Diffuse infiltrating retinoblastoma is an extremely rare form of retinoblastoma which is characterized by its atypical growth pattern. This unusual presentation adds complexity to the diagnostic process. The purpose of this paper is to report a rare presentation of diffuse infiltrating retinoblastoma presenting after an ocular trauma. We described a 7-year-old Filipino boy presenting with total hyphema following an ocular trauma. Comprehensive ophthalmologic clinical and diagnostic evaluations were performed including visual acuity, slitlamp biomicroscopy, ocular ultrasound, neuroimaging, and histopathology post enucleation to determine diagnosis. The misleading, atypical presentation of diffuse infiltrating retinoblastoma may delay diagnosis. While this dilemma is expected in these scenarios, it should be remembered that timing of diagnosis in retinoblastoma is crucial, as this also equates to optimal management. One should remain vigilant for these uncommon presentations especially in the setting of any intraocular inflammation in children.

Human ; Male ; Child: 6-12 Yrs Old ; Wounds And Injuries ; Visual Acuity ; Retinoblastoma ; Research Report ; Neuroimaging ; Inflammation ; Hyphema ; Contusions

Introduction: Pheochromocytoma is a catecholamine-secreting adrenal tumor associated with major perioperative hemodynamic instability. When concurrent major pelvic pathology requires surgery, operative planning becomes particularly challenging. We describe the successful single-stage management of pheochromocytoma and a giant uterine fibroid, highlighting the importance of multidisciplinary coordination and perioperative optimization. Case: A 49-year-old female with symptomatic uterine fibroid was found to have proliferative endometrium on a pipelle biopsy. Computed tomography (CT) abdomen incidentally detected a right adrenal mass alongside a large posterior uterine fibroid (11.9 × 17.4 × 14.6 cm). CT adrenal protocol demonstrated a heterogeneously enhancing right adrenal mass (6.9 × 6.9 × 9.6 cm) with high unenhanced attenuation. Biochemical evaluation revealed markedly elevated 24-hour urinary metanephrine (4.7× upper limit) and normetanephrine (2.4× upper limit). Following multidisciplinary discussions, a single-stage surgical approach was planned after careful assessment of feasibility and perioperative risk in view of the uncertain malignant potential of the pelvic mass and to minimize repeated exposure to anesthesia. Preoperative optimization included transitioning from terazosin to phenoxybenzamine, with subsequent addition of bisoprolol for hemodynamic control. The operative strategy prioritized pheochromocytoma resection first, given its potential for significant hemodynamic instability. Progression to hysterectomy was contingent upon achieving adequate intraoperative hemodynamic stability following adrenalectomy, with continuous reassessment by the anesthetic and surgical teams. Right adrenalectomy was performed first, followed by total abdominal hysterectomy with bilateral salpingooophorectomy. Significant hemodynamic lability occurred during tumor manipulation, with hypertensive surges managed using sodium nitroprusside and remifentanil infusions. Following adrenal vein ligation and tumor removal, hypotension was managed with noradrenaline and additional adrenaline support as required. Total operative time was approximately 6 hours. Postoperatively, transient noradrenaline support was required but was rapidly weaned as hemodynamic stability was achieved. Conclusion Single-stage adrenalectomy and major pelvic surgery can be safely performed in selected patients with pheochromocytoma when guided by meticulous preoperative optimization, clear intraoperative sequencing, and close multidisciplinary coordination.
Pheochromocytoma ; Adrenalectomy ; Leiomyoma ; Hysterectomy

