Hereditary tumor predisposition syndromes of the central nervous system(CNS)are a group of genetic disorders caused by germline mutations,which significantly increase the risk of CNS tumors in carriers.However,awareness of these syndromes remains limited in current clinical and pathological practice,leading to a high risk of un-derdiagnosis and missdiagnosis.Pathologists should integrate clinical history,family history,tumor morphology,and molecular testing results to identify underlying hereditary tumor predisposition syndromes.This approach not only helps assess multi-organ tumor risks and guide personalized treatment but also enables early intervention through genetic counseling and testing for family members,ultimately improving patient outcomes and aiding in disease prevention and reproductive decision-making.

The 5th edition of the World Health Organization central nervous system(5th WHO CNS)incorporated molecular alterations as essential diagnostic criteria,placing increased demands on pathologists.Understanding the e-volving relationship between molecular changes and traditional histological features is challenging,and integrating both to establish a definitive pathological diagnosis requires substantial experience and expertise.This article aimed to pro-vide a practical reference for domestic pathologists by interpreting the standardized dataset for central nervous system tumors released by the International Collaboration on Cancer Reporting(ICCR)in 2024,covering histological,molecu-lar,and integrated diagnostic components.

Purpose To investigate the correlation between two autophagy-related proteins,JMY and WHAMM,and autophagic dysfunction and prognosis in gliomas.Methods A total of 113 cases of diffuse gliomas and 14 control brain tissues were collected.The expression of JMY,WHAMM,and autophagy-related markers were evaluated using the EnVision two-step method of immunohistochemistry.Correlations between the expression of JMY and WHAMM and clinicopathological features,prognosis,and autophagy markers were analyzed.Results The high expression rates of JMY and WHAMM in control brain tissue were significantly higher than those in diffuse gliomas.The expressions of JMY and WHAMM were associated with pathological grade and age.Compared with low-grade gliomas(LGG),high-grade gliomas(HGG)showed significantly lower high-expression rates of JMY and WHAMM.Patients with low expres-sion of JMY and WHAMM had shorter overall survival than those with high expression.Cox regression analysis indica-ted that the high pathological grade and low expression of JMY were independent prognostic risk factors.The expression profiles of autophagy markers suggested reduced autophagic activity in HGGs,and JMY expression was positively corre-lated with autophagy markers.Conclusion The high expression rates of JMY and WHAMM are significantly lower in HGGs compared to LGGs.JMY and WHAMM may serve as potential molecular markers for the prognostic evaluation of diffuse gliomas.

Objective:To investigate the clinicopathological features, immunophenotype and prognosis of SWI/SNF complex-deficient sinonasal carcinomas.Methods:The clinicopathological, immunohistochemical profiles of 13 SWI/SNF complex-deficient sinonasal carcinomas diagnosed at Xuanwu Hospital, Beijing, China between Januay 2019 and December 2024 were reviewed and followed up.Results:The patients′ ages ranged from 33-81 years, median 59.0 (41.5, 64.5) years, including 10 males and 3 females. Imaging findings showed space-occupying lesions in the nasal cavity and sinuses. Microscopically, tumors predominantly exhibited invasive growth in medium-to-large nests or sheets, with relatively uniform morphology, mainly basaloid and/or small cells, while one recurrent case displayed epithelioid morphology. Focal necrosis was observed in 7 cases. Immunohistochemical results showed loss of SMARCA4/BRG1 in 7 cases, loss of SMARCB1/INI1 in 6 cases, and concurrent loss of SMARCA2 in 5 cases. CKpan was expressed to varying extent in all cases, 10 cases were EMA positive, and 5 cases were partially positive for p63/p40. Among neuroendocrine markers, 10 cases showed focal expression of syn or CgA. The Ki-67 proliferation index ranged from 40% to 90%. PD-L1 staining showed combined positive score (CPS) was ≥1 in 3 SMARCB1-deficient cases (CPS ranging from 2 to 3) and CPS <1 in the other 10 cases. Among the 13 patients, 2 were lost to follow-up, 6 died (postoperative survival: 1-25 months), and 5 remained alive, with the longest survival time of 130 months (follow-up range, 8-130 months).Conclusions:SWI/SNF complex-deficient sinonasal carcinoma is a rare undifferentiated malignancy in the head and neck, characterized by distinct pathological and molecular genetic features. SMARCA4-deficient and SMARCB1-deficient carcinomas both exhibit basaloid or small cell-like morphology. Compared to SMARCB1-deficient carcinomas, SMARCA4-deficient carcinomas show reduced expression of squamous cell markers but increased expression of neuroendocrine markers. The positive PD-L1 staining is more likely present in SMARCB1-deficient carcinomas than SMARCB4-dificient ones. Co-loss of SWI/SNF and SMARCA2 correlates with poorer prognosis. Comprehensive evaluation of histopathology, immunohistochemistry, and molecular genetics is critical for accurately diagnosing this rare entity.

