General
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• Rare, locally infiltrative mesenchymal tumor of women of reproductive age and infrequently men (see Testis chapter), usually arising in perineal region
• Originally described by Steeper and Rosai in 1983 (Am J Surg Pathol 1983;7:463)
• > 250 cases reported to date

Terminology
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• Also called deep angiomyxoma (IARC: Pathology and Genetics of Tumours of the Breast and Female Genital Organs, 2003)

Epidemiology
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• Women: predominantly in early reproductive years
• Adult men: less commonly affected
• Female to male ratio ~ 6:1
• Rare in children (Pediatr Surg Int 2005;21:563)

Sites
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• Women: tumors arise in perineal and pelvic regions, may cross the pelvic diaphragm
• Men: tumors originate from spermatic cord (Indian J Urol 2009;25:137), inguinal region (J Med Case Rep 2010;4:396) and scrotum (Clin Imaging 2013;37:1122; Rare Tumors 2011;3:e31)
• Non-perineal sites include thigh (J Med Case Rep 2010;4:396; Skeletal Radiol 2008;37:673)

Pathophysiology
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• Unclear, but tumor is mesenchymal in origin
• Hormonal (estrogen and progesterone) influence may also play a role

Clinical features
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• May be an incidental finding
• Slow growing palpable or visible tumor of vulva, gluteal region or suprapubic region
• Imaging frequently reveals pelvic extension of huge mass
• Patients often complain of mass, dull aching pain, urinary and gastrointestinal symptoms such as dysuria, urinary retention, dyspareunia (Can J Urol 2011;18:5908)

Diagnosis
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• Histologic examination of core biopsies or more commonly the resection specimen

Radiology
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• Extensive imaging to assess extent of tumor is necessary prior to surgery.
• Ultrasound (abdominal, endorectal and scrotal) demonstrates a soft, hypoechoic, solid mass (Can J Urol 2011;18:5908)
• CT scan: (Abdom Imaging 2011;36:739)
  • Unenhanced CT scan shows a low density mass
  • Contrast enhanced CT scan shows a mildly enhancing mass with an internal swirling pattern
• MRI: (Case Rep Oncol 2013;6:373)
  • Shows bulky perineal and intrapelvic tumor displacing rather than infiltrating surrounding structures
  • Diffusion weighted MRI has diagnostic and prognostic value
  • T1 weighted imaging: tumor is isointense to muscle
  • T2 weighted imaging: tumor shows high signal intensity with layered strands of lower signal intensity and swirled architecture
  • May have finger like projections into surrounding fat
  • Follow-up MRI useful to detect recurrence after resection

Radiologic images
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CT scan, c/o Dr. Mark R. Wick

Axial noncontrast CT

Prognostic factors
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• Recurrence is common due to incomplete excision
• Involvement close to urethra, vagina, rectum and anal sphincter as well as extension through pelvic diaphragm is associated with incomplete resection
• Vascular invasion is associated with distant metastasis to lungs and mediastinum, leading to death (Korean J Radiol 2012;13:90, Hum Pathol 2003;34:1072, N Engl J Med 1999;341:1772)

Case reports
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• Scrotal tumors:
  • 64 year old man with aggressive angiomyxoma of the scrotum mimicking huge hydrocele (Case Rep Med 2009;2009:157624)
• Inguinal tumors:
  • 68 year old man with aggressive angiomyxoma in inguinal region (J Med Case Rep 2010;4:396)
• Vulva:
  • 23 year old woman with deep angiomyxoma of retroperitoneum presenting as perineal lump (BMJ Case Rep 2013;2013)
  • 25 year old woman with multifocal aggressive angiomyxoma (J Clin Pathol 2000;53:798)
  • 28 year old woman with aggressive angiomyxoma of vulva recurring 8 years after initial diagnosis (Arch Gynecol Obstet 2009;280:485)
• Pregnancy:
  • 25 year old woman with aggressive angiomyxoma of vulva in pregnancy (MedGenMed 2007;9:16)
  • Aggressive angiomyxoma (Eur J Surg Oncol 2006;32:1217)

