Case 1: Metastatic paraganglioma without an identified pathogenic germline variant.
A 12-year-old male presented with weight loss of 4.5 pounds over 18 months, loss of appetite, intermittent vomiting, constipation, and fatigue. CT of the chest, abdomen and pelvis showed a heterogeneous left paraspinous/retroperitoneal mass with multiple pulmonary nodules that were suspicious for metastases; both adrenals were normal. A right ileo-ileal intussusception was also present and initial differential considerations included inflammatory myofibroblastic tumor (IMT), sarcoma, lymphoma, and neuroblastoma. Biopsy yielded a broad differential, with low-grade spindle-cell sarcoma and extra-intestinal GIST variant among the considerations. Staging18F-FDG-PET/CT (Fig. 1A-D) showed low-level uptake in the abdominal mass and the pulmonary nodules, but no other sites of FDG-avid disease were detected. Upon surgical resection, the mass appeared to be paraspinous in orgin, extending into the retroperitoneum. Pathology was consistent with paraganglioma, with cells positive for chromogranin, synaptophysin, INSM1, CH56, GATA3, and S100, with evidence of multifocal vascular invasion and positive resection margins. Germline pathogenic variants in genes typically associated with hereditary paraganglioma were not identified. 68Ga-DOTATATE PET was performed to evaluate for metastatic disease and revealed widespread somatostatin receptor-expressing disease throughout the axial and appendicular skeleton, lungs, and right hepatic lobe (Fig 1E). The hepatic lesions were seen by MRI, but were not initially evident by CT. Based on the extensive burden of systemic disease,131I-MIBG therapy was a consideration. Staging123I-MIBG scintigraphy (Fig. 1F) demonstrated a similar distribution of disease compared to the68Ga-DOTATATE PET, with numerous axial and appendicular lesions, although there were far fewer MIBG-avid lesions (no MIBG uptake seen in the ribs, humeri, left scapula, and tibiae) in comparison with the 68Ga-DOTATATE PET/CT. Known liver lesions detected by DOTATATE PET were also not well visualized on the123I-MIBG study, due to background physiologic hepatic MIBG uptake. These studies were all performed within 21 days of each other, and 68Ga-DOTATATE PET showed both increased sensitivity and specificity for detecting disease.