Ovarian Ependymoma. A Case Report

PATHOLOGY RESEARCH AND PRACTlCE

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Ovarian Ependymoma. A Case Report Victoria Garcia-Barriola, Mirian Naranjo de G6mez, Jose A. Suarez, Carmen Lara, Jesus E. Gonza lez and Jorge Garda-Tamayo Instituto Anatomopatol6gico "Dr. Jose A O'Daly", Universidad Central de Venezuela, Caracas, Venezuela

Summary

be considered monodermal teratomas f1 , 5, 9, 12, 13, 14].

We present the case of a 30-year-old woman who was referred to our institution with an erroneous diagnosis of poorly differentiated carcinoma of the ovary. The patient presented pelvic pain for one year prior to surgery. A second laparotomy revealed a bilateral pure ovarian ependymoma that infiltrated the uterus and presented implants on the omentum. Differential diagnosis included mainly endometrioid and small cell carcinoma of the ovary. Presence of typical ependymal rosettes and positivity to GFAP confirmed the diagnosis of ependymoma. Other teratomatous elements were not observed. Ovarian ependymomas are rare tumors: only eight cases, to our knowledge, have been reported in the literature. They have a favorable prognosis; patients with advanced stage disease are reported alive and well after treatment with surgery and chemotherapy.

Key words: Ependymoma - Ovarian - Monoderrnal teratoma

Introduction Tumors of the ovary with an exclusive component of neuroectodermal differentiation are rare. Kleinman et al. [13 J reported twenty-five primary neuroectodermal tumors of the ovary which they classified according to their histologic features as differentiated tumors consisting almost exclusively of ovarian ependymomas, primitive tumors and anaplastic neuroectodermal tumors. These two latter groups were associated with teratomatous elements . Interestingly, ovarian ependymomas did not contain teratomatous elements in their series. Association with dermoid cysts in ovarian ependymomas suggests an origin from germ cells; they should Pathol. Res. Pract. 196: 595- 599 (2000)

Ovarian ependymomas described in the literature have shown different histologic appearances posing difficulty in the differential diagnosis with primary or metastatic ovarian neoplasms. We present a case of a pure bilateral ependymoma referred to our institution with an erroneous diagnosis of poorly differentiated carcinoma of the ovary in a previous biopsy.

Case Presentation A 30-year-old woman, gravidity IV, parity IV, who had presented pelvic pain for the past year, was referred to the University Hospital with the diagnosis of poorly differentiated carcinoma of the right ovary for further treatment. Before referral a laparotomy was performed. The surgeon observed a large pelvic mass difficult to excise, comprising the uterus and adnexa. A eft l ovarian resection was performed, the specimen weighed 1.800 grams and measured 20 cm in greatest diameter. It had a glistening surface, brownish color, and on cut section it showed cystic spaces which contained a mucous Ouid: solid areas between these cystic spaces were cream colored and of elastic consistency. A biopsy of the right ovary was also done: it consisted of two fragments measuring 3 x 2 em and I x 0.8 cm, respectively. A diagnosis of poorly differentiated carcinoma of the ovary was made. Operative findings at a second laparotomy performed after her referral were residual ovarian tumor with metastatic spread to both uterine cornua, sigmoid Address for correspondence: Victoria Garcia-Barriola. Instituto Anatomopatol6gieo ·'Dr. Jose A. O'Daly" Apartado Postal 50647, Saban. Grande, Caracas 1050, Venezuela. Or: POBA International'60, P.O.Box 52-1308, Miami , F133152. Fax: ++58-2-6 05-34 28. Tel. : ++58-2-6053478 0344-0338/2000/196/8·595 $12.0010

596 . V. Garcia-Barriola et aJ.

colon, omentum and abdominal wall, plus 1,000 cc of ascitic fluid. The surgical procedure done was a total abdominal hysterectomy with partial tumorectomy, omentectomy and appendectomy. The patient had an uneventful postoperative period; she received six cycles of combined chemotherapy (Ciclofosfamide, 1,500 mg TV and Platinum, 75 mg IV) and is free of disease four years after surgery.

