Recurrent Aggressive Angiomyxoma: A Single-Institution Case Series on Management and Outcomes

Recurrent Aggressive Angiomyxoma: A Single-Institution Case Series on Management and Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Recurrent Aggressive Angiomyxoma: A Single-Institution Case Series on Management and Outcomes Maksim Isachanka, Sergey Mavrichev, Yana Kamko, Hanna Trukhan, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7069223/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Aggressive angiomyxoma (AA) is a rare, locally infiltrative mesenchymal tumor of the pelviperineal region that carries a significant management challenge due to its high rate of local recurrence. While histologically benign, its clinical behavior can be unpredictable. Optimal strategies for managing recurrent disease and the full biological potential of AA are not well defined. Case Presentation: We present two cases of recurrent AA managed at our institution. First case involved a 31-year-old woman with a margin-positive resection of a pelvic recurrence, initially misdiagnosed as a capillary hemangioma, who showed partial tumor regression with adjuvant tamoxifen and radiotherapy. Second case describes a 33-year-old woman with a large, recurrent pelvic tumor successfully managed with resection and adjuvant tamoxifen. Conclusion: This series identifies several key clinical lessons. First, AA can mimic other benign lesions, emphasizing the need for expert pathological and radiological review. Second, while complete surgical excision is the goal, adjuvant therapy may play a role in managing residual or recurrent disease. Lastly, as late recurrence is well documented, lifelong imaging surveillance remains crucial even after successful treatment. Oncology Aggressive angiomyxoma Pelvic-perineal tumor Margin-positive resection Endocrine therapy Figures Figure 1 Figure 2 Figure 3 Figure 4 Introduction Deep aggressive angiomyxoma (AA) is a rare mesenchymal soft tissue tumor characterized by a locally infiltrative growth pattern and low metastatic potential. It typically involves the vulvovaginal region, perineum, and pelvis in women, with a peak incidence during the reproductive years [1-6]. According to the 5 th edition of the WHO classification, AA is considered a benign tumor. The term "aggressive" is therefore used to highlight its potential for infiltrative local behavior and high rate of recurrence, rather than malignant potential [7,8]. The clinical behavior of AA is characterized by slow growth, high expression of estrogen and progesterone receptors, and an infiltrative pattern that often involves surrounding soft tissues. This tumor type shows a high local‑recurrence rate (30–70 %) but a low metastatic potential, although rare distant metastases have been reported [9-11]. Definitive preoperative diagnosis is challenging due to the tumor's rarity and non-specific presentation, often making the final diagnosis possible only after surgical resection. Incomplete excision is a common challenge due to the lack of a clear tumor capsule and infiltrative margins that are often visible only on histological examination [12]. Local recurrence frequently occurs even after macroscopically complete resection and surgical radicality has not been shown to prolong the progression‑free interval [12]. Management may also include systemic therapy, primarily hormone‑based, and, in selected cases, radiotherapy. Gonadotropin-releasing hormone (GnRH) agonists are the agents most frequently used as adjuvant treatment and disease control, although aromatase inhibitors and selective estrogen‑receptor modulators have also been reported [13]. Prophylactic bilateral oophorectomy has been described, but its role remains uncertain [14]. Aggressive angiomyxoma was first described in 1983 and since then, fewer than 250 cases have been reported in the literature [15]. Due to its rarity, the optimal treatment strategy remains unclear. Therefore, two cases presented in this article offer additional evidence that may inform future discussion and the development of clinical guidelines. Case 1 A 31-year-old female (gravida 1, para 1) was referred to our institution for evaluation of a pelvic mass. In 2018 she underwent excision of a right gluteal tumor at a regional hospital. The pathology at that time was reportedly consistent with a capillary hemangioma with secondary changes. However, the original slides were unavailable for review. The patient remained asymptomatic until 2023, when she developed pain in the postoperative scar, exacerbated by prolonged sitting. An initial ultrasound of the scar revealed no abnormalities. Due to the progression of her symptoms, a pelvic magnetic resonance imaging (MRI) was performed in April 2024. The scan revealed a large, well-circumscribed mass measuring 7.6 x 9.4 x 7.2 cm in the right pelvic soft tissues, which displaced the vagina, uterus, and rectum to the left without definitive signs of invasion (Fig. 1). In May 2024 the patient was referred to National Cancer Center of Belarus. In June 2024, she underwent surgical resection of the tumor. A soft, elastic, multinodular mass measuring 13.0 x 8.0 x 6.0 cm was removed. The final histopathological diagnosis was aggressive angiomyxoma. Microscopic examination confirmed that the surgical margins were positive for tumor. Immunohistochemistry (IHC) showed positivity for Desmin, STAT6, estrogen receptors (100%), progesterone receptors (100%), and focally positive for smooth muscle actin (SMA). The stain was negative for h-Caldesmon, CD10, CD34, CD117, CyclinD1, DOG1, and S100. The Ki-67 was less than 1% (Fig. 2). Given the positive surgical margins and strong hormone receptor expression, a multidisciplinary decision was made to proceed with adjuvant therapy. The patient was started on tamoxifen 20 mg daily and subsequently underwent stereotactic radiotherapy to the tumor bed. At three-month follow-up after the completion of radiotherapy, a pelvic MRI showed partial regression of the residual tumor. Case 2 A 33-year-old female (gravida 2, para 2) presented to our center in 2018 with a progressively enlarging left labia majora, a symptom she first noted in 2015. Initial workup included CT and MRI of the abdomen and pelvis. The imaging revealed a large, complex, cystic-solid mass measuring 10.5 x 10.2 x 28.0 cm, originating in the pelvis and extending into the presacral space, right iliac region and left labium. The tumor displaced the rectum and vagina to the right, the uterus and ovaries anteriorly, and the cecum superiorly and leftward. The mass demonstrated a layered structure with a high T2-weighted signal, low T1-weighted signal, and heterogeneous peripheral contrast enhancement (Fig. 3). In January 2019, the patient underwent a laparotomy with a perineal approach for resection of the retroperitoneal tumor. The final pathology confirmed aggressive angiomyxoma, but the status of the resection margins was not recorded. The patient was therefore followed with close surveillance. In September 2024, a routine follow-up CT scan revealed a recurrent, irregular, hypodense mass in the left pelvic region that was inseparable from the left wall of the rectum and cervix. Subsequent pelvic MRI confirmed a recurrent heterogeneous tumor measuring 3.4 x 10.5 x 10.0 cm in the presacral space, which was closely abutting the rectum without definite evidence of invasion (Fig. 4). In October 2024 the patient underwent repeat surgery for excision of the recurrent pelvic tumor. The procedure required partial resection of the lateral vaginal wall and the left lateral wall of the rectum, with the creation of a diverting loop sigmoidostomy. Histopathology was again consistent with aggressive angiomyxoma. Immunohistochemistry showed positivity for Desmin, smooth muscle actin (SMA), estrogen receptors (90%), and progesterone receptors (90%), while negative for CD34 (though positive in endothelial cells as an internal control). The Ki-67 proliferation index was approximately 1%. Given the tumor's recurrent nature and hormone receptor positivity, the patient was started on long-term adjuvant therapy with tamoxifen 20 mg daily. A follow-up pelvic MRI six months after surgery demonstrated no residual or recurrent disease. Table 1. Main characteristics of the presented cases. First case Second case Age at first visit 31 y.o. 33 y.o. Localization