Metaiodobenzylguanidine Scan Research Articles

Liver metastasized pancreatic neuroendocrine tumor in a 17-year-old female: A case report.

Pancreatic neuroendocrine tumors (PNETs) are rare and often misdiagnosed due to their vague symptoms and tumor heterogeneity. Early detection using computed tomography (CT) is essential, particularly in regions without access to advanced diagnostic tools like immunohistochemistry and genetic testing. Neuroendocrine tumors (NETs) are rare tumors in adults and extremely rare in the pediatric population, as pancreatic NETs (pNETs) have an incidence rate of <0.1 per million. We present a case of a 17-year-old female with a liver metastasized pNET. A 17-year-old female with a history of intermittent abdomen-back pain presented to the clinic with severe upper abdominal pain radiating to the shoulder. The routine tests were normal. An ultrasound showed multiple lesions in the liver, which were confirmed by a computed tomography (CT) that uncovered a pancreatic lesion too. A liver biopsy proved it was a metastasized pNET with positive NET markers on IMC staining. The metaiodobenzylguanidine (MIBG) scan flared the liver lesion. The patient was started on Octreotide long-acting release (LAR) 30 mg once monthly. The rarity of these tumors makes their diagnosis difficult, but they should not be omitted and must be considered when there are long-lasting symptoms that are not compatible with common illnesses. These tumors are curable in their early stages.

12394 "Sugar And Tumors: A Case Report On New-onset Diabetes In Metastatic Pheochromocytoma With Elevated Dopamine Levels"

Abstract Disclosure: B. Agrawal: None. V. mehta: None. R. naseem: None. M. Renzu: None. R. rashid: None. Introduction: Metastatic pheochromocytoma is a rare neuroendocrine tumor with potential complication of new-onset diabetes mellitus (DM). We present a case highlighting the challenges in managing a patient with metastatic pheochromocytoma and concurrent DM. Case presentation: A 66-year-old male with a history of hypertension and gout initially presented in 2010 with an adrenal mass, later identified as pheochromocytoma and resected. In 2018, he presented with bilateral leg pain, revealing metastatic disease-causing spinal cord compression along with metastatic lung nodules and metastasis in adrenalectomy bed. Despite interventions including T6,7,8 laminectomy in 2020 and radiation therapy, metastases persisted. In 2024, he presented with polyuria, polydipsia, and hyperglycemia (blood glucose &amp;gt;500 mg/dL). Laboratory findings showed elevated a1c of 15 in addition to elevated normetanephrines, metanephrines, and dopamine with levels of 3880, 48 and 488 respectively. He was diagnosed with new-onset DM and started on insulin therapy in addition to metformin and jardiance. Discussion: Secondary diabetes mellitus (DM) in secretory pheochromocytoma occurs in approximately 50% of cases, manifesting from mild insulin resistance to severe presentation like DKA. Epinephrine-secreting tumors contribute to glucose intolerance by activating beta receptors, thereby stimulating gluconeogenesis. Patients with higher levels of epinephrine and preoperative glucose intolerance were more prone to developing postoperative hypoglycemia, requiring close monitoring during the postoperative period. Additionally, research by DiSalvo et al. Epinephrine-secreting tumors have a more significant impact on hyperglycemia by impairing insulin secretion and stimulation GLP-1. Tumor resection has been found to be more effective effective in restoring normal glucose homeostasis in these patients. Dopamine-secreting pheochromocytomas are rare neoplasms characterized by the presence of immature catecholamine vesicles that inhibit dopamine conversio owing to localized dopamine beta hydroxylase. Typically presenting around the age of 48, these tumors often lack excess catecholamines, leading to atypical symptoms such as local discomfort or pain from tumor compression. These neoplasms are less detectable on metaiodobenzylguanidine (MIBG) scans, necessitating positron emission tomography (PET) for accurate diagnosis. Surgical resection is the treatment, with preoperative management involving metyrosine instead of alpha blockers. These tumors are frequently diagnosed late, often in a malignant stage, contributing to poor prognosis Conclusion: Overall, understanding the complex interplay between catecholamines and glucose metabolism is crucial for the comprehensive management of patients with pheochromocytoma and secondary DM. Presentation: 6/1/2024

