Extra-axial Ependymoma

Dr. Robert Soslow
New York, NY

Introduction Extra-axial ependymomas are extremely uncommon tumors. They are a particularly interesting topic to discuss not only because of their rarity, but also because of their histologic similarity to much more commonly occurring gynecologic neoplasms. Extra-axial ependymomas have been reported in the sacrococcygeal region, the mediastinum, omentum, lung, broad ligament and ovary. Probably the most comprehensive descriptions have been provided in papers concerning the broad ligament and ovarian tumors [1, 2, 3]. First described by Bell, Woodruff and Scully in 1984 [1], broad ligament ependymoma was characterized as a tumor bearing substantial histologic similarity to its better-known cousin occurring in the central nervous system. The authors commented on its morphologic resemblance to papillary serous carcinomas (and the consequent pitfalls in differential diagnosis) and described the slowly progressive clinical course. Kleinman, Young and Scully, who also reported 3 cases of ovarian ependymoma in 1984 [2], then provided a framework for understanding ependymomas in the context of other primary ovarian neuroectodermal tumors in their report of 25 such cases [3]. According to their classification, primary neuroectodermal ovarian tumors could be divided into differentiated, primitive and anaplastic tumors. Examples of differentiated tumors included ependymoma and retinal anlage tumor. Ependymoblastoma and neuroblastoma belonged to the primitive group while glioblastoma multiforme was typical of the anaplastic group. This publication also highlighted the correlation between clinical outcome and morphology. The authors reiterated the frequently slowly progressive but infrequently lethal nature of ependymoma and contrasted that with the rapidly progressive and frequently fatal course of the primitive and anaplastic tumors. Clinical characteristics Extra-axial ependymomas are largely tumors of the second, third and fourth decade. About half of patients have had Stage I (organ-confined) disease at presentation. Approximately one-third have had an uncomplicated clinical course, whereas the rest have suffered recurrences. These have occurred in pelvic soft tissues, regional lymph nodes, retroperitoneum, omentum, liver and lymph nodes of the head and neck. We are aware of only one reported death, which is remarkable given the high rate of recurrence in this disease and that many of these patients have been followed for decades. Surgery, chemotherapy and radiotherapy have all been tried. The use of hormonal agents is largely unexplored, but this may prove beneficial. Morphology Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Ovarian ependymomas are unilateral tumors, measuring between 1 and 20 cm, with a solid and cystic gross appearance. Although it has been proposed that these tumors represent a type of monodermal teratoma, it is very unusual to find them associated with a teratoma. They are said to be histologically and immunophenotypically similar, if not indistinguishable, from central nervous system teratomas, but this appears a generalization. Instead, the extra-axial ependymomas that we have studied show a much broader range of architectural patterns and immunophenotypes than do individual typical central nervous system tumors. Most extra-axial cases demonstrate cribriform, microcystic, macrocystic, trabecular, pseudopapillary, papillary and solid components within each tumor. Tumors may also focally take on the appearance of a myxopapillary ependymoma, with abundant basophilic, mucinous material surrounding blood vessels and forming microcysts. Essentially all cases contain perivascular pseudorosettes, but not every tumor contains ependymal rosettes. Tumor cells are cuboidal to columnar, with pink or clear cytoplasm. Prominent cytoplasmic vacuolization can be encountered and signet ring forms are occasionally seen. The cells constituting perivascular pseudorosettes are columnar with characteristically thin, tapered processes that anchor tumor cells to the blood vessel. Cilia may be prominent in cells lining cystic spaces. Nuclei are bland and round-to-oval in shape. They often have either finely dispersed or stippled chromatin, frequently leading to the appearance of a neuroendocrine tumor. Nuclei may contain one or more small nucleoli, but macronucleoli are not common. Nuclear grooves can be prominent. The mitotic rate is low, perhaps less than 5 mitotic figures per 10 high power fields in most cases. Immunohistochemistry It should not be difficult to find GFAP immunoreactivity in an extra-axial ependymoma, but it is not uncommon to also find expression of cytokeratins and EMA. The distribution of immunoreactivity for these different markers is geographic and appears to be related to or an expression of tumor architecture. For example, GFAP expression is most commonly encountered in perivascular pseudorosettes while cytokeratin expression is notable in cells lining cysts and in papillae. We have also described the very frequent expression of ER and PR and the occasional expression of WT1. In addition to proposing the possible therapeutic relevance of ER/PR expression, we showed that this finding sets apart the extra-axial tumors from those of the central nervous system, which only rarely show ER/PR expression. Diagnosis: Extra-axial ependymoma Differential diagnosis The differential diagnosis is extensive because of the great spectrum of architectural patterns. The process of narrowing the differential diagnosis should start with a good clinical evaluation so that metastasis to the ovary can be excluded. If the tumor has a predominant tubular, trabecular or microacinar appearance, the differential would include endometrioid borderline tumor or carcinoma, Brenner borderline tumor or carcinoma, adult granulosa cell tumor, Sertoli-Leydig cell tumor, a Wolffian tumor such as a female adnexal tumor of probably Wolffian origin (FATWO), or carcinoid. A papillary tumor would make one think about papillary serous borderline tumor or carcinoma, endometrioid borderline tumor or carcinoma, Brenner borderline tumor or carcinoma, transitional carcinoma, retiform Sertoli-Leydig cell tumor and mesothelioma. If the tumor is noted to be neuroectodermal, other primary ovarian tumors that can show neuroectodermal differentiation should be considered: mature or immature teratoma; primitive neuroectodermal tumor, Sertoli-Leydig cell tumor and carcinosarcoma (MMMT). Attention to the nuclear features and mitotic rate should allow exclusion of carcinoma, carcinosarcoma and primitive neuroectodermal tumor (including ependymoblastoma) in particular. It may be difficult to exclude the other possibilities, especially if clinical information is not forthcoming and the pathologist is not familiar with the less common entities in the differential diagnosis. Immunohistochemistry can be useful in these cases. Aside from expression in other tumors with neuroectodermal elements, GFAP should not be found in significant numbers of tumors on the list (although anecdotal experience suggests that some serous carcinomas might express GFAP). Of course, cytokeratin, EMA, ER/PR and even WT1 expression might confuse things a bit, but GFAP is something you can rely upon as long as the other clinicopathologic features are taken into consideration. Many of the other tumors to consider have characteristic immunophenotypes, something to keep in mind as you use immunohistochemistry in concert with routine morphologic examination and clinical correlation. References Bell DA, Woodruff JM, Scully RE. Ependymoma of the broad ligament. A report of two cases. Am J Surg Pathol. 1984 Mar;8(3):203-9. Kleinman GM, Young RH, Scully RE. Ependymoma of the ovary: report of three cases. Hum Pathol. 1984 Jul;15(7):632-8. Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol. 1993 Aug;17(8):764-78.