of primary tumor Gluteal area Pelvic cavity, left iliac region with involvement of the left labia majora Number of recurrences 1 1 Time to first relapse 5 years 5 years Localization of the recurrent tumor Soft tissues of the perineum Pelvic cavity, left iliac region Dimensions of the recurrent tumor 13.0x8.0x6.0 cm 3.4х10.5х10 cm Primary treatment of the recurrence Surgery, R2 Surgery, R0 Adjuvant treatment Tamoxifen 20 mg daily long-term; stereotactic radiotherapy to the area of residual tumor Tamoxifen 20 mg daily long-term Pathology review, IHC Desmin+, SMA+ (focal), r-Estrogen+ (100%), r-Progesterone+ (100%), DOG1-, S100-, STAT6+, Ki-67<1% Desmin+, SMA+, r-Estrogen+ (90%), r-Progesterone+ (90%), CD34- (+ in the vascular endothelium), Ki-67 ~1% Duration of observation 12 months 8 months Status at last follow-up MRI without signs of progression, patient without complaints MRI with no residual or recurrent disease. Discussion Aggressive angiomyxoma (AAM) is a rare, locally infiltrative connective-tissue tumor that affects predominantly women of reproductive age, shows marked variability in biological behavior with a high propensity for local recurrence, and rarely metastasizes. The prevailing pathogenetic hypothesis is that AAM originates from a primitive multipotent mesenchymal cells of the lower female genital tract, capable of divergent differentiation [ 8 ]. Clinical course Angiomyxomas can exhibit slow, subtle growth. As a result, patients may remain asymptomatic for a long period. The initial clinical presentation can range from an asymptomatic tumor nodule to large masses occupying a significant portion of the pelvis, causing pain, discomfort, a feeling of heaviness in the pelvis, dyspareunia, and deformation of the abdomen, perineum, or external genitalia. Data suggest that deep aggressive angiomyxoma almost exclusively affects the genital, perineal, and pelvic regions in women of reproductive age, especially the vulva. Less commonly, it can involve the buttocks, retroperitoneal space, and inguinal region. Aggressive angiomyxoma typically displaces neighboring organs without overt invasion. However, its infiltrative margins may ultimately extend into adjacent organs over time, necessitating extensive resections during surgical interventions [ 8 ]. It has been reported that the recurrence rate is high, ranging from 30–70% [ 8 ]. No statistically significant association has been established between patient age or tumor size and recurrence frequency [ 12 ]. Multiple recurrences (three to six) are common, and more than half of the recurrences involve neighboring organs [ 8 ]. Like primary tumors, recurrences often remain asymptomatic, with most cases recurring within two years. However, recurrence can occur as early as a few months and as late as 20 years after the initial treatment [ 1 , 17 , 18 ], highlighting the importance of prolonged dynamic monitoring for timely diagnosis. Despite the high frequency of local recurrences, distant metastases and death from the disease are extremely rare. In the reviewed literature, only three cases of distant metastases and two deaths have been reported [ 9 – 11 ]. Preoperative diagnosis Pre-operative diagnosis is often challenging because of the rarity of these tumors and the absence of pathognomonic signs. Most cases are diagnosed histologically after the initial surgical resection. Incisional (pre-operative) biopsy also seems often inconclusive, as a larger tissue sample is usually required for an accurate diagnosis. Precise imaging is therefore crucial to assess tumor extent, detect any trans-levator spread, and evaluate the lesion’s relationship to the anal sphincter, urethra, bladder and lateral pelvic wall. This information guides operative planning and patient counselling. Ultrasound may also be used. CT appearances are variable but generally show a homogeneous, well-defined mass that is hypodense relative to muscle, or a predominantly cystic lesion with dense inclusions. Contrast-enhanced MRI with gadolinium is an important modality, particularly T2-weighted sequences, on which the tumor appears hyperintense relative to muscle [ 19 , 20 ]. MRI is reliable for identifying both primary disease and recurrence, as recurrent lesions exhibit the same signal characteristics as the original tumor. Ultrasound can additionally serve for dynamic follow-up. Morphological, Immunohistochemical, and Molecular Characteristics of the Tumor Macroscopically, the tumor often has a smooth surface and homogeneous consistency and may appear partially or completely encapsulated, although a true capsule is usually absent. The cut surface is shiny and gelatinous, with a bluish-gray color and focal areas of hemorrhage [ 1 ]. Tumor size varies but typically ranges from 10–20 cm or more. Microscopically, the classic type of deep aggressive angiomyxoma is characterized by a hypocellular mesenchymal lesion composed of a small number of spindle-shaped and stellate cells scattered within a loose myxoid stroma that contains wavy collagen fibers and numerous small- to medium-sized blood vessels [ 1 – 5 ]. The cells have abundant, finely eosinophilic cytoplasm with bland, oval nuclei [ 21 ]. There is no cytological atypia, no abnormal mitotic activity, and no coagulative necrosis. Immunohistochemically, tumor cells show diffuse staining for estrogen receptor (ER), progesterone receptor (PR), desmin, smooth-muscle actin (SMA) and vimentin. CD34 expression is variable—positive in many but not all tumors [ 22 ]. Deep aggressive angiomyxoma may enlarge or recur during pregnancy, presumably because PR positivity confers hormone responsiveness [ 23 ]. A chromosomal anomaly involving 12q15, corresponding to HMGA2 (formerly HMGIC) gene rearrangement, has been identified in aggressive angiomyxoma [ 16 , 24 ]. Absence of consistent HMGA2 expression in the vascular component, together with its high frequency in spindle-shaped stromal cells, suggests that the stromal cells constitute the true neoplastic element, whereas the prominent vasculature is likely secondary. Immunohistochemical detection of HMGA2 in stromal cells can aid margin assessment when histological boundaries are difficult to define [ 15 , 24 ]. Surgical procedure and prognostic factors Due to the high risk of local recurrence, wide local excision with tumor-free margins has traditionally been considered the treatment of choice. Repeat excision is also recommended if the initial surgery is incomplete. In cases of angiomyxoma, involvement of the urinary tract, gastrointestinal tract, and bone has been described. Therefore, extensive surgical resection may be required to achieve “clean” margins, leading to significant operative morbidity. It is logical to assume that positive surgical margins are a strong predictor of local recurrence. However, a review of more than 100 cases published in 2020 showed that patients with positive margins had a recurrence rate similar to those with negative margins [ 23 ]. This finding correlates with that of Chan et al., published in 2000, in which patients with negative surgical margins remained disease-free at ten years in 50% of cases, compared with 40% of those with positive margins [ 12 ]. By contrast, a retrospective analysis of 17 patients with aggressive angiomyxoma published by Li et al. in 2022 revealed that positive tumor margins were associated with significantly lower disease-free survival (hazard ratio = 3.41, 95% CI 2.73–15.74; P = 0.012) [ 17 ]. In another case review, the authors suggested that the tumor’s location and size influence treatment outcomes. Specifically, patients with pelvic tumors had the worst prognosis, while those with vaginal tumors had a better prognosis [ 8 ]. Additionally, Li and colleagues noted that patients with tumors measuring 5–10 cm had the lowest disease-free survival, while those with tumors smaller than 5 cm had the highest disease-free survival rates. They also reported a non-significant trend toward a higher risk of recurrence in patients over the age of 34 (P = 0.67) [ 17 ]. Thus, while complete excision remains the goal, leaving microscopic disease may be acceptable when the tumor invades adjacent critical structures and an ultra-radical resection would cause disproportionate morbidity. Adjuvant treatment Most aggressive angiomyxomas are estrogen- and progesterone-receptor positive and are therefore