8769 A Case of Metastatic and Catecholamine Producing Bilateral Pheochromocytoma in a Patient with RET Gene Mutation

Abstract Disclosure: R.A. Mayers: None. A. Szafran-Swietlik: None. RET mutation, observed in multiple endocrine neoplasia type 2 syndromes, is implicated in the development of pheochromocytomas of the kinase signaling cluster. Such tumors have lower metastatic risk and adrenergic production compared to the ones from the other clusters. We present a case of a metastatic, bilateral, small and biochemically active pheochromocytoma .This is the case of a 27-year-old man diagnosed with MEN 2A. He underwent total thyroidectomy due to medullary thyroid carcinoma at 2 years old. He was deemed cured and started on levothyroxine replacement. Since then, his plasma metanephrines by liquid chromatography-mass spectrometry and urine metanephrines done in a yearly basis as screening, were always within range of normality. Over the years, he developed substance abuse disorder with use of Kratom and methamphetamines and was admitted in a rehabilitation center multiple times in the last three years. During this time, the patient was reported to be slightly tachycardiac which was initially attributed to the use of substances. On the last year, an echocardiogram done as evaluation of his tachycardia showed an ejection fraction of 35%. Later, his annual metanephrine levels were markedly elevated (free metanephrine: 137 pg/mL and free normetanephrine : 157 pg/mL, normal ranges reported as less than 57 pg/mL and less than 148 pg/mL respectively). Abdominal tomography showed a right adrenal nodule of 1.2 cm and a left adrenal nodule of 1.6 cm, both with more than 10 Hounsfield Units. A Metaiodobenzylguanidine scan revealed a left adrenal nodule of 1.8 cm with diffuse radiotracer uptake, a right adrenal nodule of 1.2 cm with radiotracer activity and 3 subtle areas of focally increased radiotracer activity in the liver, two in left hepatic lobe and other in posterior right upper lobe. He underwent bilateral adrenalectomy with cortical sparring. Pathology results evidenced a left adrenal with a unifocal mass of 1.8 cm and a right adrenal with a mass of 1.2 cm , both without lymphovascular, capsular, local invasion or necrosis, a mitotic rate of 1-2 without atypical mitosis, not encapsulated with clean margins and positive for synaptophysin , chromogranin and S100 stains. An additional mass of 0.7 cm on the right adrenal gland was described with similar characteristics to the described before except for the involvement of the surgical margins. Currently on the literature there are different opinions regarding screening approach for pheochromocytomas in the presence of RET mutations. There are not strong recommendations regarding the use of imaging as a screening tool in this group of patients. It is important to consider that there are cases, as the one described in this report, that might present metastatic disease even with the presence of small pheochromocytomas that belong to the cluster of kinase signaling. Presentation: 6/3/2024

Postural Orthostatic Tachycardia Syndrome (POTS) of Autoimmune Origin - Case and Review

Introduction: Postural Orthostatic Tachycardia Syndrome (POTS) belongs to a group of orthostatic intolerance syndromes. It is defined by the increase in heart rate ≥30 bpm or heart rate higher than 120/min during first 10 minutes after standing, without significant decrease in blood pressure. It is a rare disease, typically affecting younger females. The dysregulation of autonomic nervous system plays a key role in the pathogenesis. The autonomic dysbalance can be caused by various neurohumoral mechanisms, receptor hypersensitivity, hypovolemia, mast cell dysregulation and last but not least, autoimmunity. The presence of autoantibodies targeted against various adrenergic and muscarinic receptors, as well, as angiotensin or endothelin receptors, has been identified in some but not all patients with POTS. Case Description: We present a case of a young patient with an overlap syndrome of POTS and vasovagal vasodepressoric syncope diagnosed with the head up tilt test, without any identified trigger. The laboratory investigation documented the presence of anti-alpha-1, beta-1 and beta-2 adrenergic receptor antibodies, antimuscarinic receptor 3 antibodies and antibodies against angiotensin II type 1 receptor. MIBG (metaiodobenzylguanidine) scan has not revealed any changes in the sympathetic inervation of the heart. The initial treatment by betablockers, as well as by ivabradine failed. On midodrine medication, the symptoms of postural tachycardia and the reflex syncope improved. Conclusion: The role of autoimmunity in POTS is currently studied, though the role of autoantibodies against autonomic nervous system in the pathogenesis of vasovagal syncope remains unclear.

FRI265 I123-MIBG Positive, CU64-Dotatate PET Negative Pheochromocytoma In A Patient With Bilateral Adrenal Incidentalomas

Abstract Disclosure: P. Pagadala: None. V. Patel: None. Bilateral incidental adrenal nodules represent 10-23% of all incidental adrenal nodules. Most are benign nonfunctioning adenomas however these can be catecholamine-secreting tumors that arise from chromaffin cells of the adrenal medulla called pheochromocytomas. Identifying pheochromocytoma using anatomic imaging alone in cases of bilateral adrenal nodules is challenging. Functional imaging with radioisotope tracers can be helpful such as MIBG (meta-iodobenzylguanidine) and DOTATATE scans. We describe a case of pheochromocytoma, which was negative on DOTATATE but positive on MIBG scan which localized the pheochromocytoma. A 65-year-old male with a history of hypertension, chronic kidney disease and obstructive sleep apnea was found to have bilateral adrenal nodules on routine imaging. MRI abdomen showed a right adrenal nodule 1.7cm x 1.8cm x 1.7cm and a left adrenal nodule 2.3 cm in maximum dimension. He had no apparent symptoms of catecholamine excess. Biochemical testing revealed elevated total plasma metanephrines on serial assessments along with elevated 24-hour urine dopamine levels. A CT scan with adrenal protocol further characterized the right adrenal nodule with precontrast density of 43 Hounsfield Units (HU) with a rapid washout of 75% within 5 minutes, consistent with benign adrenal adenoma. The left adrenal gland had 2 nodules. A smaller superior nodule 1.3 cm AP x 1.0 cm transverse x 0.9 cm craniocaudal in size, density of -3 HU on the precontrast images, with approximately 85% washout most consistent with a benign adrenal adenoma. A larger inferior nodule was 2.3 cm AP x 2.2 cm transverse x 2.3 cm craniocaudal in size and precontrast density of 32 HU, rising to 58 HU during the portal venous phase and remaining at about 58 HU on the delayed images, indicating no significant washout and is indeterminate. A Cu64 labeled DOTATATE scan showed the 1.6 cm right adrenal nodule demonstrated activity similar to that of contralateral background adrenal activity. There was no comment regarding the two left adrenal nodules. A I123 MIBG scan showed the larger of the two left adrenal nodules had a strong uptake of the MIBG highly likely to be a pheochromocytoma. The smaller left adrenal nodule and the right adrenal nodule had no significant MIBG uptake, making these adrenal adenomas. The patient underwent left robotic adrenalectomy and pathology confirmed a 2.3 cm pheochromocytoma in addition to adrenocortical nodular disease. Three months post-surgery, plasma and 24-hour urinary measurements for metanephrines and catecholamines had normalized. Further research is needed to assess the benefit of I123MIBG when DOTATATE is negative. A potential cause of false negatives on DOTATATE is variability in somatostatin receptor subtype expression. Better imaging modalities for pheochromocytomas and guidelines for the management of bilateral adrenal nodules would assist in treatment decisions. Presentation: Friday, June 16, 2023

