Context Bladder cancer management is challenged by limited therapeutic targets and heterogeneous treatment responses. Ribosomal S6 kinase 4 (RSK4) has been established as an oncogenic driver in several malignancies, although its clinical significance in bladder cancer remains undefined.Objective To evaluate RSK4 protein expression in bladder cancer specimens and assess its association with clinicopathologic features and patient outcomes.Design RSK4 expression was analyzed by immunohistochemistry in a retrospective cohort of 143 bladder cancer specimens, including 93 cases represented in a tissue microarray. Statistical analyses were performed to evaluate the associations between RSK4 expression levels, standard clinicopathological parameters, and overall survival.Results RSK4 immunoreactivity was detected in 65.7% (94/143) of tumor tissue samples but in 36.5% (23/63) of matched normal urothelial tissue samples (P < 0.0001). Elevated RSK4 expression was significantly correlated with the following established markers of disease progression: muscularis propria invasion (P < 0.001), high tumor grade (P < 0.01), advanced TNM stage (P < 0.001), lymph node metastasis (P < 0.01), and distant metastasis (P < 0.05). No significant associations were observed with patient age, sex, or tumor size. Multivariate analysis confirmed RSK4 as an independent predictor of reduced overall survival (HR = 2.34, 95% CI 1.42-3.85, P < 0.001). Subcellular studies indicate that RSK4 overexpression enhances the invasive and metastatic capabilities of bladder cancer cell lines, and vice versa.Conclusions This study elucidates the expression pattern and mechanism of action of RSK4 in bladder urothelial carcinoma, confirming that its overexpression is a key factor for predicting poor prognosis. This discovery highlights the potential value of RSK4 as a significant therapeutic target, providing a new theoretical basis for improving clinical outcomes in bladder cancer.

The molecular classification of endometrial carcinomas (ECs) is now integrated into clinical practice. However, identification of polymerase-ε (POLE) variants remains reliant on DNA sequencing, which limits broader implementation. Given the strong prognostic value of pathogenic POLE mutations and the established efficacy of immunohistochemistry (IHC) for detecting mismatch repair (MMR) deficiency and p53 abnormalities, there is a clear need for IHC-based screening strategies to identify patients likely to carry POLE variants and prioritize them for confirmatory sequencing. In this study, we analyzed 24 cases with POLE pathogenic mutations (POLEmut ECs), 3 with benign POLE variants, and 32 matched cases with no specific molecular profile (NSMP) from a cohort of 378 ECs. IHC evaluation of the ataxia telangiectasia mutated (ATM) protein revealed that POLE-mutated ECs (with pathogenic or benign POLE variants) exhibited significantly higher frequencies of non-diffuse positive staining patterns, including null, heterogeneous positive, and subclonal loss, compared with NSMP cases. Targeted next-generation sequencing of all exons across 474 cancer-related genes in the 27 POLE-mutated ECs and 20 NSMP cases with ATM non-diffuse positive staining patterns confirmed that POLE-mutated ECs typically had high tumor mutational burden and were enriched for ATM truncating variants. ATM molecular alterations, including various variant subtypes and multisite mutations, also closely correlated with these staining patterns. Based on these findings, we refined the ATM IHC interpretation framework to integrate staining patterns with sequencing data for improved molecular correlation. Specifically, the null and subclonal loss patterns showed high specificity (96.9%), positive predictive value (94.1%), and accuracy (79.7%) for identifying POLE variants. Notably, the null pattern appeared exclusively in ECs with pathogenic POLE mutations. These results suggest that ATM IHC staining is an effective screening tool for identifying patients who may benefit from confirmatory POLE sequencing among those lacking MMR deficiency or p53 abnormalities.