likely to be hormonally dependent. This correlation suggests that therapy with estrogen-receptor antagonists (e.g., tamoxifen), gonadotropin-releasing hormone (GnRH) agonists, or aromatase inhibitors can be considered as treatment options for angiomyxoma [ 25 ]. All of these agents may be prescribed both as pre-operative therapy—to reduce tumor size and improve resectability—and as post-operative therapy to enhance local control. GnRH agonists have been used in several pre-menopausal women with aggressive angiomyxoma. However, the adverse effects of prolonged GnRH-agonist use (e.g., menopausal symptoms and bone loss) and tumor regrowth after treatment cessation, as observed in one patient, limit their routine application [ 26 ]. Tumor progression despite tamoxifen has also been reported in a single case [ 27 ]. Given the tumor’s low mitotic activity, radiation therapy or chemotherapy is unlikely to be useful as an adjunct to primary surgery. There are no data on the use of conventional chemotherapy in aggressive angiomyxoma. In one report, pre-operative external-beam radiotherapy combined with intra-operative electron-beam therapy was applied to reduce recurrence risk, but follow-up data were unavailable [ 28 ]. In our series, one patient received stereotactic radiotherapy for residual disease, although the outcome remains uncertain. Two other cases in the literature have described successful control of recurrent angiomyxoma with relatively high-dose external-beam radiotherapy [ 29 , 30 ]. Dynamic follow-up may be an appropriate strategy for asymptomatic tumors or for recurrences in which surgery would entail a high risk of resecting adjacent organs [ 31 ]. Conclusion Our two cases highlight several practical lessons. First, aggressive angiomyxoma can mimic other mesenchymal lesions. One of the tumors was initially incorrectly labeled as capillary hemangioma. The combination of the characteristic “swirl” pattern on T2-weighted MRI and confirmatory immunohistochemistry for ER, PR and desmin was the deciding factor, underlining the importance of specialist radiological interpretation and sarcoma-trained pathology in case where large myxoid lesion arises in the vulvo-pelvic region. Second, margin status alone should not dictate ultra-radical surgery. The first patient remains disease-free 12 months after a margin-positive resection supplemented by tamoxifen and stereotactic radiotherapy, whereas the second achieved the same outcome after an R0 excision plus endocrine therapy. It suggests that function-sparing removal combined with endocrine therapy can control ER/PR-positive tumors while avoiding excessive morbidity. A tailored abdomino-perineal surgical approach allowed for effective mobilization and resection of large pelvic aggressive angiomyxomas, permitting selective margin sacrifice when necessary, without adversely affecting early postoperative outcomes. Since late local recurrence is well recognized, continued imaging surveillance remains essential even after apparently successful treatment. Cumulatively, these observations support a multidisciplinary, risk-adapted strategy: confirm the diagnosis with MRI and expert histology, aim for organ-preserving resection even if microscopic disease is left behind, integrate endocrine therapy for hormone-receptor-positive tumors, and maintain lifelong follow-up. Collaborative registries are now necessary to determine the optimal duration of endocrine therapy and to identify predictors of recurrence. Declarations Conflicts of interest The authors declare that they have no conflict of interest. Financial declaration The authors received no financial support for the research, authorship, and publication of this article. Acknowledgements The authors have no acknowledgements to declare. Ethical Approval and Patient Consent This study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from both patients for the publication of this case series and any accompanying images. Authors' contributions Maksim Isachanka: Conceptualized case series, writing original draft, editing, literature review. Sergey Mavrichev: Supervised the project, revised the manuscript critically for intellectual content, and approved the final version Yana Kamko: collected clinical, radiological, pathological, or laboratory data, reviewed the chart and summarized finding, performed a comprehensive literature search Hanna Trukhan: performed a comprehensive literature search, Supervised the writing and publication process Aliaksandra Hryshel: Supervised the writing and publication process Alena Dalamanava: Supervised the writing and publication process Dmitry Rovski: Critically revised the manuscript for intellectual content References Steeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum: Report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm*. The American Journal of Surgical Pathology. 1983 Jul;7(5):463–76. Bégin LR, Clement PB, Kirk ME, Jothy S, Elliott McCaughey WT, Ferenczy A. Aggressive angiomyxoma of pelvic soft parts: A clinicopathologic study of nine cases. Human Pathology. 1985 Jun;16(6):621–8. Fetsch JF, Laskin WB, Lefkowitz M, Kindblom LG, Meis-Kindblom JM. Aggressive angiomyxoma: A clinicopathologic study of 29 female patients. Cancer. 1996 Jul 1;78(1):79–90. Granter SR, Nucci MR, Fletcher CDM. Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma in a series of 16 cases. Histopathology. 1997 Jan;30(1):3–10. Amezcua CA, Begley SJ, Mata N, Felix JC, Ballard CA. Aggressive angiomyxoma of the female genital tract: a clinicopathologic and immunohistochemical study of 12 cases. Int J Gynecol Cancer. 2005 Jan;15(1):140–5. Magro G, Angelico G, Michal M, Broggi G, Zannoni GF, Covello R, et al. The Wide Morphological Spectrum of Deep (Aggressive) Angiomyxoma of the Vulvo-Vaginal Region: A Clinicopathologic Study of 36 Cases, including Recurrent Tumors. Diagnostics. 2021 Jul 28;11(8):1360. Herrington CS, (ed.), Editorial Board WHOCOT. WHO Classification of Tumours Female Genital Tumours. 5th ed. International Agency for Research on Cancer, 2020. Dellino M, Magazzino F, Domenici L, Cicogna S, Miano ST, Pignata S, et al. Aggressive Angiomyxoma of the Lower Female Genital Tract: A Review of the MITO Rare Tumors Group. Cancers. 2024 Mar 31;16(7):1375. Siassi RM, Papadopoulos T, Matzel KE. Metastasizing Aggressive Angiomyxoma. N Engl J Med. 1999 Dec 2;341(23):1772–1772. Blandamura S, Cruz J, Faure Vergara L, Machado Puerto I, Ninfo V. Aggressive angiomyxoma: a second case of metastasis with patient’s death. Human Pathology. 2003 Oct;34(10):1072–4. Siddiqui SF. Rare case of metastatic aggressive angiomyxoma-first case of renal metastasis. Gynecology & Obstetrics Case report. 2020 Oct 19;6. Chan IM, Hon E, Ngai SW, Ng TY, Wong LC. Aggressive angiomyxoma in females: is radical resection the only option? Acta Obstet Gynecol Scand. 2000 Jan;79(3):216–20. Fucà G, Hindi N, Ray-Coquard I, Colia V, Dei Tos AP, Martin-Broto J, et al. Treatment Outcomes and Sensitivity to Hormone Therapy of Aggressive Angiomyxoma: A Multicenter, International, Retrospective Study. The Oncologist. 2019 Jul 1;24(7):e536–41. Dahiya K, Jain S, Duhan N, Nanda S, Kundu P. Aggressive angiomyxoma of vulva and vagina: a series of three cases and review of literature. Arch Gynecol Obstet. 2011 May;283(5):1145–8. Haldar K, Martinek IE, Kehoe S. Aggressive angiomyxoma: A case series and literature review. European Journal of Surgical Oncology (EJSO). 2010 Apr;36(4):335–9. Nucci, Fletcher. Vulvovaginal soft tissue tumours: update and review. Histopathology. 2000 Feb;36(2):97–108. Li J, You L, Wang C, Zhao H, Guo W, Yu J, et al. Clinicopathological characteristics and prognosis analysis of Aggressive angiomyxoma: A Retrospective Study [Internet]. In Review; 2022 [cited 2025 Jul 5]. Available from: https://www.researchsquare.com/article/rs-2335657/v1 Schwartz PE, Hui P, McCarthy S. Hormonal Therapy for Aggressive Angiomyxoma: A Case Report and Proposed Management Algorithm. Journal of Lower Genital Tract Disease. 2014 Apr;18(2):E55–61. Jeyadevan NN, Sohaib SAA, Thomas JM, Jeyarajah A, Shepherd JH, Fisher C. Imaging Features of Aggressive Angiomyxoma. Clinical Radiology. 2003 Feb;58(2):157–62. Raptin C, Lucot JP, Bassil A, Poncelet E, Prolongeau JF, Phalippou J. Aggressive angiomyxoma of the perineal region. SAGE Open Medical Case Reports. 