D2-40 is a sensitive and specific marker in differentiating primary adrenal cortical tumours from both metastatic clear cell renal cell carcinoma and phaeochromocytoma.

BACKGROUND: The morphological similarities between the cells of clear cell renal cell carcinoma (CCRCC) and those of the adrenal cortex impose diagnostic difficulties, for example in the context of a solitary nodule in the adrenal gland in a patient with renal cell carcinoma (RCC). This problem is confounded by the variable and patchy staining seen with the established panel of antibodies utilised in this context, namely EMA, cytokeratins, vimentin, inhibin, melan-A, and RCC marker; particularly on biopsy material. D2-40, an antibody commonly used to highlight lymphatic endothelial cells, is consistently positive in the normal adrenal cortex.

AIMS: To investigate the utility of D2-40 in distinguishing neoplastic and non-neoplastic adrenal cortical cells from those of CCRCC, and from phaeochromocytoma.

METHODS: D2-40 antibody was applied to tissue sections from 10 normal adrenal glands, 15 renal carcinomas (13 clear cell, 2 papillary variants), 1 metastatic CCRCC in the adrenal gland, 6 adrenal cortical hyperplasias, 5 adrenal cortical adenomas, 3 adrenal cortical carcinomas, and 4 phaeochromocytomas.

RESULTS: D2-40 was strongly and diffusely positive in the cells of the neoplastic and non-neoplastic adrenal cortex, but negative in the cells of the CCRCC, both primary and metastatic, in 100% of the cases. The cells of the adrenal medulla, and those of the phaeochromocytomas, were negative for D2-40.

CONCLUSIONS: D2-40 may be a useful marker for distinguishing primary adrenal cortical neoplasms from both metastatic CCRCC and phaeochromocytoma.