AIMS:Ferroptosis shows promise as a cancer treatment due to lipid hydroperoxide accumulation in an iron-dependent manner. Isocitrate dehydrogenase 1 (IDH1) mutation is common in gliomas and D-2-hydroxyglutarate (D-2HG) sensitizes cancer cells to ferroptosis. However, the regulation of ferroptosis in IDH1 mutant gliomas remains unclear. We hypothesize that IDH1 mutations induce glioma ferroptosis by regulating iron metabolism and antioxidant systems through the heme-BACH axis. RESULTS:IDH1 mutation induces ferroptosis in astrocytes and glioma cells demonstrated by growth inhibition, mitochondrial damage, and lipid peroxidation. In IDH1-mutant gliomas, both Fe2+ and reactive oxygen species accumulate due to impaired heme biosynthesis and thus BACH activation-dependent transcriptional repression of iron homeostasis and antioxidant response-related genes. The heme analogs zinc and tin protoporphyrin IX (ZnPP and SnPP) function as competitive inhibitors to reduce heme-dependent degradation of BACH and to exacerbate ferroptosis, especially for IDH1 mutants at extremely low concentrations. Primary mouse astrocytes and human glioma cell lines were used to determine the effect of IDH1 mutation on ferroptosis, while orthotopic xenograft models were used to evaluate heme analog efficacy. The drug affinity responsive target stability assay was used to determine the interaction between heme and its analog and BACH. INNOVATION AND CONCLUSIONS:We discover that IDH1 mutation induces ferroptosis by activating the heme-BACH axis. ZnPP, previously believed to function exclusively as a heme oxygenase-1 inhibitor, can competitively bind to BACH to exacerbate ferroptosis and potently suppress IDH1-mutant gliomas. This study reveals a novel metabolic mechanism for inducing ferroptosis and provides a potential therapeutic target for IDH-mutant gliomas. Paraffin-embedded human glioma samples were collected from Xijing Hospital, the First Affiliated Hospital of the Fourth Military Medical University (China) (project number: KY20233192-1). Antioxid. Redox Signal. 44, 145-163.

Solid pseudopapillary neoplasm of pancreas (SPN) is a rare low-grade malignant pancreatic tumor. The morphology of SPN exhibits considerable diversity. Accurate diagnosis is crucial due to the morphological similarity of SPN to other pancreatic tumors, including pancreatic neuroendocrine tumors (NETs), acinar cell carcinoma (ACC) and pancreatoblastoma (PB), especially in the preoperative biopsy specimen. Image-guided biopsy techniques are essential for preoperative diagnosis, but the limited tissue in biopsy samples can complicate the diagnosis of SPN from other tumors. In this study, we evaluate the diagnostic utility of ATP Binding Cassette Subfamily D Member 1 (ABCD1), a novel immunohistochemical (IHC) marker previously identified in surgically resected SPN specimens, for distinguishing SPN in biopsy samples. We analyzed biopsy samples from a cohort of 55 SPN patients (55 biopsy samples and 6 paired surgical resected samples) and compared them with samples from 61 pancreatic ductal adenocarcinoma (PDAC), 90 NET, 13 intraductal papillary mucinous neoplasm (IPMN), 7 ACC and 3 PB patients from four institutions. Our findings show that ABCD1 positively marks SPN biopsy samples consistently as surgical resected samples, with 100% overall positivity and 96.37% exhibiting moderate to strong expression. In contrast, moderate to strong ABCD1 expression was significantly lower in PDAC (3.28%) and NET (6.66%). However, strong expression was observed in 57.14% of acinar cell carcinomas (ACC). Furthermore, ABCD1 complements β-catenin in cases where nuclear β-catenin staining is ambiguous (100% ABCD1 positivity). ROC curve analysis revealed that ABCD1 exhibits excellent diagnostic performance for distinguishing SPN from other pancreatic tumors, achieving a sensitivity of 96.36% and a specificity of 93.10%, establishing it a reliable complementary diagnostic marker in biopsy samples. These results suggest that ABCD1 could serve as a valuable tool for the accurate preoperative diagnosis of SPN, thereby improving clinical management and patient outcomes.

