==== Front Ann Saudi MedAnn Saudi MedAnnals of Saudi Medicine0256-49470975-4466King Faisal Specialist Hospital and Research Centre 1839827210.5144/0256-4947.2008.128asm-2-128Case ReportOvarian hemangioma occurring synchronously with serous papillary carcinoma of the ovary and benign endometrial polyp Akbulut Metin aBir Ferda aÇolakoğlu Nagihan aSoysal Mehmet Emin bDüzcan Süleyman Ender a a Department of Pathology, Pamukkale University, Denizli, Turkey b Department of Obstetrics and Gynecology, Pamukkale University, Denizli, TurkeyCorrespondence and reprints: Dr. Metin Akbulut, Department of Pathology, Pamukkale University, Morfoloji Binasi Kinikli Kampusu, Denizli 20030, Turkey, F: +902-58-213-3105, makbulut@pau.edu.trMar-Apr 2008 28 2 128 131 01 8 2007 Copyright © 2008, Annals of Saudi Medicine2008This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. ==== Body Ovarian hemangiomas are extremely rare tumors, most of which are asymptomatic and of the cavernous type.1 Considering the rich vascular supply of the ovary, the low incidence of ovarian hemangiomas is somewhat surprising. There are about 50 documented cases in the literature. The 12 described in Table 1 were associated with gynecologic tract disease including endometrial hyperplasia, endometrial carcinoma and endometriosis.1–34 Ovarian hemangiomas have been reported in both adults and children and most of the reported cases have been unilateral and small.2,3 Although often an incidental finding at operation, ovarian hemangioma may rarely be associated with gynecologic cancers.4–8 The tumor in our case was an additional and incidental finding in a surgical specimen removed because of a serous papillary carcinoma involving the left tuba and ovary. CASE A 65-year-old woman was admitted to the Department of Obstetrics and Gynecology of Pamukkale University for irregular bleeding and pelvic pain. The medical history of the patient was unremarkable. The serum androgen, estrogen, and progesterone levels were not examined preoperatively, although they were within normal limits postoperatively. Pelvic examination revealed a normal-sized uterus and palpable abdominopelvic mass. Serum hormonal levels including FSH (follicle-stimulating hormone), LH (luteinizing hormone), TSH (thyroid-stimulating hormone), prolactin, estradiol and tumor markers including CA125, CA19-9 and CEA (carcinoembryonic antigen) were within normal limits. On ultrasonographic examination, the mass was solid and measured approximately 6 centimeters. The patient underwent laparatomy for a left adnexal mass. Macroscopically a tumor mass 6×4×2.5 centimeter in size was recognized in the adnexal region. The right ovary measured 3×2×1 centimeter, and grossly was unremarkable. The patient underwent a total abdominal hysterectomy, a bilateral salpingo-oophorectomy, appendectomy, partial omentectomy, and pelvic lymph node dissection. Ascites was not detected at operation. Macroscopic examination of the uterus (125 grams) showed an endometrial polyp measuring 1×1×0.6 centimeters and no leiomyoma was observed. The specimen was fixed in 10% neutral formalin. The paraffin-embedded tissue sections were stained with hematoxylin and eosin. Using the avidine-biotin peroxidase complex method, we performed an immunohistochemical analysis for vimentin, CD34, CD31, inhibin, estrogen and progesterone. Immunohistochemically, we found expression of CD34, CD31, vimentin and no expression of inhibin, estrogen and progesterone receptors. Histologically, the tumor was a serous papillary carcinoma involving the left tuba and ovary (Figure 1). Also, a small capillary hemangioma was incidentally diagnosed, composed of numerous small vascular spaces lined by a single layer of endothelial cells. The hemangioma was clearly distinct from the neoplastic elements. Mitotic activity was not noted and no atypical cells were seen (Figure 2). Neither teratomatous components nor luteinization of the