Aiolos is a member of the Ikaros zinc-finger protein family and is encoded by the Ikaros family zinc finger 3 (IKZF3) gene. Aiolos not only plays a crucial role in controlling the normal differentiation and proliferation of lymphocytes, but studies have also found that it exhibits abnormally high expression in the early stages of the onset and development of multiple tumors. It influences the biological behavior of tumor cells not only by regulating tumor invasion and metastasis through mediating signaling pathways such as 66-kilodalton Src homology 2 domain-containing transforming protein (p66Shc), phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/Twist, cellular myelocytomatosis oncogene, interferon regulatory factor 4, B-cell receptor, and nuclear factor kappa B, but also the instability of its gene affects tumor therapy, drug resistance, and patient prognosis. This suggests that IKZF3 is a good biological indicator for tumors and may become a new therapeutic target for tumors. A systematic elaboration of the latest research progress on the IKZF3 gene structure, physiological functions, tumor regulation, and treatment resistance can provide reference and scientific basis for future tumor therapy.

Accurate preoperative evaluation of lymph node metastasis (LNM) status in patients with papillary thyroid carcinoma (PTC) is essential for the development of individualized diagnosis and treatment strategies; however, the predictive performance of current clinical approaches remains limited. This study aims to identify key molecular biomarkers associated with LNM in PTC, construct LNM-risk prediction models using machine learning (ML) algorithms, and assess their potential value in supporting clinical decision-making.

To explore the clinical presentation and genetic etiology of a case with Xeroderma pigmentosum in conjunct with basal cell carcinoma and melanoma.

Objective: To investigate the characteristics of human epidermal growth factor receptor 2 (HER2) protein expression and gene status in uterine serous carcinoma (USC) patients. Methods: A total of 36 formalin-fixed and paraffin-embedded USC tissue specimens obtained between 2021 and 2022 in Peking Union Medical College Hospital were collected. The expression of HER2 protein and the gene status were detected by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) respectively, and the results were interpreted according to the 2020 International Society of Gynecological Pathologists recommendations. Results: Among the 36 cases, 11, 8, 12 and 5 cases showed HER2 IHC scores of 0, 1+, 2+, and 3+, respectively. All IHC 3+cases were pure USC. Out of 25 samples with different level of HER2 expression (IHC 1+, IHC 2+and 3+), 16 (64.0%) tumors with heterogeneous stain, which mainly affects the diseases with IHC 2+ (10/12) and IHC 3+ (3/5) lesions. Ten pure USC cases (27.8%, 10/36), involving HER2 IHC 0, IHC 1+, IHC 2+and IHC 3+tumors, harbored HER2 gene amplification by FISH (1, 1, 3 and 5 cases, respectively). All amplified cases exhibited a HER2/CEP17 ratio≥2.0. In addition, the incidences of chromosome 17 (CEP17) polysomy and monosomy were 25.0% (9/36) and 19.4% (7/36), respectively. Conclusions: Most of USC tumors exhibit intratumoral heterogeneity in HER2 IHC stain. Both HER2 IHC positive (3+) and FISH positive occur exclusively in pure USC tumors. HER2 gene amplification can be observed in any HER2 IHC levels.

