Diagnostic sensitivity and specificity of INSM1 in pheochromocytomas versus adrenal cortical lesions.

OBJECTIVES

While neuroendocrine markers such as chromogranin can be used to distinguish pheochromocytomas (positive) from adrenal cortical lesions (negative), other neuroendocrine markers such as synaptophysin can be positive in both entities. Insulinoma-associated protein 1 (INSM1) is a relatively novel marker often used in the diagnostic assessment of neuroendocrine tumors but with unexplored sensitivity/specificity in distinguishing between pheochromocytomas and adrenal cortical lesions.

METHODS

Herein, semi-quantitative immunohistochemical expression for INSM1 was investigated in 35 pheochromocytomas and 64 adrenal cortical lesions (4 adrenal rests, 6 adrenal cortical hyperplasias, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, 7 adrenal cortical carcinomas) and compared to relatively more traditional markers chromogranin and GATA3.

RESULTS

INSM1 demonstrated diffuse strong nuclear staining in all pheochromocytomas (100%) and focal weak nuclear staining in rare adrenal cortical lesions (8%). Substratification showed INSM1 positivity in a subset of adrenal cortical hyperplasias (17%) and adrenal cortical adenomas (9%). For pheochromocytomas, overall sensitivity (and specificity compared to adrenal cortical lesions) was 100% (92%) for INSM1, 91% (97%) for GATA3, and 100% (100%) for chromogranin.

CONCLUSIONS

When attempting to distinguish pheochromocytomas from adrenal cortical lesions, INSM1 and GATA3 can be effective immunohistochemical tools with excellent sensitivity and specificity. However, while they may be helpful adjuncts in diagnostically challenging cases, chromogranin remains the gold-standard marker with even higher sensitivity and specificity.