中华病理学杂志最新文献

Objective: To investigate the clinicopathological and prognostic features, immunophenotypic characteristics, and key points of differential diagnosis of multifocal EBV-associated smooth muscle tumors (EBV-SMT). Methods: The clinicopathological data of 7 cases of EBV-SMT diagnosed in Sun Yat-sen University Cancer Center from June 2020 to March 2025 were retrospectively analyzed. Immunohistochemical staining, Epstein-Barr virus-encoded small RNAs (EBERs) in situ hybridization, and next-generation sequencing were performed, and the relevant literature was reviewed. Results: All 7 patients were children or young adults, with a median age of 7 (2, 33) years. Five patients were immunocompromised due to congenital immune deficiency, autoimmune disease or post-transplant treatment. All the 7 cases presented with multifocal lesions, involving the brain, liver, lungs and adrenal glands. Histologically, 3 cases exhibited a classic spindle cell leiomyoma-like morphology, while the other 4 showed a more primitive round cell morphology resembling smooth muscle cells. All cases expressed smooth muscle markers, such as SMA, calponin, HHF35, h-caldesmon, and desmin, among others. The proliferation index of Ki-67 ranged from 1% to 30%. All cases were diffusely and strongly positive for EBERs by in situ hybridization. Next-generation sequencing identified an ITK gene deletion in one case (case 2). During a follow-up period of 1 to 44 months after diagnosis, 2 patients died, while the remaining 5 survived. Conclusions: EBV-associated smooth muscle tumors are more likely to occur in children or young adults with immune deficiency, often manifesting as multifocal lesions in different organs. Accurate diagnosis relies on a comprehensive assessment incorporating clinical history, histopathological features, and findings of immunohistochemistry and EBERs in situ hybridization.

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.

Objective: To investigate the clinical and pathological characteristics of massive perivillous fibrin deposition (MPFD) in twin placentas. Methods: A retrospective analysis was performed on 11 cases of MPFD in twin pregnancies diagnosed at the Obstetrics and Gynecology Hospital Affiliated to Fudan University between January 2018 and December 2024. Maternal and fetal clinical features, as well as placental pathological findings, were summarized. Results: MPFD cases accounted for 2.8% (11/390) of all twin placentas submitted for pathological examination during the study period. Clinical analysis revealed that 6/11 cases were conceived via in vitro fertilization-embryo transfer; 10/11 women had a history of spontaneous abortion, with 3/11 meeting the criteria for adverse obstetric history (≥3 spontaneous abortions or perinatal deaths). Prenatal abnormalities in fetuses primarily included intrauterine growth restriction, intrauterine distress, and intrauterine death. Placental pathological examination showed generally low placental weight, advanced maturation in most cases, and more than 25% of villi surrounded by abundant amorphous eosinophilic fibrinoid material, leading to complete obstruction of the intervillous spaces. In one case of recurrent MPFD, only one placenta in a dichorionic diamniotic twin pregnancy was affected, with the corresponding fetus exhibiting intrauterine growth restriction. The rate of adverse obstetric outcomes was 10/11, including miscarriage (3/11), single or twin intrauterine death (3/11), and preterm birth (5/11). Follow-up for over 4-72 months indicated that one case was lost to follow-up, while the remaining mothers recovered well and live-born infants demonstrated normal development. Conclusions: MPFD can occur in twin pregnancies and may manifest as discordant involvement between co-twins, primarily presenting as adverse pregnancy outcomes such as fetal growth restriction. MPFD has a tendency for recurrence, and clinicians should remain vigilant for its consequence in high-risk twin pregnancies. Placental pathological examination plays a critical role in confirming diagnosis and guiding subsequent pregnancy management.

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, 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.

Renal cell carcinoma with tumor thrombus is a subtype of urinary system malignancy with high clinical challenges. In recent years, with the development of pathological techniques and growing insights into molecular mechanism research, significant progress has been made in the fields of molecular regulation of tumor thrombus formation, precise pathological assessment, and optimization of staging systems. This article focuses on the pathological features of renal cell carcinoma with tumor thrombus, systematically sorts out the application differences of the clinical staging and grading system of tumor thrombus, explores the impact of pathological assessment on clinical staging, treatment strategy selection and patient prognosis, and analyzes the formation mechanism of tumor thrombus from the perspectives of relevant molecular and cellular ecology.

Objective: To investigate the clinical, radiologic, pathological and molecular genetic features of polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Methods: A retrospective analysis was performed on fourteen PLNTY cases, diagnosed at the Department of Pathology, Xuanwu Hospital, Capital Medical University, from August 2018 to December 2024. The clinical, radiologic, prognostic, histopathological, molecular genetic features, and DNA methylation clustering were analyzed. Results: Among the 14 patients (10 males, 4 females), the age range was 8-34 years, with a median age of 21 (14, 29) years. The patient's major, initial clinical symptom was epilepsy (13/14). Among 9 MRI exanimated cases, 4 showed cystic-solid abnormal signals, and 5 appeared as solid masses. Most were hypointense on T1 and hyperintense on T2. Five cases had enhancement, with no obvious diffusion restriction on DWI. Among 5 CT examined cases, 4 showed high density, and 1 showed low density. The characteristic histopathologic features of the tumor cells were oligodendroglioma-like, spindle, pleomorphic and associated with foci of calcifications. GFAP and Olig2 were expressed in tumor cells in all 14 cases (14/14). Neuronal markers (NeuN, NF) were negative in 13/13 cases. CD34 showed diffuse strong positivity in all cases (14/14). BRAF V600E was positive in 8/11 cases. Thirteen cases (13/13) harbored mitogen-activated protein kinase (MAPK) pathway alterations, including BRAF (10/13) and FGFR2/3 (3/13) gene mutations. In 7 PLNTY cases, t-SNE cluster analysis of DNA methylation profiles showed clustering with ganglioglioma, PLNTY, and pilocytic astrocytoma. Until November 2025, 13 patients have been seizure-free postoperatively, and all 14 patients showed no tumor progression or recurrence. Conclusions: PLNTY usually occurs in adolescents and is associated with epilepsy. Its diagnosis necessitates a combination of clinical, histopathological, and molecular genetic alterations. In molecular level, PLNTY exhibits alterations in the MAPK pathway; while its DNA methylation profile demonstrates diversity. Most patients achieved seizure-free outcomes postoperatively, indicating a favorable prognosis.