European Journal of Surgical Oncology
Volume 36, Issue 4 , Pages 335-339, April 2010

Aggressive angiomyxoma: A case series and literature review

Oxford Cancer Centre, Department of Gynaecologic Oncology, Churchill Hospital, Old Road, Oxford OX3 7LJ, United Kingdom

Accepted 9 November 2009.

Article Outline

Abstract 

Background

Aggressive angiomyxoma was identified as a distinct clinicopathologic entity in 1983 and since then fewer than 250 cases of these rare tumors have been reported in world literature. These tumors usually arise in the pelvis and perineal regions, most often in women of the reproductive age group; however a few cases of its occurrence outside the pelvis have also been reported.

Patients and methods

We report a series of 7 women treated in our institute in the last 8 years. Relevant literature on aggressive angiomyxoma was looked at and various management options reviewed.

Conclusion

Aggressive angiomyxomas are locally aggressive, notorious for local recurrence and extremely rare to metastasize. While surgery remains the mainstay of treatment, there has been a definite shift towards less radical forms of excision, over the years. Various adjuvant treatment modalities have also been tried to reduce tumor recurrence.

Keywords: Management, Pregnancy, Aggressive, Angiomyxoma

 

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Introduction 

Aggressive angiomyxoma (AA) is a rare, locally aggressive myxoid mesenchymal neoplasm preferentially arising in the pelvic and perineal regions of young adult females, most commonly in the reproductive age group.1 In men, the tumor involves analogous sites including the scrotum and inguinal area and usually appears at an older age.2 AA was first described in 19833 and since then less than 250 cases have been reported in literature, mostly in the form of small case series or isolated case reports. Though most of these tumors are locally aggressive occasional distant metastasis has also been reported.4, 5

Diagnosis, more often than not, is at histological examination following surgical resection. Pre-operative diagnosis is difficult because of rarity of these tumors and lack of typical presenting signs and symptoms. The tumor is characterised by a soft, non-encapsulated mass with finger like projections into the adjacent soft tissue.

Surgery is usually the first line of treatment. Incomplete excision is common because of the infiltrating nature of the neoplasm and absence of a definite capsule. Local recurrence is common even after complete excision. Non-surgical interventions like hormonal manipulation, radiotherapy, arterial embolization, etc. have been tried with variable success rates.

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Patients and methods 

From 2002–2009, 11 women with aggressive angiomyxoma were managed in our institution. Seven of these cases were directly managed in our centre while the others were referred for expert opinion only. Among the seven, one interesting case of AA in a pregnant woman (case 1 – Table 1) has previously been reported separately.6 We also performed a MEDLINE search from 1983 to July 2009 with the key words “aggressive” and “angiomyxoma” and reviewed relevant literature.

Table 1. Summary of patients with aggressive angiomyxoma (AA).
CaseOriginal presentation & sizeAge at initial presentationLocationSurgical treatment/OutcomeResection MarginsAdjuvant treatmentDFI/number of recurrences
1Right sided 3cm vulva swelling22Right vulva & vagina extending into right ichiorectal -fossa & levator ani (Fig 2)3×WLE/successful pregnancy after third surgery, currently stable size & awaitingPositiveGnRH analogue after the first and second surgery5 months after first WLE/3 recurrences
28cm Lt vulval lesion with unsuccessful initial GnRH analogue treatment47Left vulva and perineumWLE+3 subsequent perianal abscesses drainedPositiveN26 months/none
3Bowel habit changes, urinary urgency, bulky uterus, 8-9cm pelvic mass on exam58Left paravesicalLaparotomy & excision of paravesical mass.PositiveN11 months/none
45 year intermittent swelling in perineum with 8cm mass on palpation46Left paravaginal and perineal areaAbdomino-perineal excisionPositiveN16 months/none
5Anterior vaginal wall mass49Anterior vaginal wallWLE followed by VH and second WLE in 2 monthsNegativeN48 months/none
6Recurrent left Bartholin's cyst diagnosed as AA after a year44Left vulvaWLEPositiveGnRH analogues to shrink recurrent tumorFirst recurrence at 24 months, currently 9cm extending into left ischio-rectal fossa
7Mistaken as cystocele48Vulvo-vaginal massWLEPositiveN48 months/none

GnRH analogue: gonadotropin-releasing hormone agonist therapy; DFI: disease Free Interval; WLE: Wide Local Excision.

