Choroid plexus tumors differ from metastatic carcinomas by expression of the excitatory amino acid transporter–1

Summary

Tumors of the choroid plexus (CPTs) are rare neoplasms of neuroectodermal origin usually arising in pediatric patients. However, CPT may occur at any age, and their distinction from metastatic carcinomas is often difficult in adult cases. Because CPTs frequently show focal glial differentiation, we now investigated 35 CPTs (19 males and 16 females 0.3-70 years old; median age, 25.0 years), including 21 choroid plexus papillomas (CPPs), 5 atypical CPP, and 9 choroid plexus carcinomas regarding their expression of the excitatory amino acid transporter–1 (EAAT1, corresponding to rodent GLAST/GLAST-1) by immunohistochemistry. In addition, 77 metastatic carcinomas, including 64 adenocarcinomas with mostly papillary formations, derived from different organs were examined. Of the 35 CPTs, 23 (66%) showed membranous EAAT1 expression in variable numbers of tumor cells, including all atypical CPP and 3 of 9 choroid plexus carcinomas (33%). None of the metastatic carcinomas showed membranous immunostaining. Excitatory amino acid transporter–1 expression in CPT was significantly age dependent (P < .0001), with the proportion of EAAT1-positive tumor cells increasing with age, but not sex dependent. There was a highly significant difference between EAAT1 expression in CPT and in metastatic carcinomas (P < .0001). Establishing a cutoff value of 1% immunoreactive tumor cells served in adult cases to distinguish CPT from metastatic adenocarcinomas with 100% specificity and 70% sensitivity and was associated with positive and negative predictive values of 100% and 91%, respectively. Our findings indicate that EAAT1 immunohistochemistry may be useful in differentiating CPT from metastatic carcinomas.

Introduction

Choroid plexus papillomas (CPPs) are rare benign neoplasms accounting for 0.4% to 0.6% of all brain tumors and 2% to 4% of tumors in children [1]. Choroid plexus papilloma showing 1 or a few histologic signs of malignancy (atypical CPP) and choroid plexus carcinomas (CPC) are even rarer [1], [2]. The annual average incidence of choroid plexus tumors (CPT) is approximately 0.3 per 1 000 000 population [3]. In larger epidemiologic series, the ratio of all primary central nervous system (CNS) tumors to secondary (metastatic) CNS tumors ranges from 1.0 to 1.4 with carcinomas representing most of the metastasis [4], [5]. Thus, metastatic carcinomas in CNS outnumber CPTs by a ratio of approximately 166:1 to 350:1, and an even higher ratio has to be expected in adult cases. Because CPTs can arise at any age, their distinction from metastatic carcinomas is of great importance, particularly in adult cases.

Beside a typical papillary growth pattern closely resembling normal choroid plexus, CPTs may rarely show unusual histologic features, for example, tubular glandular architecture [6] or mucinous degeneration [7]. Thus, the distinction of CPTs from metastatic carcinomas by histology may be difficult. Choroid plexus tumors usually express cytokeratin and vimentin, whereas S-100 protein and glial fibrillary acid protein (GFAP) have been found in 54% to 90% and 20% to 68% of CPTs, respectively [2], [8]. Consequently, CPTs lack S-100 protein and GFAP in up to 46% and 80% of cases, respectively. Furthermore, metastatic carcinomas may also express S-100 [9], [10], [11] and have exceptionally been reported to show immunostaining for GFAP [12], [13].

The well-known focal glial differentiation of neoplastic choroid plexus epithelium is consistent with its derivation from a specialization of segments of primitive neuroepithelial cells at sites of the neural tube [10], [11]. Glial cells, predominantly astrocytes, contribute to the regulation of extracellular glutamate concentrations via reuptake of glutamate through glutamate transporters [13], [14]. We thus investigated whether the expression of the glial excitatory amino acid transporter–1 (EAAT1, corresponding to rodent GLAST/GLAST-1) may help to distinguish CPTs from metastatic carcinomas.