Context. Succinate dehydrogenase-deficient renal cell carcinoma (RCC) is a newly classified subtype of RCC in the World Health Organization classification of urinary and male genitaj tumours. However, systemic reports on this tumor are limited. Objective-To give new insights into the clinicopathologic and molecular features of succinate dehydrogenase complex iron sulfur subunit B (SDHB)-deficient RCC. Design. Data from 5 SDHB-deficient RCC patients diag-nosed at our hospital between 2016 and 2022 were collected and studied through light microscopy, immunohistochemistry (IHC), ultrastructural analysis, and Sanger sequencing. Results. The median age of of patients patients w was 34 years; 2 were male and 3 were female. Grossly, the tumors were well defined, with an average diameter of 7 cm. Histologically, the cells were arranged in diverse patterns: solid, nested, glandular, or tubular with scattered cysts containing eosinophilic, wispy, or bubbly appearances. One patient's tumor exhibited an obvious papillary structure with focal aggregation of foam cells, and 3 tumors displayed focal micro-papillary structures. Two patients presented with high-grade International Society of Urologic Pathology 3 nuclei. The tumor cells in all cases lacked SDHB expression by IHC stain. In addi-tion, the average value of the combined positive score of pro-grammed death ligand-1 (PD-L1, SP263) in all patients was 18. Electron microscopy revealed significant mitochondrial abnor-malities. Genetic testing confirmed SDHB germline mutations in all tumors. One patient's tumor presented a novel, previously unreported mutation: c.697_700del in exon 7. Follow-up revealed metastasis in 1 patient, leading to mortality. Conclusions. Our findings broaden the morphologic spectrum and highlight a new point mutation in the SDHB gene, providing a genetic change spectrum for this tumor entity. (Arch Pathol Lab Med. 2025;150:310-316; doi: 10.5858/arpa.2025-0233-OA)

Recently, Papke et al. reported two cases of myxoid inflammatory myofibroblastic sarcoma with PML::JAK1 fusion. Smith et al. identified a high-grade PML::JAK1 fusion sarcoma. Here, we present the fourth case of a PML::JAK1 fusion sarcoma, the first to harbor a concomitant KRAS hotspot mutation (KRAS Q61H). Morphological manifestations include prominent myxoid stroma, lobulated but infiltrative growth patterns, and branching blood vessels. In contrast to Papke et al., we observed distinct non-myxoid stromal fascicular herringbone solid architecture and perivascular spaces, thereby expanding the morphological spectrum of PML::JAK1 fusion. The tumor was approximately 80% myxoid and 20% solid in composition. Importantly, a needle biopsy confirmed liver metastases of myxoid inflammatory myofibroblastic sarcoma in this case, suggesting its bland morphology but aggressive clinical behavior, which is a major potential diagnostic pitfall for this tumor. In addition, the presence of both myxoid lobular and herringbone regions in the present case suggests that the PML::JAK1 fusion sarcomas reported by Papke et al. and Smith et al. might be on a biological spectrum.

Disulfidptosis, a new identified form of regulated cell death, has been implicated in cancer. However, the mechanisms through which disulfidptosis-related long noncoding RNAs (lncRNAs) predict prognosis in cervical cancer (CC) remain unclear. Here, we identified disulfidptosis-related genes and lncRNAs in the cancer genome atlas database. Least absolute shrinkage and selection operator and Cox regression analyses were used to construct a prognostic risk signature based on optimal disulfidptosis-related lncRNAs. The prognostic performance of the signature was evaluated using Kaplan-Meier survival analysis and receiver operating characteristic curves. Correlation between the risk signature, gene mutation landscape, tumor immune microenvironment, and immunotherapy or chemotherapy sensitivity was determined. Additionally, the expression levels of disulfidptosis-related lncRNAs in CC were validated by quantitative PCR. A total of 403 disulfidptosis-related lncRNAs were identified, among which 9 disulfidptosis-related lncRNAs were used to construct a prognostic risk signature that classified patients with CC into high-risk and low-risk groups. Kaplan-Meier, receiver operating characteristic curves, and the concordance index demonstrated that the risk signature exhibited good sensitivity and specificity. The low-risk group exhibited improved survival outcomes and increased sensitivity to immunotherapy, whereas the high-risk group showed heightened sensitivity to to bexarotene, bicalutamide, embelin, FH535, and pazopanib. Quantitative PCR results indicated that ILF3-DT and PPP1R14B-AS1 were downregulated in CC tissues, whereas RUSC1-AS1 was upregulated. In conclusion, we developed a novel prognostic risk signature based on 9 disulfidptosis-related lncRNAs, which may serve as an independent predictor of immunotherapy response and chemotherapy sensitivity in CC.

