Fusion genes represent a core molecular mechanism in the pathogenesis of acute promyelocytic leukemia (APL). In recent years, a novel type of tripartite retinoic acid receptor (RAR) fusion genes has been identified in atypical APL (aAPL), exhibiting distinct structural characteristics and pathogenic mechanisms compared to the classical bipartite fusion. This article systematically introduces relevant content in this field: it begins by outlining the long-standing scientific puzzle of inconsistent clinical resistance versus in vitro sensitivity in aAPL patients; subsequently, it describes the discovery process and structural features of tripartite fusion genes in all RARG and specific RARA-related cases, and elucidates the key molecular mechanism by which tripartite fusion leads to all-trans retinoic acid (ATRA) resistance at the protein conformational level; finally, the discovery of transposon involvement in the formation of tripartite fusions and its implications for the mechanism of fusion gene are discussed.

A retrospective analysis was conducted on the clinical course of two children with PICALM-MLLT10-positive acute leukemia treated at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, between July 2021 and July 2023. The patients were diagnosed with acute T-lymphoblastic leukemia with central nervous system involvement and high-risk acute myeloid leukemia, respectively. Both achieved bone marrow complete remission after conventional chemotherapy combined with venetoclax. Following conversion to molecular negativity, they underwent sequential allogeneic hematopoietic stem cell transplantation. At the latest follow-up, both patients were alive and in good clinical condition. These observations suggest that proceeding to hematopoietic stem cell transplantation after venetoclax-based chemotherapy may improve the long-term survival of children with PICALM-MLLT10-positive leukemia.

Acute myeloid leukemia (AML) is the most common type of acute leukemia in adults. Isocitrate dehydrogenase (IDH) is a key enzyme in the tricarboxylic acid cycle and one of the common mutated genes in AML. Although the 2022 version of the ELN guidelines suggests that IDH mutations cannot be used as a separate prognostic stratification indicator, multiple studies have indicated that IDH mutations have prognostic significance for AML. Early identification of IDH mutations and selection of appropriate treatment options are crucial. This review summarizes the research progress on the characteristics, carcinogenic mechanisms, prognosis of IDH mutations in AML patients, and treatment options, in order to provide reference for further improving the prognosis of IDH -mutated AML patients.

To analyze the clinical features of acute myeloid leukemia patients with DEK-NUP214 fusion gene positive.

To explore the correlation between single nucleotide polymorphisms (SNPs) of ARID5B gene and the risk of acute lymphoblastic leukemia (ALL) and minimal residual disease (MRD) in children of Hui and Han nationality in Ningxia.

To investigate the clinical characteristics, treatment and prognosis of adult AML patients with NUP98::HOXA9 fusion gene.

To explore the impact of age on the genetic variant spectrum and prognosis of patients with previously untreated Diffuse large B-cell lymphoma (DLBCL).

The clinical data of patients with acute myeloid leukemia (AML) treated at Hebei Yanda Lu Daopei Hospital between August 1, 2024, and March 1, 2025 were retrospectively included, to differentiate AML with the same recurrent t(11;12)(p15;q13) karyotype but harboring distinct rare fusion genes, namely NUP98::RARG::LINE-L2a and NUP98::HOXC13. Two patients were included: Patient 1, a 12-year-old male, visited Hebei Yanda Lu Daopei Hospital on August 8, 2024, due to "fever for 4 days accompanied by sore throat"; Patient 2, a 33-year-old female, visited the hospital on September 22, 2024, due to "recurrent fatigue and cough for over one month". Case 1 and Case 2 carried the NUP98::RARG::LINE-L2a and NUP98::HOXC13 fusion genes, respectively. The patient with NUP98::RARG::LINE-L2a fusion genes exhibited bone marrow morphology and immunophenotypic features resembling acute promyelocytic leukemia (APL) but was resistant to all-trans retinoic acid. Although initial treatment achieved remission, early relapse occurred. The patient with NUP98::HOXC13 fusion genes showed increased myeloblasts, the presence of Auer rods, and an elevated proportion of promyelocytes, along with mutations in FLT3-TKD gene, RUNX1 gene and, WT1 gene, demonstrating resistance to multiple chemotherapy regimens. Both patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) without achieving complete remission. After transplantation, they were followed for 8 and 9 months, respectively, with quantitative monitoring of fusion genes showing negative results. Although the patients with NUP98::RARG::LINE-L2a and NUP98::HOXC13 fusion genes have completely identical chromosomal abnormalities, but they are different rare molecular subtypes. Both involve the NUP98 gene. The former partner gene is RARG, with clinical manifestations, bone marrow morphology, and immunophenotype similar to APL. The latter partner gene is HOXC13, with the characteristics of NUP98-AML patients.

