.973)] and that of muscularis mucosa [ RR=1.818, P<0.01,95% CI (1.491,2.216)]. Conclusions:The important pathological features for diagnosing EGE of the stomach and duodenum are that eosinophils are clustered or distributed in sheets with epithelial infiltration. However, epithelial infiltration by neutrophils, edema and background lymphoplasmacytosis are relatively rare.

A 15-year-old boy developed abdominal pain and melena two weeks after COVID-19 infection, which was followed by gross hematuria and proteinuria. Laboratory studies revealed significantly elevated inflammatory markers. Endoscopic examinations showed multiple jejunal and ileal ulcers. Renal biopsy suggested mesangial proliferative glomerulonephritis with crescent formation, necrosis of capillary loops, and mesangial IgA deposits. IgA vasculitis without purpura was considered as a possible diagnosis, and the treatment with prednisone led to remission of both gastrointestinal and renal diseases.