Álvaro Lopes de Oliveira, Oncology Resident at A.C. Camargo Cancer Center, shared a thread on X/Twitter:

“The patient presented with lumbar pain and a significant decrease in weight. No hypertension or hyperaldosteronism. A family history of a 1st-degree cousin with pheochromocytoma, SDHB mutated. CT scan showed multiple liver and adrenal lesions.

Liver Biopsy: metastatic paraganglioma. Microscopy positive for Chromogranin A, Synaptophysin, and S-100, Ki-67 index at 2%. What imaging/ lab tests are recommended for initial work up of patients with metastatic paraganglioma/pheochromocytoma (PPGL)?

• SSTR-PET/CT
• FDG-PET/CT
• MIBG Plasma free or 24 urine

Mini Tweetorial 1:

• PPGL are rare and nearly 50% are associated with germline pathogenic variants in SDHx, and less often in VHL, RET or NF1
• All patients with PPGL should have genetic testing

Mini Tweetorial 2:

PPGL are molecularly classified into 3 types:

• Pseudohypoxic (HIF, VHL, SDHx alterations)
• kinase signaling (RET alterations)
• Wnt-altered: They typically have low TMB and rare actionable mutations

Mini Tweetorial 3:

• Functional imaging with MIBG, SSRT-PET/CT and FDG-PET/CT are recommended to stage patients with PPGL with suspicious metastasis
• Imaging also guides treatment in Pts with metastatic Dz with peptide-receptor radionuclide therapy (PRRT)

Back to the Case:

Patient staged positive on MIBG, SSTR Gallium68 PET/CT. 24h Urine metanephrines normal. Iso-somatic and germline NGS SDHB germline pathogenic: c. 293G>A (p.Cys98Tyr).(VAF 87%) Somatic NGS: TMB7, TP53 subclonal normal BP and liver function.

Treatment Timeline:

• MIBG-I131 therapy x 4 doses till Surgery debulking
• After 14 months, liver PD with new lesions
• What are the treatment options for metastatic PPGL after PD on 1st line MIBG therapy?

Mini Tweetorial 4:

Approx 20% of PPGL become metastatic. mOS= 4 to 6 years; outcomes are heterogeneous. Prognostic factors in metastatic PPGL of MIBG uptake and functional tumors associated with survival.

Treated with sunitinib 37.5mg/day for 9 months with partial response AEs:

• G2 hand-foot syndrome
• G3 hypothyroidism”

Source: Álvaro Lopes de Oliveira/X