Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379852
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To investigate the clinicopathological and molecular genetic characteristics of SMARCB1-deficient sinonasal adenocarcinoma. A retrospective analysis was performed on 51 cases of poorly differentiated adenocarcinoma, yol...To investigate the clinicopathological and molecular genetic characteristics of SMARCB1-deficient sinonasal adenocarcinoma. A retrospective analysis was performed on 51 cases of poorly differentiated adenocarcinoma, yolk sac tumor, and SMARCB1-deficient carcinoma, diagnosed in the Eye, Ear, Nose and Throat Hospital of Fudan University between January 2016 and December 2024. Four cases of SMARCB1-deficient sinonasal adenocarcinoma were identified. The histological features, immunophenotypes and molecular characteristics were analyzed, and relevant literatures were reviewed. Among the 4 patients, 2 were male and 2 female, with age of 75, 52, 47 and 59 years, respectively. The clinical manifestations included nasal obstruction, epistaxis, and specific symptoms associated with the affected sites. Imaging studies revealed a mass lesion in the nasal cavity and ethmoid sinus, with invasion into surrounding structures. Histologically, the tumor demonstrated glandular, nested, trabecular, and cribriform patterns. The tumor cells displayed moderate to abundant eosinophilic cytoplasm with epithelioid or plasmacytoid features, while a few showed basaloid characteristics. Three cases showed a yolk sac tumor-like differentiation, including case 1 with Schiller-Duval body, case 4 characterized by a cribriform structure, and case 2 consisting of areas of basaloid cells and reticular/microcystic yolk sac tumor-like component. SMARCB1 protein was absent in all cases. SMARCA2 was detected in 3 cases, of which 2 cases (cases 1 and 4) were loss of expression. SMARCA4, ARID1A, and ARID1B proteins were retained. CK7 and CK19 immunoreactivity was variable. CDX2, SALL4 and Glypican-3 were predominantly present in the yolk sac tumor-like region, but not limited to this area. Only case 1 demonstrated focally positive for CK20, whereas S-100 and SOX-10 were negative in all cases. The Ki-67 index was 30% to 50%. Three cases (cases 1, 3 and 4) underwent FISH and next-generation sequencing analyses. Two cases demonstrated SMARCB1 deletion, whereas case 3 was negative. Tumor mutation burden ranged from 0.2 to 3.2 Muts/Mb. Follow-up data were available for 3 cases (excluding case 1), with durations of 29, 20, and 7 months, respectively. Case 2 died, and case 3 and case 4 were alive. SMARCB1-deficient sinonasal adenocarcinoma is a rare tumor, characterized by various degree of glandular differentiation and/or yolk sac tumor-like structures. It should be differentiated from other tumors with similar morphology, particularly intestinal-type and non-intestinal adenocarcinomas as well as yolk sac tumors. To avoid misdiagnosis, SMARCB1 immunohistochemistry should be routinely applied in the diagnosis and differential diagnosis of high-grade sinonasal malignant tumors.
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379851
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To investigate the clinicopathological and molecular characteristics of primary renal Ewing sarcoma. Seventeen cases of primary renal Ewing sarcoma were collected, diagnosed from January 2011 to May 2023 at Peking Unive...To investigate the clinicopathological and molecular characteristics of primary renal Ewing sarcoma. Seventeen cases of primary renal Ewing sarcoma were collected, diagnosed from January 2011 to May 2023 at Peking University Third Hospital (11 cases), Peking University Institute of Urology (4 cases), and Peking University Cancer Hospital (2 cases). The clinical, histopathological, and molecular features were studied using HE staining, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and targeted next-generation sequencing (NGS). The prognostic correlations were assessed. The cohort included 9 males and 8 females, aged 32 (24, 46) years. Presenting symptoms included hematuria and lumbar pain (13/17), right lower limb/buttock edema (1/17) and persistent low fever (1/17), and other two cases were incidentally detected by imaging in physical examination. All tumors showed renal venous/inferior vena cava tumor thrombosis and were treated with radical nephrectomy and thrombectomy. The tumor maximum diameters were 13.0 (9.0, 15.5) cm. Histologically, tumors showed morphology of diffuse sheets of small round cells with indistinct borders, round nuclei, fine chromatin, and frequent mitoses. Focal rosette-like structures were identified. The morphological heterogeneity was noted in 11 cases, including short spindle-shaped cells, gland-like structure formations, and hemangioma-like patterns. Renal pelvis invasion (5/17) and perirenal fat involvement (10/17) were identified. Immunohistochemistry showed diffuse positive for CD99 (17/17) and NKX2.2 (12/12), while FLI1 was positive in 6/12. Ki-67 indices ranged from 5% to 85%. FISH results confirmed EWSR1 rearrangement in all cases, and NGS (6/17) validated EWSR1-FLI1 fusions. Follow-up (3-84 months; 13/17) revealed metastases in 6 patients (adrenal gland, liver, bone, lung and peritoneum; 3-36 months post-surgery), of which 2 patients died, 1 patient with unknown time of death. The other 6 patients remained disease-free. All the metastatic cases showed elevated Ki-67 index (50%-70%) and necrosis. Primary renal Ewing sarcoma is an aggressive malignant tumor, often diagnosed at advanced stages with venous tumor thrombosis. The morphological heterogeneity and high rate of hemorrhage and necrosis are correlated with more invasive potential, suggesting prognostic significance.