Objective: To investigate the clinicopathological features, molecular characteristics and differential diagnosis of extraskeletal myxoid chondrosarcoma (EMC). Methods: A total of 16 cases of EMC diagnosed from January 2016 to February 2025 were collected from Luoyang Orthopedic-Traumatological Hospital of Henan Province (Henan Provincial Orthopedic Hospital, 3 cases) and Beijing Jishuitan Hospital, Capital Medical University (13 cases) for clinicopathological, immunohistochemical, fluorescence in situ hybridization (FISH) and next generation sequencing analyses and follow-up. Results: There were 11 males and 5 females, with a median age of 51(30, 73) years. The tumor sites included extremities (n=12), trunk (n=3), and sacrum (n=1). Histologically, EMC showed two distinct subtypes. Fourteen cases (14/16) were classic subtype with pale-blue myxoid or chondromyxoid matrix. The cells characteristically interconnected with one another to form cords, small clusters, and complex trabecular or cribriform patterns. The tumor cells were round, ovoid, short spindle or star-shaped; some may be rhabdoid with eosinophilic cytoplasm and eccentrically placed nuclei. Two cases were cellular subtype, demonstrating solid sheets of epithelioid cells with minimal intervening myxoid matrix, large vesicular nuclei, prominent nucleoli, and brisk mitotic activity. Immunohistochemistry showed that the cells diffusely or partially expressed vimentin, CD117, Syn, INSM-1, CD34, SMA and NSE, but were negative for pan-keratin (AE1/AE3), S-100, calponin, desmin and brachyury. INI1 expression was not deleted. The proliferation index of Ki-67 ranged from 2% to 15% in the classic subtype and 5% in the cellular subtype. NR4A3 gene rearrangement was detected by FISH in 15 cases (15/16), and EWSR1::NR4A3 fusion was confirmed by next-generation sequencing in 4 cases. Follow-up data were available in 14 patients (1-104 months), of whom 7 (7/14) developed local recurrence and 2 (2/14) developed distant metastases. Conclusions: EMC is a rare mesenchymal malignancy that arises not only in soft tissues but also in bone. The predominant histological subtype is classical EMC, with a minority presenting as cell-rich EMC. FISH detection of NR4A3 gene rearrangements provides a crucial value for the diagnosis. It needs to be differentiated from myoepithelial tumors, chordomas and myxoid liposarcomas.

Objective: To study the clinical and pathological features of anaplastic sarcoma of the kidney(ASK) in children, and to explore its molecular profiles and differential diagnosis. Methods: Five cases of pediatric ASK diagnosed at Beijing Children's Hospital, Beijing, China from January 2018 to June 2025 were collected. The clinical, histological, and immunohistochemical features were analyzed. Three cases were subjected to TP53 detection using fluorescent in-situ hybridization (FISH), and DICER1 and TP53 detection using PCR amplification and Sanger sequencing. Results: There were 3 males and 2 females. The patients' ages ranged from 1.6 years to 17.7 yeas, with an age of 8.2 (3.8, 12.7). A renal mass was accidentally found in 1 case, and abdominal pain with hematuria was present in 4 cases. Four cases were presented as a unilateral tumor, while one as bilateral tumors. The radiographic features of ASK were cystic and solid masses. The tumors were staged as stage Ⅰ, Ⅴ, Ⅳ, Ⅱ and Ⅱ, respectively. Histologically, all tumors showd both cystic and solid areas, spindle cell components with anaplastic changes and frequent atypical mitotic figures, arranged in a fascicular pattern. Chondroid differentiation and rhabdomyoblasts features were present. Multiloculated cysts showed cystic nephroma-like foci, and subepithelial primitive cells with cambium-like layer appearance. Immunohistochemistry showed that desmin was positive in 3 of the 5 cases, and myogenin and MyoD1 were positive in 2 of the 5 cases. p53 was overexpressed(mutated type) in 2 cases, loss of expression(null type) in 1 case and wild type in 1 case. Ki-67 positive rates were 30%-90%. Three cases with sequencing information harbored DICER-1 mutations(somatic and truncating mutations) and loss of TP53 gene. One patient with bilateral tumors died during follow-up. Another patient had distant metastasis, while the others had no recurrence or metastasis. Conclusions: ASK in children is a rare DICER1-related tumor, with distinct histologic features and biological behavior. The differential diagnosis includes anaplastic Wilms tumor, clear cell sarcoma of the kidney, etc. Integration of clinical manifestations, histology, immunohistochemistry, and molecular studies may be required to render correct diagnosis.