2019 Jan;7:2050313X19843391. Van Roggen JFG, Van Unnik JAM, Briaire-de Bruijn IH, Hogendoorn PCW. Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up. Virchows Arch. 2005 Feb;446(2):157–63. Choi H, Park C, Ji YI. Alternative surgical approaches for aggressive angiomyxoma at different sites in the pelvic cavity. Obstet Gynecol Sci. 2015;58(6):525. Xu H, Sun P, Xu R, Wang L, Shi Y. Aggressive angiomyxoma in pregnancy: a case report and literature review. J Int Med Res. 2020 Jul;48(7):0300060520936414. Nucci MR, Weremowicz S, Neskey DM, Sornberger K, Tallini G, Morton CC, et al. Chromosomal translocation t(8;12) induces aberrant HMGIC expression in aggressive angiomyxoma of the vulva. Genes Chromosomes & Cancer. 2001 Oct;32(2):172–6. Li J, You L, Wang C, Zhao H, Guo W, Yu J, Yuan Z, Qi S, Huang Y. Clinicopathological characteristics and prognosis analysis of aggressive angiomyxoma: a retrospective study. Res Sq. 2022. McCluggage WG, Jamieson T, Dobbs SP, Grey A. Aggressive angiomyxoma of the vulva: Dramatic response to gonadotropin-releasing hormone agonist therapy. Gynecologic Oncology. 2006 Mar;100(3):623–5. Magtibay PM, Salmon Z, Keeney GL, Podratz KC. Aggressive angiomyxoma of the female pelvis and perineum: a case series. Int J Gynecol Cancer. 2006 Jan;16(1):396–401. Nyam DCNK, Pemberton JH. Large aggressive angiomyxoma of the perineum and pelvis: An alternative approach Report of a case. Diseases of the Colon & Rectum. 1998 Apr;41(4):514–6. Rhomberg W, Jasarevic Z, Alton R, Kompatscher P, Beer G, Breitfellner G. Aggressive Angiomyxoma: Irradiation for Recurrent Disease. Strahlentherapie und Onkologie. 2000 Jun 1;176(7):324–6. Suleiman M, Duc C, Ritz S, Bieri S. Pelvic excision of large aggressive angiomyxoma in a woman: irradiation for recurrent disease. International Journal of Gynecological Cancer. 2006 Feb;16(S1):356–60. Behranwala KA, Thomas JM. ‘Aggressive’ angiomyxoma: a distinct clinical entity. European Journal of Surgical Oncology (EJSO). 2003 Sep;29(7):559–63. Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7069223","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":482044377,"identity":"58f2262d-c905-46ac-a3b7-cd7846c81260","order_by":0,"name":"Maksim Isachanka","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYFACNgaGBAYJOTb25gNAnoQMsVosjPl5jiWAtPAQp4WBoSJx5gwfAxCLsBbd9mPJHx7mSBgb3OD5/OpGjQUPA/vhoxvwaTE7k3ZMInGbhJzB7d5t1jnHgA7jSUu7gVfLgfQ2BqAWY4M7Z7cZ57ABtUjwmOHXcv558weglsQNN3KeGef8I0bLjbQDIIcBvZ/D/Di3jSgtz9JAWkCBbMac2yfBw0bQL+fTjD/+3FYHisrHn3O+1cnxsx8+hlcLMmCTAJPEKgcB5g+kqB4Fo2AUjIKRAwCLjksAkGyakQAAAABJRU5ErkJggg==","orcid":"https://orcid.org/0009-0004-1727-7994","institution":"Boston Medical Center - Brighton","correspondingAuthor":true,"prefix":"","firstName":"Maksim","middleName":"","lastName":"Isachanka","suffix":""},{"id":482044378,"identity":"abea7789-c0e7-48cd-ba6b-e6703366821a","order_by":1,"name":"Sergey Mavrichev","email":"","orcid":"","institution":"Oncological gynecological department, N.N. Alexandrov National Cancer Centre of Belarus","correspondingAuthor":false,"prefix":"","firstName":"Sergey","middleName":"","lastName":"Mavrichev","suffix":""},{"id":482044379,"identity":"61bf17d1-8cf3-4962-a237-0d28bdc9cacc","order_by":2,"name":"Yana Kamko","email":"","orcid":"","institution":"Oncological gynecological department, N.N. Alexandrov National Cancer Centre of Belarus","correspondingAuthor":false,"prefix":"","firstName":"Yana","middleName":"","lastName":"Kamko","suffix":""},{"id":482044380,"identity":"899db89a-4281-4ad0-beca-427cf92a07e1","order_by":3,"name":"Hanna Trukhan","email":"","orcid":"","institution":"Department of Oncology, Belarusian State Medical University","correspondingAuthor":false,"prefix":"","firstName":"Hanna","middleName":"","lastName":"Trukhan","suffix":""},{"id":482044381,"identity":"270eea24-1cbe-4387-8708-58bc27659107","order_by":4,"name":"Aliaksandra Hryshel","email":"","orcid":"","institution":"Oncological gynecological department, N.N. Alexandrov National Cancer Centre of Belarus","correspondingAuthor":false,"prefix":"","firstName":"Aliaksandra","middleName":"","lastName":"Hryshel","suffix":""},{"id":482044382,"identity":"9d8c5f97-d375-4051-bc9c-11b97d9a5149","order_by":5,"name":"Alena Dalamanava","email":"","orcid":"","institution":"Oncological gynecological department, N.N. Alexandrov National Cancer Centre of Belarus","correspondingAuthor":false,"prefix":"","firstName":"Alena","middleName":"","lastName":"Dalamanava","suffix":""},{"id":482044383,"identity":"5f20cbc5-09c3-4729-ad82-2ecdc9b0e77a","order_by":6,"name":"Dmitry Rovski","email":"","orcid":"","institution":"Oncological gynecological department, N.N. Alexandrov National Cancer Centre of Belarus","correspondingAuthor":false,"prefix":"","firstName":"Dmitry","middleName":"","lastName":"Rovski","suffix":""}],"badges":[],"createdAt":"2025-07-08 00:42:28","currentVersionCode":1,"declarations":{"humanSubjects":true,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":true,"humanSubjectConsent":true,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":true,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-7069223/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7069223/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":86301926,"identity":"8e3903bf-c6ae-4d41-8589-fde492738f9e","added_by":"auto","created_at":"2025-07-09 06:31:24","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":336420,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI-scans of the recurrent tumor of the first case\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-7069223/v1/369e94e4b5bd573325c20a09.png"},{"id":86302282,"identity":"1b7015ba-c0af-49cb-91d4-eeabd89ad493","added_by":"auto","created_at":"2025-07-09 06:39:26","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":734282,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHistopathology and IHC of the tumor of the first patient.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-7069223/v1/d0f49b53dd3e1f40a1bf6358.png"},{"id":86301924,"identity":"22ea33db-59ca-454b-a15b-692bf45ce441","added_by":"auto","created_at":"2025-07-09 06:31:24","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":354196,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI-scans of the primary tumor of the second patient.\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-7069223/v1/798d19a6583328177420e0e4.png"},{"id":86301929,"identity":"6e4a2f46-72ab-46cc-a584-7380c77ddf0a","added_by":"auto","created_at":"2025-07-09 06:31:24","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":155591,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eMRI-scans of the recurrent tumor of the second patient\u003c/strong\u003e\u003cem\u003e\u003cstrong\u003e.\u003c/strong\u003e\u003c/em\u003e\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-7069223/v1/f6fd6f82c991314ed5f3abd6.png"},{"id":86363706,"identity":"5d21e0a1-bb59-40b5-9d4c-d58cfe22c9ed","added_by":"auto","created_at":"2025-07-09 20:00:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2288647,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7069223/v1/77099c14-54c4-499d-88ef-616ca750b8f8.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003eRecurrent Aggressive Angiomyxoma: A Single-Institution Case Series on Management and Outcomes\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Introduction","content":"\u003cp\u003eDeep aggressive angiomyxoma (AA) is a rare mesenchymal soft tissue tumor characterized by a locally infiltrative growth pattern and low metastatic potential. It typically involves the vulvovaginal region, perineum, and pelvis in women, with a peak incidence during the reproductive years [1-6]. According to the 5\u003csup\u003eth\u003c/sup\u003e edition of the WHO classification, AA is considered a benign tumor. The term \"aggressive\" is therefore used to highlight its potential for infiltrative local behavior and high rate of recurrence, rather than malignant potential [7,8].\u003c/p\u003e\n\u003cp\u003eThe clinical behavior of AA is characterized by slow growth, high expression of estrogen and progesterone receptors, and an infiltrative pattern that often involves surrounding soft tissues.