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Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 509-512
Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: A rare co-existence with therapeutic dilemma

1 Department of Pathology, M.S. Ramaiah Medical College, Bangalore, India
2 Department of Obstetrics and Gynecology, M.S. Ramaiah Medical College, Bangalore, India
3 Department of Pathology, Kidwai Memorial Institute of Oncology, Bangalore, India

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Date of Web Publication4-Mar-2013


A 21 year old female presented with amenorrhea, hirsutism and change in voice along with an elevated serum β-HCG (human chorionic gonadotrophin) level and normal CA-125 level. Laparotomy revealed an enlarged right ovary measuring 6 × 5 × 1 cms with presence of an ovarian hemangioma along with stromal luteinization and HCG producing mononucleate as well as multinucleate cells of uncertain histogenesis on histopathological examination. Immunohistochemistry for inhibin and calretinin were positive in the luteinized component whereas β-HCG and Ki-67 were positive in the multinucleate cell component. The diagnostic rarity and therapeutic dilemma of such a rare mixed tumor within a single ovary has proven to be an exceptional case and an excellent investigative opportunity.

Keywords: Choriocarcinoma, HCG, Hemangioma, Leydig, Luteinization, Ovary, Stromal, Teratoma

How to cite this article:
Anand MS, Shetty S, Mysorekar VV, Kumar RV. Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: A rare co-existence with therapeutic dilemma. Indian J Pathol Microbiol 2012;55:509-12

How to cite this URL:
Anand MS, Shetty S, Mysorekar VV, Kumar RV. Ovarian hemangioma with stromal luteinization and HCG-producing mononucleate and multinucleate cells of uncertain histogenesis: A rare co-existence with therapeutic dilemma. Indian J Pathol Microbiol [serial online] 2012 [cited 2022 May 29];55:509-12. Available from: https://www.ijpmonline.org/text.asp?2012/55/4/509/107793

   Introduction Top

Vascular tumors of the female genital tract, especially those of the ovary, are very rare. The rich vascular supply however, contradicts the rare occurrence of a hemangioma within the ovary. A comprehensive search yields about 50 cases of ovarian hemangioma in the literature, of which seven cases show associated stromal luteinization. Hence, a co-existence of a hemangioma having stromal luteinization and HCG (human chorionic gonadotrophin) - producing cells found within a single ovary is a very rare occurrence and to our knowledge, has never been reported earlier. Ovarian hemangiomas are "nonfunctional'' neoplasms. However, it is well known that luteinization of ovarian stromal cells commonly occurs as a reactive phenomenon, and may be associated with androgenic, estrogenic or progestagenic effects. The histogenesis of hemangioma of the ovary is however debatable. In addition to the diagnostic difficulty, the therapeutic management of such an entity poses a challenge to the clinician which is compounded by the lack of evidence of supporting literature.

   Case Report Top

A 21 year old female, gravida 1, para 1, presented with amenorrhea since 9 months, along with hirsutism, acne and deepening voice since 4 months. Menarche was attained at 16 years. She delivered a full term infant by cesarean section 2 years ago. External genitalia appeared normal. Serum β-HCG levels done five months ago were markedly elevated to 1063.92 mIU/ml along with an elevated serum LDH of 182.7IU/ml and normal serum CA-125 level of 25 IU/ml. Serum testosterone was not assessed pre-operatively. Ultrasound examination and CT (computed tomography) scan of abdomen showed a right adnexal mass with focal areas of necrosis. The gross specimen consisted of an enlarged right ovary measuring 6 × 5 × 1 cms with a smooth external surface and cut surface revealing irregular grey-brown to grey-tan solid areas and a few hemorrhagic spongy foci [Figure 1]a and b. The sections from various areas of the right ovary showed a tumor which was replacing the ovarian stroma and was composed of two distinct components. The predominant component showed sheets of polyhedral cells having abundant granular eosinophilic cytoplasm and minimally pleomorphic nuclei found in close relation to numerous blood vessels of variable sizes [Figure 1]c and d. The endothelium lining these vessels was flattened without any atypical features. The less prominent component was represented by clusters of mononucleate and multinucleate cells found within a background of loose vascular spaces filled with RBCs (red blood corpuscles) [Figure 2]a and b, and these tumor cells were beta HCG and Ki-67 immunostain positive [Figure 3]b and c respectively. The luteinized cells are strongly reactive for inhibin and calretinin [Figure 3]a immunostains and the syncytiotrophoblast cells are strongly reactive for β-HCG immunostain. Immunohistochemical staining for estrogen and progesterone receptors was negative in the endothelial cells of the hemangioma. The left ovary and uterus were grossly and microscopically unremarkable. The beta HCG levels gradually returned to the baseline, postoperatively. A clinical assessment of the patient revealed gradual disappearance of hirsutism and acne.
Figure 1: (a) Outer surface of right ovary cut into two halves along with attached  Fallopian tube More Details. (b) Cut surface of both halves of right ovary with grey brown to grey tan spongy areas. (c) Ovarian hemangioma showing numerous thin walled blood vessels with solid luteinized areas surrounding the blood vessels (upper part) (hematoxylin and eosin, × 40). (d) Area with marked proliferation of luteinized cells, (hematoxylin and eosin, × 400)