Introduction: Hemorrhagic suprarenal masses presenting with hypertensive emergency pose a significant diagnostic challenge, particularly when biochemical and radiological findings are inconclusive. The clinical presentation may mimic catecholamine-secreting tumors, necessitating consideration of a broad differential diagnosis, including pheochromocytoma, adrenocortical carcinoma, retroperitoneal hemorrhage, and hematological-related extramedullary lesions. Accurate diagnosis is essential, as management strategies differ significantly. Case: We report a 48-year-old male smoker with no known prior medical illness who presented with sudden left-sided chest pain radiating to the epigastrium, associated with vomiting. On arrival, he was markedly hypertensive (207/131 mmHg). He reported a 1-year history of paroxysmal palpitations, headaches, migraines, and intermittent diaphoresis. Computed tomography angiography excluded aortic dissection but demonstrated a left retroperitoneal hemorrhage with non-visualization of the adrenal gland, suggestive of adrenal or tumor-related hemorrhage. He was initially managed empirically as a pheochromocytoma while undergoing biochemical evaluation; however, urinary metanephrines were only mildly elevated. Repeat imaging demonstrated interval enlargement of a non-enhancing suprarenal mass, raising concern for tumor-related hemorrhage. Subsequent ultrasonography, however, favored a liquefied hematoma, and percutaneous drainage yielded 750 mL of sanguineous fluid, resulting in marked clinical improvement. Notably, an elevated hematocrit prompted further evaluation for erythrocytosis. Subsequent testing confirmed JAK2 mutation-positive polycythemia rubra vera, providing a unifying explanation for both the erythrocytosis and spontaneous adrenal hemorrhage. The patient was commenced on hydroxyurea and referred for hematology follow-up. Conclusion Adrenal hemorrhage may closely mimic pheochromocytoma in hypertensive emergencies. A systematic, multidisciplinary approach integrating clinical, biochemical, and imaging findings is essential to avoid misdiagnosis and guide appropriate management, particularly in patients with underlying hematological disorders.
Hypertensive Crisis ; Pheochromocytoma ; Polycythemia Vera ; Hematoma

Introduction: Pheochromocytoma is a catecholamine-secreting tumor with diverse cardiovascular manifestations, including myocardial infarction with non-obstructive coronary arteries (MINOCA). We report a case of biochemically confirmed pheochromocytoma initially presenting as non-ST-elevation myocardial infarction (NSTEMI), later reclassified as MINOCA. Case: A 62-year-old female with type 2 diabetes mellitus and hypertension was admitted with presumed NSTEMI and commenced on dual antiplatelet therapy. Further history revealed recurrent presyncope associated with paroxysmal headache, palpitations, and profuse diaphoresis. During admission, her blood pressure was markedly labile, ranging from 75/45 to 220/122 mmHg, raising suspicion of pheochromocytoma. Biochemical evaluation demonstrated markedly elevated 24-hour urinary normetanephrine of 36.19 µmol/day (reference 0–2.13) and methoxytyramine of 3.90 µmol/day (reference 0.10– 1.79), consistent with catecholamine excess. Dedicated adrenal computed tomography identified a 3.8-cm right adrenal lesion with high attenuation (44 Hounsfield Unit [HU]), arterial enhancement (119 HU), and low washout (absolute 40%, relative 24%), without calcification or necrosis. Electrocardiography showed sinus rhythm with T-wave inversion in leads I, aVL, and V5–V6. Transthoracic echocardiography demonstrated a preserved left ventricular ejection fraction of 67% without regional wallmotion abnormalities. Coronary angiography subsequently showed normal coronary arteries, supporting a diagnosis of MINOCA likely secondary to pheochromocytoma-related catecholamine excess and hypertensive crisis. Antiplatelets were discontinued. She was commenced on α-blockade, with additional felodipine and low-dose β-blocker for blood pressure optimization, and subsequently underwent successful open right adrenalectomy. Postoperatively, she required transient inotropic support but was weaned within 36 hours. Conclusion Pheochromocytoma-associated MINOCA is uncommon but important to recognize. Catecholamine surges may cause myocardial injury through coronary vasospasm, myocardial oxygen supply-demand mismatch, and direct catecholamine-mediated cardiotoxicity. Recognition is crucial, as management differs fundamentally from atherosclerotic acute coronary syndrome and requires α-blockade before β-blockade.
MINOCA ; Non-ST Elevated Myocardial Infarction ; Pheochromocytoma

