中华病理学杂志最新文献

Objective: To investigate the clinicopathological characteristics, immunophenotype and differential diagnosis of atypical forms of microglandular hyperplasia of the cervix (AMGH). Methods: A total of 29 cases of AMGH diagnosed at the Obstetrics and Gynecology Hospital of Fudan University, Shanghai, China from January 2010 to December 2024 were analyzed. Relevant clinical and pathological data of the patients were collected using the electronic medical record system and medical records copied from the outside hospitals. The patients were followed up. Results: Among the 29 cases, 28 were consultation cases, 22 (79%) of the 28 cases were considered as glandular neoplastic lesions by the original institutions. The nature of the lesion was uncertain in 1 case, the diagnosis was suspicious for AMGH in another 1 case, and only 4 cases were clearly diagnosed as AMGH. The median age of the 29 patients was 44 (43, 48) years. Eighteen (62%) of the 29 cases presented as cervical polyp. Twelve of the 16 tested cases were negative for human papillomavirus. The pathological presentation was complex and diverse, including solid, trabecular, cribriform, and papillary patterns, forming pseudo-invasive structures. The glandular epithelium and proliferating reserve cells had diverse morphologies, which presented with abundant eosinophilic cytoplasm or clear cytoplasm. Signet-ring or hobnail cells were also seen. The nuclear atypia was mild, with 0-7 mitotic figures per 10 HPF. Immature squamous metaplasia was noted. The stroma showed edema, myxoid change and hyaline degeneration, accompanied by infiltration of acute and chronic inflammatory cells. Immunohistochemistry demonstrated that p16 was negative in 8/16 of the cases or patchy positive in the other 8/16, Ki-67 positive rate was less than 10% in all 16 cases, p53 was wild phenotype (9/9), and carcinoembryonic antigen was negative in 4/5 cases and focally positive in 1/5 cases, while p63 was positive in 6/9 of the tested cases. Conclusions: AMGH is a benign non-neoplastic lesion of the cervical glands. Half of the cases occur in perimenopausal or postmenopausal women, often presenting as polypoid hyperplasia or localized cervical thickening/elevation with a friable, fragile texture. Microscopically, it may show a pseudoinvasive pattern, making it prone to misdiagnosis as a malignant lesion. Thus, differentiation from cervical adenocarcinoma, clear cell carcinoma and microglandular endometrioid carcinoma is required. Integration of clinical history, immunohistochemistry and molecular testing may aid in the differential diagnosis.

Objective: To investigate the clinicopathological and molecular genetic characteristics of pediatric tumors with DICER1 mutations. Methods: A total of 90 patients diagnosed with various types of pediatric tumors at Beijing Children's Hospital, Capital Medical University, Beijing, China from July 2023 to September 2025 were included in this study. PCR amplification and Sanger sequencing were performed to detect the coding-region mutations of the DICER1 gene. The clinical, histopathological, and molecular genetic features of the cases with DICER1 mutation were then analyzed. Results: Among the 90 patients, 39 were male and 51 were female, with an age of onset ranging from 1 month to 17 years [median 7.13 (2.77, 10.37) years]. DICER1 mutations were detected in 37 patients (37/90, 41.1%). Among them, 9 cases harbored one mutation [6 pleuropulmonary blastomas (PPBs), 2 sex cord stromal tumors (SCSTs), and 1 cystic nephroma (CN)], 27 cases carried two mutations [10 PPBs, 3 anaplastic sarcomas of the kidney (ASKs), 3 SCSTs, 3 thyroid adenoma, 2 nodular thyroid goiters, 2 thyroid follicular lesions, 2 CN, 1 embryonal rhabdomyosarcoma, and 1 case with multiple primary tumors], and 1 case exhibited three mutations (bilateral ASKs). Despite variations in the site of origin, DICER1-mutant tumors shared several morphological features. Grossly, they presented as multilocular cystic, cystic-solid to solid masses. Microscopically, they exhibited a subepithelial layer of mesenchymal cells, with focal rhabdomyoblastic/chondroid/chondrosarcomatous differentiation, as well as cellular anaplasia. Germline testing using peripheral blood in the 31 patients with DICER1 mutation confirmed germline origin in 61.3% (19/31) of them. Parental analysis (n=12) demonstrated genetic inheritance in 8 cases, predominantly from families with tumor history. Germline variants scattered throughout DICER1 and consisted of loss-of-function mutations (nonsense, frameshift, and splice-site). Somatic mutations showed distinct clustering in exons 24 and 25 hotspots (codons 1705, 1709, 1809, 1810 and 1813), primarily missense variants. Notably, one multiple primary tumor case harbored a somatic mosaic p.E1705K mutation. Conclusions: DICER1 mutations are frequently detected in pediatric PPB, CN, SCST, ASK, nodular thyroid goiter, thyroid adenoma, and genitourinary rhabdomyosarcoma, which often represent as the index case of DICER1 syndrome. Performing DICER1 mutation testing in these patients not only facilitates tumor diagnosis and secondary cancer surveillance, but also enables the comprehensive genetic risk assessment and management for patient's family members.

Over the past decade, pathology technology in China has undergone rapid development. Through continuous efforts to strengthen normative foundations and quality control, the three-tiered quality control network (national, provincial, and municipal) has been consolidated. These efforts have effectively driven the homogenization of pathology technical quality nationwide. Concurrently, the standardization of laboratory quality management systems and the advancement of automated pathological equipment have laid a solid foundation for the evolution of pathological diagnosis. Breakthroughs in cutting-edge technologies, including digital pathology, artificial intelligence, and molecular pathology, are further catalyzing a paradigm shift from traditional morphological analysis toward next-generation diagnostic pathology. Marking the 70th anniversary of this journal, the field's evolution over the past decade and chart its future course were reviwed systematically, aiming to provide an insightful roadmap for the ongoing progress of the discipline.

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 investigate the clinicopathological characteristics and diagnostic criteria of cutaneous melanocytic tumor with CRTC1::TRIM11 fusion (CMTCT), and to improve understanding of this entity. Methods: The clinical features, histology, immunohistochemistry (IHC) and molecular characteristics of 3 CMTCT cases were analyzed, supplemented by a literature review. Results: All patients were female, aged 53, 46 and 46 years, respectively. Grossly, the lesions presented as dermal/subcutaneous nodules protruding from the skin surface. Histologically, tumor cells were arranged in nested and fascicular patterns separated by delicate fibrous septa. Tumor cell infiltration was observed in the epidermis of case 1, but not in that of cases 2 and 3. Tumor cells exhibited epithelioid, spindle-shaped, or oval morphology, with eosinophilic or pale cytoplasm and mild to moderate nuclear atypia. Tumor mitotic figure was <5/10 HPF. Scant melanin pigment was observed in case 2. IHC demonstrated diffuse and strong positivity for SOX-10, S-100 protein and MITF. HMB45 was negative in two cases (case 1 and case 3) and focally positive in case 2; Melan A was negative in two cases (case 1 and case 3) and partially positive in case 2. The Ki-67 proliferation index was approximately 5%-8%. Molecular analysis revealed CRTC1::TRIM11 fusion in three cases via RNA sequencing, and CRTC1 rearrangement in two cases (case 1 and case 3) via fluorescence in situ hybridization. Conclusions: CMTCT shares histological and immunophenotypic features with melanoma and clear cell sarcoma but is defined by the presence of CRTC1::TRIM11 fusion, necessitating molecular confirmation for definitive diagnosis. Complete excision with clear margins is recommended. While most of the CMTCTs exhibit indolent biological behaviors, rare cases may recur locally or metastasize, warranting close follow-up.