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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 5  |  Issue : 2  |  Page : 80-84

Aggressive angiomyxoma of scrotum in a man: A case report and literature review of 73 cases of aggressive angiomyxoma in men


1 Department of Urology, National University Hospital, National University Health System, Singapore
2 Department of Pathology, National University Hospital, National University Health System, Singapore

Date of Web Publication11-Oct-2018

Correspondence Address:
Dr. Yu Xi Terence Law
Department of Urology, National University Hospital, 1E Kent Ridge Road, NUHS Tower Block, Level 8, 119228
Singapore
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jina.jina_31_17

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  Abstract 


Aggressive angiomyxoma is a mesenchymal tumor arising from the pelvis and perineum, classically seen in women and rarely found in men. Due to its rarity, there is a low index of suspicion for diagnosis. We describe an unusual case of aggressive angiomyxoma in a male with intellectual disability. A thorough review of existing 73 cases was also conducted. This report affirms vimentin as the most sensitive marker and S-100 is the most specific marker. Desmin seems to stain positively and negatively in a sporadic fashion, making it less reliable as an immunohistochemical marker. Wide excision is commonly regarded as the treatment for aggressive angiomyxoma in men. To date, there are no established clinical guidelines on the optimal duration of follow-up. Long-term follow-up may be required even up to 10 years to detect local recurrences.

Keywords: Aggressive angiomyxoma, immunohistochemistry, mesenchymal tumor, scrotal masses


How to cite this article:
Law YX, Tan JH, Lee KC. Aggressive angiomyxoma of scrotum in a man: A case report and literature review of 73 cases of aggressive angiomyxoma in men. J Integr Nephrol Androl 2018;5:80-4

How to cite this URL:
Law YX, Tan JH, Lee KC. Aggressive angiomyxoma of scrotum in a man: A case report and literature review of 73 cases of aggressive angiomyxoma in men. J Integr Nephrol Androl [serial online] 2018 [cited 2018 Dec 14];5:80-4. Available from: http://www.journal-ina.com/text.asp?2018/5/2/80/243118




  Introduction Top


Aggressive angiomyxoma is a rare mesenchymal tumor of the pelvis and perineum arising predominantly in premenopausal women.[1] The tumor is usually locally infiltrative with a high rate of recurrence after resection.[1] It is rarely found in men and may mimic hernias, testicular tumors, hydrocele, and spermatoceles. We report an unusual case of aggressive angiomyxoma of the scrotum presenting as a scrotal mass.


  Case Report Top


A 38-year old Chinese male with intellectual disability presented with a right scrotum mass that had progressively enlarged over 1 year. Patient was unable to provide any history but appeared generally well.

On examination, the left testis was normal; however, the right testis felt firm and enlarged measuring 10 cm × 6.5 cm. The patient was generally uncooperative during examination, and it was not possible to elicit signs of tenderness on palpation. His abdomen was otherwise soft, nontender, without any palpable masses. There was no obvious inguinal lymphadenopathy. His lungs were clear.

Lactate dehydrogenase, alpha-fetoprotein, and beta-human chorionic gonadotropin levels were not elevated. Ultrasound (US) scrotum revealed a large heterogeneous solid mass in the right scrotum [Figure 1]. There was internal vascularity. Although the mass appeared distinct from the right testis at some areas, the invasion could not be entirely excluded. The left testis was normal. Given this patient's history of intellectual disability (Down syndrome) and a known association with testicular cancer,[2] an orchidectomy was performed to exclude testicular cancer, especially since invasion could not be entirely ruled out.
Figure 1: Ultrasound scrotum. (a and b) A 6.4 cm × 4.7 cm × 10.3 cm heterogeneous solid mass in the right scrotum. (c) The solid mass shows internal vascularity. (d) The mass appears inseparable from the right testis at certain parts. Red asterisk: Right testis. Red #: Solid mass. (e and f) The right testis measures 3.4 cm × 1.8 cm × 1.9 cm with the solid mass seen on the lateral to it

