An exploration in pitfalls in interpreting SDHB immunohistochemistry

Area of Science:

• Oncology
• Molecular Pathology
• Biochemistry

Background:

• Succinate dehydrogenase complex (SDHx) mutations are linked to various tumors, with SDH-deficiency impacting patient management.
• Immunohistochemistry (IHC) for SDHB subunit loss is a key indicator of SDH-deficiency.
• Aberrant cytoplasmic SDHB-IHC staining can mimic retained expression, posing a diagnostic challenge.

Purpose of the Study:

• To characterize aberrant SDHB-IHC staining patterns in SDH-deficient tumors.
• To improve the diagnostic accuracy of SDHB-IHC in identifying SDH-deficient malignancies.

Main Methods:

• Analysis of 23 tumors with known germline SDHx variants or confirmed tumor SDHx pathogenic variants.
• Detailed examination of SDHB-IHC staining patterns in tumor cells versus non-neoplastic cells.
• Comparison of staining across multiple tissue blocks for cases with suspected heterogeneity.

Main Results:

• Eight of 23 (35%) SDH-deficient tumors exhibited significant SDHB-IHC staining.
• Aberrant staining in tumor cells showed distinct intensity and intracellular distribution compared to non-neoplastic cells.
• Intratumoral heterogeneity of SDHB-IHC was observed in one case, requiring additional tissue analysis.

Conclusions:

• Distinguishing aberrant cytoplasmic SDHB-IHC from true retained expression is critical.
• Diagnostic pitfalls in SDHB-IHC interpretation necessitate careful evaluation.
• Molecular testing may be required to confirm SDH-deficiency in equivocal cases.