dromlakhani Assess metastasis risk in pheochromocytoma and paraganglioma
STEP 1 — Gather Information
Collect age at diagnosis, tumor size (cm), catecholamine secretion pattern (adrenergic/noradrenergic dominance), timing of metastatic lesion diagnosis (if any), tumor localization (adrenal vs extra-adrenal, head/neck vs abdominal/pelvic), disease type (sporadic vs hereditary, PCC vs PGL), histopathological findings (capsular/vascular invasion, necrosis, SDHB immunostaining), SDHB gene pathogenic variant status, SDHB immunohistochemistry, presence of metastases at initial diagnosis, number of metastases, chromogranin A level, plasma fractionated metanephrines (≥5× ULN), and plasma 3‑MT level.
STEP 2 — Rule In / Rule Out
Are there lesions in non‑chromaffin tissues (bone, lung, liver, lymph nodes) on imaging or biopsy? If yes → rule in metastasis (high risk). If no → proceed to risk stratification.
STEP 3 — Classify or Stratify
Assign one point for each of the following: age <40 years, tumor size >5 cm, extra‑adrenal/PGL location, noradrenaline dominance, SDHB pathogenic variant, negative SDHB immunostaining, histopathological capsular/vascular invasion, presence of metastases at initial diagnosis, ≥2 metastases, chromogranin A elevated (not covered by insurance), plasma fractionated metanephrines ≥5× ULN, elevated plasma 3‑MT. 0‑1 points = low risk, 2‑3 points = intermediate risk, ≥4 points = high risk.
STEP 4 — Decide
Low risk: annual biochemical testing and symptom review. Intermediate risk: imaging (CT/MRI or 123I‑MIBIG scintigraphy) every 12 months plus biochemical testing every 6 months. High risk: imaging every 6 months, consider genetic counseling, discuss clinical trial eligibility, and consider adjuvant therapy in multidisciplinary meeting.
Clinical Guardrails / Mimics / Pitfalls
Do not rely solely on tumor size; SDHB immunohistochemistry can have false negatives—confirm with genetic testing if suspicion remains. Do not assume low risk in head/neck PGLs; they may metastasize despite low SDHB mutation rate. Avoid missing catecholamine pattern clues; noradrenaline dominance raises risk. Do not overlook plasma 3‑MT elevation as an independent risk factor.
Concrete Clinical Example
A 35‑year‑old with a 6 cm extra‑adrenal PGL, noradrenaline dominance, negative SDHB immunostaining, and no metastatic lesions on initial work‑up scores 4 points (age<40, size>5, extra‑adrenal, noradrenaline dominance, negative SDHB IHC) → high risk → schedule 6‑month imaging and genetic counseling.
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