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Patient underwent a right radical orchiectomy through an inguinal approach. The tumor turned out to be paratesticular and was separable from the testis and spermatic cord [Figure 2]a and [Figure 2]b. Grossly, the tumor had no necrotic or hemorrhagic areas. It was well circumscribed and enveloped by an intact rim of fibrous capsule.
Figure 2: Image of the aggressive angiomyxoma. (a) The right testis and the large solid tumor measuring 11.5 cm × 6 cm is removed in entirety. (b) Red asterisk: The testis (3.5 cm × 2.5 cm × 1.5 cm) appears small but is otherwise unremarkable. There is a well-circumscribed, fully encapsulated, ovoid-shaped paratesticular tumor (10.5 cm × 6.5 cm × 5.7 cm) with overlying fibroadipose and muscle tissue (4.5 cm × 2.5 cm × 0.5 cm). Red #: The tumor is separate from the testis and spermatic cord. The cut surface of this tumor has a solid homogeneous tan to pinkish gelatinous appearance with no necrotic or hemorrhagic areas

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Microscopic examination showed the specimen to be hypocellular, containing abundant vessels and stromal cells in a background of myxoedematous and finely collagenous stroma [Figure 3]a and [Figure 3]b. The vessels were of varying caliber ranging from small thin-walled vessels to medium and large vessels with thick muscularized walls. Hyalinization of the vessel walls was prominent. Inflammatory infiltrates including aggregates of lymphocytes, plasma, and mast cells were seen. There was no evidence of cytological atypia, pleomorphism, or increased mitotic activity (0–2 mitoses per 10 high power field) in cellular areas.
Figure 3: Microscopic examination of the aggressive angiomyxoma. (a) Fibrous tissue capsule of variable thickness. The tumor is mostly hypocellular containing abundant vessels and stromal cells in a background of myxoedematous (paler, more whitish area) and finely collagenous stroma (pinker areas). (b) More cellular area. Most of these spindle cells are the stromal cells – bland with no atypia. Note the small blood vessels and myxoedematous (pale whitish) background. (c) Estrogen receptor staining – note focal positive cells (brown nucleus). (d) S100 staining - note focal positive cells (brown nucleus)

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There is no evidence of lymphovascular invasion, a malignant adipocytic component, lipoblasts, or redifferentiation.

Immunohistochemistry studies revealed that the neoplastic stromal cells were focally weak to moderately positive for S100 and estrogen receptor (ER) protein [Figure 3]c and [Figure 3]d. Focal moderate expression for desmin was noted in some scattered stromal cells. The cells were stained negatively for AE1/3, CAM5.2, ALK-1, CD-34, and progesterone receptor protein.

Overall, the clinical site, morphological, and immunohistochemical features were most compatible with a deep angiomyxoma of the scrotum.

Patient was surveyed with yearly computed tomography (CT) abdomen and pelvic with no recurrence after 12 months.


  Discussion Top


Aggressive angiomyxoma is a rare locally infiltrative benign mesenchymal tumor that is paratesticular in nature. It was first described in 1983, in the perineum of premenopausal women.[1] It was only in 1985 that such lesion was described to arise in the inguinoscrotal region of males.[3] In men, the sites commonly involved are the scrotum, spermatic cord, the perineum region, and the groin.[4] As it is rarely found in the men, there is a low index of suspicion for diagnosis; many of which were initially diagnosed as hernias, testicular tumors, hydrocele, and spermatoceles [Table 1].
Table 1: Summary of the 73 cases of aggressive angiomyxoma in male

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Classically, these tumors present as a painless slow-growing mass in the inguinoscrotal region of males with no associated urinary symptoms.[5] De la Ossa et al. described the sonographic appearance of an aggressive angiomyxoma of the scrotum as a well-demarcated, hypoechoic, extratesticular, extraepididymal mass with internal septa and without significant flow on color Doppler sonography.[6] However, for our case, the US of the mass revealed a heterogeneous mass with internal vascularity, appearing inseparable from the testis, leading us to think that this was a testicular tumor. Such initial impressions were consistent with reports by Gaunay et al.'s study.[7]

On the CT scan, an aggressive angiomyxoma usually adopts a “swirled” appearance, especially on enhanced scans.[8] However, none of these imaging tools can differentiate aggressive angiomyxoma from other malignancies including sarcomas.[7] Without specific symptoms and radiological diagnostic criteria for aggressive angiomyxomas, a preoperative misdiagnosis rate of 70%–100% is not unusual.[9] The mainstay of management is surgical exploration and complete surgical resection of the tumor with clear margins.

Histologically, aggressive angiomyxomas consist of mesenchymal spindle-shaped or stellate cells widely separated by loose, myxoid background of collagen fibers, low mitotic activity, and a prominent vascular component.[1] This corresponds with our histology.