Objective: To investigate the clinicopathological and molecular characteristics of neurocutaneous melanosis in children caused by NRAS gene variants. Methods: Three cases of neurocutaneous melanosis from Children's Hospital of Fudan University (case 1 and case 2) and Shanghai Children's Hospital, School of Medicine Shanghai Jiaotong University (case 3) from July 2022 to February 2023 were collected. The clinical, histopathological, immunohistochemical and genetic results of three patients were retrospectively analyzed. The literatures were reviewed. Results: The patients were all female, aged 5, 4 and 3 years, respectively. The patients presented with severe headache with other symptoms of increased intracranial pressure. Physical examination showed multiple congenital melanocytic nevi throughout the body. Imaging examination showed intracranial masses, which were located in the right cerebellum, pineal gland and left temporal lobe, respectively. The maximum diameters were 39.1 mm, 72.8 mm and 52.2 mm, respectively. Histologically, the tumor showed diffuse sheets of round or oval-shaped cells arranged in nests, with marked nuclear atypia, eosinophilic cytoplasm, dark nuclei, and prominent nucleoli. Giant tumor cells were seen and mitotic figures were easily observed. There were hemorrhage and necrosis. Pigment granules were found in the cytoplasm and stroma in case 1 and case 2. Immunohistochemically, the tumor cells showed diffuse and strong staining of SOX10, S-100, HMB45 and Melan A, but did not express GFAP and CKpan. The Ki-67 proliferation index ranged from 30% to 80%. Genetic testing showed that case 1 and case 2 had NRAS Q61K matation, and case 3 had NRAS Q61R mutation. Case 1 and case 3 underwent complete resection of the tumor combined with chemotherapy. Case 2 was diagnosed by biopsy and underwent resection after chemotherapy and radiotherapy. All patients were followed up for 18, 21 and 25 months, respectively. All patients died due to complications such as increased intracranial pressure and hydrocephalus. Conclusions: Neurocutaneous melanosis is a congenital neurocutaneous syndrome caused by abnormal development of embryonic neuroectodermal melanoblasts. Most cases are associated with somatic mutations of NRAS gene. Clinicians should pay attention to the skin manifestations and neuroimaging examination in patients with unexplained intracranial hypertension or epilepsy. The diagnosis of neurocutaneous melanosis depends on histopathology and genetic testing.

Objective: To investigate clinicopathological and molecular genetic characteristics of CD117-positive eosinophilic renal cell tumors (ERCTs) with unusual morphological and immunophenotypic features. Methods: Formalin-fixed, paraffin-embedded tissues from 10 cases (9 cases from Xiangya Hospital, Central South University and 1 case from Bishan Hospital of Chongqing Medical University) of diagnostically challenging CD117-positive ERCTs between January 2017 and October 2024 were collected. Histological reviews were performed on HE-stained sections, followed by immunostaining and whole-exome sequencing (WES). Results: The 10 patients were composed of 4 males and 6 females, with ages ranging from 29 to 57 years, median 49.5 (36.8, 51.8) years. The sizes of tumors ranged from 2.5 to 6.0 cm, median 4.8(2.9,5.2) cm. All 10 ERCTs were composed of variably eosinophilic cells and characterized by prominent morphological features including exclusively eosinophilic (2 cases), focal chromophobe-like (3 cases), prominent nested (2 cases), prominent flocculent cytoplasm (1 case), a collision of renal oncocytoma (RO)/chromophobe renal cell carcinoma (ChRCC) (1 case), and diffusely degenerative atypia (1 case). Immunohistochemically, a subset of 10 tumors variably expressed CK7 (7/10) and vimentin (3/10), while they were all positive for CD117 (10/10), PAX8 (10/10), SDHB (10/10), and FH (10/10) and negative for CAⅨ (10/10) and 2SC (10/10). The Ki-67 proliferation index ranged from 1% to 5%. WES identified a GNAS mutation in one case of the RO/ChRCC collision tumor, while no characteristic mutations of other renal cell tumor types were detected in the remaining 9 cases. The analysis of copy number variations revealed complex karyotypic alterations in 4 tumors, harboring various gain of chromosomes 4, 5, 7, 12, 13, 15, 16, 18, and 22, with 3 cases showing variable loss of chromosomes 1, 2, 6, 10, 13, and 17. These 4 cases were molecularly classified as eosinophilic ChRCC. The remaining 6 cases, including 2 cases with a normal diploid karyotype and 4 cases with slight karyotypic alterations, were molecularly classified as 5 ROs and 1 RO-dominant RO/ChRCC collision tumor. Finally, the original diagnosis was retained in 4 cases and revised in 6 cases. Conclusions: CD117-positive ERCTs with uncertain classification may exhibit various morphological overlaps, non-classic histological features, and aberrant immunophenotypes. Combined immunostaining of CK7, CD117, vimentin, SDHB, FH, and 2SC can greatly help discriminate among these tumors and their mimics. When the diagnosis is challenging based only on morphology and immunohistochemistry, molecular genetic tests may be useful.