Aberrant positive metaiodobenzylguanidine (MIBG) scan in a patient with gastrointestinal stromal tumor

123I-metaiodobenzylguanidine (MIBG) scintigraphy is an effective means of diagnosing chromaffin-cell tumors such as pheochromocytoma. We report a very rare case of a 45-year-old patient with large intra-abdominal mass and elevated urinary normetanephrines. 123I-MIBG scintigraphy showed mild MIBG uptake. Although initial findings suggested a pheochromocytoma, histologic examination along with immunohistochemical staining revealed features suggestive of gastrointestinal stromal tumor (GIST).

The role of MIBG scan in the diagnosis of pheochromocytoma.

e15064 Background: Pheochromocytoma is an uncommon adrenal medulla tumor. Metaiodobenzylguanidine (MIBG) scintigraphy is the current gold standard functional imaging method for evaluating pheochromocytoma, due to its excellent 100% specificity, 80% sensitivity, and general availability. In addition to establishing an extension evaluation and monitoring medication efficacy, MIBG scintigraphy is essential to confirm the diagnosis of suspected pheochromocytoma, especially when there is a tumor-like adrenal mass whose etiology is to be determined and biopsy is contraindicated given the risk of catecholamine discharge with hypertensive flare and the risk of bleeding. Our aims are to determine the efficacy of scintigraphy in the diagnosis of pheochromocytoma by examining the epidemiological characteristic and uptake patterns of the disease. Methods: In a retrospective analysis from January 2010 to December 2020, we examined pheochromocytoma patients medical records who had been referred for MIBG scintigraphy to the regional western Algerian Nuclear Medicine department at the University Hospital Center of Tlemcen. Prior to a progressive intravenous injection of 40–80 MBq of l-MIBG, patients underwent preparation (discontinuation of interfering drugs with I-MIBG especially antihypertensive treatment, thyroid blocking, and hydration). Imaging acquisition was carried out 48 and 72 hours later. Results: Fifty patients with probable pheochromocytoma (sex ratio = 0,78; mean age = 43 [17-74] years) completed I-MIBG scintigraphy prior to adrenalectomy. The MIBG scan has a high specificity and positive predictive value (100%). It confirms the presence of pheochromocytoma in 21 cases (42%), even if the metanephrine is normal in a patient with a non-secreting pheochromocytoma. In 18 cases, the main pattern is a single, homogenous, and intense intra-abdominal uptake. For the three remaining patients, a voluminous and heterogeneous uptake with a photopenic center that was associated to a necrotic adrenal mass larger than 10 cm in size, seen on abdominal Computerized Tomography (CT). In this retrospective analysis, no cases of metastatic or multiple diseases were documented. The sensitivity and negative predictive value are 84% and 86%, respectively. In 29 patients (58%), the scan reveals no abnormalities in uptake. This is attributed, in part, to 30% false positive biology (sampling conditions of urinary and/or plasmatic metanephrines and/or normetanephrines), 20% false positive CT imaging (differential diagnosis of adrenal mass: benign or malignant adrenal nodule), and 8% false negative MIBG scintigraphy (subcentimetric, cystic and necrotic lesion). Conclusions: Due to its exceptional specificity, robust sensitivity, and whole-body staging, MIBG scintigraphy—along with biology and morphology imaging—is a crucial noninvasive diagnostic method for the management of pheochromocytoma prior to adrenalectomy.