Materials and Methods Samples of the surgical specimen that consisted of the uterus, partial tumorectomy, omentectomy and appendix were fixed in 10% formalin, dehydrated and included in paraffin. One paraffin block of tissue proceeding from the right adnexa was received for consultation. Sections of 6 microns were obtained and stained with hematoxylin-eosin, periodic acidSchilf (PAS), Gomori's trichrome, Grimelius argentic impregnation and immunohistochemistry for Glial Fibrillary Acidic Protein. prediluted bd-2 and CD99 I: 100 (DAKD®, Santa Barbara. California), using a monoclonal antibody and the methods of avidin-biotin-peroxidase were employed.

Pathological Findings Grossly, the specimen consisted of a mass attached to the uterus that weighed 315 grams and measured Il x 7 x 5 em in greatest dimensions. The tumor was lobulated, yellowish-white in color, with a smooth surface. On cross-section it was of soft consistency and exhibited cysts of variable sizes filled with a whitish mucous substance, necrosis and hemorrhage. The uterus weighed 240 grams, and measured 8 x 5.5 x 4.5 em in greatest dimensions; it was deformed due to the presence of tumor masses located in both cornua infiltrating approximately 50% of the adjacent myometrium. These masses measured 10.5 x 7.5 x 4 em in the right comuS and 4.5 x 4 x3.5 em in the left comus. They were also yellowish-white, soft, and exhibited areas of necrosis and hemorrhage. The uterine cavity and the cervix were grossly unremarkable. The fallopian tubes were not identified. The great omentum measured to x 5 x 1.5 em and exhibited three tumor nodules each measuring

Fig. I. Round or oval cells arranged in a solid pattern and lining gland-like spaces (H&E, 100x). Fig. 2. Detail of a gland-like space lined by small to medium sized round or oval cells with fibrillary processes towards the lumen. Note the absence of basement membrane. The surrounding stroma is fibrillary and has a scarce collagen content (H&E, 400x). Fig. 3. Typical ependymal rosette (GFAP, 400x). Fig. 4. Typical ependymal rosettes (H&E, 400x).

Ovarian Ependymoma . 597

surrounding stroma was fibrillary and had a scarce collagen content. Histologic sections of the nodules in the omentum exhibited small to medium sized cells arranged mostly in a solid pattern, and perivascular rosettes were occasionall y seen. Immunohistochemistry showed positivity for GFAP in the cytoplasm of the cells of the ependymal rosettes, (Fig. 3) and in the cytoplasm and fibrillary processes of the cells in the solid areas of the tumor, bcl-2 and CD99 were negative. The appendix was normal. The paraffin block of the right ovary sent for consultation presented the same histologic features. Other teratomatous elements were not observed.

1.5 cm in diameter. Microscopically, small to medium sized round or oval cells with nuclei containing disperse chromatin and inconspicuous nucleoli lined multiple irregular gland-like spaces, tubules and thick branched papillae. A solid pattern was also observed in some areas of the tumor. The cells lining the gland-like spaces and tubules exhibited fibrillary processes towards the lumen and lacked a basement membrane, they were in continuity with the surrounding tumor cells (Figs. I and 2). Typical ependymal rosettes composed of cells with cytoplasmic fibrillary processes towards the center and perivascular rosettes were also observed (Figs. 3 and 4). The cells did not contain intracytoplasmic glycogen, the Table I. Pure ependymomas of the ovary Reference

Age

Kleinman etal.fl3J

25

Macroscopic

Stage Treatment

Follow up

Recurrence

Left ovary: two smoolh-walled

IA

TAHBSO

5 yrNED

No

16

Left ovary: 16 cm diameter mass

IA

TAHBSO

?

?

36

Righi ovary: 16 cm in diameler multiloeulated cystic & solid mass, 838 gr; adhesion with tumor on colon

IIA

TAHBSO

3 yrNED

No

cysts, one with a lan mural nodule

35

Left ovary: lO x IO x 8.5 cm 1Il TAHLSO,CT 5 yrAWD Yes cystic tumor with papillae smooth muscle focally penelraled by tumor, implants on omentum & diaphragm ------------------ - ---- - -------- ------ ------ -- ----------._------------. - ----- - - --- ----._----.----.30 Right ovary: 8 em diameter friable III Yes TAHBSO,OT, 5 yr DOD gray tumor involving CT.RT uterus. urinary bladder, pelvic walls, cul-de-sac, left ovary: implants on omentum and diaphragm

- - - --- - --- - ---- - ---- -- -- -- ------ ---- ----- ---- ---------.------- - - _.----.-------------. __ .--- -- ------

