Radiol Oncol 2024; 58(3): 320-325. doi: 10.2478/raon-2024-0050 320 review Anastomosing hemangioma of the ovary – a comprehensive review of this rare ovarian entity Sebastjan Merlo1,2,3, Gregor Vivod1,2, Barbara Gazic4, Nina Kovacevic1,2,3 1 Department of Gynecological Oncology, Institute of Oncology Ljubljana, Ljubljana, Slovenia 2 Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia 3 Faculty of Health Care Angele Boskin, Jesenice, Slovenia 4 Department of Pathology, Institute of Oncology Ljubljana, Ljubljana, Slovenia Radiol Oncol 2024; 58(3): 320-325. Received 9 April 2024 Accepted 14 August 2024 Correspondance to: Assist. Prof. Nina Kovačević M.D., Ph.D., Department of Gynecological Oncology, Institute of Oncology Ljubljana, Zaloška cesta 2, SI-1000 Ljubljana, Slovenia. E-mail: nkovacevic@onko-i.si Disclosure: No potential conflicts of interest were disclosed. This is an open access article distributed under the terms of the CC-BY license (https://creativecommons.org/licenses/by/4.0/). Background. Anastomosing hemangioma of the ovary is a rare vascular tumor that predominantly affects middle- aged women. Despite its benign nature, its histological appearance can mimic aggressive vascular lesions, posing diagnostic challenges. This review aims to provide an overview of this uncommon entity. Methods. The PubMed and Scopus databases were searched for relevant articles published in English. Information on all retrieved cases was extracted and reviewed in detail. Results. We found 33 cases with relevant details of anastomosing heamangioma of the ovary. Despite the small number of cases we found, our study demonstrated the importance of an accurate hystopathological evaluation. Conclusions. Although the preliminary imaging and initial microscopic features may appear alarming, careful micro- scopic examination reveals benign behavior. There is a need to raise awareness of this unusual and rare entity to im- prove morphologic recognition and avoid misdiagnosis that could lead to unnecessary treatment or patient anxiety. Key words: anastomosing hemangioma; ovary; ovarian hemangioma; urogenital tract Introduction Anastomosing hemangioma is a rare benign vas- cular tumor reported to occur in the kidney, testis, paravertebral soft tissue, gastrointestinal tract, liv- er, and in rare instances, in the ovary.1-4 It was first described in 2009 by Montgomery and Epstein.5 Since then, only a limited number of cases have been reported in the literature, contributing to its diagnostic uncertainty. Most cases of anasto- mosing hemangioma of the ovary presents as a solitary, well-circumscribed mass or is incidental findings.1 Occasionally, ovarian anastomosing hemangiomas have been associated with ascites and elevated serum CA 125 levels raising concern for an epithelial malignancy. Ovarian hemangio- mas can be mistaken for malignant ovarian tu- mors due to their appearance on imaging studies. Appropriate preoperative diagnostics, including ultrasound, MRI, and sometimes CT scans, are es- sential to differentiate hemangiomas from more serious conditions such as ovarian cancer, which would require a different surgical approach and postoperative management.6,7 Histologically, anastomosing hemangioma is characterized by anastomosing sinusoidal capil- lary sized blood vessels lined by bland endothelial cells with hobnail appearance, in a hyalinized and edematous stroma. The cells may show minimal atypia, which can be mistaken for low-grade an- Radiol Oncol 2024; 58(3): 320-325. Merlo S et al. / Anastomosing hemangioma of the ovary 321 giosarcoma.7 Immunohistochemical staining may reveal positivity for endothelial markers such as CD31 and CD34, aiding in its diagnosis.8 We reviewed the current and relevant literature on anastomosing hemangiomas of the ovary to in- crease awareness of this rare entity. Prior to our review, only 33 cases of anastomosing hemangio- ma of the ovary have been reported in the English- language literature.1,3,6-15 Most of reviews are pre- sented as case reports or small case series, and the largest series includes 