\u0026nbsp;This tumor type shows a high local‑recurrence rate (30–70 %) but a low metastatic potential, although rare distant metastases have been reported\u0026nbsp;[9-11]. Definitive preoperative diagnosis is challenging due to the tumor's rarity and non-specific presentation, often making the final diagnosis possible only after surgical resection. Incomplete excision is a common challenge due to the lack of a clear tumor capsule and infiltrative margins that are often visible only on\u0026nbsp;histological examination [12]. Local recurrence frequently occurs even after macroscopically complete resection\u0026nbsp;and surgical radicality has not been shown to\u0026nbsp;prolong\u0026nbsp;the progression‑free interval [12].\u0026nbsp;Management may also include systemic therapy, primarily hormone‑based, and, in selected cases, radiotherapy. Gonadotropin-releasing hormone (GnRH) agonists are the agents most frequently used as adjuvant treatment and disease control, although aromatase inhibitors and selective estrogen‑receptor modulators have also been reported [13]. Prophylactic bilateral oophorectomy has been described, but its role remains uncertain [14].\u003c/p\u003e\n\u003cp\u003eAggressive angiomyxoma was first described in 1983 and since then, fewer than 250 cases have been reported in the literature [15]. Due to its rarity, the optimal treatment strategy remains unclear.\u0026nbsp;Therefore, two cases presented in this article offer additional evidence that may inform future discussion and the development of clinical guidelines.\u0026nbsp;\u003c/p\u003e"},{"header":"Case 1","content":"\u003cp\u003eA 31-year-old female (gravida 1, para 1) was referred to our institution for evaluation of a pelvic mass. In 2018 she underwent excision of a right gluteal tumor at a regional hospital. The pathology at that time was reportedly consistent with a capillary hemangioma\u0026nbsp;with secondary changes. However, the original slides were unavailable for review.\u003c/p\u003e\n\u003cp\u003eThe patient remained asymptomatic until 2023, when she developed pain in the postoperative scar, exacerbated by prolonged sitting. An initial ultrasound of the scar revealed no abnormalities. Due to the progression of her symptoms, a pelvic magnetic resonance imaging (MRI) was performed in April 2024. The scan revealed a large, well-circumscribed mass measuring 7.6 x 9.4 x 7.2 cm in the right pelvic soft tissues, which displaced the vagina, uterus, and rectum to the left without definitive signs of invasion (Fig. 1).\u003c/p\u003e\n\u003cp\u003eIn May 2024 the patient was referred to National Cancer Center of Belarus. In June 2024, she underwent surgical resection of the tumor. A soft, elastic, multinodular mass measuring 13.0 x 8.0 x 6.0 cm was removed. The final histopathological diagnosis was aggressive angiomyxoma. Microscopic examination confirmed that the surgical margins were positive for tumor. Immunohistochemistry (IHC) showed positivity for Desmin, STAT6, estrogen receptors (100%), progesterone receptors (100%), and focally positive for smooth muscle actin (SMA). The stain was negative for h-Caldesmon, CD10, CD34, CD117, CyclinD1, DOG1, and S100. The Ki-67 was less than 1% (Fig. 2). Given the positive surgical margins and strong hormone receptor expression, a multidisciplinary decision was made to proceed with adjuvant therapy. The patient was started on tamoxifen 20 mg daily and subsequently underwent stereotactic radiotherapy to the tumor bed. At three-month follow-up after the completion of radiotherapy, a pelvic MRI showed partial regression of the residual tumor.\u003c/p\u003e"},{"header":"Case 2 ","content":"\u003cp\u003eA 33-year-old female (gravida 2, para 2) presented to our center in 2018 with a progressively enlarging left labia majora, a symptom she first noted in 2015. Initial workup included CT and MRI of the abdomen and pelvis. The imaging revealed a large, complex, cystic-solid mass measuring 10.5 x 10.2 x 28.0 cm, originating in the pelvis and extending into the presacral space, right iliac region and left labium. The tumor displaced the rectum and vagina to the right, the uterus and ovaries anteriorly, and the cecum superiorly and leftward. The mass demonstrated a layered structure with a high T2-weighted signal, low T1-weighted signal, and heterogeneous peripheral contrast enhancement (Fig. 3).\u003c/p\u003e\n\u003cp\u003eIn January 2019, the patient underwent a laparotomy with a perineal approach for resection of the retroperitoneal tumor. The final pathology confirmed aggressive angiomyxoma, but the status of the resection margins was not recorded. The patient was therefore\u0026nbsp;followed with close surveillance.\u003c/p\u003e\n\u003cp\u003eIn September 2024, a routine follow-up CT scan revealed a recurrent, irregular, hypodense mass in the left pelvic region that was inseparable from the left wall of the rectum and cervix. Subsequent pelvic MRI confirmed a recurrent heterogeneous tumor measuring 3.4 x 10.5 x 10.0 cm in the presacral space, which was closely abutting the rectum without definite evidence of invasion (Fig. 4).\u003c/p\u003e\n\u003cp\u003eIn October 2024 the patient underwent repeat surgery for excision of the recurrent pelvic tumor.\u0026nbsp;The procedure required partial resection of the lateral vaginal wall and the left lateral wall of the rectum, with the creation of a diverting loop sigmoidostomy. Histopathology was again consistent with aggressive angiomyxoma. Immunohistochemistry showed positivity for Desmin, smooth muscle actin (SMA), estrogen receptors (90%), and progesterone receptors (90%), while negative for CD34 (though positive in endothelial cells as an internal control). The Ki-67 proliferation index was approximately 1%.\u003c/p\u003e\n\u003cp\u003eGiven the tumor\u0026apos;s recurrent nature and hormone receptor positivity, the patient was started on long-term adjuvant therapy with tamoxifen 20 mg daily. A follow-up pelvic MRI six months after surgery demonstrated no residual or recurrent disease.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 1. Main characteristics of the presented cases.\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"804\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\u003cbr\u003e\u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eFirst case\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e\u003cstrong\u003e\u003cem\u003eSecond case\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge at first visit\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e31 y.o.\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e33 y.o.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocalization of primary\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003etumor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eGluteal area\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003ePelvic cavity, left iliac region with involvement of the left labia majora\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eNumber of recurrences\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTime to first relapse\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e5 years\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e5 years\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLocalization of the\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003erecurrent tumor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eSoft tissues of the perineum\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003ePelvic cavity, left iliac region\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDimensions of the \u0026nbsp; \u0026nbsp; \u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003erecurrent tumor\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e13.0x8.0x6.0 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e3.4х10.5х10 cm\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePrimary treatment of the\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003erecurrence\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eSurgery, R2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003eSurgery, R0\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAdjuvant treatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eTamoxifen 20 mg daily long-term; stereotactic radiotherapy to the area of residual tumor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003eTamoxifen 20 mg daily long-term\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePathology review, IHC\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eDesmin+, SMA+ (focal), r-Estrogen+ (100%), r-Progesterone+ (100%), DOG1-, S100-, STAT6+, Ki-67\u0026lt;1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003eDesmin+, SMA+, r-Estrogen+ (90%), r-Progesterone+ (90%), CD34- (+ in the vascular endothelium), Ki-67 ~1%\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eDuration of observation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003e12 months\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003e8 months\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 222px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eStatus at last follow-up\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 283px;\"\u003e\n \u003cp\u003eMRI without signs of progression, patient without complaints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 298px;\"\u003e\n \u003cp\u003eMRI with\u0026nbsp;no residual or recurrent disease.