Moderators: Robert H.Young and Jaime Prat
Primitive Neuroectodermal Tumor of the Ovary.
Professor and Chairman of Pathology
Hospital de la Santa Creu i Sant Pau
Autonomous University of Barcelona, Spain
A 22 year-old woman was admitted to the hospital
emergency room because of abdominal pain and swelling. Two months prior to admission she underwent a
D&C for retained POC of about 9 weeks of gestational age. At that time pelvic examination was
unremarkable. Subsequently, she developed massive abdominal enlargement and pain over a two months
period. Abdominal examination revealed a large mobile mass in the left lower quadrant that extended up
to 2 cm below the umbilicus. A CT scan showed a cystic and solid heterogeneous tumor (18 x 17 x 14 cm).
Serum levels, CA19.9: 100 KU/l (normal range <37); CA125:192 KU/l (normal range <35); b-hCG: 2.2
UI/l; CEA and a-FP were normal. At laparotomy there was a large cystic and solid left ovarian tumor with
ruptured capsule (3.5 cm). A left salpingooophorectomy, biopsy of the contralateral ovary and
appendectomy were performed.
Primitive neuroectodermal tumor of the ovary.
- Unilateral ovarian tumor, 21 cm in greatest diameter (1,280 g).
- Cystic and solid.
- Solid component with hemorrhage and necrosis (malignant appearance).
- Capsular rupture, 3.5 cm.
- Unremarkable Fallopian tube.
NB. The microscopic features were reminiscent of those of PNET found in the CNS of children.
- Hypercellularity (high grade malignant tumor).
- Extensive necrosis.
- Patternless sheets or lobules separated by fibrous septa.
- Closely packed small cells with hyperchromatic round to oval nuclei.
- Occasional rhabdoid cells.
- Vesicular nuclei with prominent nucleoli.
- Scanty/abundant, clear/eosinophilic cytoplasms.
- High mitotic rate (> 10/10 HPF).
- Homer Wright rosettes and ribbons (resembling medulloblastoma or neuroblastoma).
- Follicle-like spaces (resembling small cell carcinoma or juvenile granulosa cell tumor).
- Microscopic foci of endodermal-like ciliated mucosecretory glands (teratomatous nature).
- Ascitic fluid negative for malignant cells (Stage Ic).
The following immunostains were positive: neuron-specific enolase (NSE), synaptophysin, neurofilament
protein, and CD99. The following stains were negative: Cytokeratin CAM 5.2, EMA, S100 protein, and
chromogranin. Alpha-inhibin was only positive in the luteinized stromal cells.
Postoperatively the patient was given four cycles of chemotherapy (platinum and etoposide). Five
months later a CT scan revealed recurrent tumor (3.0 cm) in the anterior abdominal wall, above the
bladder, and retroperitoneal lymph node metastases (3.0 cm).
Primitive neuroectodermal tumors (PNET) of the ovary are rare. Following the original 1982
description by Aguirre and Scully, less than 50 cases have been reported. These tumors are considered
monodermal teratomas composed exclusively or almost exclusively of
neuroectodermal tissue resembling CNS neoplasms of children.
The average age of the patients was 23 years and the presenting symptoms were similar to those of
other cancers of the ovary. Like almost all immature teratomas of the ovary all tumors were unilateral.
On gross examination they ranged from 4 to 20 (average 14) cm in diameter and appeared cystic and solid.
On microscopic examination all tumors contained masses of poorly differentiated small cells exhibiting
slight to marked nuclear pleomorphism. Necrosis was common and peripheral pseudopalisading of the tumor
cells similar to that of glioblastoma multiforme was seen. Most tumors contained areas of
medulloepithelioma, neuroblastoma, ependymoblastoma, and medulloblastoma. The tumors may be associated
with mature cystic teratomas (dermoid cysts) or teratomatous elements may be encountered in small amounts
such as in the case under discussion.
