Ependymomas of the Central Nervous System and Adult Extra-axial Ependymomas are Morphologically and Immunohistochemically Distinct—A Comparative Study With Assessment of Ovarian Carcinomas for Expression of Glial Fibrillary Acidic Protein

Abstract

Extra-axial ependymomas are very rare but have been reported in the ovary, broad ligament, sacrococcygeal region, lung, and mediastinum. The histogenesis is obscure, and a thorough immunohistochemical analysis is lacking. We reviewed the morphologic and immunohistochemical features of 5 extra-axial ependymomas occurring in adults, 1 arising in an infantile sacrococcygeal teratoma, and a control group of 10 central nervous system (CNS) ependymomas in adults. All cases were evaluated for expression of epithelial membrane antigen, estrogen receptor (ER), progesterone receptor (PR), WT1, CD99, CK18, AE1:3, CAM 5.2, 34betaE12, CK7, CK20, synaptophysin, chromogranin, and glial fibrillary acidic protein (GFAP) using formalin-fixed, paraffin-embedded tissue. One hundred twelve ovarian carcinomas in 3 tissue microarrays were also studied with GFAP. The adult extra-axial cases demonstrated more architectural variability than the CNS cases. We observed that both the CNS and adult extra-axial ependymomas expressed GFAP diffusely, whereas only 9 stage III, high-grade ovarian serous papillary carcinomas stained with GFAP (2 strongly and diffusely and 7 exhibiting focally weak expression). There were significant immunophenotypic differences between adult extra-axial and CNS ependymomas, with extra-axial cases preferentially expressing 34betaE12 (60% vs. 0%), CK18 (100% vs. 20%), CAM 5.2 (60% vs. 10%), CK7 (80% vs. 10%), ER (100% vs. 10%), and PR (80% vs. 20%). Two spinal cord ependymomas expressed CK18, 1 expressed CK7, and 1 expressed CAM 5.2. CNS ependymomas more frequently expressed CD99 (100% vs. 20%). The following stains were not differentially expressed: epithelial membrane antigen (expressed in 2 of 15 cases, including both extra-axial and CNS ependymomas), synaptophysin (1/15), chromogranin (0/15), WT1 (8/15), AE1:3 (10/15), and CK20 (0/15). The ependymal elements of the sacrococcygeal tumor failed to express 34betaE12, CK18, CAM 5.2, and CK7, like most CNS ependymomas. The morphologic and immunophenotypic differences between extra-axial and CNS ependymomas suggest that they derive from distinct precursors and/or differentiate along distinct pathways. The differential diagnosis of extra-axial ependymomas is extensive, and GFAP expression in primary ovarian serous carcinomas, although rare, could theoretically contribute to diagnostic difficulties. ER and PR expression in extra-axial ependymomas may provide targets for hormonal therapy.

A primary malignant ependymoma of the abdominal cavity: a case report and review of the literature

“…Histomorphology of the case presented here was dominated by a "glial" picture. Tumor cell morphology and nuclear chromatin speckling were suggestive of an ependymoma respecting the fact that extraneural ependymomas can demonstrate a wider architectural variability compared to ependymomas of the CNS [14]. Perivascular pseudorosettes were reported in all published cases, whereas true ependymal rosettes were Fig.…”

Primary Ependymoma in the Posterior Mediastinum

“…[6][7][8][9][10][11] Histological and immunohistochemical analysis has indicated differences between CNS and extra-axial ependymomas. 5) Extra-axial ependymomas demonstrate more architectural varieties than their CNS counterparts. The most striking difference is that extra-axial ependymomas preferentially express CK7, CAM5.2, ER, and PR, but do not express CD99, to which CNS ependymomas are strongly immunopositive.…”

“…With the exception of CAM5.2, these features coincide with those mentioned in a previous report. 5) Immunoreactivity for CK7 and non-reactivity for CK20 generally indicate the site of origin of a given carcinoma, such as the lung, breast, ovary, endometrium, thyroid, or salivary gland. 12) Immunoreactivity for both ER and PR is associated with target organs of female hormones.…”

“…1) They rarely arise in the extra-axial region, outside the CNS. A few cases have been reported in the ovary, broad ligament, sacrococcygeal region, lungs, and mediastinum [2][3][4][5][6][7][8][9][10][11] ; however, the exact origin of such extra-axial ependymomas has not been clarified.…”

Cauda equina paraganglioma with ependymoma-like histology: a case presentation

“…However, ependymomas exhibit their glial heritage in the form of GFAP immunoreactivity mainly in pseudorosettes (16). GFAP is diffusely expressed in 90-100% of axial (5,15) and 83% of extraaxial ependymomas (5). Alternatively ependymoma cells may sometimes be nonreactive for GFAP both in classic (9) or in anaplastic ependymoma (12).…”