\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eAggressive angiomyxoma (AAM) is a rare, locally infiltrative connective-tissue tumor that affects predominantly women of reproductive age, shows marked variability in biological behavior with a high propensity for local recurrence, and rarely metastasizes. The prevailing pathogenetic hypothesis is that AAM originates from a primitive multipotent mesenchymal cells of the lower female genital tract, capable of divergent differentiation [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eClinical course\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAngiomyxomas can exhibit slow, subtle growth. As a result, patients may remain asymptomatic for a long period. The initial clinical presentation can range from an asymptomatic tumor nodule to large masses occupying a significant portion of the pelvis, causing pain, discomfort, a feeling of heaviness in the pelvis, dyspareunia, and deformation of the abdomen, perineum, or external genitalia. Data suggest that deep aggressive angiomyxoma almost exclusively affects the genital, perineal, and pelvic regions in women of reproductive age, especially the vulva. Less commonly, it can involve the buttocks, retroperitoneal space, and inguinal region. Aggressive angiomyxoma typically displaces neighboring organs without overt invasion. However, its infiltrative margins may ultimately extend into adjacent organs over time, necessitating extensive resections during surgical interventions [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. It has been reported that the recurrence rate is high, ranging from 30\u0026ndash;70% [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. No statistically significant association has been established between patient age or tumor size and recurrence frequency [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Multiple recurrences (three to six) are common, and more than half of the recurrences involve neighboring organs [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Like primary tumors, recurrences often remain asymptomatic, with most cases recurring within two years. However, recurrence can occur as early as a few months and as late as 20 years after the initial treatment [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e], highlighting the importance of prolonged dynamic monitoring for timely diagnosis. Despite the high frequency of local recurrences, distant metastases and death from the disease are extremely rare. In the reviewed literature, only three cases of distant metastases and two deaths have been reported [\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cem\u003ePreoperative diagnosis\u003c/em\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003ePre-operative diagnosis is often challenging because of the rarity of these tumors and the absence of pathognomonic signs. Most cases are diagnosed histologically after the initial surgical resection. Incisional (pre-operative) biopsy also seems often inconclusive, as a larger tissue sample is usually required for an accurate diagnosis. Precise imaging is therefore crucial to assess tumor extent, detect any trans-levator spread, and evaluate the lesion\u0026rsquo;s relationship to the anal sphincter, urethra, bladder and lateral pelvic wall. This information guides operative planning and patient counselling.\u003c/p\u003e\u003cp\u003eUltrasound may also be used. CT appearances are variable but generally show a homogeneous, well-defined mass that is hypodense relative to muscle, or a predominantly cystic lesion with dense inclusions. Contrast-enhanced MRI with gadolinium is an important modality, particularly T2-weighted sequences, on which the tumor appears hyperintense relative to muscle [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. MRI is reliable for identifying both primary disease and recurrence, as recurrent lesions exhibit the same signal characteristics as the original tumor. Ultrasound can additionally serve for dynamic follow-up.\u003c/p\u003e\u003cp\u003e\u003cem\u003eMorphological, Immunohistochemical, and Molecular Characteristics of the Tumor\u003c/em\u003e\u003c/p\u003e\u003cp\u003eMacroscopically, the tumor often has a smooth surface and homogeneous consistency and may appear partially or completely encapsulated, although a true capsule is usually absent. The cut surface is shiny and gelatinous, with a bluish-gray color and focal areas of hemorrhage [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Tumor size varies but typically ranges from 10\u0026ndash;20 cm or more. Microscopically, the classic type of deep aggressive angiomyxoma is characterized by a hypocellular mesenchymal lesion composed of a small number of spindle-shaped and stellate cells scattered within a loose myxoid stroma that contains wavy collagen fibers and numerous small- to medium-sized blood vessels [\u003cspan additionalcitationids=\"CR2 CR3 CR4\" citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The cells have abundant, finely eosinophilic cytoplasm with bland, oval nuclei [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. There is no cytological atypia, no abnormal mitotic activity, and no coagulative necrosis. Immunohistochemically, tumor cells show diffuse staining for estrogen receptor (ER), progesterone receptor (PR), desmin, smooth-muscle actin (SMA) and vimentin. CD34 expression is variable\u0026mdash;positive in many but not all tumors [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. Deep aggressive angiomyxoma may enlarge or recur during pregnancy, presumably because PR positivity confers hormone responsiveness [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. A chromosomal anomaly involving 12q15, corresponding to HMGA2 (formerly HMGIC) gene rearrangement, has been identified in aggressive angiomyxoma [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. Absence of consistent HMGA2 expression in the vascular component, together with its high frequency in spindle-shaped stromal cells, suggests that the stromal cells constitute the true neoplastic element, whereas the prominent vasculature is likely secondary. Immunohistochemical detection of HMGA2 in stromal cells can aid margin assessment when histological boundaries are difficult to define [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003e\u003cem\u003eSurgical procedure and prognostic factors\u003c/em\u003e\u003c/p\u003e\u003cp\u003eDue to the high risk of local recurrence, wide local excision with tumor-free margins has traditionally been considered the treatment of choice. Repeat excision is also recommended if the initial surgery is incomplete. In cases of angiomyxoma, involvement of the urinary tract, gastrointestinal tract, and bone has been described. Therefore, extensive surgical resection may be required to achieve \u0026ldquo;clean\u0026rdquo; margins, leading to significant operative morbidity.