Adrenal Incidentaloma With the Diagnosis of Normotensive Pheochromocytoma: A Case Report

Background: Pheochromocytomas (PCCs) are catecholamine-producing neuroendocrine tumors that originate from the adrenal medulla. Their clinical presentations most commonly include hypertension, headache, palpitations, and sweating; however, PCCs are sometimes normotensive and clinically silent. Case Presentation: A female patient with abdominal pain as well as persistent and crushing left flank pain for the past six months was examined. The imaging studies revealed a mass in the upper pole of the left kidney indicative of a potential adrenal gland tumor; however, she had normal blood pressure (BP). Histopathologic examination of the mass from exploratory laparotomy showed that it was a PCC. Findings from sonography and computed tomography (CT) scan of the left adrenal tumor, along with elevated urinary normetanephrine level and positive iodine-123 metaiodobenzylguanidine (MIBG) scan led to preoperative diagnosis of PCC in our case. Conclusion: This study highlighted the importance of imaging and biochemical testing in diagnosing PCCs in patients with adrenal incidentalomas (AIs), even though they were normotensive and entirely asymptomatic.

PS-R04-7: UNSOLVED CASE OF RESISTANT HYPERTENSION: A CHALLENGING ISSUE IN A DEVELOPING COUNTRY

Introduction: It is difficult to find a definite etiology of resistant hypertension (RH) in developing countries due to limited resources. We present a case report and discuss RH's diagnosis and treatment approaches, which we suspected owing to Obstructive Sleep Apnea (OSA) after extensive assessment, including nuclear imaging and renal arteriography. Case presentation: A 58-year-old female was referred to Hasan Sadikin General Hospital for RH assessment. Having conducted ambulatory blood pressure monitoring and echocardiography, which suggested hypertensive heart disease, we confirmed the diagnosis of RH in this patient. The patient has a 4-year history of hypertension, accompanied by throbbing headaches and snores. She underwent percutaneous coronary intervention two years ago due to angina. During the physical examination, she was fully alert with a blood pressure of 170/90 mmHg and a heart rate of 62 times/minute, mild exophthalmos, and cardiomegaly. Her renal (including proteinuria), and thyroid function were within normal limits. Echocardiography revealed concentric left ventricular (LV) hypertrophy with normal LV systolic function. An abdominal Computed Tomography indicated pheochromocytoma or adrenal tumor. Metanephrines examination was not feasible due to cost issues. Using metaiodobenzylguanidine scan (Tc-99 and I-131), nuclear imaging failed to establish diagnosis of pheochromocytoma. Renal artery ultrasonography increased the suspicion of renal artery stenosis; however, renal arteriography showed mild renal artery stenosis. We referred the patient to a neurologist for OSA screening, from STOP-Bang questionnaire result indicated that the patient was likely to have OSA. Unfortunately, the diagnosis was inconclusive due to unavailability of polysomnography facility. The unavailability of minoxidil, renal denervation and continuous positive airway pressure (CPAP) hinders the optimal treatment in this patient. The blood pressure target remains unachievable despite Amlodipine 1x10 mg, candesartan 2x16 mg, bisoprolol 1x10 mg, tamsulosin 1x400 mg, spironolactone 1x50 mg, dan isosorbide mononitrate 2x2.5 mg consumption. The unavailability of chromatography-mass spectrometry for evaluation of medication adherence was also a significant limitation. Conclusion: This case showed that the blood pressure remains uncontrolled despite six different medications, which may be due to the untreated etiology of secondary hypertension. Furthermore, although extensive examinations have been performed, a definite diagnosis could not be made due to cost/facility issues for other diagnostic approach. To further complicate matters, the evaluation of medication adherence and optimal treatment were not available. Therefore, RH remains a challenging issue in developing countries.

The Accuracy of Pre-Operative Ultrasonography in Localizing Parathyroid Adenoma for Minimally Invasive Parathyroidectomy (MIP)

OBJECTIVES To determine the sensitivity of pre-op ultrasonography in localizing parathyroid adenoma for minimally invasive parathyroidectomy (MIP) technique. METHODOLOGY The study was conducted at the department of ENT and Head &amp; Neck Surgery, MTI Hayatabad Medical Complex Peshawar. It included a retrospective analysis of records of patients who underwent MIP from Jan 1, 2019, to July 31, 2022. All patients had pre-operative meta-iodobenzylguanidine (MIBG) scans, and serum PTH, Serum calcium levels were determined. A pre-op ultrasound scan was acquired to mark the site of the parathyroid adenoma. MIP was carried out using a 3.5 to 4 cm transverse skin incision over the marked site to expose the thyroid gland. If the marked parathyroid gland was identified without using any other aids, the result was labelled as "True positive". The sensitivity of pre-op ultrasonography was calculated using SPSS v 26.0. RESULTS A total of 53 cases were included in the study. The male: female ratio was 1:1.8. The ages of patients ranged from 23-70 years with a mean age of 48.49 years with a standard deviation of +_ 10.818. Pre-op ultrasonography accurately localizes the site of parathyroid adenoma in 49 patients. Statistical analysis showed this to be a significant finding. CONCLUSION Pre-op ultrasonography is significantly helpful in localizing the parathyroid adenoma. Therefore its routine use is recommended to help localize the adenoma in minimally invasive parathyroidectomy.

