OBJECTIVE: To explore the genetic variants and phenotypic characteristics of patients with Neurofibromatosis type I (NF1). METHODS: Twenty two NF1 patients who presented at Enze Medical (Center) Group in Taizhou between 2018 and 2024 were selected as the study subjects. Clinical phenotype and family history were collected for the patients. Whole exome sequencing (WES) was carried out for the 22 probands to screen the variants of NF1 gene. Candidate variants were verified by Sanger sequencing of their family members. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No.: K20230902). RESULTS: The 22 probands were diagnosed between the age of 5 months to 47 years old, and have all shown cafe au lait spots on their skin. Seventeen patients exhibited the phenotype at birth, and 11 had various degrees of neurofibromatosis. Among them, probands 1 and 13 underwent surgical resection of the tumor but had recurred, while proband 12 had amputation due to the huge size and serious impact of the neurofibroma and had no recurrence. Five patients had various degrees of scoliosis. In total 22 germline mutations and one somatic mutation were identified among the 22 families, with 5 variants unreported previously, including 1 nonsense mutation c.1603C>T (Q535*), 3 frameshift mutations [c.7268_7269delCA (Thr2423fs), c.2293del (Arg765Alafs*26), and c.5433_5438delinsGC (Phe1812ArgfsTer50)], and 1 deletion involving exons 41-44 of the NF1 gene and adjacent introns. Proband 13 was found to harbor germline mutation c.6796C>T (Gln2266Ter) and somatic mutation c.1019_1020del (Ser340Cysfs Ter12) in the peripheral blood and tumor tissue, respectively. Among the 22 NF1 probands, 6 had received treatment due to severe illness. Proband 1 had tumor resection in the right upper limb, but was found to have malignant lung tumor and died during follow-up. Proband 12 had multiple recurrence of neurofibroma in the left ring finger. Proband 4 underwent spinal correction surgery due to severe scoliosis. Proband 11 had died due to a central nervous system disease. Among the 22 germline mutations, 6 had led to the occurrence of truncated proteins, which may have a more severe impact on the phenotype. CONCLUSION This study investigated the genetic variants and clinical phenotypes of 22 NF1 families and identified 5 novel variants of the NF1 gene, which has expanded the genotypic and phenotypic spectra of the NF1. Preliminary studies have identified an association between truncated mutations, young age, and severe phenotypes, which may provide important clues for prognosis evaluation. For the clinical diagnosis and treatment of NF1, it is necessary to consider the phenotypic characteristics and genetic testing in combination with genetic counseling and long-term follow-up.
Humans ; Neurofibromatosis 1/pathology* ; Male ; Female ; Pedigree ; Adult ; Child ; Child, Preschool ; Middle Aged ; Adolescent ; Infant ; Young Adult ; Neurofibromin 1/genetics* ; Phenotype ; Asian People/genetics* ; Mutation ; Exome Sequencing ; East Asian People

Intraoperative hemorrhage is a life-threatening complication during neurosurgery, especially in posterior fossa surgery, where critical vasculature and brain structures are present. Adenosine has been used in neurovascular surgery, particularly in the management of intraoperative aneurysm rupture and hemorrhage for its ability to produce transient flow arrest. This case report describes a novel application for adenosine, in which adenosine-induced flow arrest was used to facilitate control of a vascular injury sustained during meningioma surgery.

A 46-year-old female diagnosed with a petroclival meningioma after presenting with a several-month history of headache, dizziness, and loss of balance underwent craniotomy and excision of the meningioma. The patient received general endotracheal anesthesia, and was maintained on remifentanil, propofol, and low-dose sevoflurane. During posterior excision of the meningioma, the basilar artery was inadvertently lacerated, resulting in significant blood loss. Adenosine was given through a subclavian catheter, and produced severe bradycardia, hypotension, then asystole for approximately 50 seconds. Adenosine-induced flow arrest allowed for initial control of the vascular injury through coagulation, while further hemostasis was achieved through hemostatic agents and muscle tamponade.

