Article Text
Abstract
Aggressive angiomyxoma (AAM) is a very rare, benign, locally infiltrative mesenchymal tumour with a high chance of recurrence following surgical excision. In the male population, it is so rare that less than only 50 cases have been reported so far. We present a case of a large recurrent perineal AAM in a man who presented with swelling in the perineal region following surgical excision 3 years ago. After evaluation, the diagnostic dilemma of a possible perineal hernia or recurrence remained. Surgical exploration ruled out hernia and the tumour was excised with difficulty. Immunohistochemical examination showed tumour cells with diffuse nuclear positivity for oestrogen receptor and patchy cytoplasmic positivity for desmin (A2). Histological and immunohistochemical features confirmed the diagnosis. Being very rare, AAMs need to be considered as a differential diagnosis of pelvic/perineal tumours among males. With no standardised therapy for AAM, complete resection would be the goal of therapy.
- general surgery
- surgical oncology
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Background
Aggressive angiomyxoma (AAM) is a rare, benign, mesenchymal tumour that arises primarily from the soft tissue of the pelvis and perineum.1 It is more commonly seen among women of reproductive age and its incidence among the male population is extremely rare. With only about 350 cases of AAM described in the literature, less than 50 cases have been reported among males.1 2 Due to its nature of local infiltration with a high chance of recurrence, it was termed AAM. The recurrence rate varies over a wide range between 2% and 47%.1 Due to its high chance of recurrence, differentiating it from the other mesenchymal tumours of the pelvis and perineum becomes important.3 Herein, we report an extremely rare case of a large recurrent perineal AAM in a male patient and would like to highlight the difficulties involved in the diagnostic dilemma and surgical management of the same.
Case presentation
A 39-year-old man with no significant medical history presented with a 3-year history of a swelling in the perineal region which was progressively increasing in size with no associated history of pain, skin changes or discharge from the swelling. He gave a history of a similar swelling in the perineal region for 3 years for which he underwent surgical excision 3 years prior at another centre. However, the swelling recurred a few months following the surgical procedure and he did not have any medical records of the same. He denied any history of weight loss, nausea, vomiting, melaena or haematochezia. He did not give any history of neurological weakness, sexual dysfunction, abdominal pain or any change in his bowel or bladder habits. He did not have family history of any malignancy. On assessment, his vital examination was normal. Examination of the perineum revealed a large, ovoid swelling measuring 10×12 cm extending from behind the root of the scrotum and perineal region on to the right of the perianal region, laterally extending up to the right ischial tuberosity. The swelling was soft with a few nodular areas and the superior extent could not be appreciated. An expansile cough impulse was absent and this swelling was neither compressible nor reducible. Rectal examination did not reveal any palpable mass and the rectal mucosa appeared to be normal. No mass was palpable per abdomen. The rest of the general and systemic examination was unremarkable.
Investigations
MRI of the pelvis showed a smooth-walled, pedunculated, T1-weighted (T1W) hypointense, T2-weighted (T2W) hyperintense and Spectral attenuated inversion recovery (SPAIR) hyperintense lesion in the inferior pelvis, with a sheet of multiple linear flow voids suggestive of prominent vessels within the lesion. The epicentre of the mass was in the low anterior mesorectum (figures 1–3). The pelvic component of the mass was indenting the seminal vesicles and prostate anteriorly and the anterior wall of the rectum, posteriorly. Inferiorly, the mass had two components: first, there was a predominantly large cystic mass that had herniation through a defect in the right levator ani into the right ischioanal fossa, with a component bulging inferiorly, and second, the other component of the pelvic mass protruded anteroinferiorly into the perineum (figure 4). However, with ultrasound correlation, the mass in the perineum and inferior scrotal region that was echogenic with a lobulated appearance had a cough impulse and hence, features could not rule out an underlying large hernia.
