Second recurrence of aggressive vulvar angiomyxoma: a case report

Abstract

Aggressive angiomyxoma is a rare benign tumor with diverse clinical and radiologic presentations, making its differential diagnosis challenging. Here we report the second recurrence of an aggressive angiomyxoma of the vulva in a 33-year-old woman who presented with pain and swelling. Clinical examination revealed a well-circumscribed large palpable mass extending from the inferior part of the right labia major into the right side of the gluteus. A second recurrence of aggressive angiomyxoma was suspected based on the patient’s history, clinical examination, and magnetic resonance imaging report, and the patient underwent surgical resection with a negative margin. Histological evaluation of the extracted lesion confirmed the diagnosis of aggressive angiomyxoma. At the 1-year follow-up, the patient was recurrence-free. The present report urges more awareness regarding the aggressiveness of angiomyxoma of the vulva. Closer attention should be given to margin-free removal of such tumors, and patients should be routinely followed up for at least 2 years postoperatively for early diagnosis of recurrence, thereby reducing the risk of morbidity.

Introduction

Aggressive angiomyxoma is a slow-growing benign mesenchymal neoplasm that generally presents as a painless mass in the vulvo-perineal region. ¹ In 2003, aggressive angiomyxoma was reclassified by the World Health Organization as “deep angiomyxoma.” ² It is a rare tumor, with only about 350 cases reported in the literature to date. ¹ Aggressive angiomyxoma usually affects women of reproductive age and has a high tendency for local invasion and local recurrence. ¹

Misdiagnosis of aggressive angiomyxoma is common because of the rarity of this tumor, leading to delayed treatment with adverse consequences. Wide excision with an adequate negative margin is the treatment of choice for aggressive angiomyxoma. Adjuvant therapy, such as radiation and gonadotropin-releasing hormone agonists, are frequently used to reduce the risk of recurrence. ¹

We herein report a case of aggressive angiomyxoma of the vulva in a 33-year-old woman with two recurrences within 5 years. We also provide a review of the current knowledge about different aspects of aggressive angiomyxoma, including the clinical presentation, diagnosis, and treatment.

Case report

A 33-year-old married woman was referred to the gynecology clinic of our institute for evaluation of pain and swelling of the right vulva. The patient had undergone surgical resection of a mass in the right labia majora 5 years before the current referral, and the mass was histopathologically diagnosed as an aggressive angiomyxoma. She underwent no postoperative adjuvant therapy. The lesion recurred 2 years later, and the pathologic diagnosis was the same. The mass was again managed with surgical resection performed by the same general surgeon in the same center. The patient was then referred to our tertiary referral hospital because of a second recurrence of the vulvar mass.

The patient had no history of specific diseases or medications. Clinical examination revealed a well-circumscribed 8- × 8-cm palpable mass on the right gluteus, extending from the labia majora to the ischiorectal fossa. The mass was non-tender and soft in consistency. There was no evidence of any bowel or bladder dysfunction, and the patient had no anemia, cyanosis, lymphadenopathy, or weight loss. Her menstrual cycles were regular. Gynecological examination showed that the uterus, cervix, and vagina were normal. Additionally, ultrasonographic evaluation of the abdomen and pelvis showed no abnormality. Pelvic magnetic resonance imaging (MRI) revealed a tubular mass with heterogenous signal intensity in T2-weighted sequences and low signal intensity in T1-weighted sequences; the mass had a laminated appearance and was located in the right perineal region, extending from the right side of the vulva into the right intergluteal cleft. Contrast injection resulted in weak patchy enhancement.

Based on the patient’s history, clinical examination, and MRI report, recurrence of aggressive angiomyxoma was suspected, and surgical resection was scheduled. With the patient under general anesthesia, the tumor was resected with about 1.5-cm margins, and the intraoperative frozen section analysis confirmed that the margins were tumor-free. After tumor extraction, the base of the defect was closed using multiple absorbable simple sutures in several layers. Flap reconstruction was not required.

The extracted mass was sent to the pathology department. Histopathological examination showed a composition of stellate and spindle-shaped cells in a myxoid matrix, consistent with the diagnosis of aggressive angiomyxoma (Figure 1).

Figure 1.

Histopathological examination showing a composition of stellate and spindle-shaped cells in a myxoid matrix consistent with aggressive angiomyxoma.

Immunohistochemical analysis was not performed. The patient’s postoperative course was uneventful, and she was discharged 3 days after the operation in good general condition. Because of the highly aggressive nature of the tumor and to prevent further recurrence, postoperative radiation was recommended. However, the patient declined radiotherapy. At the 1-year follow-up, the patient was recurrence-free. No wound-related postoperative complications were recorded.

The patient provided written informed consent for treatment and publication of this report. Our institute does not require ethics approval for case reports. The reporting of this study conforms to the CARE guidelines. ³

Discussion

Although aggressive angiomyxoma is a benign neoplasm, it locally recurs in up to 72% of cases within 2 to 4 years after surgical removal. ⁴ Accurate preoperative diagnosis is crucial for planning the extent of surgical resection. However, because of its rarity and absence of typical features, aggressive angiomyxoma is often clinically misdiagnosed as more common entities such as a Bartholin cyst, vaginal cyst, leiomyoma, lipoma, polyp, or hernia. ⁵ Therefore, greater awareness regarding the clinical presentation, diagnosis, and treatment of aggressive angiomyxoma is required.