Although clearly of germ cell origin, PNETs should be classified according to Aguirre and Scully
separately from immature teratomas with predominant immature neuroectodermal components (Grade III
teratomas) and for two main reasons:
a) Ovarian PNETs represent a distinctive form of monodermal teratoma in
which the neoplastic tissues do not resemble stages of embryonic development of the CNS.
b) Whereas the immature teratoma with predominant neuroectodermal differentiation is easily
recognized because of the presence of many other teratomatous elements, the pure or almost pure
neuroectodermal tumor is frequently confused with other types of ovarian tumors such as granulosa cell
tumor, small cell carcinoma of the hypercalcemic type, and endometrioid carcinoma.
When one considers the frequency with which tissue of neural type is encountered within teratomas it
is not surprising that occasionally pure neural tumors similar to those found in the central nervous
system occur in the ovary. Several cases of pure ependymoma arising in the ovary have also been
The presence of the Homer Wright rosettes are helpful in the diagnosis of PNET. In the absence of
rosettes and ribbons, PNETs may be erroneously taken for small cell malignant tumors of other type,
including malignant lymphoma and leukemia, rhabdomyosarcoma, small cell carcinoma associated with
hypercalcemia, desmoplastic small round cell tumor, granulosa cell tumor, endometrial stromal sarcoma,
and metastatic melanoma and small cell carcinoma of lung. In the case under discussion, the presence of
follicle-like spaces initially suggested the diagnosis of small cell carcinoma or juvenile granulosa cell
tumor. Immunohistochemistry may be helpful in the differential diagnosis: PNETs are positive for GFAP,
synaptophysin, neurofilament protein, vimentin, NSE, and CD99. Cytokeratin and desmin are negative.
Alpha-inhibin is helpful in the differential diagnosis with granulosa cell and sex cord-stromal tumors.
In the current case only the luteinized stromal cells were decorated by the immunoreaction but the tumor
cells appeared negative.
Neuroblastoma of adrenal or extra-adrenal origin metastasizes to the ovary in about 25% of the autopsy
cases. The tumors are usually bilateral and are not associated with teratomatous elements. Some of the
reported neuroblastomas of the ovary are grade 3 immature teratomas.
The tumor under discussion was interpreted as a PNET of the CNS associated with teratoma; in other
words, a monodermal teratoma of germ cell origin. Recently, an ovarian PNET of the peripheral type
(PNET/Ewing's sarcoma family) has been reported. In contrast to the CNS type, pPNET exhibits the
characteristic translocation t(11;22)(q24;q12) and expresses EWS/FLI-1 chimeric mRNA which could not be
detected in the current case. However, CD99, stated to be negative in PNET of the CNS, resulted positive
in the seminar case.
The pathologist dealing with difficult problems in the differential diagnosis of malignant ovarian
tumors, particularly in young patients, should be aware of the existence of malignant neuroectodermal
tumors of various types. An identical tumor has been described in the testis. Although these tumors are
rare and the largest reported series was mainly composed of consultation cases (and different treatments
were administered to these patients) it appears that these neoplasms do not respond to the chemotherapy
used for non seminomatous germ cell tumors (vinblastine, bleomycin and platinum). In the current case,
para-aortic and pelvic recurrence occurred only 5 months after administration of chemotherapy.
- Aguirre P, Scully R.E. Malignant neuroectodermal tumor of the ovary, a distinctive form of monodermal teratoma. Report of five cases. Am J Surg Pathol 1982; 6:283-292.
- Kanbour-Shakir A, Sawady J, Kanbour AI, et al. Primitive neuroectodermal tumor arising in an ovarian mature cystic teratoma: immunohistochemical and electron microscopic studies. Int J Gynecol Pathol 1993; 12:270-275.
- Kawauchi S, Fukuda T, Miyamoto S, et al. Peripheral primitive neuroectodermal tumor of the ovary confirmed by CD99 immunostaining, karyotypic analysis, and RT-PCR for EWS/FLI-1 chimeric mRNA. Am J Surg Pathol 1998; 22:1417-1422.
- Kleinman GM, Young RH, Scully RE. Primary neuroectodermal tumors of the ovary. A report of 25 cases. Am J Surg Pathol 1993; 17:764-778.
- Scully RE, Young RH and Clement PB. Tumors of the ovary, maldeveloped gonads, fallopian tube, and broad ligament. In Atlas of Tumor Pathology, third series. Fascicle 23. Washington, D.C. Armed Forces Institute of Pathology, 1998; pp300-303.