Ms. S, 49, presented with symptoms of intermittent vaginal bleeding for 10 years and urinary retention for 2 years. Her pelvic exam noted a friable mass at the cervix, which was descending toward the vagina. Ms. S underwent renal and pelvic ultrasound (transvaginal ultrasound), revealing a 5.5 cm x 4.5 cm x 3 cm mass on the posterior cervix adjacent to the right side of the vaginal wall. MRI confirmed a well-delineated mass at the cervix (see Sagittal view of T2 of MRI). Subsequently, Ms. S underwent open total abdominal hysterectomy with bilateral salpingo-oophorectomy (see Uterus and angiomyxoma).
The pathology report indicated an ill-defined benign tumor with numerous spindle, stellate shapes that were interspersed throughout and varied in size and thickness; thin-walled blood vessels were embedded in an abundant myxoid stroma (see Spindle-shaped cells). Ms. S was diagnosed with aggressive angiomyxoma (AAM). The case was discussed at the multidisciplinary tumor board with a consensus that Ms. S will be treated surgically and no further medical treatment was recommended. Ms. S will require a 5-year surveillance follow-up due to AAM's high risk for recurrence.
AAM
AAM is a rare mesenchymal tumor with predilection for the pelvic and perineal regions; it was first described by Steeper and Rosai in 1983.1,2 The latest World Health Organization classification lists AAM as a "tumor of uncertain differentiation."3 It is defined as a rare, benign tumor that infiltrates into the skeletal muscle and fat; less than 350 cases have been reported.4 The name "angiomyxoma" was chosen because of the similarity to myxoma, a tumor of primitive connective tissue as well as the notable vascular component.
An AAM tumor preferentially arises in the pelviperineal region of females (female-male ratio 6:1) during reproductive age. Extremely rare in men, the tumor most commonly develops in the scrotum and inguinal area.5 The disease is considered aggressive due to the nature of blood vessels of the tumor and its local infiltration and recurrence.6 The local recurrence rate varies from 9% to 72%, and the recurrence can occur between 2 months to 15 years following the initial diagnosis.7,8
Clinical presentation
Patients with AAM are often asymptomatic until the tumor becomes significant in size. The true extent of AAM is often underestimated during a physical exam because only a fraction of the tumor may be visible during the exam.8,9 AAM tends to displace adjacent organs without invading them, but the locally infiltrative nature seems to lead to the invasion of adjacent organs during longstanding growth.9,10 Therefore, some patients may experience symptoms such as pelvic fullness, pressure, perineal swelling, vulvovaginal pain, dysmenorrhea, dyspareunia, and changes in bowel and bladder function.3,4
On exam, the tumors are rubbery, white or yellow, and soft and gelatinous, with areas of congested blood vessels, hemorrhage, or fibrosis.2,3 AAM is often clinically mistaken for more common entities (for example, a Bartholin cyst, vaginal cyst, abscess, leiomyoma, fibroepithelial polyp, or inguinal or perineal hernia).1 Although the tumor is benign in nature, the term "aggressive" emphasizes the frequent local recurrence and its infiltrative nature.11
Diagnosis
Because AAM is a rare tumor, patients need to understand the nature of the disease, treatment plan, and long-term follow-up. The misdiagnosis rate was reported to be approximately 82%.1,3 Early recognition requires a high index of clinical suspicion because the tumor is rare, and the symptoms are nonspecific.