Aggressive angiomyxoma generally presents as a single visible vulvo-perineal mass of varying sizes. Affected patients are frequently asymptomatic. The overlying skin may be normal in appearance, and the lesion may be incidentally discovered during routine gynecologic examination. However, symptoms such as perineal swelling and a mass effect, pelvic fullness, pelvic pressure, pain, dysmenorrhea, dyspareunia, and bowel and bladder dysfunction have also been reported. ⁶ A large aggressive angiomyxoma may be noticed by the patient, as in the present case. The tumor extension is generally underestimated on physical examination because the involvement of the deep soft tissue in the pelvis and retroperitoneum is clinically invisible. ⁷ Considering the nonspecific clinical presentation, early diagnosis of aggressive angiomyxoma requires a high level of clinical suspicion.

The imaging appearance of angiomyxoma is also diverse, making its preoperative diagnosis difficult. Various imaging modalities can be used for preoperative evaluation of aggressive angiomyxoma, including ultrasonography, computed tomography, and MRI. In ultrasonography, aggressive angiomyxoma typically presents as a cystic or hypoechoic mass. ⁸ In computed tomography, it generally appears as a mass that has well-defined margins and is slightly hypodense relative to the adjacent muscle. ⁹ MRI is the preferred imaging modality because it provides a better depiction of the tumor spread, which is helpful in surgical planning. Characteristic findings on MRI are a hypointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. The signal is avidly enhanced after the administration of intravenous contrast, indicating hypervascularity. A distinct “swirling” pattern related to the myxoid composition of angiomyxoma might also be detected following contrast administration. ⁶

Macroscopically, aggressive angiomyxoma is generally unencapsulated with a smooth surface and a glistening, gelatinous appearance on the cut surface. The tumor is commonly bluish-gray in color. Areas of hemorrhage and congestion are often present. The lesion usually has a homogenous consistency with no nodularity. ⁹ Microscopically, histological evaluation reveals a hypocellular mesenchymal lesion composed of sparse spindle-shaped and stellate cells on a background of loose myxoid stroma. No evidence of cytologic atypia, atypical mitotic features, or coagulative tumor cell necrosis is found. Numerous blood vessels of varying sizes are generally seen. ⁹ There is no known immunohistochemical marker specific for aggressive angiomyxoma. However, the tumor often shows a characteristic pattern of immunoreactivity to different combinations of markers, including vimentin, desmin, actin, CD34, estrogen, and progesterone receptor. ⁵

Although achieving negative resection margins for aggressive angiomyxoma is difficult because of ‏the tumor’s infiltrative nature and lack of a defined capsule‏, surgical excision is still the first-line treatment. Whereas small and superficial tumors can be removed by wide ‏excision, large and deeply located tumors might require more invasive surgery ‏entailing partial or complete resection of some pelvic structures, which is associated with a higher risk of morbidity. Nevertheless, incomplete removal of the lesion can be performed to avoid extensive surgical morbidity or loss of fertility. ¹⁰ When a negative margin is not achievable for any reason, adjuvant therapies can be implemented to prevent local recurrence of aggressive angiomyxoma. Tumor embolization and preoperative radiotherapy have been used to shrink the tumor preoperatively and increase the chance of obtaining negative margins. ¹¹ Although postoperative radiotherapy has also been used to treat recurrence of aggressive angiomyxoma,^6,12 the role of this treatment is not well-defined given the low mitotic activity of aggressive angiomyxoma and the absence of follow-up data. ⁶ Suleiman et al. ¹³ reported a case of a large angiomyxoma of the pelvis that was managed with surgical excision followed by radiation therapy with a total dose of 60 Gy. They observed no recurrence throughout a 3-year follow-up period. ¹³ Nevertheless, local recurrence of angiomyxoma after local postoperative radiotherapy was noted in a literature review. ¹⁴ Considering the two recurrences of the lesion in the present case, we recommended postoperative radiotherapy to prevent further recurrences; however, this was not performed because the patient declined.

Given that aggressive angiomyxoma shows positivity for estrogen receptors and progesterone receptors, hormonal manipulation using gonadotropin-releasing hormone analogues has recently been used for treatment. However, the efficacy of this approach remains unknown because of the lack of evidence. Regrowth of the tumor was observed in one patient after discontinuation of therapy. ⁵

Overall, aggressive angiomyxoma is a rare tumor and is thus frequently misdiagnosed at initial presentation, leading to delayed diagnosis and a higher risk of recurrence and morbidity due to the lower possibility of obtaining negative resection margins. MRI is a viable imaging modality for the diagnosis of aggressive angiomyxoma. Surgeons should strive to achieve wide resection with negative surgical margins.

The present case was initially managed by a general surgeon. This case is unique because it shows how incomplete surgical resection of an aggressive angiomyxoma by a less experienced surgeon and inattention to tumor-free resection margins can result in recurrence of the lesion. The reporting of the second recurrence of aggressive angiomyxoma of the vulva can be considered a strength of this case because similar cases are extremely rare. However, the main limitation of this report is the absence of clinical images, which led to incomplete presentation of the case.

With respect to its clinical implication, the present report urges greater awareness regarding the aggressiveness of angiomyxoma of the vulva and closer attention to margin-free removal of the tumor. Routine follow-up should be performed for at least 2 years after the operation to increase the chance of early diagnosis of recurrence and reduce morbidity. Treatment of the lesion by a multidisciplinary team, including a radiotherapist, medical oncologist, surgical oncologist, and pathologist, can provide better management of tumor recurrence. Intraoperative frozen section analysis is also recommended to ensure a negative margin.

Conclusion

Aggressive angiomyxoma of the vulva is very rare and can be easily misdiagnosed as more common vulvar lesions such as fibroma and lipoma, particularly if managed by less experienced physicians. Considering the aggressiveness of the lesion and the high rate of recurrence, greater awareness is required regarding the differential diagnosis and postoperative monitoring of the lesion to prevent recurrence.

Data availability statement

The data generated or analyzed during this study are available from the corresponding author upon reasonable request.