Transformation of a Nonfunctional Paraganglioma With I-123 MIBG Scintigraphy Correlation

A 35-year-old woman presenting with abdominal pain was found to have mildly elevated catecholamine levels and a retroperitoneal mass. The patient underwent a negative I-123 MIBG scintigraphy scan and a nondiagnostic fine needle aspiration. Eleven years later the patient presented with a hypertensive emergency and markedly elevated catecholamine levels. A subsequent I-123 MIBG scintigraphy scan showed intense uptake corresponding to the previously seen retroperitoneal mass. The patient underwent surgical resection and pathology confirmed the presence of a paraganglioma A paraganglioma is an extra-adrenal pheochromocytoma that contains chromaffin cells and is thus capable of producing catecholamines. I-123 metaiodobenzylguanidine (MIBG) scintigraphy has become the imaging study of choice for paragangliomas and has a sensitivity of 77% to 100% in detecting functional paragangliomas. This case demonstrates scintigraphic correlation of the functional transformation of a nonfunctional paraganglioma in a time span of 10 years. Although there are previously published case reports of scintigraphic positive, nonfunctional paragangliomas and scintigraphic negative chromaffin cell tumors, there has been no prior documented case of scintigraphic transformation on MIBG. (Medicine 95(2):e2501) Abbreviations: CT = computed tomography, DOPA = dopamine, DTPA = diethylenetriamine pentaacetate, FDG = fluorodeoxyglucose, MIBG = metaiodobenzylguanidine. CASE PRESENTATION A 35-year-old woman presented to an emergency department with abdominal pain, nausea, and vomiting. A computed tomography (CT) scan was performed (unavailable) and she was diagnosed with gallstones. Her CT scan also revealed a 4 en Dave, MD, Hon hD, nd John Shim, MD gland were all considerations at this time. The patient was admitted for pain control and additional work-up of the right upper quadrant mass. Her work-up included a fine needle aspiration of the mass, but this was unfortunately nondiagnostic. The patient’s pain subsided after a few days and she was discharged due to a desire to be home for the Thanksgiving holiday. The patient presented to our nuclear medicine department after the holiday to undergo an MIBG study (Figure 1). The patient never received any treatment for the mass and was subsequently lost to follow-up. Eleven years after the initial work-up, the patient returned to our institution after suffering an episode of severe epigastric pain, headache, and acute loss of consciousness. Her urine catecholamines (norepinephrine and vanillylmandelic acid) were found to be markedly elevated: epinephrine–7 (0– etaiodobenzylguanidine) MIBG scinties) and 24 h (right images) after infusion eased uptake. This study was performed patient presenting with hypertensive increased right-sided MIBG uptake. lguanidine. www.md-journal.com | 1 FIGURE 2. Axial (A) and coronal (B), contrast-enhanced CT of the abdomen/pelvis demonstrating a large, heterogeneous mass containing solid and cystic components within the right retroperitoneum (white arrow). Incidentally noted large, fibroid uterus (black arrow). Axial, T2-weighted fat-saturation magnetic resonance imaging (MRI) (C) demonstrating a complex mass within the right retroperitoneum (white arrow). Note the relative hyperintensity of the cystic components within the mass. Axial, T1-weighted MRI (D) demonstrates a hypointense mass within the right retroperitoneum. CT1⁄4computed tomography. FIGURE 3. I-123 MIBG scintigraphy showing intense uptake corresponding to the right retroperitoneal mass at 6 h (white arrows) and 24 h (black arrows) after infusion. MIBG1⁄4metaiodobenzylguanidine. Davalos et al Medicine Volume 95, Number 2, January 2016 2 | www.md-journal.com Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. FIGURE 4. Hematoxylin and eosin (HE) stain at 20 (A) and 200 (B) magnification and neuron-specific enolase (NSE) stain at 200 (C) magnification of the surgically excised right upper quadrant mass. The tumor is well circumscribed and encapsulated by a fibrous capsule. cre d e Medicine Volume 95, Number 2, January 2016 Transformation of Nonfunctional Paraganglioma normal limits: epinephrine–18, norepinephrine–91, and vanillylmandelic acid-4. Another CT scan was performed and this time revealed a 7 5 cm mass in the right upper quadrant, below the third portion of the duodenum (Figure 2). Subsequent evaluation with I-123 MIBG scintigraphy revealed markedly increased uptake within the right upper quadrant mass (Figure 3). The patient underwent surgical resection and pathology confirmed the presence of a paraganglioma (Figure 4). The patient was unreachable to discuss consent for publication. DISCUSSION I-123 MIBG will concentrate by active transport in catecholamine-producing paragangliomas. At the time of the patient’s initial presentation, we believe the I-123 MIBG scan was negative due to a nonfunctioning paraganglioma that eventually transformed to a functioning paraganglioma. This scenario is also corroborated by the marked elevation in catecholamine levels that occurred between the patient’s initial and secondary presentations. Another possibility that could have explained the initially negative MIBG scan would be poor patient preparation; MIBG uptake can be inhibited by any drug that compromises transport into adrenergic tissue, such as antihypertensives, antidepressants, or antipsychotics. However, a review of the patient’s chart and medications revealed no history of such medications. The overall sensitivity and specificity of I-123 MIBG for the detection of paragangliomas is 56% to 76% and 84% to 100%, respectively. However, it has been reported that the sensitivity of I-123 MIBG decreases when evaluating for metastatic or recurrent paragangliomas. The reason for this decreased sensitivity may be explained by a lost expression of specific transporters that result in a lack of accumulation of I123 MIBG. In addition, the sensitivity of I-123 MIBG is substantially lower (<50%) for the detection of paragangliomas in patients with an associated germline mutation. In these cases, I-123 MIBG is not the functional imaging radionuclide of choice and imaging with F-18 dopamine (DOPA), F-18 fluorodeoxyglucose (FDG), or In-111 diethylenetriamine pentaacetate (DTPA) pentetreotide, depending on the specific germline Nest of polygonal tumor cells interspersed with small blood vessels immunostain is positive for tumor cell nests. HE1⁄4hematoxylin an of I-123 MIBG for sporadic versus hereditary paragangliomas is also likely to be the result of differences in gene expression that Copyright # 2016 Wolters Kluwer Health, Inc. All rights reserved. account for the accumulation of I-123 MIBG. Although our case differs from the above scenarios, which relate to sporadic versus hereditary paragangliomas and primary versus recurrent or metastatic paragangliomas, it is conceivable that alterations in gene expression over time could also be responsible for the development of a functional paraganglioma in our case. To our knowledge, this is the first reported case of the transformation of nonfunctioning paraganglioma to a functioning paraganglioma.