12 cases of anastomosing hemangioma of the ovary.9 To add to the literature, we present and describe our case of anastomosing hemangioma of the ovary. Materials and methods Search strategy The PubMed database was searched for relevant articles published in English between January 1990 and December 2023. The search strategy in- cluded the following terms: (Hemangioma[mesh] OR Hemangioma*[tiab]) AND (anastomosing Hemangioma*[tiab] OR anastomosing[tiab] OR anastomos*[tiab]) AND (Ovary[mesh] OR Ovary[tiab] OR ovaries[tiab] OR ovarina[tiab] OR Ovarian Neoplasms[mesh] OR Ovarian Neoplasms[tiab] OR Cancer of Ovary[tiab] OR Cancer of the Ovary[tiab] OR Ovarian Cancer*[tiab] OR Ovary Cancer*[tiab] OR Ovary Neoplasms[tiab] OR ovarian malignancy[tiab] OR ovarian tumor*[tiab] OR Ovarian Carcinoma[tiab]) AND 1990/01/01:2024/01/01[Date - Publication]. The Scopus database was also searched. The referenc- es of all relevant reviews found were also exam- ined to avoid omitting qualified studies. In addi- tion, references to related articles were searched to identify studies that might meet the criteria. Evaluation of each article was conducted indepen- dently by three reviewers (S.M., G.V. and N.K.). Inclusion criteria The inclusion criteria were as follows: Women with a histopathological diagnosis of anastomo- sing hemangioma of the ovary; all published retro- spective small studies and case reports containing patient-relevant information; clinical presentation, size of the hemangioma; stromal lutenization. In the case of duplicates in the literature, the most re- cent and comprehensive articles were selected. We also included the case report by Metodiev et al. in which the abstract was written in English.12 Exclusion criteria The articles were excluded for one of the following reasons: Articles not specifying the type of ovar- ian tumor and articles not in English language. Data extraction Study information that were extract and reviewed in detail: Patient age at diagnosis, tumor size and location, histopathological type, clinical presenta- tion, and presence of stromal luteinization. Results A new case A 60 years old woman was sent to Department of Gynecological Oncology, Institute of Oncology Ljubljana with a suspected left-sided ovarian mass. Vaginal ultrasound showed a mixed cystic and solid appearance. The largest diameter of the mass was 50 millimeters. Family history was negative for malignancy. Her medical history was unremarkable. The tumor markers CA 125, CEA, HE4, CA 19-9, CA 72-4 and CA 15-3 were all nega- tive. She underwent laparoscopic bilateral sal- pingo-oophorectomy. Left ovary was partly frag- mented. In one of the fragments, there was a well circumscribed lesion, measuring 25 mm in diam- eter, with yellow-brown, spongy appearance was present. Microscopic examination of H&E-stained FIGURE 1. Literature review flowchart. Radiol Oncol 2024; 58(3): 320-325. Merlo S et al. / Anastomosing hemangioma of the ovary322 slides revealed well-demarcated vascular prolif- eration, composed mostly of capillary-sized blood vessels with an anastomosing growth pattern and some larger vessels of medium size. Vessels lin- ing was composed of a single layer of endothelial cells without cytologic atypia or mitotic figures (Figure 2). The lesion was surrounded by lutein- ized ovarian stroma. Immunohistochemically the tumor cells were positive for CD31, CD34 and ERG (Figure 3). Review of literature A flowchart showing the phases of the search strat- egy is shown in Figure 1. Our search in the Scopus and PubMed databases initially returned 30 re- sults. After the initial screening, 18 articles were excluded due to duplicates and non-English lan- guage. Of the remaining 12 articles, the titles and abstracts were screened by reviewers and were classified as relevant and were subjected to a full text and literature review. For the final analysis all 12 papers with relevant details were selected. The mean age of the 32 women diagnosed with anastomosing hemangioma of the ovary was 59.2 years. In 18 women tumor was incidental finding, three