Indolent form of adrenocortical carcinoma: clinico-morphological features of 7 patients.

Adrenocortical carcinomas (ACC) usually tends to be highly aggressive tumor with very poor prognosis, but some patients may have more indolent form of disease with much longer progression-free period despite of presence of distant metastases or repeated recurrence of disease. Stable tumor size (no growth of recurrent tumor or distant metastases for more than 12 months) was considered as indolent form of disease. We have analyzed clinical and histological characteristics (Weiss criteria, Ki-67 index, expression of p53, b-catenin) of recurrent or metastatic ACCs in 7 patients with indolent disease, and have compared it with control group consisting of 157 patients with ACC, who have undergone surgical treatment. Seven patients underwent repeated surgical treatment (up to 5 times) because of indolent form of recurrent or metastatic ACC. Longest time to progression was 37 months. There were no significant differences in clinical characteristics, Weiss score, Ki-67 index and expression level of p53 between two groups of patients. Indolent form of ACC was characterized by the absence of both nuclear and cytoplasmic expression of b-catenin expression; differences between two groups were statistically significant. Biological and molecular features of primary tumor, which usually does not correlate with clinical features, determine indolent form of ACC. Probably, inactivation of Wnt/b-catenin signaling pathway is one of the main mechanism leading to less aggressive disease progression. The phenomenon of unusually low aggressive natural history of ACC and its  biological basis needs to be further investigated.

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