Dian Diagnostics (China)

Malignant Triton Tumor (MTT) is a rare, highly aggressive peripheral nerve sheath tumor characterized by rhabdomyoblastic differentiation, seldom occurring primarily in the thoracic cavity. This report presents a rare case of MTT initially manifesting as chest pain, and reviews relevant literature to summarize its clinical features and therapeutic strategies. A 23-year-old woman experienced chest pain for ten days and her condition worsened within 3 days. The patient had a known history of neurofibromatosis type 1 (NF1) and exhibited classic café-au-lait spots on physical examination. Diagnosis was confirmed via chest CTA, PET-CT, bronchoscopy, ultrasound, and histopathology. After surgical resection, the tumor recurred rapidly, prompting multiple treatments including chemotherapy, targeted therapy, and combination immunotherapy. Pathology after right lower lobectomy and chest wall resection confirmed MTT (S-100+/Desmin+/Myogenin+). Recurrence in the mediastinum was detected two months postoperatively. Disease stabilization was achieved using cadonilimab, apatinib, and ifosfamide/etoposide. Notably, the first application of single-cell RNA sequencing (scRNA-seq) in MTT, combined with the CopyKAT algorithm, distinguished malignant from non-malignant cells and revealed a heterogeneous tumor microenvironment composed of distinct functional cell populations, highlighting the tumor's high degree of heterogeneity. This case underscores the importance of considering MTT in young NF1 patients presenting with intrathoracic masses. An individualized, multimodal treatment approach may extend survival. scRNA-seq provides valuable insights into the molecular landscape of MTT and hold promise for guiding precision therapy in the future.

BACKGROUNDSMARCB1/INI1-deficient pancreatic undifferentiated rhabdoid carcinoma is a highly aggressive tumor, and spontaneous splenic rupture (SSR) as its presenting manifestation is rarely reported among pancreatic malignancies.CASE SUMMARYWe herein report a rare case of a 59-year-old female who presented with acute left upper quadrant abdominal pain without any history of trauma. Abdominal imaging demonstrated a heterogeneous splenic lesion with hemoperitoneum, raising clinical suspicion of SSR. Emergency laparotomy revealed a pancreatic tumor invading the spleen and left kidney, with associated splenic rupture and dense adhesions, necessitating en bloc resection of the distal pancreas, spleen, and left kidney. Histopathology revealed a biphasic malignancy composed of moderately differentiated pancreatic ductal adenocarcinoma and an undifferentiated carcinoma with rhabdoid morphology and loss of SMARCB1 expression. Immunohistochemical analysis confirmed complete loss of SMARCB1/INI1 in the undifferentiated component, along with a high Ki-67 index (approximately 80%) and CD10 positivity. The ductal adenocarcinoma component retained SMARCB1/INI1 expression and was positive for CK7 and CK-pan. Transitional zones between the two tumor components suggested progressive dedifferentiation and underlying genomic instability. The patient received adjuvant chemotherapy with gemcitabine and nab-paclitaxel and maintained a satisfactory quality of life at the 6-month follow-up.CONCLUSIONThis study reports a rare case of SMARCB1/INI1-deficient undifferentiated rhabdoid carcinoma of the pancreas combined with ductal adenocarcinoma, presenting as SSR - an exceptionally uncommon initial manifestation of pancreatic malignancy.

The association between high-risk HPV (hrHPV) infection and cervical cancer or precancerous lesions has been extensively established, highlighting the importance of preventing hrHPV infection in cervical lesions patients. This study aims to investigate the risk factors associated with hrHPV infection in patients with cervical lesions and develop a nomogram model for predicting the risk of infection. The study involved 154 patients with cervical lesions, all of whom underwent human papillomavirus (HPV) gene typing. Retrospectively analyze the HPV genotyping and assess the prevalence of HPV infection in patients. The patients with cervical lesions were separated into hrHPV (n = 100) and non-hrHPV group (n = 54) based on the results of HPV genotyping tests. Univariate and multivariate regression analyses were employed to identify independent risk factors and develop nomogram model. The performance of the nomogram model were evaluated using ROC analysis. There were a total of 114 patients who tested positive for HPV, comprising 100 hrHPV and 14 low-risk HPV. The most common types of HPV are HPV 16 (65.00%), followed by HPV 52 (3.00%) and HPV 58 (3.00%). Univariate and multivariate analyses showed that age of first sexual intercourse (odds ratio [OR] = 3.312), miscarriage (OR = 7.115), menopause (OR = 2.508), cervicitis (OR = 2.710), number of sexual partners (OR = 5.259) were identified as significant risk factors for hrHPV infection. The nomogram model shows an area under the curve value of 0.861 (95% confidence interval = 0.795–0.927), with a sensitivity of 95.6% and specificity of 92.3%. These findings indicate the significant practical value of the clinical risk nomogram model. Age of first sexual intercourse, miscarriage, menopause, cervicitis, and number of sexual partners were identified as risk factors for hrHPV infection in patients with cervical lesions. This nomogram model holds significant clinical value.