Guerrieri and larlsfelt

68

[9J

Left ovary: large 18 x II x 8cm multicystic mass. Normal righl ovary and uterus, ascitis

IA

TAHBSO OT

I yr NED

No

- --- -- ---- -------------- ----- -- -- ------- ------ - -- ------ ------ - -- - - ----- ---- - ------ -----------------

Carr el al. [5J

25

Righi ovary: 20 x 20 em, Left ovary 8 x 16 em. diffuse involvement of peritoneal surfaces, 20 cm mass in upper right liver lobe and diaphragm

IV

TAH BSO: OT; I yr NED Resection of right liver lobe and diaphragm, aspiration of tumor implants. CT, and RT after residual disease

No

------ -------------- - ----- ------- --------------- ------ -------- --- - -------- --- --- -------- -- - - ------Carlsson el al. 46

[4J

Right, broad ligament, rectouterine pouch, liver, spleen. right iliac fossa, abdominal wall, colon

IV

Tumor resections at different limes upon recurrences, Ct

50 yr AWD*

Yes

-------------- -- --------- -- ------ --- -- ----------------- ------ - ---- ----- --- --- -------- --------- ----Presenl case 30 Right ovary: 20 cm in First operation 4 yr NED III No diameter, left ovary II x 7 x em. 5 bOlh masses infiltrated Ihe uterus, implants on the omentum

Rcseclion of the right

ovary; second operation:

TAH, LSO, OT, CT

598 . V. Garcia-Barriola et al.

Discussion Extra-cranial ependymomas have been described in the extraspinal, sacrococcigeal regions , in pre-sacral tissues and in the sacrum as well. They originate from the coccygeal medullary vestige of the embryonic neural tube. Other localizations have included the ovary, paraovarian tissues, broad ligament, omentum, mediastinum and the lung [2, 8]. Glial tissues and ependymal structures have been identified in mature cystic teratomas of the ovary. Recognition of malignant neuroectodermal elements in a mature cystic teratoma have also been interpreted as malignant transformation within the neuroectodermal component [3]. Ependymomas, primiti ve or anaplastic neuroectodermal tumors, ovarian retinal anlage tumors, malignant neuroectodermal tumors in the form of astrocytomas and primitive tumors are di fferent forms of neuroectodermal tumors described in the ovary. Ovarian tumors composed exclusively of neuroectodermal elements are considered monodermal teratomas [1, 5, 7, 9,12,13,15]. Pure ovarian ependymomas are rare tumors, and only eight cases, to our knowledge, have been reported in the literature (Table I). They occur in young, middle-aged and menopausal patients [3, 4, 5, 9, 15]; hormonal responsiveness of this neoplasm has been reported [5]. Our case was that of a 30-year-old patient who presented the tumor in both ovaries; it had infiltrated the uterus and developed implants on the omentum. These tumors are usually unilateral [3, 13], although bilateral cases have been described [5 , 15] with extension to adjacent pelvic tissues, as in our case. Differential diagnosis included tumors of the surface epithelium, which are far more common. The gland-like areas and tubules resembled endometrioid carcinoma of the ovary but were devoid of basement membrane, and the cells lining these structures were in continuity with the cells observed in the solid pattern. Thick branching papillae may suggest papillary serous carcinoma of the ovary; the presence of rosettes and pseudorosettes in our case excludes this diagnosis [14]. Structures similar to rosettes also reminded us of Call Exner bodies of granulosa cell tumors; however, in our case the nuclei lacked the characteristic groove of granulosa cells, and even though juvenile granulosa cell tumors do not always exhibit the nuclear groove, the cells in our case were slightly smaller and more elongated than granulosa cells [7]. Small cell carcinoma of the ovary associated with hypercalcemia was also considered in the differential diagnosis, although our patient did not present hypercalcemia, and the cells in our case were not as small and pleomorphic as the cells in small cell carcinoma [1l}. Gland-like spaces were lined by cells resembling those of the ependyma of the central nervous system, and the rosette-type structures characteristically are analogue to those observed in tumors arising in the ependyma. Positivity for GFAP

