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.