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Results 

Table 1 summarizes the most relevant details for the 7 patients managed in our institution. In all but one case (case no 2), the diagnosis of AA was made only after initial surgery. The average age at diagnosis in our group of patients was just under 45 years (range 22–58 years), with an average disease free interval (DFI) of over 25 months. In 6 out of 7 cases histopathology confirmed involved resection margins. Five women had no recurrence following initial surgery. AA did not recur in the patient with clear margin. Case no 1 did respond well to GnRH-agonist therapy each time however recurred after discontinuation of treatment. Case no 2 was given GnRH-agonist as a neo-adjuvant treatment with the aim of tumor reduction but the treatment was unsatisfactory and the patient had to undergo surgery.

The MEDLINE search yielded 93 single case reports of this rare neoplasm in women if limited to the perineum and pelvis, and thirty-four of them in men. Ten cases of AA are reported in other parts of the body as well as two rare cases of lung metastases. A further 98 patients including both sexes are reported in series (n=2–29 cases) bringing the whole number of cases reported in the literature to under 250 since the first description of AA in 1983.

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Discussion 

Aggressive angiomyxomas are locally invasive connective tissue tumors presenting in about 90% of cases in women of reproductive age group with a peak incidence in the fourth decade of life.7 The initial presentation varies from an asymptomatic perineal or vulval nodule/polyp or perineal hernia to a pelvic mass diagnosed on imaging studies. Occasionally, the tumor can be cystic and mistaken for a Bartholin's, labial or Gartner's duct cyst. They can exhibit a slow and insidious growth pattern and hence patients may be asymptomatic for long time until they become conscious of the significant size of the tumor. Tumor recurrences, like the primary ones, are often asymptomatic.

Pre-operative diagnosis is often a problem because of the rarity of these neoplasms and lack of typical features and most cases are diagnosed on histology after primary surgical excision. Accurate diagnosis before surgical excision is important in planning extent of excision and patient counseling.

Imaging characteristics of angiomyxomas 

Ultrasound is helpful in this regard and usually demonstrates a hypo echoic soft tissue mass that may even appear cystic. CT appearances are variable and include a well-defined homogenous mass hypo dense relative to muscle, a hypo attenuating solid mass with swirling internal pattern with contrast or a predominantly cystic appearing mass with solid components.8 With MRI imaging an iso intense or less commonly hypo intense mass (compared to muscle) on T1 and hyper intense on T2 weighted images is characteristic. MRI imaging is accurate in detecting trans-levator spread and also is helpful in surgical planning by defining relation of the mass with anal sphincter, urethra, bladder and pelvic side-wall.8 Recurrent tumor is also detected consistently in MRI scans and recurrent lesions have similar signal characteristics as that of primary tumor.

Histopathological findings 

Macroscopically these tumors often have a smooth surface, partially or completely encapsulated and cut surface gives a glistening, gelatinous appearance, bluish grey in color, with areas of hemorrhage and congestion. They are usually homogenous in consistency with no obvious nodularity.3

Histologically they reveal a hypo cellular mesenchymal lesion consisting of a sparse population of bland spindled and stellate cells scattered in a background of loose myxoid stroma (Fig 1) composed of wavy collagen fibrils. The cells have abundant wispy pink cytoplasm with bland nuclei. There is no cytologic atypia, no atypical mitotic features or discernible mitotic activity and no evidence of coagulative tumor cell necrosis either. The lesion often also shows numerous blood vessels of varying caliber.3 The stromal cells can show immunoreactivity to different combinations of vimentin, desmin, smooth muscle actin, muscle specific actin, CD 34, estrogen and progesterone receptors.9 Recurrent tumors usually show similar histological characteristics.

Angiomyxoma genetics 

Chromosomal abnormality involving chromosome 12, associated with rearrangement of HMGIC gene, has been reported in cases of AA.10 On one hand the lack of consistent HMGIC expression in the vascular component and on the other hand very high frequency of HMGIC expression in the spindled stromal cells might suggest that this is the true neoplastic component and that the admixture of blood vessels may be a secondary phenomenon. Localization of HMGIC to neoplastic stromal cells of aggressive angiomyxoma by immunohistochemistry might be applied as a diagnostic tool in assessing margins status, which might be extremely difficult to assess on morphologic grounds alone.10