confirmed the diagnosis of ovarian ependymoma. These tumors may also stain positively for S-IOO, vimentin, neuron-specific enolase, epithelial membrane antigen cytokeratin, bcl-2 and CD99; the pattern of staining differs in various types of ependymomas in the central nervous system and in pelvic tumors [9, 15, 16]. Due to its localization it should also be differentiated from the pelvic presacral ependymoma, which usually exhibits a myxopapillary pattern [10]. The prognosis of ovarian ependymomas is favorable. Only one case reported in the literature died of disease [13]. Carlsson et al. [4] reported a case of a patient who had a mature cystic teratoma with extensive glial tissue removed at the age of 16. Thirty years later she presented with a right ovarian tumor, probably granulosa cell tumor and received radiotherapy. During the following 20 years she presented four episodes of recurrence; after reviewing the slides of the tumor an ovarian ependymoma was suggested. The recurrences were consistent with metastasis from ovarian ependymoma. She received chemotherapy and was well at the age of 67. Four of the cases reported are free of disease on follow up. Our case received combined chemotherapy and is free of disease four years later. Acknowledgement. To Dr. Robert E. Scully, Harvard University, for his valuable suggestions.

References I. Aguirre P, Scully RE (1982) Malignant neuroectodermal tumor of the ovary, a distinctive form of monodermal teratoma. Am J Surg Pathol 6 (4): 283-292 2. Bell DA, Woodruff 1M, Scully RE (1984) Ependymoma of the broad ligament. Am J Surg Pat hoI 8: 203-209 3. Burke M, Beilby JOW (1984) Unusual malignant neuroectodermal tumors of the ovary-case report and literature review. Histopathology 8: 1059-1067 4. Carlsson B, Havel G, Kindblom LG, Knutson F, Mark J (1989) Ependymoma of the ovary. APMIS 97:

1007-1023 5 . Carr KA, Roberts JA , Frank TS (1992) Progesterone receptors in bilateral ovarian ependymoma presenting in pregnancy. Hum Pathol 23 (8): 962- 965 6. Cruz-Sanchez FF, Rossi ML, Hughes, JT, Cervos-Navarro J (1988) An immunohistochemical study of 66 ependymomas. Histopathology 13: 443-454 7. Dickersin GR, Kline IW, Scully RE (1982) SmaJi Cell Carcinoma of the Ovary with hypercalcemia: a report of II cases. Cancer 49: 188-197 8. Duggan MA, Hugh J, Nation JG, Robertson 01 , Stuart GCE (1989) Ependymoma of the Uterosacral ligament. Cancer 64: 2565-2571 9. Guerrieri C, Jarlsfelt I (1993) Ependymoma of the ovary: A case report with Immunohistochemical, Ultrastructural and DNA Cytometric Findings, as well as Histogenetic Considerations. Am J Surg Pathol J7 (6): 623- 632

Ovarian Ependymoma . 599 10. Helwig EB, Stern JB (1984) Subcutaneous sacrococcigeal myxopapillary ependymoma. Am J Clin Pathol 81: 156-161 11. Kawauchi S, Sufkuda T, Miyamoto S, Yoshioka J, Shirahama S, Saito T, Tsukamoto N (1988) Peripheral Primitive Neuroectodermal Tumor of The Ovary Confirmed by CD99 Immunostaining, Karyotypic Analysis, and RTPCR for EWSIFL I-I Chimeric mRN A. Am J Surg Pathol 22 (11): 1417-1422 12. Kleinman GM, Young RH, Scully RE (1984) Ependymoma of the ovary: report of three cases. Human Pathology 15:632-638 13. Kleinman GM, Young RH, Scully RE (1993) Primary Neuroectodermal Tumors of the Ovary. A Report of 25 Cases. Am J Surg Pathol17 (8): 764-778

14. Scully RE (1998) Tumors of the Ovary and Maldeveloped Gonads. In Atlas of Tumor Pathology. Armed Forces Institute of Pathology. Washington, D.C. 15. Selvaggi SM (1992) Cytologic features of malignant ovarian monodermal teratoma with an ependymal component in peritoneal washings. Int J Gynecol Pathol 11: 299-303 16. Morrinson AL, Gyure KA (1999) Extracranial/extraspinal ependymomas: A clinicopathologic study including bcl-2 and CD99 immunohistochemistry. J Neuropathol Exp Neurol58 (5) (Abstract 124)

Received: April 29, 1999 Accepted in revised version: March 16, 2000