Expression of Extracellular Signal-regulated Kinase 5 and Ankyrin Repeat Domain 1 in Composite Pheochromocytoma and Ganglioneuroblastoma Detected Incidentally in the Adult Adrenal Gland

Abstract

Composite pheochromocytoma (cPC) is extremely rare, arising in the adrenal medulla as a mixture of PC and other tumors of neural origin. We herein report on a case of adrenal incidentaloma post-operatively diagnosed as cPC with ganglioneuroblastoma (GNBL). The PC component had 7 points on the PASS, a Ki-67 index of 5.1%, a focal absence of sustentacular cells, and no genetic aberrations in succinate dehydrogenase subunit B. The GNBL component exhibited no N-myc amplification. Tumor cells of both components were stained positively for extracellular signal-regulated kinase 5 and ankyrin repeat domain 1. The aberrant activation of growth signaling may play a role in the marginal malignancy of cPC.

The Value of Histological Algorithms to Predict the Malignancy Potential of Pheochromocytomas and Abdominal Paragangliomas—A Meta-Analysis and Systematic Review of the Literature

“…In total, 50 published studies were identified by the PubMed search engine when employing the term “PASS pheochromocytoma”. After an initial assessment of eligibility, including the presence of a PASS stratified pheochromocytoma cohort as well as an exclusion of irrelevant studies and reviews, 28 original studies and case reports were initially included in the review [1,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29]. After careful revision of each study, eight additional studies were disqualified from inclusion based on the failure to meet our fourth inclusion criterion of “clearly identified subgroup information (number of tumor samples with and/or without evidence of synchronous or metachronous evidence of malignancy respectively, with the associated PASS score clearly identifiable)” [5,6,8,9,13,14,18,28].…”

“…After careful revision of each study, eight additional studies were disqualified from inclusion based on the failure to meet our fourth inclusion criterion of “clearly identified subgroup information (number of tumor samples with and/or without evidence of synchronous or metachronous evidence of malignancy respectively, with the associated PASS score clearly identifiable)” [5,6,8,9,13,14,18,28]. Therefore, a total of 20 studies were included in the meta-analysis [1,3,4,7,10,11,12,15,16,17,19,20,21,22,23,24,25,26,27,29]. These studies and the associated outcomes are detailed in Table 1 and illustrated in Figure 2A.…”

“…When applying a cut-off score of ≥4, the PASS algorithm correctly identified all 33 metastatic PCCs as no case scored <4—thereby ensuring a sensitivity of 100% and a risk stratification model with the potential to correctly “rule in” metastatic PCCs [1]. The PASS algorithm has since been assessed in several studies [3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29], of which numerous has verified the value of this approach and some which could not wholly reproduce the original findings. However, the algorithm also carries inter- and intraobserver variation, and the clinical value of the method has been debated [8,10].…”