women presented with elevated CA 125 se- rum level and ascites. Only ascites was present in one patient and five women have ultrasound de- tected ovarian mass. The mean maximum diame- ter of tumor was 20.6 mm. The detailed data of the patients and the tumor characteristics are listed in Table 1. Discussion The definition of anastomosing hemangioma was established in 2009.5 The most likely theory that explaining the pathogenesis of this phenomenom characterizes anastomosing hemangioma of ova- ry as behaving like enlarging follicles that cause pressure on the neighboring tissue and lead to the development of luteinized stromal cells.6 In our review of literature, we found 33 cases of anastomosing hemangiomas of the ovary reported in the English literature. In our case the patient was 60 years old, while the mean age in the previ- ous literature was 52.9 years (range from 26 to 81) (Table 1). The tumor size ranged from 1 millimeter to 100 millimeters, with the mean size being 20.6 millimeters. In our case tumor size was 50 millim- eters. Anastomosing hemangioma of the ovary typi- cally affects women in their middle age, although cases have been reported across a wide age range.6 Clinically, patients may present with nonspecific symptoms such as abdominal pain, discomfort, or palpable pelvic mass. However, due to its rar- ity and lack of specific clinical features, anastomo- sing hemangioma is often an incidental finding on imaging studies or during surgical exploration for unrelated conditions. The absence of pathogno- monic symptoms underscores the importance of histopathological evaluation for definitive diagno- sis.16 Radiological imaging, including ultrasound and MRI, may demonstrate a hypervascular mass, although definitive diagnosis often relies on histo- logical examination following surgical excision.10 In our case, too, the ovarian mass was an inciden- tal finding with no specific clinical signs. Tumor markers were all negative and the ultrasound re- FIGURE 2. HE: Anastomosing sinusoidal-like vessels lined by endothelial cells without cytologic atypia. FIGURE 3. CD 31 highlights endothelial cells lining numerous vessels. Radiol Oncol 2024; 58(3): 320-325. Merlo S et al. / Anastomosing hemangioma of the ovary 323 sults were non-specific. The final histologic find- ings were decisive for the final diagnosis. Stromal luteinization as a unique feature of ovarian anastomosing hemangiomas was reported in 22 of 28 cases (78.6%), and in 5 cases this data was not available (Table 1). Some of the prior cases presented association between anastomosing he- mangioma of ovary with ascites and elevated se- rum CA 125, mimicking an epithelial ovarian ma- lignancy.1,6,7 These findings were not observed in our experience. Particular histologic characteristics are de- scribed as non-lobular proliferation of anastomo- sing capillary sized vessels with sinusoidal-like ar- TABLE 1. Published cases of anastomosing hemangiomas of the ovary in the English literature No Author Age Clinical presentation Size (mm) Stromal luteinization 1 Metodiew et al.12 70 NA 7 Yes 2 Kryvenko et al.3 70 Incidental 2 No 3 Kryvenko et al.3 49 Incidental 1 No 4 Kryvenko et al.3 77 Incidental 11 Yes 5 O’Neill et al.10 NA NA NA NA 6 O’Neill et al.10 NA NA NA NA 7 O’Neill et al.10 NA NA NA NA 8 O’Neill et al.10 NA NA NA NA 9 Dundr et al.6 66 Incidental 5 Yes 10 Dundr et al.6 43 Incidental 13 Yes 11 Dundr et al.6 69 Incidental 15 Yes 12 Dundr et al.6 81 Incidental 35 Yes 13 Dundr et al.6 68 Ascites, elevated CA 125 35 Yes 14 Dundr et al.6 69 Mass 12 Yes 15 Gunduz et al.8 62 Incidental 90 Yes 16 Subbarayan et al.7 50 Ascites 30 Yes 17 Rezk et al.1 60 Ascites, elevated CA 125 65 Yes 18 Stewart and Salfinger11 48 Incidental 8 Yes 19 McHenry and Buza9 55 Mass 12 Yes 20 McHenry and Buza9 62 Mass 10 Yes 21 McHenry and Buza9 67 Incidental 5 Yes 22 McHenry and Buza9 76 Incidental 7 Yes 23 McHenry and Buza9 58 Incidental 8 Yes 24 McHenry and Buza9 53 Mass 6 Yes 25 McHenry and Buza9 73 Incidental 4 Yes 26 McHenry and Buza9 65 Incidental 10 Yes 27 McHenry and Buza9 50 Incidental 