Xu MY, Xia QY, Wang XT
… +7 more, Ding JR, Wang XX, Wu N, Fang R, Wang X, Zhang RS, Rao Q
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379850
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To investigate the clinicopathological characteristics, immunophenotype, molecular features, and differential diagnosis of low-grade eosinophilic renal tumors associated with FLCN mutations. Clinical and pathological da...To investigate the clinicopathological characteristics, immunophenotype, molecular features, and differential diagnosis of low-grade eosinophilic renal tumors associated with FLCN mutations. Clinical and pathological data from 18 cases of FLCN-mutation-associated low-grade eosinophilic renal tumors were collected from the Department of Pathology of Nanjing Jinling Hospital, Nanjing University School of Medicine. Histological morphology and immunophenotyping were performed, and high-throughput targeted gene mutation sequencing was performed on all 18 cases. Among the 18 patients, 13 were male and 5 were female, aged 55 (43, 62) years. Twelve cases were diagnosed with hereditary Birt-Hogg-Dubé (BHD) syndrome. Among patients with BHD syndrome, 10 had multifocal tumors and 7 had bilateral tumors. Of the 18 patients, 10 had typical hybrid eosinophilic/chromophobe tumors (HOCT), and 8 had unclassified eosinophilic tumors. Histologically, 10 cases of typical HOCT showed a characteristic "mosaic" pattern. The 8 cases of unclassified eosinophilic cell tumors were morphologically heterogeneous, including 4 cases resembling chromophobe renal cell carcinoma (ChRCC), 1 case resembling succinate dehydrogenase-deficient renal cell carcinoma (SDH-RCC), 2 cases rich in "histiocytic lakes," and 1 case with eosinophilic cell; all lacked the hybrid cell components and "mosaic" morphological features typical of HOCT. Immunophenotypically, in the 10 typical HOCT cases, L1CAM, E-cadherin, CD117, and CK7 predominantly showed "mosaic" -like immunohistochemical features, consistent with the histological morphology; Cathepsin K was diffusely moderate positive in 2 cases and focally positive in 3 cases; CD10 was positive in 2 cases. Eight cases of unclassified eosinophilic tumors partially lacked typical immunohistochemical features, and their immunophenotypes were inconsistent. Other commonly used immunohistochemical markers vimentin, CK20, Melan A, TFE3, and TFEB were all negative. Despite their heterogeneity, non-metastatic glycoprotein B (GPNMB) showed diffusely, strongly positive in both typical HOCT and unclassified eosinophilic cell tumors (18/18). Next-generation sequencing (NGS) confirmed the presence of pathogenic or likely pathogenic FLCN mutations in all 18 cases. FLCN-mutation-associated low-grade eosinophilic renal tumors show distinct histological morphology, immunophenotype, and molecular genetic characteristics. It is necessary to make differential diagnosis from morphologically similar renal tumors in clinical practice. GPNMB serves as an important auxiliary marker for diagnosis of FLCN-mutation-associated low-grade eosinophilic renal tumors. Clinical, molecular, and genetic testing should be integrated to assess potential association with BHD syndrome, for making a precise diagnosis.