Hereditary tumor predisposition syndromes of the central nervous system(CNS)are a group of genetic disorders caused by germline mutations,which significantly increase the risk of CNS tumors in carriers.However,awareness of these syndromes remains limited in current clinical and pathological practice,leading to a high risk of un-derdiagnosis and missdiagnosis.Pathologists should integrate clinical history,family history,tumor morphology,and molecular testing results to identify underlying hereditary tumor predisposition syndromes.This approach not only helps assess multi-organ tumor risks and guide personalized treatment but also enables early intervention through genetic counseling and testing for family members,ultimately improving patient outcomes and aiding in disease prevention and reproductive decision-making.

The 5th edition of the World Health Organization central nervous system(5th WHO CNS)incorporated molecular alterations as essential diagnostic criteria,placing increased demands on pathologists.Understanding the e-volving relationship between molecular changes and traditional histological features is challenging,and integrating both to establish a definitive pathological diagnosis requires substantial experience and expertise.This article aimed to pro-vide a practical reference for domestic pathologists by interpreting the standardized dataset for central nervous system tumors released by the International Collaboration on Cancer Reporting(ICCR)in 2024,covering histological,molecu-lar,and integrated diagnostic components.

Purpose To investigate the correlation between two autophagy-related proteins,JMY and WHAMM,and autophagic dysfunction and prognosis in gliomas.Methods A total of 113 cases of diffuse gliomas and 14 control brain tissues were collected.The expression of JMY,WHAMM,and autophagy-related markers were evaluated using the EnVision two-step method of immunohistochemistry.Correlations between the expression of JMY and WHAMM and clinicopathological features,prognosis,and autophagy markers were analyzed.Results The high expression rates of JMY and WHAMM in control brain tissue were significantly higher than those in diffuse gliomas.The expressions of JMY and WHAMM were associated with pathological grade and age.Compared with low-grade gliomas(LGG),high-grade gliomas(HGG)showed significantly lower high-expression rates of JMY and WHAMM.Patients with low expres-sion of JMY and WHAMM had shorter overall survival than those with high expression.Cox regression analysis indica-ted that the high pathological grade and low expression of JMY were independent prognostic risk factors.The expression profiles of autophagy markers suggested reduced autophagic activity in HGGs,and JMY expression was positively corre-lated with autophagy markers.Conclusion The high expression rates of JMY and WHAMM are significantly lower in HGGs compared to LGGs.JMY and WHAMM may serve as potential molecular markers for the prognostic evaluation of diffuse gliomas.