Treatment
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• Wide surgical resection as an en-bloc specimen is usually accomplished by a combined transperineal and abdominopelvic approach, with preservation of surrounding structures
• Preoperative vascular embolization may decrease the tumor size
• Lifetime follow up to monitor for recurrence is mandatory
• Chemotherapy and radiotherapy are ineffective due to the low proliferative potential of the lesional cells, but high dose radiotherapy has been used successfully to treat recurrent disease (Int J Gynecol Cancer 2006;16:356)
• Hormonal therapy with gonadotrophin-releasing hormone (GnRH) inhibitors such as leuprolide is useful for recurrent tumors that are positive for estrogen and progesterone receptors (J Low Genit Tract Dis 2014 Jan 7 [Epub ahead of print])
• Non-steroidal selective estrogen receptor modulators (SERM) such as raloxifene have also been used (Gynecol Oncol 2011;123:172)

Clinical images
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Well-defined polypoidal pedunculated

 

Pedunculated mass

Gross description
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• Typically a pendunculated vulvar mass
• Usually large, partly encapsulated, relatively circumscribed and soft to firm in consistency
• Cut surface is homogenous, gelatinous and usually glistening with no obvious hemorrhage or necrosis

Gross images
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Courtesy of Dr. Mark R. Wick

 

Various images

Well-circumscribed fleshy tan gelatinous mass

Specimen cut open

Micro description
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• Monotonous and hypocellular, composed of small spindled and stellate fibroblasts with no atypia, extremely rare mitoses and no atypical mitotic figures
• Stroma is myxoid with collagen fibers and prominent, dilated, thick walled vessels, which may be hyalinized with a prominent vascular smooth muscle layer
• Peripheral infiltrative margins with extension into surrounding muscles, nerves, adipose tissue and rarely vascular structures
• Red blood cell extravasation may be present (J Clin Pathol 2000;53:798)
• Some tumors have a component of admixed adipose tissue, unclear if due to extensive infiltration (Can J Plast Surg 2007;15:163)

Micro images
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Courtesy of Dr. Mark R. Wick

 

Aggressive angiomyxoma

Ectatic blood vessel

Prominent myoid differentiation

Myoid differentiation

     

Various images

 

Thick walled vessels: H&E and Trichrome

       

Various images

CD34+

ER+

Vimentin+

Cytology description
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• Smears show arborizing capillaries in a loose myxoid background containing dispersed cells
• Cells are spindled or stellate with delicate elongated cytoplasm and bland vesicular nuclei with fine chromatin and inconspicuous nucleoli (Cytopathology 2010;21:207)

Positive stains
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• CD34, vimentin, ER± , PR±, SMA focal, Desmin focal, MSA focal (J Clin Pathol 2000;53:603)
• HMGA2 is a sensitive but nonspecific marker (Am J Surg Pathol 2010;34:1037)

Negative stains
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• CD117, β-Catenin, cytokeratin, S100, EMA
• Caldesmon, MDM2, Factor VIII, CEA

Electron microscopy
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• Lesional cells show myofibroblastic differentiation consisting of irregular but delicate cellular processes, prominent golgi apparatus, dilated rough endoplasmic reticulum
• Cytoplasm has several intermediate filaments, while the stroma contains aggregates of collagen fibers and fine granular material (Hum Pathol 1985;16:621)

Molecular and cytogenetic findings
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• Most cases tested show involvement of HMGA2 gene at 12q15
  • t(12;21)(q15;q21.1) (Cancer Genet Cytogenet 2008;181:119)
  • t(11;12)(q23;q15) (Virchows Arch 2006;448:838)
• One case reported a t(5;8)(p15;q22) involving the COX6C gene (Int J Gynecol Pathol 2007;26:494)

Molecular / cytogenetic images
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t(12;21)

Differential diagnosis
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• Clinical differential diagnosis:
  • Angiomyofibroblastoma (Obstet Gynecol Sci 2013;56:349)
  • Bartholin gland cyst
  • Sarcoma botryoides
  • Superficial angiomyxoma (J Cutan Pathol 2010;37:672)
  • Vulvar hypertrophy with lymphedema (Arch Pathol Lab Med 2000;124:1697)
• Histologic differential diagnosis:
  • Myxoma
  • Myxoid liposarcoma
  • Myxofibrosarcoma
  • Nerve sheath myxoma
  • Sarcoma botryoides
  • Vulvar hypertrophy with lymphedema
  • Other soft tissue tumors with secondary myxoid change

Additional references
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• Arch Pathol Lab Med 2012;136:217, Arch Gynecol Obstet 2011;283:1145, Eur J Surg Oncol 2010;36:335, Histopathology 2009;54:156, Int J Gynecol Pathol 2005;24:26, Int J Gynecol Pathol 2001;20:105

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