9.Clinicopathological and molecular genetic characteristics of embryonal rhabdomyosarcoma in the middle ear: an analysis of 11 cases
Hongqin LIU ; Lin YU ; Ji SUN ; Lan LIN ; Chunyan HU
Chinese Journal of Pathology 2025;54(10):1062-1068
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.
10.Expression of keratin 1/sialyl-Tn antigen in primary and metastatic cervical squamous cell carcinomas
Yuchen TAO ; Lingchuan GUO ; Xia GUO ; Renpeng HUANG ; Qianqian YANG
Chinese Journal of Pathology 2025;54(10):1069-1074
Objective:To investigate the expression of keratin 1 (KRT1) and sialyl-Tn antigen (sTn) in cervical squamous cell carcinoma and its possible mechanism.Methods:Six cervical squamous cell carcinoma specimens were collected at the First Affiliated Hospital of Soochow University, Suzhou, China from 2022 to 2023. Spatial transcriptomics analysis was performed on the paraffin sections of 6 patients to analyze the transcriptomes of invasive squamous cell carcinoma and adjacent normal cervical squamous epithelium. The differential gene KRT1 was selected. Kaplan-Meier survival analysis was used to examine the prognostic value of KRT1 in cervical squamous cell carcinoma patients using the TCGA database. The possible downstream molecule sTn was identified according to literature research. Immunohistochemistry was carried out to investigate the expression of KRT1 and sTn proteins in the primary tumor and metastases of cervical squamous cell carcinoma (40 cases with pelvic lymph node metastasis and 30 cases without). Spearman correlation analysis was conducted to analyze the correlation of their expression.Results:The spatial transcriptomic results of the 6 specimens indicated that the level of KRT1 mRNA significantly decreased in cervical squamous cell carcinoma (compared with that in adjacent normal cervical squamous epithelium), while Kaplan-Meier survival analysis revealed that cervical squamous cell carcinoma patients with low KRT1 mRNA levels (versus high) had a worse prognosis. Immunohistochemistry proved that KRT1 expression was significantly lower in cervical squamous cell carcinoma than in adjacent normal squamous epithelium ( P<0.05), but sTn showed the opposite change (increased in carcinoma, P<0.05). The expression changes of KRT1 and sTn were inversely correlated ( r=-0.217, P<0.05). In addition, the expression levels of KRT1 and sTn in lymph node metastases were not significantly different from those in primary tumors. Conclusions:The decreased expression of KRT1 in primary cervical squamous cell carcinoma and lymph node metastasis may promote tumor cell proliferation and inhibit apoptosis by upregulating sTn, contributing to the poor prognosis of advanced cervical squamous cell carcinoma.
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