Objective:To investigate the clinicopathological features, immunophenotype and prognosis of SWI/SNF complex-deficient sinonasal carcinomas.Methods:The clinicopathological, immunohistochemical profiles of 13 SWI/SNF complex-deficient sinonasal carcinomas diagnosed at Xuanwu Hospital, Beijing, China between Januay 2019 and December 2024 were reviewed and followed up.Results:The patients′ ages ranged from 33-81 years, median 59.0 (41.5, 64.5) years, including 10 males and 3 females. Imaging findings showed space-occupying lesions in the nasal cavity and sinuses. Microscopically, tumors predominantly exhibited invasive growth in medium-to-large nests or sheets, with relatively uniform morphology, mainly basaloid and/or small cells, while one recurrent case displayed epithelioid morphology. Focal necrosis was observed in 7 cases. Immunohistochemical results showed loss of SMARCA4/BRG1 in 7 cases, loss of SMARCB1/INI1 in 6 cases, and concurrent loss of SMARCA2 in 5 cases. CKpan was expressed to varying extent in all cases, 10 cases were EMA positive, and 5 cases were partially positive for p63/p40. Among neuroendocrine markers, 10 cases showed focal expression of syn or CgA. The Ki-67 proliferation index ranged from 40% to 90%. PD-L1 staining showed combined positive score (CPS) was ≥1 in 3 SMARCB1-deficient cases (CPS ranging from 2 to 3) and CPS <1 in the other 10 cases. Among the 13 patients, 2 were lost to follow-up, 6 died (postoperative survival: 1-25 months), and 5 remained alive, with the longest survival time of 130 months (follow-up range, 8-130 months).Conclusions:SWI/SNF complex-deficient sinonasal carcinoma is a rare undifferentiated malignancy in the head and neck, characterized by distinct pathological and molecular genetic features. SMARCA4-deficient and SMARCB1-deficient carcinomas both exhibit basaloid or small cell-like morphology. Compared to SMARCB1-deficient carcinomas, SMARCA4-deficient carcinomas show reduced expression of squamous cell markers but increased expression of neuroendocrine markers. The positive PD-L1 staining is more likely present in SMARCB1-deficient carcinomas than SMARCB4-dificient ones. Co-loss of SWI/SNF and SMARCA2 correlates with poorer prognosis. Comprehensive evaluation of histopathology, immunohistochemistry, and molecular genetics is critical for accurately diagnosing this rare entity.

Objective:To examine whether immunohistochemistry of methylthioadenosine phosphorylase (MTAP) and p16 could be used to predict the CDKN2A status in various brain tumors.Methods:A total of 118 cases of IDH-mutant astrocytomas, 16 IDH-wildtype glioblastoma, 17 polymorphic xanthoastrocytoma (PXA) and 20 meningiomas diagnosed at Xuanwu Hospital, Capital Medical University, Beijing, China from November 2017 to October 2023 were collected and analyzed. The CDKN2A status was detected by using fluorescence in situ hybridization or next-generation sequencing. Expression of MTAP and p16 proteins was detected with immunohistochemistry. The association of loss of MTAP/p16 expression with CDKN2A homozygous/heterozygous deletion was examined.Results:Among the 118 cases of IDH-mutant astrocytoma, 13 cases showed homozygous deletion of CDKN2A. All of them had no expression of MTAP while 9 cases had no expression of p16. Among the 16 cases of IDH wild-type glioblastoma, 6 cases showed homozygous deletion of CDKN2A. All 6 cases had no expression of MTAP, while 3 of these cases had no expression of p16 expression. Among the 17 PXA cases, 4 cases showed homozygous deletion of CDKN2A, and the expression of MTAP and p16 was also absent in these 4 cases. Among the 20 cases of meningiomas, 4 cases showed homozygous deletion of CDKN2A. Their expression of MTAP and p16 was also absent. Among the four types of brain tumors, MTAP was significantly correlated with CDKN2A homozygous deletion ( P<0.05), with a sensitivity of 100%. However, it was only significantly correlated with the loss of heterozygosity (LOH) of CDKN2A in astrocytomas ( P<0.001). P16 was associated with CDKN2A homozygous deletion in IDH-mutant astrocytoma and PXA ( P<0.001), but not with the LOH of CDKN2A. Its sensitivity and specificity were lower than that of MTAP. Conclusions:MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

One patient with gallbladder mass had transient jaundice and was diagnosed with gallbladder carcinoma by abdominal ultrasonography， contrast-enhanced CT， MRCP， and PET-CT. Surgical exploration showed enlarged gallbladder and a mass in the neck of the gallbladder pressing against the hilum of the liver， with no manifestation of tumor invasion， and there were no signs of liver metastasis. Only cholecystectomy was performed for the patient. The pathological diagnosis was tubular adenoma of the gallbladder without carcinogenesis. This case is characterized by a large gallbladder tumor， without marginal infiltration on imaging or malignant transformation based on pathology.