Hemangiopericytoma

A 39-year-old woman with menorrhagia of 7 years' duration was found to have a capillary hemangioma of the endometrium. Initial diagnosis by curettage was considered questionable but was later confirmed at hysterectomy. A thorough search and review of the literature was performed.

(Arch Pathol Lab Med. 2005;129:1326-1329)

Hemangiomas of the uterus and cervix are extremely rare. Although found at all levels of the uterine wall, including serosa, myometrium, and endometrium, most cases diffusely involve the myometrium. These lesions are associated with numerous obstetric and gynecologic complications, ranging from intermenstrual spotting, menometrorrhagia, and infertility to maternal and fetal demise from pronounced bleeding of the gravid uterus.1-3 Rare cases are associated with tuberous sclerosis and hemorrhagic telangiectasia.4,5 Only 6 cases in the literature, 2 of them in English, describe endometrial hemangiomata. This is an additional report of a capillary hemangioma involving the endometrium and causing severe menorrhagia, the third such case in the English literature.

REPORT OF A case

The patient, a 39-year-old Hispanic woman, gravida 3, para 3, presented with menorrhagia that was refractory to conservative management. Menarche had commenced at age 13 and had been regular, typically of 7 days' duration. The last normal menstrual period, 7 years earlier, had lasted 6 days and was associated with abdominal cramps and pain. There was 1 episode of breakthrough bleeding 3 years prior to presentation. All 3 prior pregnancies (the last at age 21) had resulted in normal, spontaneous, vaginal deliveries. The patient began medical treatment for unremitting menorrhagia at the age of 32, 11 years after last birth, when she first visited the emergency department complaining of heavy bleeding and dizziness. Physical examination revealed left adnexal tenderness; orthostatic hypotension; and pale, dry mucous membranes. Gynecologic exam was otherwise unremarkable. She was diagnosed with dysfunctional uterine bleeding and dehydration, treated with intravenous saline, and placed on oral contraceptives. Menorrhagia was initially responsive but later became refractory, with bleeding lasting more than 10 days and almost constant spotting (1 bleeding-free week per month). Repeated dilatation and curettage during these 7 years rendered pathologic diagnoses including "endometrial hyperplasia/' "proliferative endometrium," and "decidualized endometrial stroma with weakly proliferative glands." Pelvic ultrasound done 7 months prior to hysterectomy showed an intraluminal endometrial nodule, believed to represent a polyp or prolapsed submucosal fibroid (Figure 1). Despite diagnostic endometrial curettage 4 months before hysterectomy, the bleeding continued, so a hysterectomy was performed.

MATERIALS AND METHODS

The tissues were fixed in 10% formalin and embedded in paraffin. Paraffin-embedded tissue sections were deparaffinized and rehydrated by passage through xylenes (5 minutes X 2), graded alcohols, and deionized water. Endogenous peroxidases were blocked by incubating the slides for 5 minutes at room temperature in 3% aqueous hydrogen peroxide, followed by rinsing with copious amounts of water. Slides for all antibodies except CDlO were then subjected to microwave antigen retrieval using 1OmM citric acid, pH 6.0, followed by water rinses. All slides were soaked at room temperature for 5 minutes in Trisbuffered saline, pH 7.6, containing 0.05% Tween 20 (DakoCytomation, Carpinteria, Calif) and placed in a Dako autostainer. The slides were incubated for 30 minutes at room temperature with the following antibodies and dilutions: monoclonal antibodies to von Willebrand factor clone F8/86 (1:50; Dako), CD34 (1:50; Dako), and monoclonal anti-CDIO (1:50; Novocastra/Vector Laboratories, Burlington, Calif). The autostainer then rinsed the slides with Tris-buffered saline with Tween, incubated them for 30 minutes at room temperature with EnVision + polymer (peroxidase) (Dako), rinsed them with Tris-buffered saline with Tween, incubated them for 10 minutes at room temperature with 3,3'-diaminobenzidine tetrahydrofolate substrate solution (Dako), and finally subjected them to a final deionized water wash. The slides were then removed from the autostainer, counterstained with hematoxylin, dehydrated by passage through graded alcohols and xylenes, and cover-slipped.

