Posted May 19, 2010

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A 35-year-old man presented with a slowly growing painless mass in the scrotum. Imaging studies revealed a locally infiltrating mass that involved the scrotal wall and extended into adjacent pelvic soft tissue.

Archive Case and Diagnosis: This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2007, Case 21 and is an aggressive angiomyxoma

Criteria for Diagnosis and Comments: Aggressive angiomyxoma was first described by Steeper and Rosai in 1983 as a distinct soft-tissue tumor that involved the pelvis or perineum of premenopausal women. Although the lesion is much more common in women, more than a handful of cases have been described in middle aged men involving scrotal soft tissue, inguinal hernias, spermatic cord, and pelvis. Based on this information, aggressive angiomyxoma must be included in the differential diagnosis in men with myxoid appearing soft tissue tumors involving the pelvis or perineum.

Aggressive angiomyxomas are locally aggressive, non-metastasizing, tumors with a propensity for locally destructive recurrence in cases that are incompletely excised. They are large, soft, fleshy, gray-white, and poorly circumscribed and have a glistening appearance on cross-section. Microscopically, the tumor is paucicellular and composed of a loose myxoid background containing bland appearing bipolar to multipolar stellate shaped mesenchymal cells with small uniform vesicular nuclei, inconspicuous nucleoli, and rare mitoses. In addition, small to medium thick walled vessels, some of which contain fibrin microthrombi, are scattered throughout the tumor. The tumor cells are positive for vimentin and stain variably for muscle-specific actin and desmin, but are non-immunoreactive for S-100 protein, and keratin. Clonal cytogenetic aberrations that have been reported in aggressive angiomyxoma include loss of an X chromosome, pericentric inversion of 12p11.2, and a translocation involving 12q14-15.

Angiomyofibroblastoma is a slow growing mass predominately involving the vulva or vagina of middle aged women and rarely the scrotum of middle-aged men. Angiomyofibroblastomas are rubbery and have a light gray to tan cut surface. Histologically, these tumors show a circumscribed nodular spindle cell proliferation with alternating hypocellular loose edematous stroma and hypercellular areas. The hypercellular areas are composed of abundant ectatic sometime branching typically capillary sized vessels surrounded by plump eosinophilic epithelioid cells and spindle cells. The epithelioid cells may be dispersed or clustered around the vessels. The cells lie in cords or singly in a matrix that varies from myxoid to hyaline. Angiomyofibroblastoma usually only has a partially myxoid appearance in contrast to aggressive angiomyxoma which is a uniformly myxoid tumor. Also, angiomyofibroblastomas have epithelioid cells, more numerous typically capillary sized blood vessels, and are well circumscribed compared to aggressive angiomyxoma. Unlike aggressive angiomyxoma they usually do not recur after excision. Angiomyofibroblastomas stain for vimentin and desmin.

Neurofibromas are benign tumors of the nerve sheath that can occur sporadically or in association with neurofibromatosis type 1(NF1). Neurofibromatosis type I (NF1) is caused by mutation in the neurofibromin gene that has been mapped to the long arm of chromosome 17, which functions as a tumor suppressor gene by regulating cell growth. Of the variants, the diffuse and plexiform types have a close association with NF1. The most common variant encountered is the localized type that can occur sporadically and presents as a painless solitary nodule usually less than 5 cm in size. Localized neurofibromas are often found on the extremities, but can occur at any site. They affect both genders equally and are most common in persons between the ages of 20 to 30 years. Gross examination shows a well demarcated, unencapsulated, firm, gray to tan, glistening mass. Neurofibromas differ from aggressive angiomyxomas by having interlacing fascicles of wavy ("buckled") elongated cells closely associated with strands of collagen that has been compared to "shredded carrots", within a myxomatous background depending on the amount of myxoid degeneration. Immunohistochemically, these tumors have patchy staining with S-100, and are negative for keratin, muscle specific actin, smooth muscle actin, CD34, glial fibrillary acid protein, and desmin. Neurofibromas typically have few to no mitosis and their presence should evoke the possibility of a malignant peripheral nerve sheath tumor (MPNST). Although all types can undergo malignant transformation, the lesion with the greatest risk of transformation is the plexiform neurofibroma, and extra care must be taken to search for areas of increased cellularity, atypia, and mitosis.

Myxoid leiomyoma can be found in the pelvis and can reach a large size. They can occur at any age and have an equal sex predilection. Grossly, these lesions are well circumscribed, and have a gray-white cut surface. Histologically, they are composed of elongated bland eosinophilic cells with blunt ends ("cigar shaped cells") that show an orderly pattern of intersecting fascicles. There is minimal pleomorphism and no mitosis. Occasional perinuclear vacuolization may be noted. With myxoid degeneration, there is loss of the fascicular pattern and accumulation of myxoid material between the cells, which can be distinguished from other entities based on its staining characteristics and foci of typical appearance. Mature fat can be encountered in smooth muscle tumors of all types, and some authors have referred to these entities as lipoleiomyoma or myolipoma.6 The absence of mitosis helps differentiate between leiomyoma and leiomyosarcoma. It differs from aggressive angiomyxoma by its lack of vessels and intersecting smooth muscle fascicles which are positive for smooth muscle actin, desmin and cytokeratin (variably).