9 Yes 28 McHenry and Buza9 69 Incidental 6 No 29 McHenry and Buza9 63 Incidental 3 No 30 McHenry and Buza9 55 Incidental 2 No 31 Wang et al.13 28 Mass 40 No 32 Wu et al.14 26 Mass, ascites, elevated CA 125 46 NA 33 Jha et al.15 35 Mass 100 Yes NA = not available Radiol Oncol 2024; 58(3): 320-325. Merlo S et al. / Anastomosing hemangioma of the ovary324 rangements resembling the red pulp of the spleen, with vessels lined by bland endothelial cells.6 The lack of atypical endothelial cells and mitotic figures helps to differentiate anastomosing hemangiomas from its malignant counterpart, angiosarcoma.17 Evaluation of the entire anastomosing hemangio- ma lesion, when possible, reveals that its growth is limited, lacking a broadly infiltrative pattern. The differential diagnosis of anastomosing he- mangioma also includes capillary hemangioma, cavernous hemangioma, hemangioendothelioma, epithelioid hemangioma, and non-neoplastic vas- cular proliferations.9 Surgical excision remains the cornerstone of management for anastomosing hemangioma of the ovary. Complete resection is curative in the majority of cases, with favorable long-term out- comes. Management decisions should be indi- vidualized based on factors such as tumor size, location, and patient preferences, with a focus on preserving ovarian function and fertility when feasible. Overall, the prognosis of anastomosing hemangioma of the ovary is excellent following complete surgical resection. Recurrence rates are low, particularly with adequate surgical margins. However, cases of recurrence have been reported, highlighting the importance of vigilant long-term surveillance.18,19 Continued collaboration among multidisci- plinary teams is essential to advance our under- standing and improve outcomes for patients with this rare ovarian tumor. Although the preliminary imaging and initial microscopic features may ap- pear alarming, careful microscopic examination reveals benign behaviour.10 There is a need to raise awareness of this unusual and rare entity to im- prove morphologic recognition and avoid misdi- agnosis that could lead to unnecessary treatment or patient anxiety. Conclusions In conclusion, anastomosing hemangioma of the ovary is a rare vascular tumor that poses diagnos- tic challenges due to its histological resemblance to more aggressive lesions. Despite its benign nature, accurate diagnosis is essential to avoid unneces- sary interventions and ensure appropriate man- agement. Long-term follow-up is crucial due to reported cases of recurrence following incomplete resection. Further research is needed to better understand the pathogenesis of this rare ovarian tumor and to optimize diagnostic and therapeutic approaches. Increased awareness among clinicians and pathologists is essential for timely recognition and management of anastomosing hemangioma of the ovary, ultimately improving patient outcomes. References 1. Rezk A, Richards S, Patricia Castillo R, Schlumbrecht M. Anastomosing hemangioma of the ovary mimics metastatic ovarian cancer. Gynecol Oncol Rep 2020; 34: 100647. doi: 10.1016/j.gore.2020.100647 2. John I, Folpe AL. Anastomosing hemangiomas arising in unusual locations: a clinicopathologic study of 17 soft tissue cases showing a predilection for the paraspinal region. Am J Surg Pathol 2016; 40: 1084-9. doi: 10.1097/ PAS.0000000000000627 3. Kryvenko ON, Gupta NS, Meier FA, Lee MW, Epstein JI. Anastomosing he- mangioma of the genitourinary system: eight cases in the kidney and ovary with immunohistochemical and ultrastructural analysis. Am J Clin Pathol 2011; 136: 450-7. doi: 10.1309/AJCPJPW34QCQYTMT 4. Sun K, Wei JF, Zhao M, Teng XD. Anastomosing hemangioma of the liver containing eosinophilic hyaline globules. Int J Clin Exp Med 2017; 10: 7291- 5. 5. Montgomery E, Epstein JI. Anastomosing hemangioma of the genitourinary tract: a lesion mimicking angiosarcoma. Am J Surg Pathol 2009; 33: 1364-9. doi: 10.1097/PAS.0b013e3181ad30a7 6. Dundr P, Němejcová K, Laco J, Skálová H, BauerováL, Matěj R, et al. 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