PATHOLOGIC FINDINGS

Endometrial curettage specimens of the intraluminal nodule consisted of multiple fragments of hemorrhagic tissue, measuring 8.0 × 8.0 × 4.0 cm in aggregate. Histologie examination revealed tissue fragments with numerous small, capillary-sized vascular channels, lined by monotonous endothelial cells, consistent with a capillary hemangioma. The capillaries were relatively uniform in size, with no centrally placed larger vessels, and there was no significant associated organizing hemorrhagic lesion. Separate fragments of secretory endometrium with decidual stromal reaction and inactive glands were also seen (Figure 2, a). Immunohistochemical stains revealed that the endothelial cells were positive for von Willebrand factor F8/86 (Figure 2, b) and CD34 (Figure 2, c) and negative for CDlO, thus supporting the diagnosis of a vascular tumor. On hysterectomy, a 92.0-g uterus with attached cervix was received. The uterus measured 9.0 cm from fundus to cervix, 6.5 cm from cornu to cornu, and 3.0 cm from anterior to posterior. The cervix was 3.5 cm in diameter. The external cervical os was oval and measured 0.4 cm in widest dimension. The ectocervical mucosa was tan-pink and shiny. The endocervical canal measured 3.5 cm in length. The endometrium appeared tan-pink, measured less than 0.1 cm in thickness, and contained a 0.6-cm red, polypoid mass involving its posterior wall (Figure 3, a). The myometrial wall was 1.2 cm thick and unremarkable. Histologie examination of the mass revealed a capillary hemangioma of similar histology to that of the previous endometrial biopsy. This polypoid hemangioma was well circumscribed and covered by attenuated endometrium showing multifocal superficial ulceration. The border between hemangioma and myometrium was irregular in that, although the vascular lesion remained limited to the well-circumscribed tumor, foci of smooth muscle could be seen in the base of the polyp (Figure 3, b). Uninvolved endometrium was proliferative, and the cervix showed moderate acute and chronic inflammation.

COMMENT

Vascular lesions of the uterus are diverse. They include capillary and cavernous hemangiomas, angiomyomas, and hemangioendotheliomas. Cavernous hemangiomas, composed of large dilated vascular channels, are the most common vascular tumors of the uterus. Lesions have been found restricted to the serosa, myometrium, endometrium, and combinations thereof, as well as transmural. Myometrial lesions are the most common, and these are often diffuse,2,6,7 some with extension to the portio. The first case of diffuse uterine hemangiomas was described in 1897 and was an incidental discovery at autopsy after a young woman developed anemia and dyspnea and died 24 hours after delivering twins.2 The difference between the localized and diffuse forms of cavernous hemangioma is not clear, and transitional stages may exist.8

Congenital and acquired vascular tumors are found exceptionally with hereditary syndromes, including tuberous sclerosis5 and hemorrhagic telangiectasia.4 The cell of origin possibly represents pluripotential, embryogenie, mesodermal rests within the uterus.9 Typical acquired cases were associated with previous pelvic surgery, endometrial curettage, trophoblastic disease, endometrial carcinoma, and maternal ingestion of diethylstilbestrol.10

These vascular lesions may be asymptomatic, or they may cause menstrual irregularities or life-threatening bleeding. A case of rupture of hemangioma with hemoperitoneum and fetal demise has been reported in a gravid patient.3 The most common presenting sign was hemorrhage following curettage, when the thin endometrial tissue covering the hemangiomas was removed and the blood vessels were exposed.8 Bleeding tendencies are believed to occur from erosion of thin endometrium overlying lesions, trophoblastic growth into these vascular malformations with their fistulous connections to systernie circulation, mechanical forces, and platelet trapping.8 The epithelium covering capillary hemangiomas is usually intact, but in exposed areas, such as the cervix and vagina, traumatic ulceration of the overlying epithelium may create a lesion that bleeds with only slight contact or trauma.11 The trophoblastic tissue of the placenta may erode into the hemangioma, causing severe bleeding or placental separation.12 The vascular lumina within the hemangiomas are connected to the surrounding blood vessels."