A number of differential diagnoses of different lineages were eventually excluded after taking into account a combination of clinical, morphological, and immunohistochemical factors. For example, angiomyofibroblastoma is typically smaller and occurs in more superficial sites, with a lack of muscular walled vessels and presence of intralesional fat histologically.[10]

Currently, there are no specific markers for aggressive angiomyxoma.[11] The tumor is usually positive for vimentin, desmin, smooth muscle-specific actin, and CD34 and may be positive for estrogen and progesterone receptor protein in males. Aggressive angiomyxoma is usually negative for S100 protein, factor VIII, and Ki-67.[5] Interestingly, our immunohistochemistry studies revealed that desmin was moderate positive, weak-to-moderate positive for S100 and ER, and stained negatively for CD34 and progesterone receptor protein. S100 might have been positive due to the presence of entrapped nerves.

Studies have cited a high local recurrence rate between 36% and 72%, but no metastasis has been reported to date in men.[11] Hence, a long-term follow-up examination at intervals of 1–2 years using alternating imaging modalities of US and magnetic resonance imaging (MRI) should be considered.[4]

A thorough literature search was performed for existing cases of aggressive angiomyxoma in men. Fifty-three articles were accessed,[12],[13],[14],[15],[16] and a total of 73 cases were found including our present case [Table 1]. Although 73 cases were found, aggressive angiomyxoma is still regarded to occur more rarely in males compared to females.

The age of presentation is highly variable in males ranging from 1 to 82 years old, with a mean age of 49 years old. Majority of the patients presented with a painless enlarging mass over a duration of time.

Sixty-seven out of 73 cases were found to be located in the genitourinary region (92%), of which 43 cases in the scrotum (59%), 9 cases arose in the inguinal region (12%), 9 cases in the pelvis (12%), and 7 cases in the perineum (10%).

Out of 43 cases arising from scrotum, 10 cases were from the spermatic cord (13%), 2 cases were from the epididymis (3%), and 1 case was from the testis (1%). These suggest that it is important to consider aggressive angiomyxoma as part of the differential diagnosis for nontender enlarging paratesticular mass. More rarely, aggressive angiomyxoma can also be found outside of the genitourinary region. For instance, there has been three reported cases in the larynx (4%), two cases in the lower limb (3%), and one case in the maxillary region (1%).

A total of 46 cases established a preoperation diagnosis after investigations and 33 cases (72%) made a wrong diagnosis. Investigations included US, CT, MRI, and biopsy, but these investigations ultimately could not characterize the lesion beyond a mesenchymal tumor of unknown malignant potential. In most cases, the diagnosis of aggressive angiomyxoma could only be made when there was a local recurrence or during intraoperative frozen section. Thus, preoperative diagnosis of aggressive angiomyxoma can be extremely challenging.

Regarding immunohistochemistry, a literature review has shown that vimentin had the highest sensitivity (100%). Although Alcian blue and androgen receptor also had 100% sensitivity, these were tested only in a minority of cases. S100 was almost always negative (98% of the time). Vimentin likely has the greatest utility, especially when tested alongside S100 and/or other markers. Although desmin had largely stained negatively in the earliest reports of aggressive angiomyxoma, reports in recent years have shown a mix of desmin positivity and negativity. Interestingly, both estrogen and progesterone receptors may be positive in both genders, implying that there may be a hormonal role in the development of aggressive angiomyxoma. In our review, three out of three cases stained positively for the androgen receptor. More studies are needed to investigate if androgen receptor is truly a sensitive marker for detection.

Wide excision is commonly regarded as the treatment for aggressive angiomyxoma, with only two cases including radiation and one case using tamoxifen as adjuvant treatment. No metastases have been reported in men with aggressive angiomyxoma. Follow-up duration ranged from 3 to 144 months with wide excision. In 4 cases where there was a local recurrence, the duration to local recurrence ranged from 3 months to 7 years. In one of the four cases, despite radical orchiectomy being performed, the patient still had a local recurrence after 7 years.[14] Although there are no clinical guidelines on the optimal duration of follow-up, this seems to suggest that long term of monitoring is needed for aggressive angiomyxoma.


  Conclusion Top


Although a rare occurrence in males, aggressive angiomyxoma should be considered as an unusual but possible differential of a scrotal mass. Diagnosis may be challenging and depends largely on gross morphology. To date, there is no single panel of immunohistochemical markers that can diagnose aggressive angiomyxoma definitively. Although not performed in our case, we postulate vimentin is likely the most useful and sensitive marker, while S100 is the most specific marker. While there is a role of desmin testing, desmin seems to sporadically stain positively and negatively, making it less reliable as an immunohistochemical marker.