BACKGROUND:Dermal clear cell sarcoma (DCCS) is a rare malignant mesenchymal neoplasm. Owing to the overlaps in its morphological and immunophenotypic profiles with a broad spectrum of tumors exhibiting melanocytic differentiation, it is frequently misdiagnosed as other tumor entities in clinical practice. By systematically analyzing the clinicopathological characteristics, immunophenotypic features, and molecular biological properties of DCCS, this study intends to further enhance pathologists' understanding of this disease and provide a valuable reference for its accurate diagnosis. METHODS:A retrospective analysis was conducted on the clinicopathological data of 13 patients diagnosed with DCCS at the First Affiliated Hospital of Air Force Medical University from January 2012 to December 2024. The histopathological features, immunophenotypic profiles, and molecular characteristics of tumors were systematically assessed. Furthermore, detailed prognostic information of the patients was collected through telephone follow-up. RESULTS:Among the 13 patients diagnosed with DCCS, there were 5 males and 8 females, with a mean age of 32.7 years. Tumors were predominantly located in the distal extremities. 3 patients had a prior history of trauma or surgery, while bone destruction was identified in 5 cases via imaging examinations. Grossly, the tumors appeared as grayish-white or white nodules with a hard texture. Microscopically, 2 tumors involved both the dermis and epidermis, while the other 11 were confined to the dermis. Tumor cells were arranged in nests, fascicles, sheets, mainly spindle-shaped or epithelioid in morphology. "Wreath-like" multinucleated giant cells were observed in 3 cases, and collagenous fibrous septa were present in the stroma of all tumors. All tumors showed diffuse expression of S100 or SOX10, and HMB-45, Melan-A, and MITF were positive to varying degrees. EWSR1 (22q12) gene breakage was detected by fluorescence in situ hybridization (FISH) in all 10 tested cases. Among the cases examined by next-generation sequencing (NGS), 2 had the EWSR1::ATF1 fusion gene and 1 had the EWSR1::CREB1 fusion gene. CONCLUSION:DCCS is relatively rare in clinical practice. Its pathogenesis may be associated with a prior history of trauma or surgery; however, this potential association requires further validation through the accumulation of additional cases. Given the overlaps in morphological and immunohistochemical features between DCCS and other tumors exhibiting melanocytic differentiation, molecular testing (including the detection of EWSR1 gene rearrangement or specific fusion genes detection) holds significant value for the accurate diagnosis of primary DCCS.

Aims:Sex differences in the incidence of thyroid nodules (TNs) are broadly recognized, but further analysis is lacking. Thus, the aim of this study was to evaluate the association between TNs and anthropometric parameters in type 2 diabetic males and females. Materials and Methods:This cross-sectional study included 747 patients with type 2 diabetes mellitus (T2DM). All patients underwent clinical examination, thyroid ultrasound, laboratory tests, anthropometrics and body composition. Multivariable logistic regression assessed factors associated with TNs, and a simple nomogram was finally developed. Results:In total, the incidence of TNs was 36.95% (276/747) and was significantly higher in females (52.75%) than in males (27.85%). Age was positively correlated with TNs risk in patients with T2DM (males: OR = 4.141, 95% CI [1.999-8.577], females: OR = 4.630, 95% CI [1.845-11.618]). Obesity (OR = 2.655, 95% CI [1.257-5.607]) and hyperuricemia (OR = 1.997, 95% CI [1.030-3.873]) were only associated with the risk of TNs independent of other risk factors in type 2 diabetic females, as well as other obesity factors such as weight, BMI, waist-hip ratio, percent body fat, visceral curve area, and upper arm circumference, but not in type 2 diabetic males. However, the diameter of the largest thyroid nodule was only related to age (R = 0.226, p < 0.01). Finally, the nomogram for evaluating TNs in female T2DM patients was established, and the C-index of the nomogram was 0.704 (95% CI [0.89-0.94]). Conclusion:TNs occur with a significantly higher frequency in type 2 diabetic females than in males, especially those with hyperuricemia and obesity. Modifiable metabolic factors, such as obesity and hyperuricemia, are a major focus for improving TNs risk in women.

