Synaptophysin immunoreactivity in primary pigmented nodular adrenocorticaldisease: Neuroendocrine properties of tumors associated with Carney complex

Carney complex (CNC) is characterized by lentiginosis and myxomatosis toget her with a variety of endocrine, neural crest-derived, and other tumors, in cluding primary pigmented nodular adrenocortical disease (PPNAD). PPNAD is characterized by lipofuscin-containing, autonomously functioning, cortisol- producing nodules surrounded by mostly atrophic adrenocortical and normal a drenomedullary tissue. The nature and origin of the tumors, including the m yxomas and PPNAD, are unclear. In this study, seven paraffin embedded PPNAD tumors, one skin myxoma, and two cell lines tone myxoma and one PPNAD) est ablished from patients with CNC were stained with antisera for synaptophysi n (SYN), neuron-specific enolase, chromogranin A, tyrosine hydroxylase, and the neural cell adhesion molecule (NCAM). In addition, one PPNAD specimen and one myxoma were analyzed by electron microscopy. The results showed tha t chromogranin A and tyrosine hydroxylase stained adrenomedullary tissue, b ut not the PPNAD nodules or the extranodular adrenal cortex. SYN, neuron-sp ecific enolase, and NCAM also stained the medulla. PPNAD nodules and the PP NAD cell line, but not the extranodular adrenal cortex, stained intensely f or SYN. The myxoma cell line, but not; normal fibroblasts, stained for SYN and NCAM. Ultrastructural analysis of a PPNAD tumor and a skin myxoma revea led a well developed rough endoplasmic reticulum, prominent mitochondria, a nd vesicle-like structures dispersed throughout the cytoplasm. We conclude that immunostaining for SYN, a marker protein for neuroendocrine cells, cle arly distinguishes PPNAD nodules from surrounding adrenocortical tissue and can be helpful in the detection of small nodules in apparently unaffected cortex. The cells of a cutaneous myxoma were also stained positive by two o f the three neuroendocrine markers. Finally, both PPNAD and myxoma cells de monstrated ultrastructural features suggestive of neuroendocrine properties . These results support the previously suggested hypothesis that the geneti c mechanism leading to CNC involves genes with a neuroendocrine role.