Endometrial hemangiomas are extremely rare, possibly because of the periodic cyclical endometrial shedding. Though extension from the minimal myometrium involvement seen on the hysterectomy specimen is probable, this vascular lesion may also theoretically originate from angiomatous proliferation in a polypoid endometrial lesion that persists for a prolonged period.10 It has been proposed that the latter may occur because increased blood flow provided by the endometrial hemangioma may prohibit normal cyclic shedding associated with the usual hormonal flux.10

The differential diagnosis included hemangiopericytoma and angiosarcoma; however, a regular 1-layer architecture, bland benign-appearing endothelial cells, and virtually no nuclear atypia or mitotic activity excluded these entities.

Of the endometrial hemangiomas described in the English literature to date,4,10 including our own, all cases. studied have shown progressive symptoms of uterine bleeding, refractory to conservative therapy, including dilation and curettage. Investigative modalities including vaginal examination, endometrial curettage, ultrasound, and hysterogram were noninformative, although the uterus may on rare occasions feel or appear pulsatile.7 Pelvic angiogram and computerized tomography may confirm the vascular nature of the lesion if there is a clinical suspicion of this abnormality in cases refractory to hormonal therapy. ' Treatment of uterine vascular anomalies that occur during pregnancy includes conservative therapy such as close follow-up during the second and third trimesters, with close observation during delivery. Numerous patients have had successful vaginal and cesarean deliveries despite the presence of extensive myometrial hemangiomas. The treatment of endometrial hemangiomas remains unclear, however, because this is an extremely rare entity, with few reports in the literature. Examination of the few cases in the literature suggests that conservative therapy typically fails, and the treatment of choice is hysterectomy. Nonsurgical modalities such as radiation therapy would probably cure the lesions but in the process would destroy ovarian function.10

References

1. Malhotra S, Sehgal A, Nijhawan R. Cavernous hemangioma of the uterus. lnt ] Gynaecol Obstet. 1995;51:1 59-1 60.

2. Lotgering FK, Pijpers L, van EijckJ, Wallenburgh HC. Pregnancy in a patient with diffuse cavernous hemangioma of the uterus. Am J Obstet Gynecol. 1989; 160:628-631.

3. Dawood MY, Teoh ES, Ratnam SS. Ruptured haemangioma of a gravid uterus. I Obstet Gynecol. 1972;79:474-475.

4. Shanberge JN. Hemangioma of the uterus associated with hereditary hemorrhagic telangiectasia. Obstet Gynecol. 1994;84:708-709.

5. Jameson CF. Angiomyoma of the uterus in a patient with tuberous sclerosis. Histopathology. 1990; 16:202-203.

6. Thanner F, Suetterlin M, Kenn W, et al. Pregnancy-associated diffuse cavernous hemangioma of the uterus. Acta Obstet Gynecol Scand. 2001;80:11501151.

7. Suttcriin MW, MullerT, Rehn M, Rempcn A, Dietl J. Successful abdominal delivery in a woman with sonographic diagnosis of diffuse cavernous hemangioma of the uterus. Am J Perinatal. 1998;1 5:423-425.

8. Weissman A, Talmon R, Jakobi P. Cavernous hemangioma of the uterus in a pregnant woman. Obstct Gynecol. 1993;81:825-827.

9. Bowers VM Jr, King JD. Benign hemangiomyoma of the uterus. Obstct Gynecol. 1977;49:38-40.

10. Hunter DT Jr, Cogns FW. Endometrial hcmangiomata. Obstct Cynecol. 1965;25:538-541.

11. Ahcrn JK, Alien NH. Cervical hemangioma: a case report and review of the literature. J Reprod Mcd. 1978;228:228-231.

12. Jensen H, Petersen K, Lenz S, Hum L, Olsen CR. Life-thrcalening hemorrhage due to uterine vascular abnormality. Acta Ohstet Cynecol Scand. 1988:67: 363-365.

Cary Johnson, MD; Michelle Reid-Nicholson, MD; Lianne De/igdisch, MD; Svetlana Grinblat, MD; Suneetha Natarajan, MD

Accepted for publication June 17, 2005.

From the Department of Pathology, Mount Sinai Medical Center, New York, NY.

The authors have no relevant financial interest in the products or companies described in this article.

Reprints: Gary A. Johnson, MD, Department of Pathology, Box 1194, The Mount Sinai Medical Center, One Gustave L. Levy Place, New York, NY 10029 (e-mail: Cary.Johnson@msnyuhealth.org).

Copyright College of American Pathologists Oct 2005
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