This case report demonstrates the usefulness of adenosine-induced flow arrest in the management of intraoperative hemorrhage from an intracranial vascular injury. Adenosine-induced flow arrest has documented safety and efficacy in other neurosurgical applications. As the management of intraoperative hemorrhage is an essential component of neuroanesthesia, this technique may be considered in similar circumstances of major vascular injury to facilitate hemostasis.

Human ; Female ; Middle Aged: 45-64 Yrs Old ; Adenosine ; Basilar Artery ; Meningioma

BACKGROUND

Early-stage endometrial cancer often presents with favorable survival rates, but high-risk factors, including TP53 mutations and high-grade serous pathology, can lead to recurrence and poor prognosis. The standard primary treatment for endometrial cancer is surgical staging, and lymph node metastases significantly impact adjuvant therapy decisions. The subgroup of p53-abnormal (p53abn) indicates the worst prognosis and potential benefits from adjuvant chemotherapy. Molecular classification, while recommended, faces practical challenges due to resource constraints.

OBJECTIVES

The study aimed to assess the incidence of p53 abnormal expression in clinical stage 1 endometrial cancer cases that underwent surgery at a government tertiary hospital, and assess its relationship with clinicopathologic factors and pelvic and paraaortic lymph node metastasis (LNM).

METHODS

A cross-sectional retrospective analysis was conducted on clinical early-stage endometrial cancer cases that underwent surgical primary treatment between January 2018 and December 2022. Patient records were reviewed to gather demographics, surgical information, and pathological evaluations. Preoperative clinical staging was determined through imaging, and surgical staging involved comprehensive lymphadenectomy. Immunohistochemistry studies for p53 were carried out on formalin-fixed paraffin-embedded tissue samples.

RESULTS

A total of 233 endometrial cancer cases were included. The mean age at diagnosis was 53.7 years. Common comorbidities included hypertension (47.2%) and dyslipidemia (20.6%). Most cases were endometrioid histology (82.8%) and low-grade tumors (85.8%). Tumor grade (p=0.010), myometrial invasion (p<0.001) and lymphovascular space invasion (p<0.001) significantly correlated with lymph node metastasis. However, tumor size and p53abn were not significantly associated with lymph node metastasis. p53abn overexpression was significantly associated with non-endometrioid histology at 33% and Grade 3 tumors at 23%. Preoperative grading demonstrated moderate reliability (0.51) with postoperative grading, with an agreement of 65.4%.

CONCLUSION

Tumor grade, myometrial invasion, and LVSI were all significantly associated with lymph node involvement. While p53 immunohistochemical stains show promise in predicting metastasis and has been associated with tumor aggressiveness, this should still be correlated with clinicopathological parameters to carry out a more accurate risk stratification of early-stage patients.

Therapeutics ; Survival Rate ; Risk Factors ; Recurrence ; Prognosis ; Pathology ; Endometrial Neoplasms ; Immunohistochemistry ; Tumor Suppressor Protein P53 ; Lymph Node Excision ; Risk Assessment

Abstract Embryonal rhabdomyosarcoma (ERMS) is a primitive and aggressive soft tissue tumor that arises from premature mesenchymal cells and accounts for less than 1% of prostate malignancies. We present the case of a 26-year-old Filipino male who initially sought consultation and work-up for acute urinary retention. Although his prostate-specific antigen (PSA) level was normal, a kidney-ureter-bladder (KUB) ultrasound revealed an incidental finding of an enlarged prostate gland. Subsequent imaging tests (MRI and CT) identified a large, partially exophytic mass on the prostate with intravesical extension. The patient underwent a biopsy via transurethral resection at another institution, which yielded findings of a poorly differentiated carcinoma, primarily suggesting prostatic adenocarcinoma with a Gleason score of 10 (5+5). A request for slide review was submitted to our institution, and subsequent immunohistochemistry (IHC) studies—highlighting the tumor's immunoreactivity to myogenin and desmin—confirmed the diagnosis of ERMS. In this report, we discuss the clinical features, pathogenesis, treatment, diagnosis, and prognosis of this rare prostate tumor.
Embryonal rhabdomyosarcoma ; Immunohistochemistry ; Prostate ; Young adult

Angiomyolipoma with epithelial cysts (AMLEC) is a rare subtype of angiomyolipoma that may closely mimic both malignant and benign neoplasms. We report a case of AMLEC in an 18-year-old female presenting with acute flank pain and radiologic suspicion for malignancy. This case highlights the diagnostic challenges posed by AMLEC, emphasizes its characteristic histopathologic and immunohistochemical features, and reviews current concepts regarding its pathogenesis. This case represents the first documented case of AMLEC in the Philippines.

