dromlakhani Indicate and perform genetic testing for pheochromocytoma and paraganglioma
STEP 1 — Gather Information
Collect detailed family history (first‑degree relatives with PPGL, syndromic features) and medical history (age at onset, tumor laterality, location, hypertension, symptoms). Document any hereditary triggers: age <50 years, bilateral adrenal tumors, extra‑adrenal/paraganglioma location, or known family history of PPGL.
STEP 2 — Rule In / Rule Out
If any hereditary trigger is present, rule in for genetic testing discussion after counseling; if no triggers are identified, rule out routine germline testing but still inform the patient about the hereditary nature of PPGL and the option for testing based on preference.
STEP 3 — Classify or Stratify
Prioritize SDHB testing for patients with metastatic or high‑risk features (35–75% metastatic risk); consider SDHD for head‑and‑neck PGL, VHL for early‑onset bilateral PCC, and RET when medullary thyroid carcinoma or MEN2 features exist; use a multigene panel (MGPT) when phenotype is ambiguous or multiple genes are suspected.
STEP 4 — Decide
Obtain informed consent after genetic counseling, perform germline testing at a quality‑guaranteed facility (NGS‑based panel or Sanger as appropriate), and integrate results into management: guide surveillance for metastasis, inform at‑risk relatives, and tailor surgical approach (e.g., cortical‑sparing adrenalectomy for VHL/RET).
Clinical Guardrails / Mimics / Pitfalls
Do not order testing without pre‑test counseling; do not interpret negative SDHB immunostaining as definitive absence of germline SDHB mutation; do not rely solely on tumor SDHB loss for clinical decisions without germline confirmation; do not forget that PPGL genetic testing and counseling are not reimbursed by Japanese health insurance except in medullary thyroid carcinoma; avoid testing minors without appropriate assent/consent and age‑specific surveillance plans.
Clinical Guardrails / Mimics / Pitfalls
Do not order testing without pre‑test counseling; do not interpret negative SDHB immunostaining as definitive absence of germline SDHB mutation; do not rely solely on tumor SDHB loss for clinical decisions without germline confirmation; do not forget that PPGL genetic testing and counseling are not reimbursed by Japanese health insurance except in medullary thyroid carcinoma; avoid testing minors without appropriate assent/consent and age‑specific surveillance plans.
Concrete Clinical Example
A 32‑year‑old woman with an incidentally discovered left adrenal pheochromocytoma (normotensive) reports her paternal uncle had a carotid body paraganglioma at age 45. After genetic counseling, she undergoes SDHB germline testing, which reveals a pathogenic variant. She is enrolled in biannual plasma‑free metanephrines and whole‑body MRI surveillance, and her first‑degree relatives are offered predictive testing.
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