Context.—:Succinate dehydrogenase-deficient renal cell carcinoma (RCC) is a newly classified subtype of RCC in the World Health Organization classification of urinary and male genital tumours. However, systemic reports on this tumor are limited. Objective.—:To give new insights into the clinicopathologic and molecular features of succinate dehydrogenase complex iron sulfur subunit B (SDHB)-deficient RCC. Design.—:Data from 5 SDHB-deficient RCC patients diagnosed at our hospital between 2016 and 2022 were collected and studied through light microscopy, immunohistochemistry (IHC), ultrastructural analysis, and Sanger sequencing. Results.—:The median age of patients was 34 years; 2 were male and 3 were female. Grossly, the tumors were well defined, with an average diameter of 7 cm. Histologically, the cells were arranged in diverse patterns: solid, nested, glandular, or tubular with scattered cysts containing eosinophilic, wispy, or bubbly appearances. One patient's tumor exhibited an obvious papillary structure with focal aggregation of foam cells, and 3 tumors displayed focal micropapillary structures. Two patients presented with high-grade International Society of Urologic Pathology 3 nuclei. The tumor cells in all cases lacked SDHB expression by IHC stain. In addition, the average value of the combined positive score of programmed death ligand-1 (PD-L1, SP263) in all patients was 18. Electron microscopy revealed significant mitochondrial abnormalities. Genetic testing confirmed SDHB germline mutations in all tumors. One patient's tumor presented a novel, previously unreported mutation: c.697_700del in exon 7. Follow-up revealed metastasis in 1 patient, leading to mortality. Conclusions.—:Our findings broaden the morphologic spectrum and highlight a new point mutation in the SDHB gene, providing a genetic change spectrum for this tumor entity.

Various factors play key roles in maintaining intestine homeostasis. Disruption of the balance may lead to inflammatory bowel diseases and even colorectal cancer (CRC). Loss or gain of function of many key proteins can result in dysregulated intestinal homeostasis. Our research demonstrated that neural precursor cells expressed developmentally downregulated 4-like protein (NEDD4L, or NEDD4-2), a type of HECT family E3 ubiquitin ligase, played an important role in maintaining intestinal homeostasis. NEDD4L expression was significantly inhibited in intestinal epithelial cells (IECs) of patients with Crohn's disease, ulcerative colitis, and CRC. Global KO of NEDD4L or its deficiency in IECs exacerbated colitis induced by dextran sulfate sodium (DSS) and 2,4,6-trinitrobenzene sulfonic acid (TNBS) and CRC induced by azoxymethane and DSS. Mechanistically, NEDD4L deficiency in IECs inhibited expression of the key ferroptosis regulator glutathione peroxidase 4 (GPX4) by reducing the protein expression of solute carrier family 3 member 2 (SLC3A2) without affecting its gene expression, ultimately promoting DSS-induced IEC ferroptosis. Importantly, ferroptosis inhibitors reduced the susceptibility of NEDD4L-deficient mice to colitis and colitis-associated CRC. Thus, NEDD4L is an important regulator in IEC ferroptosis, maintaining intestinal homeostasis, making it a potential clinical target for diagnosing and treating IBDs.

IDH1/2 mutations are prevalent genetic alterations in gliomas that facilitate metabolic reprogramming and epigenetic modifications, which are essential for glioma progression. However, their exact contributions to tumorigenesis remain to be fully elucidated. Cellular senescence is a known precursor to tumorigenesis, and multiple oncogenes can initiate this senescence program. Our study demonstrated that the IDH1 mutation inhibits the proliferation of astrocytes and glioma cells, inducing cellular senescence through mechanisms involving DNA damage and increased production of reactive oxygen species (ROS). Notably, these effects were mitigated by the addition of exogenous glutamine. Within cells, glutamine synthetase (GS) serves as the sole enzyme responsible for glutamine synthesis. We found that D-2-hydroxyglutarate (D-2HG), an oncometabolite generated by mutant IDH enzymes, directly inhibits GS activity by binding to the glutamate site, substantially reducing endogenous glutamine production and exacerbating senescence in IDH1-mutant glioma cells. Additionally, in human glioma samples, a greater prevalence of GS-positive astrocytes was detected in IDH-mutant gliomas, likely providing adequate glutamine to sustain growth and mitigate senescence in these cells. Our findings suggest that D-2HG promotes senescence in IDH1-mutant glioma cells by inhibiting GS activity and that disrupting glutamine transport between astrocytes and glioma cells may constitute a promising therapeutic strategy for targeting IDH-mutant gliomas.