Neuroblastoma Presentation With Multiple Cranial Nerve Involvement

Objective NA. Background We report a case of neuroblastoma, a pediatric neuroendocrine tumor of the sympathetic nervous system, in a 3-year-old female with multiple cranial nerve involvement. Design/Methods A 3-year-old afebrile, lethargic female presented with bilateral eyelid droop, right head tilt, slurred speech, gagging, abnormal walking and no bowel movement. Neurological examination noted bilateral ptosis, dysarthria, left tongue deviation, proximal weakness in upper and lower extremities, areflexia in biceps and patellar tendons, dysmetria, and wide-based gait. MRI of the brain showed heterogeneous appearance of the clivus and MRI of the spine showed right adrenal mass and heterogeneous enhancement of multiple vertebrae, suggesting possible metastatic disease. Serum and cerebrospinal studies were unremarkable. Patient was treated with intravenous methylprednisolone and plasmapheresis for suspected paraneoplastic syndrome; however, she continued to clinically progress. Adrenal mass biopsy results and elevated urine VMA and HVA levels were consistent with the diagnosis of neuroblastoma. Nuclear imaging and meta-iodobenzylguanidine scan were negative. Paraneoplastic panels and Lambert Eaton panel were negative for autoantibodies. Total resection of the abdominal mass and right adrenal gland with continued steroid taper, resulted in reported near total symptom resolution. Results Our patient presented with antibody negative paraneoplastic polyneuropathy due to neuroblastoma. Cranial nerve involvement in neuroblastoma can result from tumor involvement of the sympathetic chain, paraneoplastic syndromes, or metastasis to the skull. Our patient's initial imaging suggested potential metastatic or inflammatory involvement of the clivus, suspected of causing her cranial nerve symptoms. However, nuclear studies were negative for metastatic disease and patient's symptoms resolved after resection of the main mass suggesting a paraneoplastic etiology. Although her paraneoplastic panel and Lambert-Eaton panel were negative for common associated antibodies, it is likely an unmeasured autoantibody, cytokine, hormones, or peptide was at play. Conclusions Neuroblastoma should be considered as a differential for a neurological presentation involving multiple cranial nerves in a child.

Left adrenal aldosteronism coexisting with left paraaortic paraganglioma presenting as bilateral adrenal and left paraaortic tumors– comprehensive adrenal evaluation aiding perfect management: a case report

BackgroundCoexistence of a catecholamine-secreting tumor and an adrenal cortical tumor is quite rare which makes both diagnosis and management challenging. The purpose of this article is to describe the presence of this condition, share a stepwise approach for preoperative evaluation, and review the related literature.Case presentationA 44-year-old male patient had a history of hypertension and aggravating hypokalemia for years. Abdominal computed tomography incidentally found concomitant bilateral adrenal and left para-aortic tumors. Comprehensive adrenal hormone tests revealed a high aldosterone renin ratio and mildly elevated 24-h urine vanillylmandelic acid and norepinephrine levels. Subsequently, a metaiodobenzylguanidine scan showed uptake over the left para-aortic tumor, and NP-59 adrenal scintigraphy showed uptake over the left adrenal tumor. Further confirmatory tests, including captopril suppression, irbesartan suppression, and saline infusion, all confirmed the diagnosis of hyperaldosteronism. Adrenal venous sampling following 2 months of preparation with an alpha blocker demonstrated a left aldosterone-producing adrenal adenoma. Combining hormonal analysis, imaging studies, and adrenal venous sampling, the patient was diagnosed with left adrenal aldosteronoma, right adrenal nonfunctional tumor, and left para-aortic paraganglioma (PGL). Accordingly, laparoscopic left adrenalectomy and left PGL excision were performed smoothly under alpha blocker maintenance. The pathology report confirmed left adrenal cortical adenoma and left para-aortic PGL. Postoperatively, the blood pressure, biochemical tests, and adrenal hormone assays returned to normal, and related symptoms disappeared and were relatively stable during the follow-up period of two years.ConclusionsThis is the first case of left para-aortic PGL coexisting with an ipsilateral aldosterone-producing adenoma presenting as a left para-aortic tumor associated with bilateral adrenal tumors. Awareness of the rarity of this coexistence can avoid unexpected disasters during the process of evaluation and management.

ODP549 From Positive to Negative, a Histidine to Aspartic Acid Change in SDHB is Breaking Bad in Cardiac Paraganglioma

