中华病理学杂志最新文献

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.

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.