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

Introduction: Paragangliomas are rare neuroendocrine tumors arising from extra-adrenal chromaffin cells, with an estimated incidence of 2–8 cases per million per year. These tumors originate from neural crest–derived cells of the sympathetic and parasympathetic paraganglia and may secrete catecholamines, resulting in malignant hypertension or symptoms such as headache, palpitations, and diaphoresis. They can occur anywhere along the paravertebral and para-aortic regions from the skull base to the pelvic floor. Case: We report a case of a 14-year-old male with no known premorbid conditions who presented with presyncope and a 1-month history of headache. On examination, he had severe hypertension (242/167 mmHg), tachycardia (127 bpm), and grade IV hypertensive retinopathy. Investigations showed preserved renal function with markedly elevated 24-hour urinary metanephrines (normetanephrine 90.75 µmol/L). Computed tomography revealed a lobulated, heterogeneously enhancing mass measuring 5.0 × 6.1 × 5.4 cm along the left margin of the abdominal aorta at the infrarenal level, suggestive of an extra-adrenal lesion. Gallium-68 PET scan demonstrated a somatostatin receptor–avid left peritoneal mass. The patient underwent exploratory laparotomy and tumor excision, complicated intraoperatively by blood pressure lability requiring nitroprusside and inotropic support. Postoperatively, he improved significantly and was able to wean off all antihypertensive medications. Histopathology confirmed left retroperitoneal paraganglioma. Conclusion Primary peritoneal paraganglioma is a rare but important cause of secondary hypertension, especially in young patients presenting with hypertensive emergency. High index of suspicion is essential for early diagnosis. Management requires a multidisciplinary approach with careful preoperative optimization to minimize perioperative complications. Surgical resection remains the definitive treatment and, as demonstrated in this case, can result in marked clinical improvement with resolution of hypertension.
Paraganglioma

Introduction: Mediastinal paragangliomas (PGLs) are extremely rare extra-adrenal neuroendocrine tumors, accounting for approximately 2% of all PGLs and commonly associated with pathogenic germline variants (PGVs), particularly those involving succinate dehydrogenase (SDH) mutations. Case: We report a 35-year-old female presenting with chronic cough and hemoptysis, accompanied by paroxysmal symptoms and new-onset hypertension. She had a history of pheochromocytoma treated 15 years earlier with right adrenalectomy and liver lobectomy due to intraoperative adrenal adherence to the liver. Histopathology confirmed adrenal pheochromocytoma, with no evidence of PGL in the liver. She remained in biochemical remission for 3 years but subsequently defaulted. Biochemical evaluation revealed markedly elevated 24-hour urinary normetanephrine (58,950 nmol/L; ~26-fold increase). Computed tomography of the thorax demonstrated a mediastinal mass compressing the right bronchus, resulting in luminal narrowing and segmental lung collapse. Endobronchial biopsy confirmed PGL (Ki-67 index 5%). Functional imaging with DOTATATE, FDG-PET, and MIBG demonstrated metastatic disease involving the lungs and lymph nodes. Genetic testing identified a heterozygous pathogenic SDHB mutation (c.79C>T; p.Arg27), consistent with autosomal dominant hereditary PGL-pheochromocytoma syndrome; family screening confirmed the same mutation in her father and two siblings. She underwent two sessions of bronchoscopic intervention, including cryoablation, balloon dilation, argon plasma coagulation, and intratumoral alcohol injection for airway control and hemoptysis. Multidisciplinary evaluation deemed complete surgical resection high risk and not feasible; therefore, peptide receptor radionuclide therapy was initiated. Conclusion This case demonstrates the aggressive and metastatic nature of SDHB-mutated PGLs. This group of patients require long term surveillance given the risk of developing new tumors even years or decades after primary tumor resection. It highlights the importance of genetic testing following pheochromocytoma surgery to guide targeted therapy, lifelong surveillance, and family screening within a multidisciplinary care approach.
Paraganglioma

OBJECTIVES

To highlight the clinical presentation, diagnostic dilemma and proposed management of a case of a transmodiolar intralabyrinthine schwannoma.

Design:Case Report

Setting:Tertiary National University Hospital

Patient:One

A 51-year-old woman consulted for a 12-year history of unilateral sensorineural hearing loss and progressively worsening vertigo. Workups revealed a hyperintense lesion approximating the entire right cochlea on Gadolinium-enhanced magnetic resonance imaging and profound hearing loss on the right on pure-tone audiometry, with no recordable response even at maximum intensity levels across all frequencies. Infectious and metastatic workups returned negative results, clinching the radiographic diagnosis of an intralabyrinthine schwannoma.

Intralabyrinthine schwannomas (ILS) are rare, benign neoplasms of the 8th cranial nerve, manifesting as progressive unilateral sensorineural hearing loss and worsening vertigo. These neoplasms are mainly detected by MRI; underdiagnosis and lack of standard treatment and diagnostic protocols result in their inaccurate diagnosis and delays in management.

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

Neuroendocrine carcinoma (NEC) represents a category of malignant tumors originating from neuroendocrine cells. Given that NEC cells exhibit characteristics of both neural and endocrine cells, they can hijack neuronal signaling pathways and dynamically regulate the expression of neuronal lineage markers during tumor metastasis, thereby constructing a microenvironment conducive to tumor growth and metastasis. Conversely, alterations in the tumor microenvironment can enhance the interactions between neurons and tumor cells, ultimately synergistically promoting the metastasis of NEC. This review highlights recent advancements in the field of cancer neuroscience, uncovering neuronal lineage markers in NEC that facilitate tumor dissemination through mediating crosstalk, bidirectional communication, and synergistic interactions between tumor cells and the nervous system. Consequently, the latest findings in tumor neuroscience have enriched our understanding of the biological mechanisms underlying tumor metastasis, opening new research avenues for a deeper comprehension of the complex biological processes involved in tumor metastasis, particularly brain metastasis. This review provides a comprehensive review of the crosstalk between tumor cells and neural signaling in the metastasis of NEC.
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Humans ; Carcinoma, Neuroendocrine/metabolism* ; Signal Transduction ; Animals ; Neoplasm Metastasis ; Neurons/pathology* ; Tumor Microenvironment ; Cell Communication

Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a high-grade neuroendocrine tumor with unique characteristics, and its treatment regimens are primarily derived from those for small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC). In recent years, the incidence rate has been on the rise, and the prognosis are affected by the interaction of multiple factors such as individual, clinical stage and treatment mode, and the heterogeneity is significant. In the study of molecular subtypes, multiple subgroups were divided according to key gene mutations such as RB1 and TP53, and genomic subtypes were associated with survival, chemotherapy response, and efficacy of precision therapy. Targeted therapy excavates multiple targets, and the efficacy of drugs is different. Immunotherapy has made remarkable progress, and immune checkpoint inhibitors (ICIs) have been effective in all stages of chemotherapy alone or in combination with chemotherapy or radiation therapy, but there is a risk of hyperprogressive diseases, and accurate prognostic markers need to be explored urgently. This review reviews the latest research progress in the study of molecular subtypes and precision therapies such as targeted therapy and immunotherapy of pulmonary LCNEC, and points out that pulmonary LCNEC treatment will develop in the direction of precision and individualization in the future.
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Humans ; Lung Neoplasms/drug therapy* ; Carcinoma, Neuroendocrine/drug therapy* ; Precision Medicine ; Immunotherapy ; Carcinoma, Large Cell/drug therapy*