Human ; Angiomyolipoma ; Kidney Neoplasms ; Immunohistochemistry

Introduction: Cranial radiotherapy is an established treatment for intracranial germinoma but may lead to late cerebrovascular complications including radiation-induced vasculopathy, cavernoma formation, and premature intracranial atherosclerosis. These complications may manifest many years after treatment and represent an important cause of stroke in young adult survivors of brain tumors. Case: We report a 39-year-old male with a history of suprasellar germinoma treated with transsphenoidal surgery followed by craniospinal radiotherapy in 2006. He subsequently developed panhypopituitarism requiring lifelong hormone replacement therapy. In October 2024, he experienced a cerebrovascular accident resulting in mild residual right-sided weakness. Brain magnetic resonance imaging demonstrated multifocal old infarcts, small vessel disease (Fazekas grade 2), and multiple susceptibility artifacts suggestive of radiation-induced cavernomas.In March 2026, he presented with new onset right-sided weakness and facial asymmetry. Initial neurological examination revealed right-sided motor power of 4/5. Computed tomography of the brain showed no acute intracranial hemorrhage but confirmed multiple old infarcts and small vessel ischemic changes. Computed tomography angiography revealed intracranial atherosclerotic disease with 25–50% stenosis of the cavernous segments of both internal carotid arteries and mild irregularities of posterior circulation vessels without evidence of large vessel occlusion or aneurysm. Radiation-induced vasculopathy is a recognized delayed complication of cranial irradiation, often presenting 5–25 years after treatment. Pathophysiological mechanisms include endothelial injury, accelerated atherosclerosis, and progressive arterial stenosis. In rare cases, cranial irradiation may also lead to secondary Moyamoya syndrome, characterized by progressive stenosis of the intracranial internal carotid arteries with development of collateral vessels. Although this patient’s vascular imaging did not demonstrate the characteristic collateral network seen in Moyamoya syndrome, it remains an important differential diagnosis in young patients presenting with recurrent stroke after cranial irradiation. In this patient, young age, prior cranial irradiation, multifocal infarcts, and coexisting radiation-induced cavernomas strongly suggest radiationrelated cerebrovascular disease as a major contributor to recurrent stroke. Conclusion Long-term survivors of intracranial germinoma treated with cranial radiotherapy remain at risk of delayed cerebrovascular complications. Early recognition and aggressive secondary stroke prevention, along with continued neurological surveillance, are essential to reduce morbidity in this population.
Ischemic Stroke ; Germinoma

Objective: This study aimed to determine the prevalence, clinicopathologic features, and immunohistochemical profile of PTs diagnosed at the Philippine General Hospital – Department of Laboratories from January 1, 2018 to December 31, 2022. Methodology: This cross-sectional study reviewed surgical pathology cases of PTs within the study period. Immunoscores for β-catenin, E-cadherin, and CD10 were evaluated, with outcomes including histopathologic grade, stromal cellularity, atypia, overgrowth, tumor margin, and mitotic count. Results: A total of 191 PTs were diagnosed, with the fewest in 2020 (27 cases) and the most in 2018 (51 cases). Benign PTs comprised the majority (52.88%), followed by borderline (34.03%) and malignant (13.09%) types. Most patients (59.16%) were 50 years or older. Tumors commonly measured 5.0–19.99 cm, with the largest proportion ranging from 15.0–19.99 cm. No significant associations were observed between immunoscores and tumor grade or morphologic features, possibly due to limited sample size and uneven group distribution. A weak positive correlation was found between β-catenin and E-cadherin, while other markers showed negligible correlation. Conclusion Larger studies are needed to clarify potential relationships between IHC expression and PT grading. This study contributes to the limited local data on PTs and highlights their possible diagnostic utility, especially in cases with overlapping features.
Phyllodes Tumor ; beta Catenin ; Cadherins