Differential diagnosis
Before any further workup of the patient and based on his presenting symptoms, the differential diagnosis was broad, with the provisional diagnosis including either a recurrent benign/malignant soft tissue neoplasm or a perineal hernia. Given the history of surgical excision of a previous perineal swelling, a recurrent soft tissue neoplasm was presumed most likely.
Following the MRI scan of the pelvis, we narrowed our differential diagnosis to a recurrent neoplasm with increased vascularity, recurrent soft tissue sarcoma or recurrent angiomyxoma. Given that the lesion was predominantly cystic and there were no clinical findings in favour of a perineal hernia, his case was discussed in the tumour board meeting and it was decided to proceed with surgical excision.
Treatment
The patient underwent excision of the perineal lesion in the Lloyd Davies position. Intraoperatively, there was a 15×12 cm tumour in the perineum between the root of the scrotum and the rectum on the right side, superiorly extending above the seminal vesicles and adherent to the anterior rectal wall (figures 5 and 6). As the tumour appeared to be similar to a perineal hernia, laparotomy was performed, and the absence of a perineal hernia was confirmed intraoperatively. The tumour was mobilised circumferentially and was excised with difficulty from the superior aspect of the rectum, where it was adherent. Following the excision, despite ligation of the pudendal vessels, haemostasis was difficult to achieve and the perineum was packed, with a plan to re-explore after 24–48 hours. However, due to persistent postoperative haemorrhage, he underwent an immediate re-exploration with proximal control of bilateral internal iliac vessels, and haemostasis was attained. During this process, due to an iatrogenic injury to the right ureter, a stent was placed and reimplantation with psoas hitch was performed. He was transferred to the surgical intensive care unit following the surgery and was haemodynamically stable.
Outcome and follow-up
Following the operation, he recovered well. The perineal skin appeared dusky on the fifth day following the operation and progressed to necrosis. On the tenth postoperative day, he underwent perineal wound debridement with the evacuation of the underlying hematoma in the subcutaneous plane. Daily dressings were attended, and the patient was discharged 2 weeks later, with a planned trial of void in 2 weeks.
Histopathological examination showed sections of a hypocellular myxoid tumour with short spindle to stellate cells with wavy band nuclei in a background of a myxoid matrix. Their intervening stroma was collagenous admixed with blood vessels of varying calibre (figures 7 and 8). Overall features were suggestive of a benign angiomyxomatous neoplasm—AAM being the most likely possibility.
On immunohistochemistry, the tumour cells showed diffuse nuclear positivity for oestrogen receptor and patchy cytoplasmic positivity for desmin (A2); CD34 was negative (figures 9 and 10).
At outpatient follow-up, 20 days following the first operation, he presented with complaints of multiple episodes of non-bilious vomiting with no associated abdominal distension, constipation or obstipation. A contrast-enhanced CT scan of the abdomen revealed mild right hydroureteronephrosis with ureteric stent in situ and did not show any features suggestive of an acute intestinal obstruction. He was diagnosed with a urinary tract infection; the urinary catheter was changed and he was managed with appropriate antibiotics. The ureteric stent was removed 6 weeks after the surgery under antibiotic cover. Seven weeks following the surgery, his surgical site was healthy, he was afebrile, tolerating normal diet and was independent with daily activities.