Neoadjuvant therapies are essential for managing high-risk early-stage breast cancer, but their effectiveness is limited, necessitating the exploration of the optimal neoadjuvant treatment strategy based on innovative subtypes. Given the heterogeneity inherent in breast cancer, there is growing need for identifying novel molecular subtypes predictive of treatment response through multi-omic analyses. A comprehensive analysis was performed using data from 142 high-risk early breast cancer patients, including genomic, transcriptomic, proteomic, and phosphoproteomic profiles. The molecular subtypes were explored based on the biological characteristics and responses to neoadjuvant treatments. The results were also validated in the TCGA-breast cancer cohort and external dataset. Three molecular subtypes were identified, each associated with different optimal treatment strategies. The immune-activated (IA) subtype displayed a significantly higher pathologic complete response (pCR) rate when treated with platinum-based neoadjuvant regimens, and exhibited heightened immune cell infiltration. The vesicular transport pathway-activated (VT) subtype, characterized by vesicular transport pathway activation, showed a favorable pCR rate to anthracycline-based neoadjuvant chemotherapy. In contrast, the kinase activation (KA) subtype demonstrated limited responsiveness to both platinum and anthracycline-based treatments and featured enrichment in non-canonical TGF-β signaling, MAPK/ATM kinase activation, and angiogenic signatures. A seven-gene classifier linked to non-canonical TGF-β signaling was created to identify the KA subtype, achieving an area under the curve value of 90%. The drug vulnerability of breast cancer cells within the KA subtype indicated potential therapeutic effectiveness of ATR/ATM inhibitors and anti-angiogenic agents. This study defined three novel molecular subtypes in high-risk early-stage breast cancer patients and provided optimal therapeutic treatment strategies based on these subtypes. Therefore, important insights about intrinsic biological properties can form the basis for new cancer treatment strategies.

Congenital heart defects (CHDs) represent the leading cause of neonatal mortality among congenital abnormalities. Genetic factors, such as EVC2 gene mutations and other genetic alterations, constitute a major cause of CHD. Thus, determining the genetic etiology of fetal CHDs is crucial for optimizing pregnancy management and informing future reproductive decisions. Here, we describe a male fetus with complex CHD who was diagnosed at 25 weeks of gestation, delivered at full term, and died prematurely within a month due to heart failure. The cardiac abnormalities observed included an atrial septal defect developing from a patent foramen ovale, mitral valve regurgitation, dilated right ventricle and left atrium, aortic stenosis, and aortic arch dysplasia. Novel compound heterozygosity of the EVC2 gene, including a non-sense mutation (p.W828Ter) and two cis missense mutations (p.E87G and p.S217C), was identified by prenatal trio-whole-exome sequencing of amniotic fluid, followed by validation using Sanger sequencing. This novel EVC2 genotype was supposed to potentially affect fetal cardiac development, given the variable clinical heterogeneity of the EVC2 mutation-associated phenotype. This case represents the first identification of the EVC2 p.E87G and p.S217C, and the isolated CHD without visible skeletal dysplasia is an important feature of our case. Our study expands the genotypic and phenotypic spectra of the EVC2 gene. We recommend including the EVC2 gene in preconception carrier screening and prenatal diagnosis for CHDs.