Introduction: 3β-Hydroxysteroid dehydrogenase (3β-HSD) deficiency and lipoid congenital adrenal hyperplasia (CAH) are rare disorders of steroidogenesis that result in impaired synthesis of all adrenal and gonadal hormones. Affected males typically present with ambiguous genitalia and concurrent mineralocorticoid and glucocorticoid deficiency. Distinguishing between these two conditions is crucial, as their management strategies differ. Case: We report a 24-year-old male, born to non-consanguineous parents, who was clinically diagnosed with 3β-HSD deficiency during infancy. He presented at day 40 of life with ambiguous genitalia, bilateral undescended testes, and generalized hyperpigmentation. His family history was significant for an elder brother with salt-losing CAH. Initial biochemical evaluation confirmed primary adrenal insufficiency and primary hypogonadism. Notably, his steroid precursors, dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxyprogesterone, were suppressed. A karyotype confirmed 46,XY. In the absence of genetic testing at that time, a clinical diagnosis of 3β-HSD deficiency was made, and he was commenced on mineralocorticoid and supraphysiological glucocorticoid replacement. He underwent bilateral orchidopexy and hypospadias repair in childhood. Pubertal induction was required, followed by maintenance testosterone therapy. Upon transitioning to adult care, a review of his biochemical profile, particularly suppressed DHEAS, which is inconsistent with 3β-HSD deficiency, raised the suspicion of a more proximal defect, such as lipoid CAH. Differentiation is imperative, as lipoid CAH requires only physiological glucocorticoid replacement, whereas 3β-HSD deficiency often needs higher doses to suppress adrenocorticotropic hormone and DHEAS. To resolve this diagnostic uncertainty and guide longterm therapy, the patient was referred for genetic studies. Conclusion Differentiating 3β-HSD deficiency from lipoid CAH is important, as both have similar clinical presentation. The absence of elevated steroid precursors, particularly DHEAS, should raise suspicion of a more proximal defect. Given the different aims of glucocorticoid therapy, establishing a precise diagnosis through genetic studies is essential to guide clinical management and minimize the morbidity associated with supraphysiological corticosteroid dosing.
Pheochromocytoma ; Mutation

BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective To investigate the expression and correlation of LY86-AS1 and KHDRBS2 in glioblastoma (GBM), and their impacts on the prognosis of patients and immune cell infiltration. Methods Based on the GSE50161 dataset from the Gene Expression Omnibus (GEO) database, LY86-AS1 and KHDRBS2, which are closely related to the development of GBM, were identified by WGCNA and differential expression analysis. The Cancer Genome Atlas (TCGA) and the Chinese Glioma Genome Atlas (CGGA) databases were used to analyze the relationship between the expression of LY86-AS1 and KHDRBS2 and the prognosis of GBM patients. Multiple datasets were employed to analyze the correlation between the expression levels of LY86-AS1 and KHDRBS2 and its relationship with immune cell infiltration. Real-time quantitative PCR was used to verify the expression of LY86-AS1 and KHDRBS2 in GBM and normal brain tissues. The Human Protein Atlas (HPA) database was accessed to obtain the protein expression of KHDRBS2, and immunohistochemical staining was conducted to verify the protein expression of KHDRBS2. Results LY86-AS1 and KHDRBS2 were lowly expressed in GBM tissues and were closely related to the development of GBM, showing a significant positive correlation. Patients with low expression levels of LY86-AS1 and KHDRBS2 had a lower overall survival rate than those with high expression levels. LY86-AS1 was positively correlated with naive B cells, plasma cells, activated NK cells, M1 macrophages, activated mast cells and monocytes. KHDRBS2 was positively correlated with naive B cells, plasma cells, helper T cells, activated NK cells and monocytes. Conclusion The low expression levels of LY86-AS1 and KHDRBS2 in GBM, which is associated with poor prognosis, affect the tumor immune microenvironment and may serve as potential new biomarkers for the diagnosis of GBM and the prognosis assessment of patients.
Humans ; Glioblastoma/metabolism* ; Prognosis ; Brain Neoplasms/pathology* ; Gene Expression Regulation, Neoplastic ; RNA-Binding Proteins/metabolism*