Tumor characteristics and surgical management 

Angiomyxomas are locally aggressive tumors and distant metastasis has only been reported in two occasions.4, 5 In view of the high risk of local recurrence, wide local excision with tumor-free margins was initially thought to be the treatment of choice. Re-excisions, if the initial surgery was deemed incomplete, were also advocated. Involvement of bladder, gastrointestinal tract and bone has been described with angiomyxomas and in such situations extensive surgical resection, with significant operative morbidity, would be necessary to achieve clear margins. A review of over 100 cases however refuted this belief and showed that patients with clear resection margins were as prone to developing recurrences. The chances of remaining disease free were not statistically different from those who had incomplete resection, 50% vs. 40% in 10 years.7 Also, excluding one case of metastasizing angiomyxoma, these tumors are not life threatening, even primary and recurrent tumors are often asymptomatic. Fertility is also an important factor as most of these tumors occur in women of the reproductive age group and radical resection in such situations may not be the best option. Thus though complete excision is still the aim, incomplete removals are acceptable when high operative morbidity is anticipated and fertility preservation is an issue.7

Adjuvant therapies 

Most of these tumors show estrogen and progesterone receptor positivity 11 and are likely to be hormone dependant. Hormonal manipulation is thus thought to be a viable treatment option. GnRH analogues have been used in a few instances in premenopausal women with AA12 but re-growth of tumor can occur, as in one of our patients, once therapy is discontinued. Pre-operative shrinking of tumors using GnRH analogues might increase chances of complete excision and minimize the radicality of surgical procedure.13 One patient treated with tamoxifen however continued to have tumor growth in spite of ongoing treatment.14

Due to low mitotic activity radiotherapy or chemotherapy is unlikely to be a useful adjunct to primary surgery.15 We could find no reports of use of chemotherapy in treatment of AA. Pre-operative external beam irradiation and intra-operative electron beam radiotherapy was used in one case to reduce risk of recurrence but follow-up data on the same is not available.16 Two cases of successful control of recurrent angiomyxoma with relatively high doses of external radiotherapy have also been reported.17, 18

Angiographic embolization has also been attempted to shrink the tumor pre-operatively and thus increase the chances of complete removal.16 The fact that the tumor might derive its blood supply from multiple sources rather than a singular feeding vessel would reduce the success of such procedure.7

Equally, a trial of watchful waiting in case of asymptomatic patients with recurrent tumors or with large tumors where surgery carries significant morbidity might be a reasonable option.19

Recurrence is one of unique characteristics of these otherwise non-malignant tumors. The usual sites of recurrence reflect the sites of the primary disease i.e. perineum, pelvis, ischio-rectal fossa and retro-peritoneum. No definite relation between patient's age, size of tumor and rate of recurrence has been established so far.7 Recurrences generally occur in the first 5 years after primary surgery, about 70% in the first 3 years, but late recurrences up to 14 years have been reported. Follow-up should be clinical, supplemented by radiological investigations; especially MRI scans.8

Angiomyxomas and pregnancy 

Though angiomyxomas are common in the reproductive age group women, very few reports are available to clearly define their behavior in pregnancy. There is one report of recurrence of previously treated angiomyxoma in a woman during her pregnancy.20 One of our patients, while being followed up for recurrent disease became pregnant. The lesion was followed up throughout her pregnancy with MRI scans showing only marginal increase in size. This could be attributable to the hormone dependency of these tumors.

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Conclusion 

Aggressive angiomyxomas are rare, locally aggressive tumors, arising mainly in the female pelvis with a high likelihood of recurrence even after complete surgical excision. Pre-operative diagnosis is difficult due to rarity and lack of diagnostic features. Hence, AA should be considered a possibility in case of atypical mass lesion in the female pelvis or perineum. Few management options are available and multimodal therapy may be a good option. Patient counseling, multi disciplinary approach and individualization of each case and follow-up are essential for adequate management.

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Conflict of interest statement 

This is to declare that Krishnayan Haldar, Igor Martinek and Sean Kehoe have no financial and personal relationships with other people or organisations that could have inappropriately influenced this work. Sean Kehoe is a member of the editorial board of this journal.

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Acknowledgements 

We thank Dr. Sunanda Dhar, Consultant Gynaecological Pathologist, for her help.

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References 

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PII: S0748-7983(09)00514-9

doi:10.1016/j.ejso.2009.11.006

European Journal of Surgical Oncology
Volume 36, Issue 4 , Pages 335-339, April 2010

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