\u003c/p\u003e\u003cp\u003eIt is logical to assume that positive surgical margins are a strong predictor of local recurrence. However, a review of more than 100 cases published in 2020 showed that patients with positive margins had a recurrence rate similar to those with negative margins [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. This finding correlates with that of Chan et al., published in 2000, in which patients with negative surgical margins remained disease-free at ten years in 50% of cases, compared with 40% of those with positive margins [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. By contrast, a retrospective analysis of 17 patients with aggressive angiomyxoma published by Li et al. in 2022 revealed that positive tumor margins were associated with significantly lower disease-free survival (hazard ratio\u0026thinsp;=\u0026thinsp;3.41, 95% CI 2.73\u0026ndash;15.74; P\u0026thinsp;=\u0026thinsp;0.012) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn another case review, the authors suggested that the tumor\u0026rsquo;s location and size influence treatment outcomes. Specifically, patients with pelvic tumors had the worst prognosis, while those with vaginal tumors had a better prognosis [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. Additionally, Li and colleagues noted that patients with tumors measuring 5\u0026ndash;10 cm had the lowest disease-free survival, while those with tumors smaller than 5 cm had the highest disease-free survival rates. They also reported a non-significant trend toward a higher risk of recurrence in patients over the age of 34 (P\u0026thinsp;=\u0026thinsp;0.67) [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThus, while complete excision remains the goal, leaving microscopic disease may be acceptable when the tumor invades adjacent critical structures and an ultra-radical resection would cause disproportionate morbidity.\u003c/p\u003e\u003cp\u003e\u003cem\u003eAdjuvant treatment\u003c/em\u003e\u003c/p\u003e\u003cp\u003eMost aggressive angiomyxomas are estrogen- and progesterone-receptor positive and are therefore likely to be hormonally dependent. This correlation suggests that therapy with estrogen-receptor antagonists (e.g., tamoxifen), gonadotropin-releasing hormone (GnRH) agonists, or aromatase inhibitors can be considered as treatment options for angiomyxoma [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. All of these agents may be prescribed both as pre-operative therapy\u0026mdash;to reduce tumor size and improve resectability\u0026mdash;and as post-operative therapy to enhance local control. GnRH agonists have been used in several pre-menopausal women with aggressive angiomyxoma. However, the adverse effects of prolonged GnRH-agonist use (e.g., menopausal symptoms and bone loss) and tumor regrowth after treatment cessation, as observed in one patient, limit their routine application [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Tumor progression despite tamoxifen has also been reported in a single case [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eGiven the tumor\u0026rsquo;s low mitotic activity, radiation therapy or chemotherapy is unlikely to be useful as an adjunct to primary surgery. There are no data on the use of conventional chemotherapy in aggressive angiomyxoma. In one report, pre-operative external-beam radiotherapy combined with intra-operative electron-beam therapy was applied to reduce recurrence risk, but follow-up data were unavailable [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. In our series, one patient received stereotactic radiotherapy for residual disease, although the outcome remains uncertain. Two other cases in the literature have described successful control of recurrent angiomyxoma with relatively high-dose external-beam radiotherapy [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eDynamic follow-up may be an appropriate strategy for asymptomatic tumors or for recurrences in which surgery would entail a high risk of resecting adjacent organs [\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e].\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eOur two cases highlight several practical lessons. First, aggressive angiomyxoma can mimic other mesenchymal lesions. One of the tumors was initially incorrectly labeled as capillary hemangioma. The combination of the characteristic \u0026ldquo;swirl\u0026rdquo; pattern on T2-weighted MRI and confirmatory immunohistochemistry for ER, PR and desmin was the deciding factor, underlining the importance of specialist radiological interpretation and sarcoma-trained pathology in case where large myxoid lesion arises in the vulvo-pelvic region.\u003c/p\u003e\u003cp\u003eSecond, margin status alone should not dictate ultra-radical surgery. The first patient remains disease-free 12 months after a margin-positive resection supplemented by tamoxifen and stereotactic radiotherapy, whereas the second achieved the same outcome after an R0 excision plus endocrine therapy. It suggests that function-sparing removal combined with endocrine therapy can control ER/PR-positive tumors while avoiding excessive morbidity.\u003c/p\u003e\u003cp\u003eA tailored abdomino-perineal surgical approach allowed for effective mobilization and resection of large pelvic aggressive angiomyxomas, permitting selective margin sacrifice when necessary, without adversely affecting early postoperative outcomes. Since late local recurrence is well recognized, continued imaging surveillance remains essential even after apparently successful treatment.\u003c/p\u003e\u003cp\u003eCumulatively, these observations support a multidisciplinary, risk-adapted strategy: confirm the diagnosis with MRI and expert histology, aim for organ-preserving resection even if microscopic disease is left behind, integrate endocrine therapy for hormone-receptor-positive tumors, and maintain lifelong follow-up. Collaborative registries are now necessary to determine the optimal duration of endocrine therapy and to identify predictors of recurrence.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eConflicts of interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no conflict of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFinancial declaration\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors received no financial support for the research, authorship, and publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no acknowledgements to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthical Approval and Patient Consent\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the principles of the Declaration of Helsinki. Written informed consent was obtained from both patients for the publication of this case series and any accompanying images.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eMaksim Isachanka: Conceptualized case series, writing original draft, editing, literature review.\u003c/p\u003e\n\u003cp\u003eSergey Mavrichev: Supervised the project, revised the manuscript critically for intellectual content, and approved the final version\u003c/p\u003e\n\u003cp\u003eYana Kamko: collected\u0026nbsp;clinical, radiological, pathological, or laboratory data,\u0026nbsp;reviewed the chart and summarized finding, performed a comprehensive literature search\u003c/p\u003e\n\u003cp\u003eHanna Trukhan: performed a comprehensive literature search,\u0026nbsp;Supervised the writing and publication process\u003c/p\u003e\n\u003cp\u003eAliaksandra Hryshel: Supervised the writing and publication process\u003c/p\u003e\n\u003cp\u003eAlena Dalamanava: Supervised the writing and publication process\u003c/p\u003e\n\u003cp\u003eDmitry Rovski: Critically revised the manuscript for intellectual content\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eSteeper TA, Rosai J. Aggressive angiomyxoma of the female pelvis and perineum: Report of nine cases of a distinctive type of gynecologic soft-tissue neoplasm*. The American Journal of Surgical Pathology. 1983 Jul;7(5):463\u0026ndash;76.\u003c/li\u003e\n \u003cli\u003eB\u0026eacute;gin LR, Clement PB, Kirk ME, Jothy S, Elliott McCaughey WT, Ferenczy A. Aggressive angiomyxoma of pelvic soft parts: A clinicopathologic study of nine cases. Human Pathology. 1985 Jun;16(6):621\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eFetsch JF, Laskin WB, Lefkowitz M, Kindblom LG, Meis-Kindblom JM. Aggressive angiomyxoma: A clinicopathologic study of 29 female patients. Cancer. 1996 Jul 1;78(1):79\u0026ndash;90.\u003c/li\u003e\n \u003cli\u003eGranter SR, Nucci MR, Fletcher CDM. Aggressive angiomyxoma: reappraisal of its relationship to angiomyofibroblastoma in a series of 16 cases. Histopathology. 1997 Jan;30(1):3\u0026ndash;10.\u003c/li\u003e\n \u003cli\u003eAmezcua CA, Begley SJ, Mata N, Felix JC, Ballard CA. Aggressive angiomyxoma of the female genital tract: a clinicopathologic and immunohistochemical study of 12 cases. Int J Gynecol Cancer. 