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379849
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To investigate the correlation between ATRX expression and alternative lengthening of telomeres (ALT) activation status in uterine smooth muscle tumors, and to evaluate the values of the two indicators in diagnosing uter...To investigate the correlation between ATRX expression and alternative lengthening of telomeres (ALT) activation status in uterine smooth muscle tumors, and to evaluate the values of the two indicators in diagnosing uterine leiomyosarcoma (uLMS). Cases of uLMS and its mimickers diagnosed at the Department of Pathology, Peking University Third Hospital, Beijing, China from January 2024 to October 2025 were retrospectively identified and analyzed. Immunohistochemistry was used to detect ATRX protein expression, while telomere-specific fluorescence in situ hybridization was applied to determine ALT activation status. Next-generation sequencing (NGS) was conducted to detect ATRX gene variations in some cases. Fisher's exact test was used to analyze the correlation between ATRX expression and ALT status, as well as the differences in ATRX expression and ALT activation among different tumor types. Kappa test was applied to evaluate the agreement between ATRX expression and ALT status. There were 60 cases of uLMS, 36 cases of smooth muscle tumors of uncertain malignant potential (STUMP), 77 cases of uterine leiomyoma (uLM), and 6 cases of high-grade endometrial stromal sarcoma. NGS revealed that ATRX gene mutations were mostly accompanied by complete loss of protein expression, while copy number reduction was mostly associated with decreased protein expression. The concordant rate between ATRX expression and ALT activation status was 86.4%, with a significant correlation (<0.001) and substantial consistency (Kappa=0.68). The rates of complete ATRX loss (35/59, 59.3%) and ALT activation (49/60, 81.7%) in uLMS were significantly higher than those in the other groups: 14.3% (5/35) and 17.1% (6/35) in STUMP, 0 (0/72) and 2.6% (2/77) in uLM, and 0 (0/6) for both markers in high-grade endometrial stromal sarcoma. All intergroup differences were statistically significant (all <0.001). ATRX loss is highly correlated with ALT activation status. Combined detection of ATRX expression and ALT activation status can effectively assist in the differential diagnosis of uLMS from its mimickers. In addition, the presence of ATRX loss and/or ALT activation in STUMP and uLM suggests a malignant potential and seems to warrant close clinical follow-up and individualized diagnosis and treatment decisions.
Huang AH, Fu YJ, Xu F
… +3 more, Wang L, Jiang ZN, Huang Y
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379848
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To compare the clinical, endoscopic, and histopathological features of pediatric inflammatory bowel disease (IBD) with IL-10 monogenic defects (IL-10 group) and those with non-IL-10 monogenic defects (non-IL-10 group)....To compare the clinical, endoscopic, and histopathological features of pediatric inflammatory bowel disease (IBD) with IL-10 monogenic defects (IL-10 group) and those with non-IL-10 monogenic defects (non-IL-10 group). A total of 67 pediatric patients with monogenic IBD diagnosed from 2016 to 2021 were included. All patients were referred by the Children's Hospital of Fudan University, Shanghai, China and pathologically reviewed and genetically confirmed at Sir Run Run Shaw Hospital of Zhejiang University School of Medicine, Hangzhou, China. A comparative analysis of the clinical presentation, endoscopic finding, pathological classification, and histopathological features was performed. A subgroup analysis was also carried out within the non-IL-10 group. Among the 67 cases, 43 in the IL-10 group (predominantly IL10RA/B mutations) and 24 in the non-IL-10 group (CYBB, PIK3CD, LRBA mutations etc.). The median age at diagnosis was significantly younger in the IL-10 group (=149.0, <0.001). Endoscopically, the IL-10 group showed more colonic involvement and severe lesions. The IL-10 group more frequently exhibited a Crohn's disease-like pattern (=8.841, <0.001). Significantly higher rates of active inflammation (=12.26, <0.001) and transmucosal inflammation (=6.847, =0.009), moderate-to-severe crypt distortion (=4.541, =0.033) were also observed as the predominant histopathological features in the IL-10 group. Granulomas and increased intraepithelial lymphocytosis were observed only in the non-IL-10 group. Subgroup analysis of the IL-10 group showed that five patients with PIK3CD mutation had moderate-to-severe crypt distortion and transmural mucosal inflammation whereas three patients with CYBB mutations presented with granulomas, lymphocyte aggregation, and small intestinal villous blunting, without moderate-to-severe crypt distortion or transmucosal inflammation. IL-10-and non-IL-10-mediated monogenic IBD cases exhibit significantly different clinical, endoscopic, and pathological features. The IL-10 group often presents severe infantile/early-childhood colitis, while the non-IL-10 group shows later onset and greater phenotypic heterogeneity.