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Figure 2: (a) Area rich in larger discrete cells which were HCG positive (as shown in Figure 3c), (hematoxylin and eosin, × 100). (b) Multinucleate syncytiotrophoblast-like cells seen in the same area as in Figure 2a along with a cluster of luteinized cells placed in close relation to thin walled blood vessels containing numerous RBCs in the lumen, (hematoxylin and eosin, × 400)

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Figure 3: (a) Strong membrane and cytoplasmic staining (Calretinin immunostain, ×400), (b) Focal nuclear staining (Ki-67 immunostain, ×100), (c) Strong membrane and cytoplasmic staining of the syncytiotrophoblast-like cells (beta HCG immunostain, × 400)

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   Discussion Top

Ovarian hemangiomas are a topic of keen interest in recent times due to various reasons. Chiefly debated is the pathogenesis of ovarian hemangiomas; especially when associated with stromal luteinization. A true ovarian hemangioma is believed to be a mass of vascular channels of variable sizes which is reasonably circumscribed and distinct from the remaining ovary or involving the ovary almost entirely. [1] In our case, the spongy hemorrhagic gross tumor was seen replacing the entire ovary grossly. On microscopy, a very small rim of intact ovarian parenchyma with a hemangioma almost completely replacing it proved that there is a true hemangioma.

Ovarian hemangiomas can occur as a benign pure parenchymal tumor or as a part of a mature teratoma. Prus et al.[2] proved that vascular tumors can arise from ovarian somatic cells rather than germ cells, using simple sequence repeat (SSR) polymorphic markers. Ovarian teratomas with prominent vascular component are distinguished from pure hemangioma by the presence of skin adnexa or other ectodermal, endodermal or mesodermal tissue components. [3] Our case lacked any such component and hence could not be classified as a teratoma.

The most controversial aspect of ovarian hemangioma is that of the association of stromal luteinization and hormonal disorders. Estrogens have known growth stimulatory effects on the vasculature and most hemangiomas demonstrate estrogen receptors. In view of this, one hypothesis is that hyperestrenism from stromal luteinization causes development of ovarian hemangiomas. In such instances, the stromal luteinization is diffuse with bilateral involvement of ovaries. The other hypothesis states that the primary event is the presence of an ovarian hemangioma which behaves like an enlarged follicle causing pressure on the adjacent tissue leading to the development of theca-like stromal cells. [4] In such scenarios, the stromal luteinization is limited to unilateral ovary and is markedly prominent in the stroma close to the tumor. [5] In our patient, the stromal luteinization was unilateral and the endothelial cells of the hemangioma showed negative immunohistochemical staining for estrogen and progesterone receptors; thus supporting the second hypothesis of stromal luteinization being a reactive phenomenon due to ovarian hemangioma.

Stromal luteinization is most frequently seen in pregnancy, but can also be seen in epithelial, germ cell and metastatic neoplasms. [6] The presence of these lesions in relation to hemangiomas has been observed in post-menopausal women in six out of seven reported cases. [7] However, in the index case, the premenopausal status of the patient as well as her history of intake of oral contraceptive pills has to be evaluated, as estrogen levels were not recorded pre-operatively.

A possibility of a Leydig cell tumor was considered in the differential diagnosis. However, the lack of an observable mass on gross examination and the absence of Reinke crystals on microscopy point the diagnosis away from a Leydig cell tumor.