Abstract Introduction Cardiac paraganglioma (PGL) are extremely rare tumors. They are derived from chromaffin cells of the neural crest. Up to 40% of PGL foster germline mutations, while some bear somatic mutations. Here, we describe a sympathetic paraganglioma presenting as a cardiac mass, found to have a novel mutation of SDHB. Clinical Case A 64-year-old man with uncontrolled type 2 diabetes mellitus presented with chest pain, progressive fatigue and unintentional weight loss. An echocardiogram demonstrated a right atrial mass. Cardiac magnetic resonance imaging showed a 6.9×5.8×4.9 cm mass in the lateral right atrial wall and right atrioventricular groove, encasing the right coronary artery. Surgical removal was attempted and aborted due to involvement of the tricuspid valve. Incisional biopsy was consistent with paraganglioma. Plasma free normetanephrine was elevated at 1.87 nmol/L (ULN 0.89 nmol/L) and plasma free metanephrine was normal at 0.14 nmol/L (ULN 0.49 nmol/L). Chromogranin A was elevated at 1,038 ng/mL (normal &amp;lt;93 ng/mL). Iodine-123 meta-iodobenzylguanidine scan demonstrated increased and persistent MIBG activity of the cardiac mass. Ga-68 DOTATATE PET/CT scan revealed DOTATATE avidity of the mass without evidence of distant metastatic disease. Next-generation sequencing of the specimen revealed a variant of unknown significance of SDHB H244D at a variant allele frequency of 62.2%. This missense mutation replaces the histidine to aspartic acid, resulting in changes in charge of the side chain from positive to negative. Systemic treatment with tyrosine kinase inhibitor (TKI) cabozantinib was initiated due to unresectable tumor. Three month surveillance with Ga-68 PET/CT DOTATATE scan revealed partial response to treatment. Chromogranin A and normetanephrine are trending down, suggesting biochemical response. Conclusion Cardiac PGL are rare and SDHB mutations are associated with worse prognosis. This is the first case of a missense mutation of SDHB at H244D, which may be clinically relevant in characterizing cardiac paraganglioma and potential response to TKI therapy. Presentation: No date and time listed

Patterns of Failure in High-Risk Neuroblastoma with or without Metastatic Site Irradiation

<h3>Purpose/Objective(s)</h3> Neuroblastoma is the most common extracranial malignancy diagnosed in childhood. Despite recent improvements in outcomes and an overall 5-year survival of >80%, the majority of children with high-risk neuroblastoma will relapse despite aggressive treatment. As part of their treatment paradigm, radiation treatment (RT) is recommended to the primary site after surgery, as well as to metastatic sites of disease that continue to be metaiodobenzylguanidine (MIBG)-avid post-induction chemotherapy. While there is an abundance of data supporting the former, data is limited on the role of RT to metastatic sites and thus our practice has generally been to withhold RT to metastatic sites. The aim of this study is to examine patterns of failure in patients with high-risk metastatic neuroblastoma to better determine the value of metastatic site RT. <h3>Materials/Methods</h3> We performed an IRB-approved retrospective review from our institutional database of patients with high-risk neuroblastoma who were treated from 2010-2020. The included patients had MIBG-avid metastatic disease at the time of diagnosis, as well as first relapse. These patients achieved a partial or complete response before first relapse, and did not receive total body radiation or therapy with ¹³¹I-MIBG prior to first relapse. We analyzed the patients who failed and compared the anatomical location of all sites at initial relapse to sites that were MIBG-avid on post-induction chemotherapy scan. <h3>Results</h3> With a median follow up of 38 months, 13 of the 41 patients (32%) treated during this time recurred, and 5 (12%) died. 3 patients who recurred were excluded from the analysis as they did not have sufficient records. Of the 10 patients analyzed with recurrent disease, there were 70 MIBG-avid metastatic sites on post-induction chemotherapy scan, and of these only 11 (16%) received RT. There were 13 total MIBG-avid metastatic sites at time of first recurrence, of which 6 (46%) were in original site present on post-induction chemo MIBG scan, 1 which received radiation treatment and the other 5 (38%) did not. Of the sites that did receive radiation treatment, 10/11 (91%) did not recur. In analysis per patient, 4/10 (40%) recurred initially in metastatic sites that were MIBG-avid on post-induction scan, while the remaining majority recurred in both initial and new sites or new sites only. <h3>Conclusion</h3> In this unique cohort of high-risk neuroblastoma patients who mostly did not receive RT to post-induction chemotherapy MIGB-avid metastatic sites, a little less than half of the patients and sites relapsed in initial areas, while the remaining relapsed at new sites. Those sites that were treated with RT had excellent local control >90%, consistent with prior reports. While this data suggests that RT to metastatic sites on post-induction chemotherapy MIBG scan may improve outcomes, the sample size is limited and caution must be taken to balance potential benefits with risks, especially in situations with several metastatic sites.

Impact of 11q Loss of Heterozygosity Status on the Response of High-Risk Neuroblastoma With MYCN Amplification to Neoadjuvant Chemotherapy.

PurposeThe aim of this study was to investigate whether 11q loss of heterozygosity (LOH) aberration would impact the response of the primary tumor to neoadjuvant chemotherapy or to the degree of surgical resection in neuroblastoma (NB) patients with MYCN amplification.MethodsThe clinical data of 42 NB patients with MYCN amplification who were newly diagnosed and received treatments at our hospital from 2011 to 2020 were retrospectively analyzed. According to the results of the segmental chromosome aberration analysis, the patients enrolled were assigned to an 11qLOH positive group and an 11qLOH negative group.ResultsThere was no significant difference in the mean number of chemotherapy courses completed before surgery between the 11qLOH positive and 11qLOH negative groups (p = 0.242). Each of the 42 patients had metaiodobenzylguanidine (MIBG) scans both before and after neoadjuvant chemotherapy. The percentage of patients who had a clinical MIBG change in the 11qLOH positive group was lower than the percentage in the 11qLOH negative group (27.27 vs. 66.67%, p = 0.030). The 11qLOH negative group seemed to have a higher rate of surgical resection (≥90%); however, the difference between the two groups was not statistically significant (p = 0.088). Furthermore, the 11qLOH negative group did not show significantly superior event-free survival and overall survival rates compared with the 11qLOH positive group.ConclusionsThis study showed that patients with NB and MYCN amplification in combination with 11qLOH might be less likely to respond to neoadjuvant chemotherapy when compared with patients with NB and MYCN amplification without 11qLOH.