surrounding ovarian stroma was observed, even in the serial sections of the ovary. Microscopic evaluation of the endometrium revealed an endometrial polyp composed of irregularly shaped, crowded, hyperplastic glands. DISCUSSION Vascular tumors of the female genital tract, especially hemangiomas of the ovary, are uncommon. The first was reported by Payne in 1869.9 A review of the literature reveals that our case was unique because of the co-existence of the hemangioma with a serous papillary carcinoma of the ovary and an endometrial polyp. In most patients, ovarian hemangiomas are discovered incidentally, and sizes range from 0.3 to 24 centimeter.10,11 The tumor is usually unilateral, but bilateral tumors have been reported.1,12,13 Although they have been found in different parts of the ovaries, the medulla and hilar region are the most common location of the tumor.12 The etiology of ovarian hemangiomas is unknown and controversial. A hemangioma is now considered a part of a mature teratoma or a benign pure ovarian parenchymal neoplasm.14–17 Similarly, some authors have proposed that hemangiomas are either hamartomatous malformations or neoplasms; both origins are probable, and formation may be stimulated by hormonal influences, pregnancy, or infection.18,19 A review of the literature revealed that some ovarian hemangiomas are associated with endometrial hyperplasia and malignancies including endometrial cancer and germ cell tumor.4–6,8,10 In a few reported cases, ovarian hemangioma was associated with stromal luteinization, generalized hemangiomatosis and Ascites, leading to abdominal and pelvic symptoms.1,8,11,14,17,20,21 Miyauchi hypothesized that multicentric abnormal proliferation of endothelial cells is the underlying pathology in generalized hemangiomatosis.13 Luteinization of the ovarian stromal cells was regarded as a reactive phenomenon to the presence of any expansile lesion, including hemangioma. 4 Although our patient did not have stromal luteinization in the affected and contralateral ovary, an endometrial polyp was observed. The pathogenesis of stromal luteinization remains controversial and there is a debate whether these luteinized cells promote the growth of the hemangioma and endometrial polyp or just represent a stromal reaction.20,21 However, it is well known that luteinization may result in androgenic or estrogenic manifestations that could stimulate the development of endometrial hyperplasia, polyp and hemangioma, because the angiotropic effects of estrogens are well established.4,7,8,10,20 It is obvious that the same growth factor may act on both the endometrial polyp and the endothelium, causing the concomitant growth of the two neoplasms. Postmenopausal bleeding and endometrial polyp-like endometrial hyperplasia may manifest hyperestrogenism. However, immunohistochemical studies have failed to reveal any affinity between the endothelium of our case and estrogen and progesterone receptors. Therefore, we suggest that ovarian hemangiomas may occur independently of stimulation by estrogen and progesterone. Hemangioma must be differentiated from proliferations of dilated blood vessels. Shweta questioned the number of true ovarian hemangiomas because of the difficulty in distinguishing a small hemangioma from dilated hilar vessels. He proposed that a mass of vascular channels, large as well as small, and with minimal amounts of stroma, should form a reasonably circumscribed lesion distinct from the remainder of the ovary and can be regarded as true hemangioma.2 Papillary tufting, significant cytologic atypia or mitotic activity, hemorrhage, and necrosis were not present, differentiating this lesion from angiosarcoma.11 Teratomas are included in differential diagnosis due to the prominent vascular component. In such cases careful sampling is important to exclude the presence of other teratomatous elements before diagnosing the tumor as a pure hemangioma.14,15 We