中华病理学杂志最新文献

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 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.

Objective: To investigate clinicopathologic characteristics and molecular genetic profiles of embryonal rhabdomyosarcoma (ERMS) of the middle ear. Methods: A total of 11 cases of primary middle ear ERMS diagnosed and treated at the Fudan University Affiliated Eye and ENT Hospital between January 2016 and June 2024 were collected. Their clinicopathologic features, immunophenotypes, and molecular genetic alterations were analyzed. Relevant literature was reviewed. Results: There were 8 male and 3 female children. The mean age was 6 years, median age, 6 (5, 7) years, with a range of 1 to 11 years. Clinical manifestations included otorrhea, ear pain, ear fullness, tinnitus, and hearing loss, with some patients also presenting with facial paralysis, hoarseness, and choking on drinking. Otoscopic examination revealed granulomatous neoplasms in the external auditory canal. Imaging studies showed irregular soft-tissue masses in the middle ear region, accompanied by bony destruction and invasion of adjacent structures. Histologically, 10 of the tumors were composed of primitive small round cells, stellate cells, and short spindle-shaped cells, with an alternating loose and dense distribution pattern, and varying degrees of rhabdomyoblastic differentiation in some areas. One tumor exhibited the classic botryoid subtype morphology. Immunohistochemistry supported the diagnosis of rhabdomyosarcoma, and the Ki-67 proliferation index ranged from 40% to 80%. Next-generation sequencing (DNA-seq) was performed on 9 cases, revealing copy number variations of chromosome 7 in 4 cases, PDE4DIP mutations in 5 cases, and C19orf69::TPM3 gene fusions in 6 cases. HPV PCR testing showed HPV11 positivity in 2 cases. All 11 patients underwent surgical treatment, with 4 patients receiving adjuvant chemoradiotherapy. Follow-up until February 2025 revealed 8 deaths, among which 4 cases harbored both C19orf69::TPM3 fusions and PDE4DIP mutations and one had C19orf69::TPM3 fusions alone. Conclusions: ERMS of the middle ear is a rare type of malignant tumor with a relatively poor prognosis. Our study indicates that the concurrence of PDE4DIP mutation and C19orf69::TPM3 gene fusion may indicate poor prognosis in middle ear EMRS, providing a potential target for subsequent individualized treatment.