Introduction: Successful management of concurrent infection with cranial Nocardia gipuzkoensis and pulmonary Klebsiella pneumoniae has never been previously described. Case Presentation: A 71-year-old female was referred to our hospital due to an intracranial space-occupying lesion persisting for over 20 days. Her initial chief complaints suggested cranial and pulmonary inflammation. Subsequently, drainage of the brain lesion was performed, and N. gipuzkoensis infection was confirmed through microbial culture and metagenomic next-generation sequencing (mNGS). Sputum culture identified K. pneumoniae infection. Based on antimicrobial susceptibility test results and allergic history, the patient showed improvement after two weeks of intravenous meropenem (2 g/8 h) combined with vancomycin (1 g/12 h). Neurological recovery was achieved, followed by over six weeks of oral Linezolid (0.6 g/12 h) and Levofloxacin (0.5 g/24 h). Conclusions: This case reports the successful management of concurrent infections, providing supporting evidence for the potential to shorten intravenous administration in nocardiosis treatment.

BackgroundAsparaginase is a critical component of chemotherapy for pediatric acute lymphoblastic leukemia (ALL), but its use is often complicated by asparaginase-associated pancreatitis (AAP). Genetic predispositions, such as variants in the SPINK1 gene, have been linked to an increased risk of pancreatitis. However, the role of genetic factors in relation to asparaginase treatment remains incompletely understood, partly because mutations in pancreatitis-causing genes are rarely found in pediatric ALL.Case descriptionA four-year and three-month-old Chinese girl was admitted to our hospital due to fever for half a day, with no history of significant prior medical history. Initial blood tests revealed hematological abnormalities, including leukopenia, anemia, and thrombocytosis. Bone marrow aspiration identified 81.5% blast cells with B-lymphocyte morphology and immunophenotype, leading to a diagnosis of B-cell acute lymphoblastic leukemia (B-ALL). The patient began treatment under the CCCG-ALL-2015 protocol, which included PEG-asparaginase (PEG-asp). On day 10 of induction, she developed AAP, which was primarily characterized by severe epigastric pain and elevated serum amylase. Despite effective symptom management with analgesics and anti-inflammatory therapy, AAP recurred following administration of L-asparaginase (L-asp). Genetic analysis revealed a heterozygous SPINK1 c.194 + 2T>C variant (rs148954387), a well-known pathogenic variant associated with increased susceptibility to pancreatitis. Sanger sequencing confirmed that the SPINK1 variant was inherited from her asymptomatic mother. The patient's AAP was managed conservatively, and an asparaginase-free regimen ultimately achieved complete remission without recurrence of pancreatitis.ConclusionsThe identification of the SPINK1 c.194 + 2T>C variant, which is recognized as pathogenic, provides valuable information for understanding the heightened risk of AAP in our pediatric ALL patient. Our case underscores the potential role of genetic predisposition in the development of AAP and highlights the importance of considering genetic screening prior to asparaginase therapy in pediatric ALL patients to identify those at increased risk.

BackgroundThis study aims to analyze the pathogenic gene in a Chinese family with non-syndromic hearing loss and identify a novel mutation site in the TNC gene.MethodsA five-generation Chinese family from Anhui Province, presenting with autosomal dominant non-syndromic hearing loss, was recruited for this study. By analyzing the family history, conducting clinical examinations, and performing genetic analysis, we have thoroughly investigated potential pathogenic factors in this family. The peripheral blood samples were obtained from 20 family members, and the pathogenic genes were identified through whole exome sequencing. Subsequently, the mutation of gene locus was confirmed using Sanger sequencing. The conservation of TNC mutation sites was assessed using Clustal Omega software. We utilized functional prediction software including dbscSNV_AdaBoost, dbscSNV_RandomForest, NNSplice, NetGene2, and Mutation Taster to accurately predict the pathogenicity of these mutations. Furthermore, exon deletions were validated through RT-PCR analysis.ResultsThe family exhibited autosomal dominant, progressive, post-lingual, non-syndromic hearing loss. A novel synonymous variant (c.5247A > T, p.Gly1749Gly) in TNC was identified in affected members. This variant is situated at the exon–intron junction boundary towards the end of exon 18. Notably, glycine residue at position 1749 is highly conserved across various species. Bioinformatics analysis indicates that this synonymous mutation leads to the disruption of the 5' end donor splicing site in the 18th intron of the TNC gene. Meanwhile, verification experiments have demonstrated that this synonymous mutation disrupts the splicing process of exon 18, leading to complete exon 18 skipping and direct splicing between exons 17 and 19.ConclusionThis novel splice-altering variant (c.5247A > T, p.Gly1749Gly) in exon 18 of the TNC gene disrupts normal gene splicing and causes hearing loss among HBD families.