suggest that the tumor described in this report is an ovarian hemangioma arising from ovarian parenchymal cells rather than a teratoma originating from germ cells. MR imaging is sometimes of value for making a preoperative diagnosis of ovarian hemangioma.17,26 Hemangiomas should be considered when a richly vascularized tumor with prominent blood flow is detected on color Doppler sonography or MRI.21,22 Although some cases may not have been recognized or recorded, to the best of our knowledge this is the first case of a capillary ovarian hemangioma synchronous with a serous papillary carcinoma of the ovary. It should be noted that an ovarian hemangioma can be associated with gynecologic cancers and hemangiomatosis; therefore surgical removal of the involved areas and careful examination of the contralateral ovary and endometrium for a possible malignancy and examination of the abdominopelvic region for hemangiomatosis is essential. This case was presented as a poster at the XXIII World Congress of Pathology and Laboratory Medicine May 26-60, 2005, Istanbul, Turkey Figure 1 Papillary serous carcinoma involving the left tuba-ovary (H&E, ×10, original magnification). Figure 2 Ovarian hemangioma composed of numerous small vascular spaces. The inset shows vascular spaces lined by a single layer of endothelial cells with no nuclear atypia and mitosis (H&E, ⋄10, ×40, original magnification). Table 1 Clinico-pathologic features of patients with ovarian hemangioma associated with gynecologic tract disease and coexistent lesions reported in the literature. Author Age Symptom Maximum size (cm) Location Type Luteinization Coexistent lesion Payne et al 1869 25 DOD Vaginal bleeding NA Bilateral NA No Abdominopelvic hemangiomatosis, uterine polyp Kusum et al 1980 45 Irregular vaginal bleeding 2 L NA No Cystic hyperplasia of endometrium Alvarez et al 1986 68 Abdominal discomfort 24 L Cavernous No Simple endometrial hyperplasia Grant et al 1986 59 Aching breasts, postmenopausal bleeding 1,5 R Mixed No Cystic hyperplasia of endometrium Savargaonkar et al 1994 69 Postmenopausal bleeding NA NA NA Yes Endometrial hyperplasia, tubal carcinoma Tanaka et al 1994 16 Abdominal mass 15 R Cavernous No Turner’s syndrome and bilateral gonadal tumors Carder et al 1995 36 Dysfunctional uterine bleeding 0,5 L Cavernous Yes Cystic hyperplasia of endometrium Carder et al 1995 62 Postmenopausal bleeding 1 L NA Yes Endometrial carcinoma Rivasi et al 1996 46 Metrorrhagia, anemia 0,5 NA Capillary No Endometrial cancer Jurkovic et al 1999 32 NA NA L Cavernous No Mucinous cystadenoma Miliara et al 2001 71 Rectosigmoid carcinoma 0,8 L NA Yes Rectosigmoid carcinoma, endometriosis Gücer et al 2004 70 Postmenapousal bleeding 1,5 L Mixed Yes Endometrial cancer Current case 65 Irregular vaginal bleeding and pelvic pain. 0,5 L Capillary No Serous papillary carcinoma of the ovary, endometrial polyp NA=Not available, DOD=Died of disease. ==== Refs REFERENCES 1 Lawhead RA Copeland LJ Edwards CL Bilateral ovarian hemangiomas associated with diffuse abdominopelvic hemangiomatosis Obstet Gynecol 1985 65 597 3982735 2 Uppal S Heller DS Majmudar B Ovarian hemangioma-report of three cases and review of the literature Arch Gynecol Obstet 2004 270 1 1 5 15205976 3 Gerbie AB Hirsch MR Green RR Vascular tumors of the female genital tract Obstet Gynecol 1955 6 499 503 13266264 4 Gucer F Ozyilmaz F Balkanli-Kaplan P Mulayim N Aydin O Ovarian hemangioma presenting with hyperandrogenism and endometrial cancer: a case report Gynecol Oncol 2004 94 3 821 4 15350380 5 Rivasi F Philippe E Walter P de Marco L Ludwig L Ovarian angioma. Report of 3 asymptomatic cases Ann Pathol 1996 16 6 439 41 9090933 6 Tanaka Y Sasaki Y Tachibana K Maesaka H Imaizumi K Nishihira H Nishi T Gonadal mixed germ cell tumor combined with a large hemangiomatous lesion in a patient with Turner’s syndrome and 45,X/46,X, +mar karyotype Arch Pathol Lab Med 1994 118 11 1135 8 7979900 