BACKGROUND:Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer. The 5th edition of the World Health Organization (WHO) Classification of Thyroid Tumors divides PTC into 13 distinct morphological subtypes based on its morphological characteristics. According to molecular features, thyroid cancer is classified into RAS-like and BRAF-like tumors. CASE PRESENTATION:Here, we present a case of ALK-rearranged papillary thyroid carcinoma (ALK-PTC) with a germline mutation in the MEN1 gene. Next-generation sequencing (NGS) detected an EML4-ALK fusion gene and a germline MEN1 mutation in this case, accompanied by a rare intragenic inversion of the ALK gene. CONCLUSION:Here we report the first case in the world of PTC with EML4-ALK fusion, accompanied by intragenic inversion of the ALK gene and germline mutation of the MEN1 gene.

Cytological examination of urine sediment is a helpful diagnostic tool for identifying renal involvement by hematological malignancies. We present the case of a 47-year-old man who was diagnosed with extranodal B-lymphoblastic lymphomas after presenting with gross hematuria as his first symptom. The presence of lymphoma cells in the urine led to a diagnosis confirmed through an immunophenotypic study using cell block sections of urine centrifuge sediment and core needle biopsy histology of the right renal pelvis mass. This case highlights the usefulness of a urine cytological study in diagnosing lymphoma involvement in the genitourinary tract. Furthermore, this paper reviews relevant literature on diagnosing lymphoma involvement from urine sediment.

Isocitrate dehydrogenase (IDH) mutations frequently occur in lower-grade gliomas and secondary glioblastomas. Mutant IDHs exhibit a gain-of-function activity, leading to the production of D-2-hydroxyglutarate (D-2HG) by reducing α-ketoglutarate (α-KG), a central player in metabolism and epigenetic modifications. However, the role of α-KG homeostasis in IDH-mutated gliomagenesis remains elusive. In this study, we found that low expression of oxoglutarate dehydrogenase (OGDH) was a common feature in IDH-mutated gliomas, as well as in astrocytes. This low expression of OGDH resulted in the accumulation of α-KG and promoted astrocyte maturation. However, IDH1 mutation significantly reduced α-KG levels and increased glutaminolysis and DNA/histone methylation in astrocytes. These metabolic and epigenetic alterations inhibited astrocyte maturation and led to cortical dysplasia in mice. Moreover, our results also indicated that reduced OGDH expression can promote the differentiation of glioma cells, while IDH1 mutations impeded the differentiation of glioma cells with low OGDH by reducing the accumulation of α-KG and increasing glutaminolysis. Finally, we found that l-glutamine increased α-KG levels and augmented the differentiation-promoting effects of AGI5198, an IDH1-mutant inhibitor, in IDH1-mutant glioma cells. Collectively, this study reveals that low OGDH expression is a crucial metabolic characteristic of IDH-mutant gliomas, providing a potential strategy for the treatment of IDH-mutant gliomas by targeting α-KG homeostasis.