Introduction: Brenner tumors are uncommon epithelial-stromal neoplasms that usually arise in the ovary and comprise a small proportion of ovarian tumors. Extraovarian Brenner tumors are exceedingly rare, and cervical involvement is exceptional. Because of their unusual location and histologic resemblance to other cervical epithelial lesions, accurate diagnosis can be challenging on limited biopsy material. Case Description: A 43-year-old woman presented with prolonged menstrual bleeding and a clinically suspicious cervical mass. An initial cervical punch biopsy demonstrated benign inflammatory and metaplastic changes. Due to persistent symptoms, a repeat biopsy was performed. Histopathologic examination revealed well-defined nests and cords of urothelial-like epithelial cells with focal cystic change embedded in a dense fibrous stroma. The tumor cells showed elongated nuclei with dense chromatin, inconspicuous nucleoli, and clear cytoplasm with distinct cell borders. Occasional mitotic figures were present without significant cytologic atypia. Immunohistochemical studies demonstrated tumor cell positivity for GATA-3, CK7, p63, and p16, with estrogen receptor positivity in the surrounding stroma, supporting the diagnosis of a borderline extra-ovarian Brenner tumor of the cervix. Discussion: Cervical Brenner tumors are extremely rare and may closely mimic squamous cell carcinoma, transitional cell carcinoma, or benign squamous metaplasia, particularly in small biopsy specimens. Recognition of the characteristic nested urothelial-like architecture, together with a focused immunohistochemical panel, is essential for accurate classification and to prevent misdiagnosis and unnecessary aggressive management. Conclusion This case highlights a rare borderline extra-ovarian Brenner tumor arising in the cervix and emphasizes the importance of correlating histomorphologic features with immunohistochemistry in establishing the correct diagnosis of unusual cervical neoplasms.
Brenner Tumor ; Immunohistochemistry ; Urothelium ; Uterine Cervical Neoplasms

OBJECTIVE: To examine the mechanism of action of tanshinone II A (Tan II A) in promoting chemosensitization of osteosarcoma cells to cisplatin (DDP). METHODS: The effects of different concentrations of Tan II A (0-80 µ mol/L) and DDP (0-2 µ mol/L) on the proliferation of osteosarcoma cell lines (U2R, U2OS, 143B, and HOS) at different times were examined using the cell counting kit-8 and colony formation assays. Migration and invasion of U2R and U2OS cells were detected after 24 h treatment with 30 µ mol/L Tan II A, 0.5 µ mol/L DDP alone, and a combination of 10 µ mol/L Tan II A and 0.25 µ mol/L DDP using the transwell assay. After 48 h of treatment of U2R and U2OS cells with predetermined concentrations of each group of drugs, the cell cycle was analyzed using a cell cycle detection kit and flow cytometry. After 48 h treatment, apoptosis of U2R and U2OS cells was detected using annexin V-FITC apoptosis detection kit and flow cytometry. U2R cells were inoculated into the unilateral axilla of nude mice and then the mice were randomly divided into 4 groups of 6 nude mice each. The 4 groups were treated with equal volume of Tan II A (15 mg/kg), DDP (3 mg/kg), Tan II A (7.5 mg/kg) + DDP (1.5 mg/kg), and normal saline, respectively. The body weight of the nude mice was weighed, and the tumor volume and weight were measured. Cell-related gene and signaling pathway expression were detected by RNA sequencing and Kyoto Encyclopedia of Genes and Genomes pathway analysis. p38 MAPK signaling pathway proteins and apoptotic protein expressions were detected by Western blot. RESULTS: In vitro studies have shown that Tan II A, DDP and the combination of Tan II A and DDP inhibit the proliferation, migration and invasion of osteosarcoma cells. The inhibitory effect was more pronounced in the Tan II A and DDP combined treatment group (P<0.05 or P<0.01). Osteosarcoma cells underwent significantly cell-cycle arrest and cell apoptosis by Tan II A-DDP combination treatment (P<0.05 or P<0.01). In vivo studies demonstrated that the Tan II A-DD combination treatment group significantly inhibited tumor growth compared to the Tan II A and DDP single drug group (P<0.01). Additionally, we found that the combination of Tan II A and DDP treatment enhanced the p38 MAPK signaling pathway. Western blot assays showed higher p-p38, cleaved caspase-3, and Bax and lower caspase-3, and Bcl-2 expressions with the combination of Tan II A and DDP treatment compared to the single drug treatment (P<0.01). CONCLUSION Tan II A synergizes with DDP by activating the p38/MAPK pathway to upregulate cleaved caspase-3 and Bax pro-apoptotic gene expressions, and downregulate caspase-3 and Bcl-2 inhibitory apoptotic gene expressions, thereby enhancing the chemosensitivity of osteosarcoma cells to DDP.
Abietanes/therapeutic use* ; Osteosarcoma/enzymology* ; Cisplatin/therapeutic use* ; Humans ; Cell Line, Tumor ; Animals ; Apoptosis/drug effects* ; Mice, Nude ; Cell Proliferation/drug effects* ; Cell Movement/drug effects* ; p38 Mitogen-Activated Protein Kinases/metabolism* ; MAP Kinase Signaling System/drug effects* ; Bone Neoplasms/enzymology* ; Cell Cycle/drug effects* ; Xenograft Model Antitumor Assays ; Mice ; Drug Resistance, Neoplasm/drug effects* ; Neoplasm Invasiveness ; Mice, Inbred BALB C