LINC-09. Coexisting glioneuronal tumor and adrenal ganglioneuroma

BACKGROUND: While both glial/glioneuronal neoplasia and ganglioneuroma have been reported as components of multiple primary neoplasms, no patient has been diagnosed with multiple primary neoplasms of cerebral glial/glioneuronal tumors with oligodendroglioma-like features and adrenal ganglioneuroma up to now. CASE: A previously healthy five-year-old girl was admitted with a two-week history of headaches and vomiting. Brain Magnetic resonance imaging (MRI) showed a massive heterogenous multi-cystic enhancing lesion in the right temporoparietal area with substantial vasogenic edema. The patient underwent craniotomy and tumor gross total resection. The intra-operative histomorphological assessment of the tumor was well-matched with a glial tumor. The patient developed systolic hypertension during postoperative care in the Intensive Care Unit. Subsequent abdominal CT scan unveiled a calcified mass of the left adrenal gland origin. Blood and urine catecholamine tests, vanillylmandelic acid (VMA), were within the normal range. The surgical excision specimen exhibited a clear cell neoplasm with diffuse infiltrative growth. A distinguishing combination of oligodendroglioma-like perinuclear haloes, clear cell appearance and vascular proliferation rendered the diffuse Glioneuronal tumor with Oligodendroglioma-like features. With the combination of oligodendroglial-like appearance, negative 1p/19q codeletion, Wild IDH, no BRAF mutation, weak GFAP, and positive synaptophysin altogether, the tumor was compatible with the novel diffuse glioneuronal tumor with oligodendroglioma-like features and nuclear clusters (DGONC). The patient underwent laparotomy and tumor resection subsequently. Morphologic histopathological examinations of the adrenal mass were in line with ganglioneuroma. After discharge, no pathological uptake was identified with iodine-131 meta-iodobenzylguanidine scan (MIBG scan). No tumor residue was apparent on postoperative brain MRI. The patient received no adjuvant therapy for brain and adrenal tumors and underwent close surveillance for both tumors. No clinical or radiologic recurrence was recognized after six months of follow-up. CONCLUSIONS: Concurrent glioneuronal tumor and ganglioneuroma can be managed safely when diagnosed timely, leading to favorable outcomes.

Impact of diagnostic and end-of-induction Curie scores in tandem autologous hematopoietic cell transplant for patients with high-risk neuroblastoma: A report from the Children’s Oncology Group.

10027 Background: Diagnostic mIBG (meta-iodobenzylguanidine) scans are an integral component of response assessment in children with high-risk neuroblastoma. The role of end of induction (EOI) Curie Scores (CS) has been previously described in patients undergoing a single autologous hematopoietic cell transplant (AHCT) as consolidation therapy. We now examine the prognostic significance of CS in patients randomized to tandem or single AHCT on the Children’s Oncology Group (COG) trial ANBL0532. Methods: A retrospective analysis of mIBG scans obtained from patients enrolled in COG ANBL0532 (n = 652) was performed. Evaluable patients (n = 179) had mIBG-avid, International Neuroblastoma Staging System (INSS) stage 4 disease, did not progress during induction therapy, consented to consolidation randomization, and received either a single (n = 99) or tandem AHCT (n = 80). In addition, evaluable patients had paired mIBG scans at time of initial diagnosis and EOI. Optimal CS cut points maximized the outcome difference (≤ vs &gt; CS cut-off) according to the Youden index. Log-rank tests compared EFS subgroups, with p &lt; 0.05 considered statistically significant. 3-year EFS is presented ± standard error. EFS was estimated for relative reductions in CS of 50% and 75% from diagnosis to EOI. Results: For recipients of tandem AHCT, the optimal cut point at diagnosis was CS = 12, with superior EFS from study enrollment for patients with CS&lt;12 (74.2±7.9%; n = 31) vs CS &gt; 12 (59.2±7.1%; n = 49) (p = 0.002). At EOI, the optimal cut point was CS = 0, with superior EFS from EOI for patients with CS = 0 (72.9±6.4%; n = 48) vs CS &gt; 0 (46.5±9.1%; n = 32) (p = 0.002). The cut point at diagnosis for recipients of single AHCT was CS = 21 (p = 0.04), while the EOI CS had an optimal cut point of 2, but without a significant difference in EFS (p = 0.29). Absolute CS at diagnosis and at EOI had a greater impact on outcome than the relative reduction in CS between diagnosis and EOI, for both single and tandem AHCT. Conclusions: In the setting of tandem transplantation for children with high-risk neuroblastoma, Curie scores at diagnosis and end-induction may identify a more favorable patient group. Patients treated with tandem AHCT who exhibited a CS&lt;12 at diagnosis or CS = 0 at EOI had superior EFS compared to those with CS above these cut points. Similar to prior reports, a CS&lt;2 was the optimal cut point for single transplant recipients. Clinical trial information: NCT00567567.