Objective: To investigate the clinicopathological features and molecular genetic alterations of the YWHAE-rearranged clear cell sarcoma of the kidney (CCSK), and to improve the diagnostic and differential diagnostic accuracy of the subtype of renal clear cell sarcoma. Methods: A retrospective analysis was performed on 7 cases of YWHAE-rearranged CCSK diagnosed and treated at the Shanghai Children's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and the Children's Hospital of Fudan University, Shanghai, China between January 2018 and October 2023.Their clinicopathological characteristics were analyzed using HE staining, immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). Patient survival was assessed based on follow-up data. Results: Of the 7 patients with YWHAE-rearranged CCSK, 4 were male and 3 were female, aged 1.0-7.0 years, with an age of 2.0 (1.6, 6.0) years. The primary symptom was predominantly an abdominal mass (6 cases), with 1 case presented with abdominal pain and vomiting. All tumors were unilateral (left side in 3 cases, and right side in 4 cases). Preoperative imaging suspected Wilms tumor in all cases. Histologically, the classic type (4/7) and spindle cell type (2/7) were predominant while one case showed a mixed classic and epithelioid pattern. Vascular invasion was present in 3 cases, and lymph node metastasis was identified in 1 case. IHC results showed diffuse positivity for cyclin D1, bcl-2, and SATB2 in all cases, with varying expression of BCOR. FISH with break-apart probes analyses confirmed YWHAE (17p13) gene fusions in all cases. NGS performed in 2 cases revealed the presence of YWHAE::NUTM2 fusions, accompanied by mutations in FBXW7 or CREBBP gene. There were 5 Stage-Ⅲ cases and 2 Stage-Ⅳ cases. Postoperative follow-up ranged from 20 to 69 months and showed 3 patients with metastasis or recurrence. One of them also developed chronic renal failure. Conclusions: YWHAE-rearranged CCSK exhibits morphological heterogeneity and aggressive behaviors. Definitive diagnosis relies on molecular testing (such as FISH or NGS), which is crucial for differential diagnosis and prognostic evaluation. This subtype of CCSK is commonly associated with advanced clinical stage and early metastasis/recurrence, highlighting the necessity for improving risk stratification and clinical management.

Objective: To investigate the clinicopathological features, immunophenotype, molecular characteristics and prognosis of acquired cystic disease-associated renal cell carcinoma (ACD-RCC). Methods: The clinicopathological data of four ACD-RCC cases diagnosed at the Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China and one case at the Ningbo Clinical Pathology Diagnostic Center, Ningbo, China between 2018 and 2025 were collected. The clinical, histological, and immunohistochemical characteristics were analyzed. FISH and high-throughput DNA targeted next generation sequencing (NGS) were carried out. Follow-up was conducted with review of relevant literature. Results: Among the five patients, four were male and one was female, aged 45-71 years. All patients had a history of chronic kidney disease (duration 9-30 years) and received dialysis treatment. Three cases occurred in the right kidney and two in the left kidney. All were single lesions with a maximum diameter of 2.0-15.0 cm. Grossly, the tumors showed a solid-cystic appearance. Histologically, various histological patterns were observed, including cystic (4 cases), tubular (4 cases), papillary (4 cases), solid (2 cases), cribriform (2 cases), and microcystic structures (1 case). Two cases were accompanied by tumor necrosis, and one case was accompanied by sarcomatoid differentiation. The tumor cells had abundant eosinophilic cytoplasm with intracytoplasmic vacuoles, conspicuous nucleoli, and high nuclear grades (World Health Organization/International Society of Urological Pathology nuclear grade 3 or 4). Two cases had focal, clear cytoplasm. Oxalate crystals were present in all tumors. In all cases, the surrounding renal parenchyma was atrophic with multiple cysts. The cysts in three cases were lined by single-or multiple-layered eosinophilic cells, which had abundant cytoplasm and visible nucleoli. Tumor cells in all five cases expressed PAX8, CD10 and P504s. Two cases partially expressed carbonic anhydrase Ⅸ(CAⅨ). Two cases focally expressed CK7, CD117, HMB45, Melan A, TFE3, TFEB, GATA3, 2SC and ALK were negative in all cases. FH, SDHB and SMARCB1 (INI1) proteins were not deficient. TFE3 gene rearrangement was not detected in two cases using FISH with break-apart probes. High-throughput DNA targeted NGS showed that one tumor had a KMT2C mutation, one had KMT2B, TSC1, SETD2 and TP53 mutations, one had an MTOR mutation, one had a TSC2 mutation, and one had an SETD2 mutation. The five cases were followed up for 6-70 months and had no recurrence or metastasis, except one case with local recurrence and retroperitoneal lymph node metastasis four years after the surgery. Conclusions: ACD-RCC is a rare renal cell carcinoma that occurs in patients with end-stage renal disease and has unique morphological features. It is often associated with favorable prognosis and alterations in genes related to the MTOR/TSC pathway or chromatin modification.