OBJECTIVE: To explore the role of the natural compound hesperidin in glycolysis, the key ratelimiting enzyme, in colorectal cancer (CRC) cell lines. METHODS: In vitro, HCT116 and SW620 were treated with different doses of hesperidin (0-500 µmol/L), cell counting kit-8 and colone formation assays were utilized to detected inhibition effect of hesperidin on CRC cell lines. Transwell and wound healing assays were performed to detect the ability of hesperidin (0, 25, 50 and 75 µmol/L) to migrate CRC cells. To confirm the apoptotic-inducing effect of hesperidin, apoptosis and cycle assays were employed. Western blot, glucose uptake, and lactate production determination measurements were applied to determine inhibitory effects of hesperidin (0, 25 and 50 µmol/L) on glycolysis. In vivo, according to the random number table method, nude mice with successful tumor loading were randomly divided into vehicle, low-dose hesperidin (20 mg/kg) and high-dose hesperidin (60 mg/kg) groups, with 6 mice in each group. The body weights and tumor volumes of mice were recorded during 4-week treatment. The expression of key glycolysis rate-limiting enzymes was determined using Western blot, and glucose uptake and lactate production were assessed. Finally, protein interactions were probed with DirectDIA Quantitative Proteomics, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: Hesperidin could inhibit CRC cell line growth (P<0.05 or P<0.01). Moreover, hesperidin presented an inhibitory effect on the migrating abilities of CRC cells. Hesperidin also promoted apoptosis and cell cycle alterations (P<0.05). The immunoblotting results manifested that hesperidin decreased the levels of hexokinase 2, glucose transporter protein 1 (GLUT1), GLUT3, L-lactate dehydrogenase A, 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 2 (PFKFB2), PFKFB3, and pyruvate kinase isozymes M2 (P<0.01). It remarkably suppressed tumor xenograft growth in nude mice. GO and KEGG analyses showed that hesperidin treatment altered metabolic function. CONCLUSION Hesperidin inhibits glycolysis and is a potential therapeutic choice for CRC treatment.
Hesperidin/therapeutic use* ; Colorectal Neoplasms/metabolism* ; Glycolysis/drug effects* ; Animals ; Humans ; Apoptosis/drug effects* ; Mice, Nude ; Cell Movement/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Glucose/metabolism* ; Cell Cycle/drug effects* ; Mice, Inbred BALB C ; Mice ; HCT116 Cells ; Lactic Acid