Diagnostic specificity of the novel marker TRPS1 compared with traditional breast-specific markers in differentiating metastatic breast carcinoma from adrenal neoplasms.

Trichorhinophalangeal syndrome type 1 (TRPS1), a novel GATA transcription factor, has emerged as a sensitive and largely breast-specific marker across various carcinoma subtypes, including metastatic tumors. However, its specificity in adrenal neoplasms has not been explored. Given the prevalence of adrenal cortical and medullary neoplasms, alongside metastatic breast carcinoma, we aimed to investigate the diagnostic specificity of TRPS1 in a cohort of adrenal lesions. Semi-quantitative immunohistochemical expression for TRPS1 was compared to GATA3 and mammaglobin in 64 adrenal cortical lesions (4 adrenal rests, 6 adrenal cortical hyperplasia, 43 adrenal cortical adenomas, 4 adrenal cortical neoplasms of uncertain malignant potential, 7 adrenal cortical carcinomas) and 35 pheochromocytomas using tissue microarray technology. TRPS1 staining was absent in all pheochromocytomas and adrenal cortical lesions. Moderate to strong nuclear GATA3 positivity was identified in the majority of pheochromocytomas (77%), while only a small subset of adrenal cortical lesions (4%) demonstrated moderate to weak nuclear staining. Mammaglobin was negative in adrenal cortical lesions, although focal patchy positivity was seen in 6% of pheochromocytomas. When characterizing adrenal gland lesions in the context of metastatic breast carcinoma, TRPS1 demonstrates excellent specificity, showing no immunohistochemical expression in primary adrenal lesions. Mammaglobin, while largely specific (94%), offers limited diagnostic value due to occasional focal, non-specific staining in pheochromocytomas. In contrast, GATA3 lacks diagnostic specificity, as it is frequently expressed in pheochromocytomas and occasionally in adrenal cortical lesions, restricting its utility in this setting. Overall, TRPS1 emerges as the preferred marker for routine diagnostic practice in this setting.