OBJECTIVE:Clear cell papillary renal cell tumour (CCPRCT) is a kind of renal epithelial cell tumor, and was renamed by the 5th WHO due to its specific epidemiology and clinicopathological characteristics. However, the biological mechanism and molecular basis of CCPRCT still need to be further clarified. This study aims to comprehensively evaluate clinicopathologic and molecular characteristics of CCPRCC, and particularly compare it with other more prevalent subtypes of renal cell carcinoma.METHODS:12 cases of CCPRCT were collected for analyzing the clinicopathological characteristics. Then, whole-exome sequencing (WES) was employed to reveal the genetic profiles, followed by comparison with the molecular genetic alterations identified in ccRCC (341) and pRCC (200) datasets obtained from the TCGA database.RESULTS:Of the 12 CCPRCT cases, the male-to-female ratio was 4:1 with a mean age of 49.5 years (48.5 ± 10.5) at diagnosis. All patients were diagnosed accidentally during routine physical examinations. All tumors (12/12, 100%）had a solid-cystic appearance with a well-defined fibrous capsule. The median size of the tumors was 3 cm (2.98 ± 1.2). Histologically, the cystic papillary structures were considered to be prominent, lined with cuboidal tumor cells away from basement membrane. The tumor cells were moderately atypia equivalent to grade 1 or grade 2 according to the ISUP nuclear grading system. Typically, the tumor cell diffusely positive for CK7 and CAIX in a "cup-like" pattern. The results of WES revealed recurrent gene alterations (mainly missense mutation) of TTN and FLT in 4 cases (4/12, 33.3%), respectively, of which, the alteration of FLT was not observed in ccRCC and pRCC of the TCGA database. Other gene alterations including POTEC (1 cases), PRADC1 (1 cases), ZZZ3 (1 case) and PTPRZ1 (1 case), etc. Moreover, all of the CCPRCT cases displayed a lower tumor mutation burden (TMB) compared to ccRCC and pRCC with median TMB of 1.04 (range: 1.94 ± 2.74). None of the patients experienced tumor metastasis, recurrence, or tumor-related deaths.CONCLUSION:CCPRCT is a renal epithelial cell tumor characterized by specific clinical and pathological features. Our study provides additional evidence supporting the favorable prognosis of CCPRCT. Furthermore, the potential molecular alterations were uncovered by this study in CCPRCT such as the FLT family and TTN. However, due to the limited sample size, larger studies are required to validate these findings.

Objective: To investigate the clinicopathological features, molecular genetic features, differential diagnosis and prognosis of ELOC mutated renal cell carcinoma. Methods: From January 2015 to June 2022, 11 cases of renal cell carcinoma with clear-cell morphology, expression of CAⅨ and CK7 and no 3p deletion were collected. Two cases of ELOC mutant renal cell carcinoma were diagnosed using whole exome sequencing (WES). The clinical features, morphology, immunophenotype, FISH and WES results were analyzed. The relevant literature was reviewed. Results: The two patients were both male, aged 29 and 51 years, respectively. They were both found to have a renal mass by physical examination. The maximum diameters of the tumors were 3.5 cm and 2.0 cm, respectively. At the low magnification, the tumors were well-defined. The tumor cells showed a pushing border and were separated by thick fibrous bands, forming nodules. The tumor cells were arranged in a variety of patterns, including tubular, papillary, solid nest or alveolar. At high magnification, the tumor cells were large, with well-defined cell borders and clear cytoplasm or fine eosinophilic granules. CAⅨ was diffusely box-like positive in both cases. Case 1 was partially and moderately positive for CK7, strongly positive for CD10, diffusely and moderately positive for P504S, and weakly positive for 34βE12. In case 2, CK7 and CD10 were both partially, moderately positive and P504s were diffusely positive, but 34βE12 was negative. FISH results showed that both cases had no 3p deletion. ELOC c.235T>A (p.Y79N) mutation was identified using WES in case 1, while ELOC c.236_237inv (p.Y79C) mutation was identified in case 2. Conclusions: As a new clinical entity, ELOC mutated renal cell carcinoma may be underdiagnosed due to its overlap with clear cell renal cell carcinoma in morphology and immunophenotype. The diagnosis of renal cell carcinoma with ELOC mutation should be confirmed by morphology, immunohistochemistry, FISH and gene mutation detection. However, more additional cases are needed to explain its biological behavior and prognosis.

滤泡样结构多见于卵巢幼年型粒层细胞瘤、高血钙型小细胞癌和Sertoli-Leydig细胞瘤，是诊断上述肿瘤的一项重要形态学线索，但是该结构还可见于其他类型的卵巢原发性和转移性肿瘤甚至瘤样病变中，可能会给诊断具有此类特殊结构的卵巢肿瘤带来困难。鉴于此，本文结合2020年第5版WHO女性生殖系统肿瘤分类和既往文献报道，对具有滤泡样结构的卵巢肿瘤进行系统的总结，旨在为国内病理同行诊断具有此类结构的卵巢肿瘤提供思路。