dromlakhani PPGL Metastasis Risk Assessment Using Clinical Factors
STEP 1 — Gather Information
Collect age at diagnosis, tumor size (cm) on imaging, catecholamine secretion pattern (adrenaline vs noradrenaline dominance via plasma free metanephrines/normetanephrines or 24‑h urine metabolites), and tumor location (adrenal PCC vs extra‑adrenal PGL, noting abdominal or head/neck PGL).
STEP 2 — Rule In / Rule Out
Determine if any high‑risk clinical feature is present: age < 40 years, tumor ≥ 4 cm, noradrenaline dominance, or PGL location (extra‑adrenal). If none are present, classify as low risk; if at least one is present, proceed to stratification.
STEP 3 — Classify or Stratify
Count the number of high‑risk features present: 1 feature = intermediate risk, 2‑3 features = high risk, ≥4 features = very high risk. Adjust for tumor size thresholds: 4‑7 cm adds one point, > 7 cm adds two points.
STEP 4 — Decide
Low risk: routine biochemical and imaging surveillance per standard follow‑up. Intermediate risk: add SDHB immunostaining on resected tissue or germline SDHB testing, and shorten surveillance interval to 6‑12 months. High/Very high risk: pursue comprehensive genetic panel (SDHB, VHL, RET, etc.), consider early functional imaging (18F‑FDG PET/CT), and discuss multidisciplinary planning for possible metastatic workup.
Clinical Guardrails / Mimics / Pitfalls
Do not rely solely on clinical factors; histopathological confirmation (SDHB loss) and genetic testing are required for definitive risk stratification. Avoid overestimating risk in elderly patients with small tumors (< 4 cm) noradrenaline‑secreting PCCs, which have low metastatic potential. Remember that head‑and‑neck PGLs, despite being extra‑adrenal, carry a low metastasis rate (< 5 %) and should not be upstaged based on location alone.
Concrete Clinical Example
A 35‑year‑old patient presents with a 5 cm abdominal PGL, plasma normetanephrine markedly elevated (noradrenaline dominance), and no family history. Two high‑risk features (age < 40, tumor ≥ 4 cm, noradrenaline dominance) yield high risk. Proceed to SDHB germline testing and schedule 18F‑FDG PET/CT at 6‑month intervals.
Source: Japan Endocrine Society Clinical Practice Guideline for the Diagnosis and Management of Pheochromocytoma and Paraganglioma 2025, Japan Endocrine Society, 2025, DOI:10.1507/endocrj.EJ25-0165