Objective: To investigate the characteristics of germline/somatic homologous recombination repair (HRR) gene variants in patients with hormone-sensitive prostate cancer (HSPC) and to analyze their associations with clinicopathological features. Methods: A retrospective study was conducted on 108 clinicopathologically high-risk HSPC patients diagnosed at the Peking University Third Hospital, Beijing, China from 2019 to 2022. Next generation sequencing (NGS) was used to simultaneously detect germline and somatic gene variants (32-98 genes, including at least 19 HRR-related genes). The HRR gene variation profiles were characterized. Their correlations with clinicopathological characteristics were analyzed. Results: Genetic mutations were found in 23 patients, the age ranged from 36 to 83, with an age of 66(56,68)years. Germline HRR gene variants were detected in 4 (3.7%, 4/108) of the 108 patients, with BRCA2 being most common (1.9%, 2/108), followed by PALB2(0.9%)/RAD51D(0.9%). Somatic HRR gene variants were identified in 14 patients (13.0%, 14/108), involving 17 variants (affecting BRCA1/BRCA2/ATM/CDK12/FANCA). CDK12 was the most frequently mutated gene. Among these 14 patients, 3 had two different variants (either in different genes or two distinct variants in the same gene). In addition to the most common point-mutations and small insertions/deletions, copy number loss of BRCA1 was detected in 1 case. Non-HRR-related gene variants were identified in 5 patients. Among them, 3(2.8%) had TP53 variants (1 case had mixed acinar and ductal adenocarcinoma) and 2 had PTEN and KRAS mutations. Compared with the patients without gene variations, the ones with somatic HRR gene variations were younger, presented with higher serum total prostate-specific antigen (PSA) levels and more advanced tumor stage (all P<0.05). No significant correlations were observed between somatic HRR gene variants and free PSA levels or grade groups (P>0.05). Conclusions: HSPC exhibits high genetic heterogeneity. BRCA2 is the most common gene with germline variations, while CDK12 is the most frequently mutated gene in somatic HRR variants. This study suggests that HRR gene testing in patients with high-risk HSPC would help identify those with more aggressive clinical features and guide prognostication and potential targeted therapeutic strategies.

Pulmonary enteric adenocarcinoma (PEAC) is a distinct subtype of non-small cell lung cancer (NSCLC) whose histomorphology and immunophenotype closely resemble those of metastatic colorectal adenocarcinoma; its pathogenesis and standard treatment strategies have yet to be clearly established. Here, we reported a case of PEAC harboring epidermal growth factor receptor (EGFR) exon 19 deletion mutation with high programmed cell death ligand 1 (PD-L1) expression. The patient showed no meaningful response to EGFR-tyrosine kinase inhibitors (EGFR-TKIs), including the first-generation (Icotinib), the second-generation (Afatinib) and the third-generation (Aumolertinib). Trophoblast cell surface antigen 2-antibody-drug conjugate (TROP2-ADC) and immune checkpoint inhibitors (ICIs) combined with Bevacizumab also resulted in limited efficacy. Based on the clinical features and treatment response of this case, we reviewed the published literature about the pathological characteristics, mutational landscape, and current therapeutic approaches for PEAC, with a particular focus on the therapeutic challenges and future research directions for EGFR-mutant PEAC, aiming to provide insights for clinical practice and further studies.
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Lung adenocarcinoma is prone to brain metastasis, and the prognosis of patients is extremely poor. The inhibitor of apoptosis-stimulating protein of p53 (iASPP) protein, encoded by the protein phosphatase 1 regulatory subunit 13-like (PPP1R13L) gene, is a key inhibitor of the p53 pathway and promotes carcinogenesis in various tumors, but its role in brain metastasis of lung adenocarcinoma is unknown. This study aims to analyze the tumor microenvironment characteristics of patients with brain metastasis of lung adenocarcinoma and explore the expression of PPP1R13L in brain metastasis tissues and its clinical significance by single-cell sequencing and clinical sample analysis.