Discussion
AAM is a very rare neoplasm of mesenchymal origin that primarily arises in the soft tissue of the pelvis and perineum of adults.1 Steeper and Rosai in 1983 reported a case series of nine female patients for the first time.2 The term ‘AAM’ was given to emphasise the neoplastic nature of the blood vessels and its nature of local infiltration and recurrence.4 The female-to-male ratio was 6.6:1 as was reported in a review of more than 100 cases.3 It occurs predominantly among women of reproductive age, with a peak incidence in the fourth decade of life, and involves the genital, perineal and pelvic regions, with the vulva being the most common site of involvement.4 This tumour has been known to occur during pregnancy when there is a state of increased progesterone and oestrogen levels.4 With less than 50 cases reported in the literature, AAM is very rare in males. It involves the perineum, spermatic cord and the scrotum and is slow growing, with a high tendency of recurrence after excision, but has no malignant potential.5 Only three cases of AAM with metastasis to the lung and mediastinum have been reported in women.6–8
Patients often have non-specific complaints, most are asymptomatic with a visible mass in the perineal or vulvar region.1 9 Due to non-specific complaints, it is often misdiagnosed with the more common entities, such as a lipoma, Bartholin’s cyst in females and perineal hernias in males.9 Due to its rarity, preoperative diagnosis is difficult and the majority of cases are diagnosed on histopathological examination after surgical excision.10 A high index of clinical suspicion helps in the early recognition of this condition and it should be considered as a differential diagnosis of tumours in the analogous regions of males.1
Macroscopically, the tumour has a smooth surface and is partially or completely encapsulated. Microscopically, it is composed of numerous blood vessels of varying calibre in a background of loose collagenous and myxoid stroma with spindle and stellate-like cells.10–12 These lesions in general show no cytological atypia, no cell necrosis and have a low mitotic activity.10 11 AAM does not have any specific immunohistochemical marker and most markers overlap with the other mesenchymal tumours,10 but the tumour exhibits a characteristic pattern of reactivity. There is diffuse positivity for vimentin, desmin and smooth muscle actin and CD34 may be positive in certain cases.1 10 The most characteristic feature of AAM is the oestrogen and progesterone receptor positivity. Strong nuclear positivity is displayed by one or both of these hormonal receptors in most tumour cells and a low proliferative index (<1% of tumour cells) is demonstrated by labelling for Ki-67.1
Genetic testing has shown a chromosomal translocation abnormality involving the high mobility group A2 (HMGA2) gene—an architectural transcription factor in the chromosome 12.13 14 Approximately one-third of AAMs harbour the rearrangement of the HMGA2 gene.15 A recent study that characterised HMGA2 immunohistochemical expression and its utility as a discriminatory marker in various neoplasms showed that AAMs had a strong nuclear positivity in 90% of cases in comparison to weaker reactivity in 27% of fibroepithelial stromal polyps and no staining in cellular angiofibroma or angiomyofibroblastoma.16
The differential diagnosis of AAM includes superficial angiomyxoma, fibroepithelial stromal polyps, myxoid leiomyoma, angiomyofibroblastoma and myxoid lipomatous tumours.
Radiological appearance on CT scan is variable; it may be predominantly cystic with solid components or may be a well-defined homogeneous lesion which is hypodense in comparison with the adjacent muscle.17 On MRI, the characteristic feature includes hyperintensity on T2W images and hypointensity on T1W images.17 After intravenous administration of contrast, AAM exhibits avid and heterogeneous enhancement and may show a distinct, low-intensity, swirling pattern.17 The abundant myxoid matrix and high water content of the tumour attribute to these radiological features.18 A summary of the features of AAM is as mentioned below (table 1).
