| name | ppgl-genetic-test-selection |
| description | Selects specific genes to test for PPGL based on clinical presentation and phenotypic characteristics. Indications include abdominal/PGL with metastasis risk (test SDHB), head/neck PGL (test SDHD), bilateral PCC or pancreatic lesions (test VHL), and MEN2-associated mucosal neuromas or medullary thyroid cancer (test RET). |
PPGL Genetic Test Selection Based on Clinical Phenotype
STEP 1 — Gather Information
Collect tumor location (adrenal PCC vs abdominal/head-neck PGL), presence of metastatic disease, family history of PPGL or related syndromes, and clinical signs suggestive of MEN2 (mucosal neuromas, medullary thyroid cancer), VHL (bilateral PCC, pancreatic cysts/lesions), and SDHB/SDHD phenotypes.
STEP 2 — Rule In / Rule Out
If tumor location is head/neck paraganglioma, proceed to test SDHD; otherwise, rule out SDHD and evaluate for abdominal/PGL or adrenal PCC.
STEP 3 — Classify or Stratify
Classify phenotype: abdominal or extra-adrenal PGL with metastasis risk/family history → test SDHB; bilateral PCC or pancreatic lesions → test VHL; mucosal neuromas or medullary thyroid cancer → test RET.
STEP 4 — Decide
Order the indicated genetic test (SDHB, SDHD, VHL, or RET) based on the classification.
Clinical Guardrails / Mimics / Pitfalls
Do not test SDHB for isolated head/neck PGL without metastasis risk; do not overlook VHL in young patients with bilateral PCC; do not miss RET in patients with mucosal neuromas even without family history; ensure genetic counseling before testing; note that testing is not covered by insurance except for medullary thyroid carcinoma.
Concrete Clinical Example
A 45-year-old patient with an abdominal paraganglioma and a family history of metastatic PPGL undergoes SDHB testing, which reveals a pathogenic variant, guiding surveillance for metastasis.
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