To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1).

Objective: To investigate the differences in clinicopathological and molecular characteristics between pure ovarian endometrioid carcinoma (POEC) and synchronous endometrial and ovarian endometrioid carcinoma (SEOEC), aiming to provide a basis for their differential diagnosis and individualized treatment. Methods: Clinical and pathological data were collected from ovarian endometrioid carcinoma patients and they were divided into POEC group (219 cases) and SEOEC group (169 cases) according to whether they had endometrioid endometrial carcinoma or not. Clinical data including the age at onset, reasons for medical consultation, maximum diameter of ovarian tumors and pathological examination results such as histologic grading of the lesions were collected. Additionally, follow-up outcomes and survival status of the patients were also recorded. Molecular subtyping results were obtained from 108 cases of POEC group and 109 cases of SEOEC group patients. Large-scale targeted sequencing using next-generation sequencing was performed on 76 POEC group samples (32 with matched peripheral blood) and 51 SEOEC group samples (46 with matched peripheral blood/normal tissue). The prognosis of POEC group and SEOEC group were analyzed. Moreover, SEOEC group were further stratified to high-risk group and low-risk group according to 2020 WHO classification of tumors and 2023 International Federation of Gynecology and Obstetrics (FIGO) staging of endometrial cancer. Results: (1) Clinicopathological characteristics: compared to the SEOEC group, POEC group patients exhibited the following characteristics: younger age at diagnosis (50.0 years vs 38.0 years, P<0.001), higher proportion presenting with typical ovarian cancer symptoms (45.7% vs 92.1%, P<0.001), higher detection rates of ovarian endometriosis (14.9% vs 56.2%, P<0.001) and uterine adenomyosis (23.0% vs 37.0%, P=0.021), higher proportion of low grade tumors (78.7% vs 95.4%, P<0.001), lower proportion of mismatch repair deficiency subtype (23.9% vs 3.7%, P<0.001). (2) Gene mutation profile: although the driver gene mutation profiles were similar between the two groups, POEC group patients had a significantly lower PTEN (22.4% vs 64.0%, P<0.001) and CTNNB1 (22.4% vs 48.0%, P=0.014) mutation rates compared to SEOEC group. Also, POEC group had a higher KRAS mutation rate than SEOEC group patients (50.0% vs 28.0%, P=0.055). (3)Prognosis: survival analysis revealed that POEC group patients had a significantly shater progression free survival time compared to the low-risk SEOEC group patients(P=0.046). However, their long-term survival outcomes (both overall survival and disease specific survival) were significantly better than those of the high-risk SEOEC group patients (P=0.018 and P=0.046, respectively). Conclusions: POEC and SEOEC represent two distinct tumor entities with significantly different clinical, pathological and molecular features. Accurate differential diagnosis is crucial for correct clinical decision-making.

To investigate whether miR-100-5p regulates the proliferation and apoptosis of acute myeloid leukemia (AML) cells by targeting Tribbles pseudokinase 1 (TRIB1).

To explore the clinical characteristics and prognostic factors of pediatric acute myeloid leukemia (AML) with monosomy 7 (-7) and deletion of the long arm of chromosome 7 (7q-).