In the same context, the additional finding of strongly β-HCG positive and focally Ki-67 positive mononucleate and multinucleate cell clusters closely admixed with the hemangioma, prompted us to a diagnosis of mixed germ cell and stromal cell ovarian neoplasm, these cells initially being interpreted as syncytiotrophoblasts. The occurrence of a Leydig cell tumor, mature teratoma and non-gestational choriocarcinoma in a single ovary is one such similar and isolated case report by Jain et al.[8] The strikingly similar clinical presentation including history of amenorrhea, virilization and deepening voice in a 33 year old woman with a unilateral ovarian tumor having immunocytochemically positive mixed stromal and germ cell neoplasms suggest a convincingly similar diagnostic possibility in our case as well. However, considering the yolk sac origin of primordial germ cells and the pluripotent placental mesenchymal cell origin of Leydig and theca cells imply the rarity of a coincidental occurrence of such mixed neoplasms. [9] The normal postoperative levels of beta HCG along with the corresponding disappearance of hirsutism and acne in the patient confirm that the ovarian tumor was the source of beta HCG production and that there were no remnants of syncytiotrophoblasts in any other location in the body. Hence, the patient was not put on chemotherapy. However, a prolonged follow-up with regular serum beta HCG estimation is being maintained. The diagnostic and prognostic dilemma that this case presents also purports a complicated pathogenesis, which has to be extensively investigated.

   Acknowledgment Top

We sincerely thank Dr. Robert Young, Pathologist, Director of Gynecological and Urological Pathology, Massachusetts General Hospital for his effort and time in helping us make a reasonable conclusion in the case.

   References Top

1.Uppal S, Heller DS, Majmudar B. Ovarian hemangioma-report of three cases and review of the literature. Arch Gynecol Obstet 2004;270:1-5.  Back to cited text no. 1
2.Prus D, Rosenberg AE, Blumenfeld A Udassin R, Ne'eman Z, Young RH, et al. Infantile hemangioendothelioma of the ovary: A monodermal teratoma or a neoplasm of ovarian somatic cells? Am J Surg Pathol 1997;21:1231-5.  Back to cited text no. 2
3.Feuerstein IM, Aronson BL, McCarthy EF. Bilateral ovarian cystic teratomata mimicking bilateral pure ovarian hemangiomata: Case report. Int J Gynecol Pathol 1984;3:393-7.  Back to cited text no. 3
4.Woodruff JD, Williams TJ, Goldberg B. Hormone activity of the common ovarian neoplasm, Am J Obstet Gynecol 1963;87:679-98.  Back to cited text no. 4
5.Gucer F, Ozyýlmaz F, Balkanlý-Kaplan P, Mulayim N, Aydýn O. Ovarian hemangioma presenting with hyperandrogenism and endometrial cancer: A case report. Gynecol Oncol 2004;94:821-4.  Back to cited text no. 5
6.Scully RE. Ovarian tumours with functioning stroma. In: Fox H, editor. Haines and Taylor: Obstetrical and Gynecological Pathology. Edinburgh: Churchill Livingstone; 1987. p. 724-6.  Back to cited text no. 6
7.Itoh H, Wada T, Michikata K, Sato Y, Seguchi T, Akiyama Y, et al. Ovarian teratoma showing a predominant hemangiomatous element with stromal luteinization: Report of a case and review of the literature. Pathol Int 2004;54:279-83.  Back to cited text no. 7
8.Jain T, VanKessel K, Reed S, Paley P. Leydig cell tumor, mature teratoma, and nongestational choriocarcinoma in a single ovary. Obstet Gynecol 2000;95(6 Pt 2):1031.  Back to cited text no. 8
9.Robboy SJ, Bernhardt PF, Parmley T. Embryology of the female genital tract and disorders of abnormal sexual development. In Kurman RJ, editor. Blaustein's pathology of the female genital tract. 4 th ed. New York: Springer Verlag; 1994. p. 3-29.  Back to cited text no. 9

Correspondence Address:
Vijaya V Mysorekar
Department of Pathology, M.S.Ramaiah Medical College, Bangalore - 560 054
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.107793

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  [Figure 1], [Figure 2], [Figure 3]

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