| name | ata-ppgl-metastasis-risk-assessment |
| description | Assesses metastasis risk in pheochromocytoma and paraganglioma using age at diagnosis, tumor size, catecholamine secretion pattern, timing of metastatic lesion diagnosis, tumor localization, disease type, histopathological findings, SDHB gene pathogenic variants, and SDHB immunohistochemistry status. Use when a clinician asks 'What is the metastasis risk for this pheochromocytoma patient?' Triggers include new PPGL diagnosis or change in clinical status during follow-up. |
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