OBJECTIVES: To identify potential plasma lipidomic biomarkers that distinguish non-metastatic medulloblastoma (nmMB) from metastatic medulloblastoma (mMB) in children. METHODS: In this prospective study, 17 children with mMB and 20 matched children with nmMB were enrolled. Plasma samples were analyzed using ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Lipid metabolites were evaluated for their associations and diagnostic performance. RESULTS: Orthogonal partial least squares discriminant analysis based on lipid profiles clearly separated nmMB from mMB, and 14 differential lipids were identified, including DG(18:2/20:4/0:0) and SM(d18:1/20:0). Receiver operating characteristic analysis showed nine metabolites with area under the curve greater than 0.7. Differential lipids were enriched in sphingolipid, glycerophospholipid, and arachidonic acid metabolism, suggesting an association with the metastatic phenotype. CONCLUSIONS Plasma lipidomics provides a new approach to identify mMB, and the identified lipid metabolites may support early diagnosis and treatment, prognostic assessment, and selection of therapeutic targets for metastatic medulloblastoma.
Humans ; Medulloblastoma/diagnosis* ; Lipidomics ; Child ; Male ; Female ; Child, Preschool ; Cerebellar Neoplasms/blood* ; Biomarkers, Tumor/blood* ; Neoplasm Metastasis ; Prospective Studies ; Adolescent ; Lipids/blood*

The clinical data of 10 patients with pathologically confirmed primary hepatic neuroendocrine neoplasms (PHNENs) were retrospectively analyzed. The cohort included 8 males and 2 females, with a median age of 63 years. None presented with carcinoid syndrome. Three cases were detected incidentally during health check-ups, 2 presented with painless jaundice, and 5 reported abdominal distension or pain (1 with concurrent jaundice). Elevated tumor markers included carbohydrate antigen 19-9 in 4 cases, alpha-fetoprotein in 2 cases, and neuron-specific enolase in 1 case. All patients underwent surgical resection, including hepatectomy and hilar cholangiocarcinoma resection, combining with resection and reconstruction of right hepatic artery, resection of liver metastases and pancreaticoduodenectomy according to the extent of tumor invasion.Preoperative imaging failed to diagnose neuroendocrine neoplasms in all cases. Final pathological diagnoses were neuroendocrine tumor (NET) G2 in 5 cases, NET G3 in 1 case, and neuroendocrine carcinoma (NEC) in 4 cases. During the follow-up, 4 patients died and 6 survived. The study demonstrates that PHNENs lack specific clinical or imaging features, and the diagnosis relies on pathological examination after excluding metastatic disease. Radical resection remains the primary treatment, with prognosis varying significantly by tumor grade.
Humans ; Middle Aged ; Male ; Female ; Neuroendocrine Tumors/pathology* ; Liver Neoplasms/pathology* ; Retrospective Studies ; Aged ; Adult

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of Cyclin D1 as an adjunct immunomarker in CD99 positive small round cell neoplasms with primary consideration of PNET/EWS. MATERIALS AND METHODS: Tissue from 2017 to 2023 with a histopathologic diagnosis of CD99 positive small round blue cell tumors with primary consideration of Primitive Neuroectodermal Tumor (PNET)/Ewing Sarcoma were retrieved and Cyclin D1 immunohistochemical staining done. Diagnostic accuracy of Cyclin D1 immunostaining was determined by calculating the sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Cyclin D1 immunohistochemical staining was performed in 19 specimens available, of which 13 yielded a positive result. Of these, 8 had a final histopathologic diagnosis of CD99 positive small round blue cell tumor with primary consideration of PNET/Ewing Sarcoma, resulting in sensitivity of 61.54%, specificity of 100%, positive predictive value of 100% and negative predictive value of 50.0%. The overall accuracy is 72.2%. CONCLUSION Cyclin D1 can be used as an adjunct immunomarker to aid in the diagnosis of CD99 positive round cell tumor with primary consideration of PNET/Ewing Sarcoma specifically in resource limited settings where molecular testing is not readily available. Given the high specificity of Cyclin D1 in such cases, it can be used to rule out other small round blue cell tumors that can also stain positive for CD99 such as Rhabdomyosarcoma. However, interpretation must be done in conjunction with the results of other immunohistochemical stains in order to increase its diagnostic accuracy.
Human ; Male,Female ; Cells ; Sarcoma, Ewing ; Sarcoma ; Neuroectodermal tumors, Primitive ; Cyclin D1