Cheng RF, Sun L, Li JX
… +3 more, Liu SS, Liang H, Sun Y
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379847
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To investigate the pathological diagnostic pitfalls in assessing biopsy specimens of gastrointestinal stromal tumors (GIST) and to explore strategies for improving the accuracy of biopsy-based diagnosis. A retrospective...To investigate the pathological diagnostic pitfalls in assessing biopsy specimens of gastrointestinal stromal tumors (GIST) and to explore strategies for improving the accuracy of biopsy-based diagnosis. A retrospective analysis was conducted on 347 GIST biopsy cases diagnosed at the Tianjin Medical University Cancer Institute and Hospital, Tianjin, China from January 2017 to March 2025. The clinicopathological features were analyzed, focusing on rare sites, atypical histomorphology, and atypical immunohistochemical expression of the GIST cases. There were 198 males and 149 females. 18 patients aged ≤40 years. 281 cases were initial biopsies, while 66 were biopsies on recurrences. Some of these cases exhibited significant atypical features, which constituted diagnostic challenges. The anatomical distribution was broad, with a high proportion of non-gastrointestinal tract locations (194/347, 55.9%), including the abdominal cavity, liver, pelvis, and rare sites such as the vagina, mediastinum, ribs, and scapula. Histologically, the morphology was diverse. While spindle cell type dominated (334 cases), epithelioid (12 cases) and the rare, dedifferentiated types (1 case) were also observed. Although 334 (96.3%) of the cases simultaneously expressed the two GIST markers, CD117 and DOG1, 13 (3.7%) cases showed single negativity or double negativity of these markers. Molecular tests confirmed that these cases were frequently associated with mutations in specific exons of the KIT or PDGFRA gene. The primary diagnostic pitfalls for GIST biopsies include non-classical anatomical sites, atypical histologic changes, and aberrant immunophenotypes. Addressing these challenges requires thorough correlation with clinical and radiological findings, combined application of both immunohistochemical markers, and proactive genetic testing for cases with atypical immunohistochemical profile. These measures are crucial for improving diagnostic accuracy and guiding targeted therapies.
Zhuo SS, Hua HJ, Yang YF
… +4 more, Chen G, Zhang Y, Bai RM, Zhang ZH
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379846
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To investigate the clinicopathological features, immunophenotype and molecular genetics of superficial serrated adenoma (SuSA), and to characterize their diagnostic features. Ten SuSA cases diagnosed at the First Affili...To investigate the clinicopathological features, immunophenotype and molecular genetics of superficial serrated adenoma (SuSA), and to characterize their diagnostic features. Ten SuSA cases diagnosed at the First Affiliated Hospital with Nanjing Medical University, Nanjing, China from January 2023 to June 2025 were collected. Their histological morphology was examined. The expression of CK7, CK20, Ki-67, β-catenin, C-MYC and mismatch repair (MMR) proteins, including PMS2, MLH1, MSH2 and MSH6, was assessed using immunohistochemistry, while KRAS and BRAF mutations were studied in 10 cases by using amplification retardation mutation system PCR. Relevant literature was also reviewed. Among the 10 patients, 5 were male and 5 were female, aged 62.0 (53.5, 72.3) years. The tumors were located in sigmoid colon (7 cases), rectum (2 cases), and descending colon (1 case). There were 9 cases of isolated SuSA that had no synchronous colonic lesions, and 1 case of SuSA with synchronous traditional serrated adenoma (TSA). Endoscopically, isolated SuSA was usually presented as small sessile polyps or large flat lateral lesions. Histologically, it showed a characteristic "double-story building" structure, with serrated changes on the surface and adenomatous structures in the deep. The SuSA with synchronous TSA showed TSA-like changes on the surface/tip of the tumor. The serrate region of the surface layer was positive for CK20 and negative for Ki-67, while the adenomatous region of the middle and lower layers showed high expression of C-MYC and Ki-67, nuclear staining of β-catenin, and no expression of CK7 and CK20. The expression of all MMR proteins (MMR intact phenotype) was found in all cases. Molecular profiling of 10 cases showed that 9 tumors harbored KRAS mutations and 1 tumor harbored a BRAF mutation. SuSA is a rare serrated colorectal lesion that predominantly arises in the left colon. It shares overlapping histological features with hyperplastic polyps, TSA and sessile serrated lesions. It is characterized by superficial serration and deep adenomatous changes, which easily lead to misdiagnosis and missed diagnosis. Understanding its histological features and immunohistochemical profile facilitates its diagnosis and differential diagnosis, including CK20 positivity and Ki-67 negativity in the superficial layer, and high Ki-67 expression with negative CK20 staining in the deep layer. KRAS gene mutation is also an important diagnostic feature.
Zhonghua Bing Li Xue Za Zhi
· 2026 Jul · PMID 42379845
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The importance of tumor deposits (TDs), also known as "cancer nodules", as an adverse prognostic factor in colorectal cancer has been increasingly recognized. Although they have been incorporated into the staging system...The importance of tumor deposits (TDs), also known as "cancer nodules", as an adverse prognostic factor in colorectal cancer has been increasingly recognized. Although they have been incorporated into the staging system of the American Joint Committee on Cancer (AJCC), ambiguities still exist. Current criteria rely heavily on the subjective judgment of pathologists, and the existing classification does not fully reflect their prognostic impact. This is particularly evident in the presence of positive lymph nodes. The definition, differentiation and clinical significance of TDs remain complex and sometimes controversial, and several unresolved issues surrounding TDs warrant our attention and further investigation.