Pseudo-pheochromocytoma due to obstructive sleep apnea: a case report.

SummaryObstructive sleep apnea (OSA) is a condition of intermittent nocturnal upper airway obstruction. OSA increases sympathetic drive which may result in clinical and biochemical features suggestive of pheochromocytoma. We present the case of a 65-year-old male with a 2.9-cm left adrenal incidentaloma on CT, hypertension, symptoms of headache, anxiety and diaphoresis, and persistently elevated 24-h urine norepinephrine (initially 818 nmol/day (89–470)) and normetanephrine (initially 11.2 µmol/day (0.6–2.7)). He was started on prazosin and underwent left adrenalectomy. Pathology revealed an adrenal corticoadenoma with no evidence of pheochromocytoma. Over the next 2 years, urine norepinephrine and normetanephrine remained significantly elevated with no MIBG avid disease. Years later, he was diagnosed with severe OSA and treated with continuous positive airway pressure. Urine testing done once OSA was well controlled revealed complete normalization of urine norepinephrine and normetanephrine with substantial symptom improvement. It was concluded that the patient never had a pheochromocytoma but rather an adrenal adenoma with biochemistry and symptoms suggestive of pheochromocytoma due to untreated severe OSA. Pseudo-pheochromocytoma is a rare presentation of OSA and should be considered on the differential of elevated urine catecholamines and metanephrines in the right clinical setting.Learning pointsObstructive sleep apnea (OSA) is a common condition among adults.OSA may rarely present as pseudo-pheochromocytoma with symptoms of pallor, palpitations, perspiration, headache, or anxiety.OSA should be considered on the differential of elevated urine catecholamines and metanephrines, especially in patients with negative metaiodobenzylguanidine (MIBG) scan results.

Global Neuroblastoma Network: An international multidisciplinary neuroblastoma tumor board for resource-limited countries.

Tumor boards are part of standard care of patients with complex cancers, but appropriate multidisciplinary expertise and infrastructure are often not available in low- and middle-income countries (LMIC) for pediatric cancers, such as neuroblastoma. Our goal was to review results of a Global Neuroblastoma Network (GNN) tumor board accessible to LMIC. De-identified clinical cases presented via internet conference during a weekly GNN virtual tumor board from 2010 through 2020 were evaluated in a standardized format, including diagnostic imaging, pathology, therapy information, resource limitations, and questions for discussion. Information summarized included the presentations, a survey of the impact on care, and a resource questionnaire. Registered GNN participants included 575 individuals from 77 countries, with a median of 39 participants per session. Total 412 cases were presented from 32 countries, including 351 unique neuroblastoma patients, 52 follow-up cases, and nine non-neuroblastoma diagnoses. Twenty-eight educational sessions were presented. Limited critical resources for diagnostics and staging of cases included MYCN analysis (54.7%), metaiodobenzylguanidine (MIBG) scans (38.7%), and International Neuroblastoma Pathology Classification (49%). Therapies were also limited, with markedly decreased use of radiation and autologous stem cell transplant for high-risk cases, and no availability of anti-GD2 antibody in LMIC. Limited sampling with a post-presentation survey showed that 100% found the GNN helpful, and 70% altered the care plan based on the discussion. This report shows the utility of an international tumor board for LMIC focused on a challenging solid tumor where local expertise may be limited, with international multidisciplinary expert participation and educational sessions.

The potential role of the cardiac MIBG scan in differentiating the drug-induced Parkinsonism from Parkinson’s disease

IntroductionConsidering the difficulties of differentiating Parkinson’s disease (PD) from drug-induced Parkinsonism (DIP) in patients receiving antipsychotics, developing robust diagnostic tools is essential. Herein, we used the metaiodobenzylguanidine (MIBG) scan to assess its diagnostic accuracy for this purpose. Methods44 DIP patients and 32 patients with PD as controls were enrolled. All the participants underwent a cardiac 131I-MIBG scan. Statistical analysis was conducted to determine the significance of the results, and accuracy analyses were conducted to calculate the related sensitivity and specificity of the MIBG scan. ResultsThe mean age of PD and DIP groups were 62.6 ± 5.9 and 51.5 ± 10.8 years, respectively. The mean duration of drug consumption in the DIP group was 52.2 ± 29.4 days (the mean interval between drug initiation and DIP onset was 28.5 ± 20.5). Symptoms relief occurred 40 ± 24.2 days after drug discontinuation. In the PD group, 15.6% showed negative and 84.4% positive results on the MIBG scan. In the DIP group, 86.4% were negative, and the remaining were positive. The difference in MIBG uptake between the two groups was statistically significant (P-value < 0.001). The sensitivity and specificity of the MIBG scan were 84.4% (CI: 84.0–84.8) and 86.36% (CI: 86.0–86.7) for the diagnosis of PD, respectively. ConclusionOur results indicated more positive MIBG scans in the PD group than the DIP. Also, the MIBG scan’s sensitivity and specificity in differentiating the PD are acceptable. Future works should assess these findings and the role of the MIBG scan in prognosis assessment of DIP and better allocation of the patients to related disciplines.