Objective: To investigate the clinicopathological features, pathological classification, and molecular characteristics of pulmonary hamartomas. Methods: A retrospective analysis was conducted on 316 cases of pulmonary hamartomas diagnosed at Nanjing Chest Hospital, Nanjing, China from January 2015 to June 2024. Next generation sequencing (NGS) was performed on 15 cases of this study. The clinical data, histopathological features, immunophenotypes, and molecular alterations were analyzed. Relevant literature was reviewed. Results: Among the 316 patients, there were 154 males and 162 females, with an average age of 56±10 years. Among the 316 cases, 310 were intrapulmonary hamartomas and 6 were intraluminal bronchial hamartomas. Microscopically, there were complex proliferative mesenchymal components and epithelial components, presenting various combinations and hamartomatous morphologies. These hamartomas were morphologically classified into mesenchymal-type hamartomas (cartilaginous, fibrous, smooth muscle, adipose tissue, and mixed types) and epithelial-mesenchymal mixed-type hamartomas (respiratory epithelial-mesenchymal mixed and mucosal gland-mesenchymal mixed types). The cartilaginous hamartomas accounted for 72.8% (230/316) of them, and the non-cartilaginous hamartoma accounted for 27.2% (86/316). Secondary changes such as calcification, ossification, collagenization, mucin degeneration, and cystic changes were commonly present. The immunophenotype was CK7+/TTF1+ for respiratory epithelial cells, or TTF1-/CK7+/p40+ for interstitial cells. Interstitial cells might express desmin, SMA, S-100, caldesmon, etc, while CD34+/CD10+/ER+ spindle-shaped interstitial cells were also commonly noted. Genetic variations were detected in 11 of the 15 cases that were subject to NGS, including HMGA2-related fusion genes, EP300 mutations, FLT1 mutations, JAK1 mutations, SETD2 and TAP2 mutations, and high-copy amplification of CDK4/PHF1/TSPAN31. The patients were followed up for 6 to 110 months without any known recurrence or metastasis. Conclusions: Pulmonary hamartomas mainly occur in the peripheral lung parenchyma, with the cartilaginous type being the most common. Their clinical pathological and molecular features of pulmonary hamartomas are characterized and the histological types are roughly ascertained in this study, with emphasis of the key points of diagnosis and differential diagnosis. Classification of pulmonary hamartomas is valuable for guiding future research. Pulmonary hamartomas overall have a good prognosis. However, those with cystic changes or intraluminal hamartomas in the bronchus may cause serious airway lesions and therefore require special attention.

Objective: To investigate the clinicopathological and molecular genetic characteristics of diffuse gliomas with the features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY) and their prognostic values. Methods: A retrospective analysis was performed on 14 cases of diffuse gliomas with PLNTY features diagnosed at the First Affiliated Hospital of Fujian Medical University, Fuzhou, China from June 2020 to August 2024. Their clinicopathological characteristics were examined, and their molecular genetic and epigenetic features were assessed using next-generation sequencing (NGS) and methylation analysis. Factors influencing prognosis were also analyzed. Results: Among the 14 patients, there were 8 males and 6 females, aged 3-62 years, median 29 (9, 50) years. All cases were initially diagnosed as low-grade diffuse gliomas histologically but exhibited the histological and immunohistochemical features of PLNTY. At the molecular level, all cases showed molecular abnormalities involving the mitogen-activated protein kinase pathway, including 5 cases with FGFR3-TACC3 (F3T3) fusion, 3 cases with FGFR2 fusion, 5 cases with BRAF V600E mutation, and 1 case with FGFR1 mutation. Among them, TERT promoter mutations were frequently observed in tumors with F3T3 fusion (5/5), while NCOR2 in-frame insertion mutations were prominent in tumors with non-F3T3 fusions. Clinical follow-up showed recurrence in 3 cases, all of which had F3T3 fusion and concurrent TERT promoter mutations. Prognostic analysis confirmed that F3T3 fusion with concurrent TERT promoter mutation was associated with poor prognosis. Conclusions: Diffuse gliomas with PLNTY features exhibit heterogeneity in clinicopathology and molecular genetics, with FGFR3/FGFR2 fusions and BRAF/FGFR1 mutations as the most common molecular alteration. They often have concurrent F3T3 fusion and TERT promoter mutations, which are related to poor prognosis. The possibility of molecular glioblastoma should be considered for these tumors. It is thus recommended to perform genetic testing on diffuse gliomas with PLNTY features in order to facilitate integrated diagnosis and provide molecular evidence for accurate evaluation of prognoses.