7 Carder PJ Gouldesbrough DR Ovarian haemangiomas and stromal luteinization Histopathology 1995 26 585 6 7665154 8 Savargaonkar PR Wells S Graham I Buckley CH Ovarian haemangiomas and stromal luteinization Histopathology 1994 25 2 185 8 7982685 9 Payne JF Vascular tumors of the liver, suprarenal capsules and other organs Trans Path Soc London 1869 20 203 10 Alvarez M Cerezo L Ovarian cavernous hemangioma Arch Pathol Lab Med 1986 110 1 77 8 3753575 11 Gehrig PA Fowler WC Jr Lininger RA Ovarian capillary hemangioma presenting as an adnexal mass with massive ascites and elevated CA-125 Gynecol Oncol 2000 76 1 130 2 10620457 12 Talerman A Hemangiomas of the ovary and the uterine cervix Obstet Gynecol 1967 30 108 113 6027477 13 Miyauchi J Mukai M Yamazaki K Kiso I Higashi S Hori S Bilateral ovarian hemangiomas associated with diffuse hemangioendotheliomatosis: a case report Acta Pathol Jpn 1987 37 8 1347 55 3673576 14 Itoh H Wada T Michikata K Sato Y Seguchi T Akiyama Y Kataoka H Ovarian teratoma showing a predominant hemangiomatous element with stromal luteinization: report of a case and review of the literature Pathol Int 2004 54 4 279 83 15028031 15 Prus D Rosenberg AE Blumenfeld A Infantile hemangioendothelioma of the ovary: a monodermal teratoma or a neoplasm of ovarian somatic cells? Am J Surg Pathol 1997 21 1231 5 9331297 16 Talerman A Nonspecific tumors of the ovary Kurman RJ Blaustein’s Pathology of the Female Genital Tract 5th edn New York Springer-Verlag 2002 1014 44 17 Kaneta Y Nishino R Asaoka K Toyoshima K Ito K Kitai H Ovarian hemangioma presenting as pseudo-Meigs’ syndrome with elevated CA125 J Obstet Gynaecol Res 2003 29 3 132 5 12841694 18 Shearer JP Hemangioma of the ovary: Report of a case of a child 3, 5 years of age Med Ann DC 1935 2 223 19 DiOrio J Lowe LC Hemangioma of the ovary in pregnancy. A case report J Reprod Med 1980 24 232 234 7401054 20 Miliaras D Papaemmanouil S Blatzas G Ovarian capillary hemangioma and stromal luteinization: a case study with hormonal receptor evaluation Eur J Gynaecol Oncol 2001 22 369 71 11766743 21 Yamawaki T Hirai Y Takeshima N Hasumi K Ovarian hemangioma associated with concomitant stromal luteinization and ascites Gynecol Oncol 1996 61 438 41 8641629 22 Paladini D Di Meglio A Esposito A Di Meglio G Riccio A Di Pietto L Formicola C Ultrasonic features of an ovarian cystohemangioma; a case report Eur J Obstet Gynecol Reprod Biol 1991 40 3 239 40 1879601 23 Shaeffer MH Cancelmo JJ Cavernous hemangioma of ovary in a girl twelve years of age Am J Obstet Gynecol 1939 38 722 723 24 Gay RM Janovski NA Cavernous hemangioma of the ovary Gynaecologia 1969 168 248 257 5384097 25 Caresano G L’emangioma cavernoso dell’ovaio. Presentazione di un caso e rassegna della bibliografia Minerva Ginecol 1977 29 103 106 854231 26 Cormio G Loverro G Iacobellis M Mei L Selvaggi L Hemangioma of the ovary. A case report J Reprod Med 1998 43 5 459 61 9610472 27 M’pemba Loufoua-Lemay AB Peko JF Mbongo JA Mokoko JC Nzingoula S Ovarian torsion revealing an ovarian cavernous hemangioma in a child Arch Pediatr 2003 10 11 986 8 14613693 28 Jurkovic I Dudrikova K Boor A Ovarian hemangioma Cesk Patol 1999 35 4 133 5 10677912 29 Mirilas P Georgiou G Zevgolis G Ovarian cavernous hemangioma in an 8-year-old girl Eur J Pediatr Surg 1999 9 2 116 8 10342121 30 Grant JW Millward-Sadler GH Haemangioma of the ovary with associated endometrial hyperplasia. Case report Br J Obstet Gynaecol 1986 93 11 1166 8 3778850 31 Loverro G Cormio G Perlino E Vicino M Cazzolla A Selvaggi L Transforming growth factorbeta1 in hemangioma of the ovary Gynecol Obstet Invest 1998 46 3 210 3 9736807 32 Kela K Aurora AL Haemangioma of the ovary J Indian Med Assoc 1980 75 10 201 2 7252186 33 DiOrio J Jr Lowe LC Hemangioma of the ovary in pregnancy: a case report J Reprod Med 1980 24 5 232 4 7401054 34 Rodriguez MA Hemangioma of the ovary in an 81-year-old woman South Med J 1979 72 4 503 4 432698