Based on our review, there are also no established clinical guidelines on the optimal duration of follow-up. We feel that long-term follow up is necessary, perhaps even up to 10 years to detect rare local recurrences. As for the frequency of follow-up, more studies will need to be conducted to establish a safe, yet efficacious time-to-follow-up duration.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for the patient's images and other clinical information to be reported in the journal. The parents understand that name and initials of the patient will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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. Am J Surg Pathol 1983;7:463-75.  Back to cited text no. 1
    
2.
Dieckmann KP, Rübe C, Henke RP. Association of Down's syndrome and testicular cancer. J Urol 1997;157:1701-4.  Back to cited text no. 2
    
3.
Bégin LR, Clement PB, Kirk ME, Jothy S, McCaughey WT, Ferenczy A, et al. Aggressive angiomyxoma of pelvic soft parts: A clinicopathologic study of nine cases. Hum Pathol 1985;16:621-8.  Back to cited text no. 3
    
4.
Medina R, Fernando J, Carrera S, Javier A, Ibáñez, Heinz O, et al. Aggressive angiomyxoma in men: Clinical case report and literature review. Rev Colomb Gastroenterol 2011;26:304-10.  Back to cited text no. 4
    
5.
Idrees MT, Hoch BL, Wang BY, Unger PD. Aggressive angiomyxoma of male genital region. Report of 4 cases with immunohistochemical evaluation including hormone receptor status. Ann Diagn Pathol 2006;10:197-204.  Back to cited text no. 5
    
6.
De la Ossa M, Castellano-Sanchez A, Alvarez E, Smoak W, Robinson MJ. Sonographic appearance of aggressive angiomyxoma of the scrotum. J Clin Ultrasound 2001;29:476-8.  Back to cited text no. 6
    
7.
Gaunay GS, Barazani Y, Kagen AC, Stember DS. Aggressive angiomyxoma of the scrotum. Clin Imaging 2013;37:1122-4.  Back to cited text no. 7
    
8.
Outwater EK, Marchetto BE, Wagner BJ, Siegelman ES. Aggressive angiomyxoma: Findings on CT and MR imaging. AJR Am J Roentgenol 1999;172:435-8.  Back to cited text no. 8
    
9.
Wang Q, Zhao M, Lin X, Zhong W, Gao Y. Aggressive angiomyxoma of the vulva: Intra-operative pathological diagnosis is useful in deciding the scope of surgery and reducing recurrence. Acta Chir Belg 2012;112:79-84.  Back to cited text no. 9
    
10.
Laskin WB, Fetsch JF, Tavassoli FA. Angiomyofibroblastoma of the female genital tract: Analysis of 17 cases including a lipomatous variant. Hum Pathol 1997;28:1046-55.  Back to cited text no. 10
    
11.
Kondo T. Aggressive angiomyxoma in the inguinal region: A case report. J Med Case Rep 2010;4:396.  Back to cited text no. 11
    
12.
Chihara Y, Fujimoto K, Takada S, Hirayama A, Cho M, Yoshida K, et al. Aggressive angiomyxoma in the scrotum expressing androgen and progesterone receptors. Int J Urol 2003;10:672-5.  Back to cited text no. 12
    
13.
Tsang WY, Chan JK, Lee KC, Fisher C, Fletcher CD. Aggressive angiomyxoma. A report of four cases occurring in men. Am J Surg Pathol 1992;16:1059-65.  Back to cited text no. 13
    
14.
Silverman JS, Albukerk J, Tamsen A. Comparison of angiomyofibroblastoma and aggressive angiomyxoma in both sexes: Four cases composed of bimodal CD34 and factor XIIIa positive dendritic cell subsets. Pathol Res Pract 1997;193:673-82.  Back to cited text no. 14
    
15.
Oshiro T, Oshiro Y, Baba H, Maehara Y, Tsuneyosh M, Sugimachi K, et al. Aggressive angiomyxoma of the inguinal region. Oncol Rep 1997;4:1001-3.  Back to cited text no. 15
    
16.
Rhomberg W, Jasarevic Z, Alton R, Kompatscher P, Beer G, Breitfellner G, et al. Aggressive angiomyxoma: Irradiation for recurrent disease. Strahlenther Onkol 2000;176:324-6.  Back to cited text no. 16
    


    Figures

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    Tables

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