From collecting pertinent history with the symptoms of AAM and performing a thorough physical exam, a clinician can identify the abnormality. Due to the gelatinous consistency, the tumor biopsy is rather difficult to obtain. Therefore, appropriate workup is suggested (for example, a magnetic resonance imaging [MRI] or computed tomography [CT] imaging study is necessary to provide objective data to delineate the extent of the tumor). For most patients with AAM, the diagnosis will not be made until the histopathology becomes available.1
Radiologic features
Several imaging modalities are useful in primary and recurrent diagnosing and evaluating for surgical treatment of AAM. MRI and CT are recommended to identify the extent of the tumor before surgical intervention. In contrast to muscle signals on MRI, AAM reveals an isointense signal on T1-weighted images and a hyperintense signal on T2-weighted images. Therefore, T1-weighted and T2-weighted MRI are the preferred views of images.12
AAM exhibits avid and heterogenous enhancement after I.V. contrast administration and may show a distinct, low-intensity swirling pattern. High signal intensity on MRI is likely to be related to the loose myxoid matrix and high water content.13,14 MRI can detect the existence of the mass in addition to identifying the infiltrating borders and the relationship between the tumor and adjacent organs, which may assist surgeons to select optimal surgical approaches.3
Pathologic features
AAM is usually unencapsulated, poorly circumscribed, and may blend with surrounding soft tissue. Tumor size varies from 1 cm to 60 cm.4 The tumor is often tan-pink to tan-gray, bulky, and has a rubbery consistency with a glistening, gelatinous surface.15
Histopathology is the gold standard for diagnosis of AAM.1,14 On Ms. S's microscopic exam, all the specimens showed typical features, including stellate to spindle-shaped tumor cells with ill-defined cytoplasmic borders, fibromyxoid stroma, and hyalinized thin-to-thick wall vessels. Mitotic figures were rare, and there was no necrosis or cellular atypia.3 In addition to histopathology, immunohistochemistry (IHC) is a special test used by pathologists to detect specific molecules on cells. It uses antibodies matching molecules that can seek out, identify, and attach themselves to these marks on cells. The antibodies themselves are designed to work with tags that can be detected under a microscope, such as fluorescent staining, which helps make precise identification.15 Although there is no specific immunohistochemical marker for AAM, most of the tumors show reactivity for desmin, smooth muscle actin, muscle-specific actin, vimentin, CD 34, estrogen, and progestin receptors in immunohistochemical analyses.15-17
The majority of these tumors show estrogen and progesterone receptor positivity, suggesting that AAM is a hormone-dependent tumor, as rapid growth and recurrence have been observed during pregnancy.1,10 Less than 1% of tumor cells show Ki-67. Ki-67 protein is a cellular marker for proliferation and is often correlated with the clinical course of cancer.3,16 The pathogenesis of these tumors is unclear; however, an association between chromosomal 12 translocations (12q13-15) has been suggested. Those translocations were found in lipomas, liposarcomas, leiomyomas, and pulmonary hamartomas.17 Further research is needed to determine if there is a genetic correlation of AAM.
Treatment
Wide surgical excision with tumor-free margins is the basis of curative treatment for AAM.1 Because AAM has a high rate of recurrence, it is important for the surgeon to completely excise a tumor with tumor-free margins. The excised lesion removed from Ms. S had achieved a close negative margin on the pathology report. Surgery remains the treatment of choice for recurrence.18-20
Most AAM express estrogen and progesterone receptors; therefore, patients may be hormone dependent. Hormonal treatment with tamoxifen, raloxifene, and gonadrotropin-releasing hormone analogs (GnRH agonists) has been used to treat tumors.19,20 GnRH agonists are used to treat primary small tumors and as an adjuvant therapy for residual tumors and even in recurrence treatment.19 When using hormonal suppressant therapy, there is a varying degree of responses.21 Some patients may select to take hormonal therapy and will be monitored for adverse reactions (for example, hot flashes, night sweats, joint pain, fatigue, headache, mood swings, and vaginal dryness).
Angiographic embolization has been used as a treatment modality to shrink the tumor as well as making it distinctive from the surrounding normal tissues.2 In case of large tumors needing extensive resection or arterial embolization, hormonal treatment may be used initially followed by surgical resection.1,22 Chemotherapy and radiation therapy do not have well-defined roles in AAM treatment, as the tumor has a low mitotic index. Many treatment options for recurrence include surgery, radiotherapy, and hormonal therapy; these options have been used with varying success, and no single modality is more beneficial than the others.22,23
Implications for practice
It is important to discuss preoperative, intraoperative, and postoperative care with patients. The types of surgery depend on the location and the extension of the tumor. Ms. S was treated surgically and had a total hysterectomy with bilateral salpingo-oophorectomy. There was discussion of postoperative care in terms of pain management and long-term sequela of infertility. The psychological issues involving potential infertility and/or alternation of self-image (secondary to potential extensive surgery) are important factors for AAM patients. Prior to the surgery, women of reproductive age should have a discussion with their healthcare providers in regards to fertility-related issues and should make plans accordingly.24 After the surgery, patients may experience depression, irritability, insomnia, impaired body image, lack of energy, lack of sexual interest, and inability to reach orgasm.
Healthcare providers need to conduct a thorough psychosocial and sexuality assessment in order to provide support and resources for them. Routine follow-up is recommended, and surveillance after treatment is necessary. MRI with pelvic examination is considered useful to detect early recurrent lesions.1,3
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