2005 Jan;15(1):140\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eMagro G, Angelico G, Michal M, Broggi G, Zannoni GF, Covello R, et al. The Wide Morphological Spectrum of Deep (Aggressive) Angiomyxoma of the Vulvo-Vaginal Region: A Clinicopathologic Study of 36 Cases, including Recurrent Tumors. Diagnostics. 2021 Jul 28;11(8):1360.\u003c/li\u003e\n \u003cli\u003eHerrington CS, (ed.), Editorial Board WHOCOT. WHO Classification of Tumours Female Genital Tumours. 5th ed. International Agency for Research on Cancer, 2020.\u003c/li\u003e\n \u003cli\u003eDellino M, Magazzino F, Domenici L, Cicogna S, Miano ST, Pignata S, et al. Aggressive Angiomyxoma of the Lower Female Genital Tract: A Review of the MITO Rare Tumors Group. Cancers. 2024 Mar 31;16(7):1375.\u003c/li\u003e\n \u003cli\u003eSiassi RM, Papadopoulos T, Matzel KE. Metastasizing Aggressive Angiomyxoma. N Engl J Med. 1999 Dec 2;341(23):1772\u0026ndash;1772.\u003c/li\u003e\n \u003cli\u003eBlandamura S, Cruz J, Faure Vergara L, Machado Puerto I, Ninfo V. Aggressive angiomyxoma: a second case of metastasis with patient\u0026rsquo;s death. Human Pathology. 2003 Oct;34(10):1072\u0026ndash;4.\u003c/li\u003e\n \u003cli\u003eSiddiqui SF. Rare case of metastatic aggressive angiomyxoma-first case of renal metastasis. Gynecology \u0026amp; Obstetrics Case report. 2020 Oct 19;6.\u003c/li\u003e\n \u003cli\u003eChan IM, Hon E, Ngai SW, Ng TY, Wong LC. Aggressive angiomyxoma in females: is radical resection the only option? Acta Obstet Gynecol Scand. 2000 Jan;79(3):216\u0026ndash;20.\u003c/li\u003e\n \u003cli\u003eFuc\u0026agrave; G, Hindi N, Ray-Coquard I, Colia V, Dei Tos AP, Martin-Broto J, et al. Treatment Outcomes and Sensitivity to Hormone Therapy of Aggressive Angiomyxoma: A Multicenter, International, Retrospective Study. The Oncologist. 2019 Jul 1;24(7):e536\u0026ndash;41.\u003c/li\u003e\n \u003cli\u003eDahiya K, Jain S, Duhan N, Nanda S, Kundu P. Aggressive angiomyxoma of vulva and vagina: a series of three cases and review of literature. Arch Gynecol Obstet. 2011 May;283(5):1145\u0026ndash;8.\u003c/li\u003e\n \u003cli\u003eHaldar K, Martinek IE, Kehoe S. Aggressive angiomyxoma: A case series and literature review. European Journal of Surgical Oncology (EJSO). 2010 Apr;36(4):335\u0026ndash;9.\u003c/li\u003e\n \u003cli\u003eNucci, Fletcher. Vulvovaginal soft tissue tumours: update and review. Histopathology. 2000 Feb;36(2):97\u0026ndash;108.\u003c/li\u003e\n \u003cli\u003eLi J, You L, Wang C, Zhao H, Guo W, Yu J, et al. Clinicopathological characteristics and prognosis analysis of Aggressive angiomyxoma: A Retrospective Study [Internet]. In Review; 2022 [cited 2025 Jul 5]. Available from: https://www.researchsquare.com/article/rs-2335657/v1\u003c/li\u003e\n \u003cli\u003eSchwartz PE, Hui P, McCarthy S. Hormonal Therapy for Aggressive Angiomyxoma: A Case Report and Proposed Management Algorithm. Journal of Lower Genital Tract Disease. 2014 Apr;18(2):E55\u0026ndash;61.\u003c/li\u003e\n \u003cli\u003eJeyadevan NN, Sohaib SAA, Thomas JM, Jeyarajah A, Shepherd JH, Fisher C. Imaging Features of Aggressive Angiomyxoma. Clinical Radiology. 2003 Feb;58(2):157\u0026ndash;62.\u003c/li\u003e\n \u003cli\u003eRaptin C, Lucot JP, Bassil A, Poncelet E, Prolongeau JF, Phalippou J. Aggressive angiomyxoma of the perineal region. SAGE Open Medical Case Reports. 2019 Jan;7:2050313X19843391.\u003c/li\u003e\n \u003cli\u003eVan Roggen JFG, Van Unnik JAM, Briaire-de Bruijn IH, Hogendoorn PCW. Aggressive angiomyxoma: a clinicopathological and immunohistochemical study of 11 cases with long-term follow-up. Virchows Arch. 2005 Feb;446(2):157\u0026ndash;63.\u003c/li\u003e\n \u003cli\u003eChoi H, Park C, Ji YI. Alternative surgical approaches for aggressive angiomyxoma at different sites in the pelvic cavity. Obstet Gynecol Sci. 2015;58(6):525.\u003c/li\u003e\n \u003cli\u003eXu H, Sun P, Xu R, Wang L, Shi Y. Aggressive angiomyxoma in pregnancy: a case report and literature review. J Int Med Res. 2020 Jul;48(7):0300060520936414.\u003c/li\u003e\n \u003cli\u003eNucci MR, Weremowicz S, Neskey DM, Sornberger K, Tallini G, Morton CC, et al. Chromosomal translocation t(8;12) induces aberrant \u003cem\u003eHMGIC\u003c/em\u003e expression in aggressive angiomyxoma of the vulva. Genes Chromosomes \u0026amp;amp; Cancer. 2001 Oct;32(2):172\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eLi J, You L, Wang C, Zhao H, Guo W, Yu J, Yuan Z, Qi S, Huang Y. Clinicopathological characteristics and prognosis analysis of aggressive angiomyxoma: a retrospective study. Res Sq. 2022.\u003c/li\u003e\n \u003cli\u003eMcCluggage WG, Jamieson T, Dobbs SP, Grey A. Aggressive angiomyxoma of the vulva: Dramatic response to gonadotropin-releasing hormone agonist therapy. Gynecologic Oncology. 2006 Mar;100(3):623\u0026ndash;5.\u003c/li\u003e\n \u003cli\u003eMagtibay PM, Salmon Z, Keeney GL, Podratz KC. Aggressive angiomyxoma of the female pelvis and perineum: a case series. Int J Gynecol Cancer. 2006 Jan;16(1):396\u0026ndash;401.\u003c/li\u003e\n \u003cli\u003eNyam DCNK, Pemberton JH. Large aggressive angiomyxoma of the perineum and pelvis: An alternative approach Report of a case. Diseases of the Colon \u0026amp; Rectum. 1998 Apr;41(4):514\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eRhomberg W, Jasarevic Z, Alton R, Kompatscher P, Beer G, Breitfellner G. Aggressive Angiomyxoma: Irradiation for Recurrent Disease. Strahlentherapie und Onkologie. 2000 Jun 1;176(7):324\u0026ndash;6.\u003c/li\u003e\n \u003cli\u003eSuleiman M, Duc C, Ritz S, Bieri S. Pelvic excision of large aggressive angiomyxoma in a woman: irradiation for recurrent disease. International Journal of Gynecological Cancer. 2006 Feb;16(S1):356\u0026ndash;60.\u003c/li\u003e\n \u003cli\u003eBehranwala KA, Thomas JM. \u0026lsquo;Aggressive\u0026rsquo; angiomyxoma: a distinct clinical entity. European Journal of Surgical Oncology (EJSO). 2003 Sep;29(7):559\u0026ndash;63.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"N.N. Alexandrov National Cancer Centre","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Aggressive angiomyxoma, Pelvic-perineal tumor, Margin-positive resection, Endocrine therapy","lastPublishedDoi":"10.21203/rs.3.rs-7069223/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7069223/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eAggressive angiomyxoma (AA) is a rare, locally infiltrative mesenchymal tumor of the pelviperineal region that carries a significant management challenge due to its high rate of local recurrence. While histologically benign, its clinical behavior can be unpredictable. Optimal strategies for managing recurrent disease and the full biological potential of AA are not well defined.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase Presentation:\u003c/strong\u003e We present two cases of recurrent AA managed at our institution. First case involved a 31-year-old woman with a margin-positive resection of a pelvic recurrence, initially misdiagnosed as a capillary hemangioma, who showed partial tumor regression with adjuvant tamoxifen and radiotherapy. Second case describes a 33-year-old woman with a large, recurrent pelvic tumor successfully managed with resection and adjuvant tamoxifen.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion:\u003c/strong\u003e This series identifies several key clinical lessons. First, AA can mimic other benign lesions, emphasizing the need for expert pathological and radiological review. Second, while complete surgical excision is the goal, adjuvant therapy may play a role in managing residual or recurrent disease. Lastly, as late recurrence is well documented, lifelong imaging surveillance remains crucial even after successful treatment.\u003c/p\u003e","manuscriptTitle":"Recurrent Aggressive Angiomyxoma: A Single-Institution Case Series on Management and Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-07-09 06:31:19","doi":"10.21203/rs.3.rs-7069223/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e77f5033-e3f0-4edc-aa88-71351d5de5c0","owner":[],"postedDate":"July 9th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":51180780,"name":"Oncology"}],"tags":[],"updatedAt":"2025-07-09T20:01:21+00:00","versionOfRecord":[],"versionCreatedAt":"2025-07-09 06:31:19","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7069223","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7069223","identity":"rs-7069223","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}