Objective: To investigate the clinicopathological characteristics and genetic alterations of undifferentiated embryonal sarcoma of the liver (UESL). Methods: Three cases of UESL diagnosed in the Department of Pathology, the Third Affiliated Hospital of Sun Yat-sen University from 2020 to 2023 were retrospectively collected. The clinical, histomorphological, immunohistochemical, and genetic profiles were reviewed and analyzed. Results: The cohort comprised of three patients, including one male and two females, aged 7, 9, and 15 years, respectively. Tumor locations were in the right lobe of the liver in two cases, and in both the right and left lobes in one case. One case exhibited tumor rupture with hemorrhage. Gross examination revealed solid tumors in gray-red fleshy appearance, with areas of hemorrhage and necrosis. Microscopically, the tumor was composed of irregularly shaped spindle and polygonal cells arranged in bundles or sheets with varying density, scattered within a myxoid matrix containing giant tumor cells and eosinophilic globules. The tumor cells were positive for Vimentin, CD56, CD68, and bcl-2, with a Ki-67 index of 30%-80%. INI1 expression was retained, while p53 exhibited a mutant pattern. CKpan, CK7, CK19, EMA, HepPar-1, Arginase-1, AFP, CD34, S-100, Myogenin, and MyoD1 were negative. All three cases harbored TP53 missense mutations. Case 1 also showed MDM2 copy number amplification (class Ⅰ mutation), and case 2 exhibited a frameshift mutation in exon 10 of TSC2 (class Ⅱ mutation). Additionally, several class Ⅲ mutations were identified in all three cases. Germline testing for tumor-related genetic variants in case 2 revealed a missense mutation in exon 12 of DICER1, an in-frame insertion mutation in exon 8 of MSH2, and a missense mutation in exon 30 of TSC2. Conclusion: UESL is a rare malignant mesenchymal tumor of the liver, predominantly affecting children, with distinctive clinicopathological features and genetic alterations. TP53 mutations may play a key role in the pathogenesis of this tumor.

In the past decade, breast pathology in China has made significant progress in diagnostic standards, technological applications, scientific research, and discipline development. The histopathological diagnostic system has been continuously refined, with the implementation of relevant guidelines and expert consensus enhancing standardization and reproducibility of diagnostic results. Immunohistochemistry and molecular testing technologies have become increasingly sophisticated, with emerging biomarkers such as low HER2 expression and PIK3CA mutations gradually integrated into clinical decision-making, promoting the advancement of precision therapy. The application of digital pathology and image-assisted analysis has steadily expanded, providing new tools to improve diagnostic efficiency and consistency. The national breast pathology group has actively advanced the development of tiered diagnostic systems, workforce training, and public education, effectively strengthening diagnostic capabilities at the grassroots level. Looking ahead, the integration of multidimensional data, optimization of auxiliary diagnostic systems, and interdisciplinary collaboration are expected to drive the continued development of breast pathology in China.

Pediatric tumors differ significantly from adult cancers, possessing unique developmental origins, histological features, and molecular genetic changes. With the rapid advancement of multi-omics technologies, such as genomics, transcriptomics, proteomics, and epigenetic analyses, the molecular characteristics of pediatric tumors have been extensively revealed, providing new possibilities for precision medicine. Concurrently, the integration of artificial intelligence and digital pathology has effectively enhanced diagnostic accuracy, presenting a broad scope for future development. While this progress positively impacts the pathological diagnosis of pediatric tumors, it also presents challenges related to data complexity, technology integration, and the promotion of clinical applications. This article aims to discuss the influence of molecular and artificial intelligence, as well as multimodal integrated pathological models on diagnosis and prognostic prediction of pediatric tumor, with the goal of fostering further exploration and in-depth research.

This study aimed to explore the biological functions and clinical value of mothers against decapentaplegic homolog (SMAD) 7 in head and neck squamous cell carcinoma (HNSCC) through bioinformatics analysis and basic experiments.