Adrenocortical carcinoma (ACC) staging uses the ENSAT classification. The immunohistochemical marker that most reliably distinguishes ACC from adrenocortical adenoma is:

• A Positive p53 and beta-catenin nuclear staining
• B IGF2 overexpression detected by in situ hybridization
• C Loss of reticulin framework pattern on reticulin stain
• D Ki-67 proliferative index ≥5% in combination with the Weiss scoring system ✓

Explanation

The Weiss scoring system (nine histological criteria including necrosis, atypical mitoses, ≥5 mitoses/50 HPF, venous/sinusoidal/capsular invasion, diffuse architecture, nuclear grade III-IV, >25% clear cells) is the standard pathological diagnostic approach for ACC vs. adenoma. A Weiss score ≥3 indicates carcinoma. Ki-67 ≥5% (particularly ≥10%) supports malignancy and is the strongest single proliferation-based criterion. Ki-67 combined with Weiss score improves diagnostic accuracy. Loss of reticulin framework is a recently validated single marker (reticulin algorithm) that has high sensitivity; beta-catenin nuclear positivity indicates CTNNB1 mutation in ~15% of ACC; p53 overexpression indicates TP53 mutation in ~25% of ACC — these are adjunctive but not the most reliable single diagnostic discriminators compared to the Weiss+Ki-67 combination.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

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Written and medically reviewed by the StethoPrep medical team.