The first line of therapy for AAM is surgical excision, however, due to its infiltrative nature and the absence of a defined capsule, achieving negative margins is difficult.11 Wide local excision may be sufficient for superficial, smaller tumours of the vulva or vagina, but deep-seated, larger tumours of the pelvis may require extensive surgery with complete or partial resection of some pelvic organs which thereby increases the morbidity of the surgical procedure.1 In a review of 111 cases of AAM, when the risk of recurrence was compared with margin status, it showed that 40% of the cases with positive margins and 50% of the cases with negative margins remained disease free after 10 years.3 There was no statistically significant difference between the two groups and hence, there was no necessity for such radical resections in AAM.3 The desired goal is complete resection; incomplete resection is acceptable when the operative morbidity is too high or when fertility preservation is a concern among female patients.3 10 19 Recurrence, when it occurs, seems to occur within five years after complete resection, and most information regarding recurrence has been obtained from female patients.11 Although tumour embolisation with intraoperative and preoperative radiation has been used to decrease the risk of recurrence in a patient with large pelvic AAM, there were no follow-up data to arrive at any conclusion.20
Hormonal status being a better predictor of treatment failure in comparison to the extent of surgical resection was speculated by Bigby et al.21 Considering that the hormonal dynamics are age and sex related, the tumour growth rate, aggressiveness and metastatic potential may vary significantly from the females.21 22 Hormonal therapy has become a newer approach to the treatment of AAM as the tumour is positive for oestrogen and progesterone receptors. Usage of gonadotropin-releasing hormone (GnRH) agonist as medical management for AAM has shown complete radiographic resolution of the tumour as reported in several case reports.23 Knowing the hormonal status of the tumour becomes necessary to assess the success of the therapy. Hormonal treatment will not be successful if oestrogen and progesterone receptors are negative and the best option available in such a case would be preoperative arterial embolisation.3 20 24
In a patient with positive receptor status and tumour limited to a certain region, surgical excision is the best therapeutic option.24 Hormonal treatment can be recommended in a patient with residual disease after surgical excision.24 In case of a very high surgical morbidity or when fertility is a concern, neoadjuvant hormonal therapy is a potential alternative that can be attempted followed by surgical excision.24
GnRH agonists are the recommended hormonal treatments in premenopausal women, with a varied response, as the receptor status in AAMs is not always strongly positive and the optimal duration of therapy is yet to be defined.12 19 23 24 Also, long-term adjuvant hormonal therapy has not been shown to prevent tumour recurrence.25 In oestrogen-positive postmenopausal women, aromatase inhibitors are preferred.24 To the best of our knowledge, hormonal therapy has not been used as a stand-alone therapy for the treatment of AAM, and no specific hormonal therapy has been described as a treatment modality for AAM occurring in males.
In situations of a non-operable tumour with no response to embolisation or hormonal treatment, radiation therapy can be considered.26 Radiation therapy and chemotherapy do not have any well-defined roles in the management of AAM. Low mitotic activity of the tumour is considered the reason for the failure of radiation therapy or chemotherapy in the management of AAM.27
Patient’s perspective
I was very apprehensive about my condition. I felt I would never be able to go back to my daily occupation of farming. I was counselled adequately before the operative intervention and agreed to undergo the procedure. Postoperatively I made a good recovery and was discharged in a stable condition. I am back at my hometown now in West Bengal, India, and continue to do my activities of daily living. I am extremely grateful to God and the staff and doctors involved in my care.
Learning points
Aggressive angiomyxomas are a highly rare group of tumours among males and a high index of suspicion must be kept in mind when dealing with perineal soft tissue tumours, especially among males, before making a diagnosis.
Complete resection is the goal of therapy; incomplete resection is acceptable when the operative morbidity is too high or when fertility preservation is a concern.
A newer approach to the treatment includes hormonal therapy as the tumour is positive for oestrogen and progesterone receptors.
Due to the high propensity for recurrence, long-term follow-up and monitoring with imaging is essential for the timely identification of recurrence.
Acknowledgments
The authors would like to thank Dr Anu Eapen, professor, Department of Radiology, Christian Medical College and Hospital, Vellore, India, for her input and guidance on radiological images in the manuscript. The authors would also like to thank Dr Ponmar Madhurima and Dr Jennifer Prabhu at Christian Medical College and Hospital, Vellore, India, for their help in providing photomicrographs for the manuscript.
References
Footnotes
Contributors NPA and VVC were involved in drafting of the manuscript and taking care of the patient reported in this case. BR was involved in editing and final submission of the manuscript. SC was involved in approving the final manuscript and taking care of the patient reported in this case.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests None declared.
Patient consent for publication Obtained.
Provenance and peer review Not commissioned; externally peer reviewed.