| name | ata-ppgl-histopathological-confirmation |
| description | This skill confirms pheochromocytoma and paraganglioma (PPGL) diagnosis on histopathology by requiring immunostaining positive for Chromogranin A and negative for cytokeratin in tumor tissue, with SDHB negativity indicating SDHx pathogenic variants that predict metastasis or recurrence. It is triggered when a clinician asks 'How do I confirm pheochromocytoma diagnosis on pathology?' or encounters resected adrenal or paraganglioma tissue needing a definitive diagnosis. |
Confirm pheochromocytoma and paraganglioma diagnosis on histopathology
STEP 1 — Gather Information
Obtain resected adrenal or paraganglioma tissue; perform hematoxylin and eosin (HE) staining to assess tumor architecture, then run immunohistochemistry for Chromogranin A (CgA), cytokeratin (CAM5.2/AE1/AE3), and SDHB.
STEP 2 — Rule In / Rule Out
If tumor cells show Chromogranin A positivity and cytokeratin negativity, rule in PPGL; if either Chromogranin A is negative or cytokeratin is positive, rule out PPGL and consider adrenal cortical neoplasm or metastatic carcinoma.
STEP 3 — Classify or Stratify
Assess SDHB immunostaining: loss of SDHB staining indicates SDHx pathogenic variants associated with higher metastasis and recurrence risk; retained SDHB staining suggests lower risk.
STEP 4 — Decide
For Chromogranin A+/cytokeratin- cases with SDHB loss, diagnose PPGL with high metastatic potential and recommend SDHx genetic testing and intensified postoperative surveillance; for SDHB-retained cases, diagnose PPGL with standard risk and advise routine follow-up per postoperative protocol.
Clinical Guardrails / Mimics / Pitfalls
Do not rely on HE staining alone; false-negative Chromogranin A or false-positive cytokeratin can occur in poorly differentiated tumors. SDHB negativity predicts increased risk but does not confirm metastasis; avoid overcalling malignancy based solely on SDHB loss. Mimics include adrenal cortical tumors (positive for melan-A, inhibin) and cytokeratin-positive metastases (e.g., renal cell carcinoma). GATA3 positivity may appear in breast cancer metastases; interpret in clinical context.
Concrete Clinical Example
A 48‑year‑old woman with a resected left adrenal mass shows HE‑stained zellballen pattern, Chromogranin A strong positivity, cytokeratin negativity, and complete SDHB loss; diagnosis: PPGL with SDHB‑related pathogenic variant, prompting SDHB genetic testing and scheduled 6‑month imaging surveillance.
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
