Moderators: John R. Srigley and Rodolfo Montironi
Angiomyofibroblastoma–like Tumor of Scrotum
Hema Samaratunga MD, FRCPA
Sullivan Nicolaides Pathology,
Brisbane, Queensland, Australia
A 63-year-old male presented with a painless left scrotal mass, which was first noted a few weeks
previously. There were no associated symptoms. The mass was found to be external to the testis. A
radical orchidectomy was performed in continuity with the mass.
An ovoid soft lobulated mass was attached to the surface of the tunica measured 4 cm in maximum
dimension. On sectioning, the cut surface was nodular brownish and reddish tan spongy tissue
interspersed with yellowish tissue resembling fat. The lesion appeared circumscribed with an apparent
Sections revealed a circumscribed mass surrounded by a pseudocapsule. The lesion was composed of a
spindle cell proliferation interspersed with numerous blood vessels within finely collagenous and focally
oedematous appearing stroma. Adipose tissue was noted throughout the lesion with adipocytes present
singly and in small clusters. The cellularity of the lesion was variable with hypercellular and
hypocellular zones. Focally, compact short fascicles were present with nuclear palisading resembling a
neurilemmomatous growth pattern. The spindle cells were wavy and had bland ovoid to elongated nuclei and
scanty eosinophilic cytoplasm. Nuclei had fine chromatin and nucleoli were inconspicuous. Mitotic
figures were not seen. Large numbers of mast cells and lymphocytes were noted throughout the lesion.
The vascular component consisted of small to medium-sized rounded thick walled blood vessels, curvilinear
thin-walled vessels and collections of capillaries. Blood vessel walls displayed fibrinoid change and
focally, fibrinoid necrosis. Perivascular hyaline fibrosis was also noted. Throughout the lesion, the
stroma contained thin collagen fibres, which were loosely textured in some areas.
Colloidal iron staining revealed moderately strong reactivity confirming presence of stromal acidic
mucin. Immunohistochemical staining revealed that the lesional cells were diffusely and strongly
positive for CD 34 and moderately strongly positive in most cells for oestrogen receptors. Spindle cells
were negative for desmin, smooth muscle actin, S-100 protein, cytokeratin, EMA and progesterone
receptors. Muscle specific actin was found in sparse numbers of spindle cells around blood vessels.
Angiomyofibroblastoma-like tumor of scrotum (cellular angiofibroma)
The term angiomyofibroblastoma (AMF) was first coined in 1992 by Fletcher
et al to describe a distinctive benign soft tissue tumour of predominantly the vulva,
rarely the scrotum, mimicking and often misdiagnosed as a cellular variant of aggressive angiomyxoma. It
was noted that unlike aggressive angiomyxoma, these tumours were well circumscribed and had no recurrence
after excision. These lesions were composed of alternating hypercellular and hypocellular oedematous
areas composed of bland ovoid to fusiform cells and epithelioid cells that had a tendency to concentrate
around blood vessels, sometimes forming solid compact foci. Abundant blood vessels, varying amounts of
adipose tissue, background delicate or thick wavy collagen fibrils and an infiltrate of mast cells and
lymphocytes were characteristically found in this lesion. Lesional cell were often positive for desmin,
but less commonly for muscle specific actin or alpha-smooth muscle actin.
AMF was given due to its prominent vascular component with a stromal cell component displaying
histological, ultrastructural and immunohistochemical features of myofibroblasts. 
Since then there have been other reports of a similar tumour occurring in the male genital system with
cases reported in the scrotum, spermatic cord and the inguinal region.
6] In the first
large series of this entity in the male genital system of 11 cases, Laskin et al  noted that
while these tumours had features of vulvo-vaginal AMF, these also had similarities to spindle cell
lipoma. They also noted that these tumours had several significant differences from the female AMF. The
mean and median age at presentation was higher for male patients than for female patients. There were
several histological differences with lesional cells primarily spindled rather than epithelioid. Spindle
cells were seen haphazardly or in loose fascicles without exhibiting perivascular growth or forming nests
or cords, typical of female AMF. More acid mucin was found in male tumours in contrast to the
oedematous, loosely textured stroma found in female tumours. Ectatic and hemangiopericytomatous blood
vessels were commonly found in males whereas they were only focally found in females. The immunoprofile
was also slightly different from that of female AMF with less desmin expression (only 40% in contrast to
female cases with> 90%)
7] and more cases reacting with anti-actin (50% compared with
15% with muscle specific or alpha smooth muscle actin)
The mean oestrogen and
progesterone receptor staining was also substantially higher in female AMF.
5] For these
reasons, the male tumours were labelled AMF-like tumours.
Recently it has been noted that AMF-like tumours have morphological features more in common with
cellular angiofibroma  with component cells displaying more prominent
fibroblastic than myofibroblastic differentiation. While it is recognised that AMF does occur in the
male genital system,
most cases reported in the literature are AMF-like tumours (cellular
In the recent WHO classification of soft tissue tumours, these are labelled
cellular angiofibroma, while it is noted that they are related to and share morphological features with
AMF. These are benign mesenchymal tumours usually arising in the superficial soft tissues of
the vulva  and the inguino-scrotal region of males.  Extra genital locations of
this tumour include the retroperitoneum and chest.
These occur most commonly in the fifth
through seventh decades of life. Reported cases are rare
with < 40 cases reported
in the male genital system.
These tumours usually present as a painless mass. Rarely, there can be intermittent genital bleeding
and pain. 
There can be an associated hydrocoele or hernia . As seen in our
case, these tumours are usually small, although they can be quite large (2.5-25cm) in males, lobulated,
well circumscribed nodules. Cut surface is solid with a brownish to pink colour. Occasional cases have
had foci of hemorrhage and necrosis and rarely there can be infiltration into surrounding tissues.
Most tumours have features similar to that seen in our case with bland, spindle-shaped cells, short
bundles of wispy collagen, numerous small- to medium-sized thick-walled vessels and intralesional fat.
Tumour cells are haphazardly arrayed or form vague fascicles. Perivascular hyaline fibrosis is seen in
most cases. Rarely there can be epithelioid appearing cells present focally, mild cytological atypia or
Female cases are more likely to have frequent mitoses. 
Significant nuclear atypia and abnormal mitoses are not found. Myxoid stroma, cystic change,
vascular thrombosis and fibrinoid necrosis may be seen.  With immunohistochemistry, most
cases express CD34. There is variable expression of muscles specific actin, smooth muscle actin and
desmin. Some cases are positive for oestrogen receptors and progesterone receptors. These lesions are
negative for S-100 protein. 
Differential diagnostic considerations of AMF-like tumour include aggressive angiomyxoma (AA),
superficial angiomyxoma, neural tumours, myxoid smooth muscle tumours, spindle cell lipoma and solitary
fibrous tumor. Differentiation from AA can be somewhat problematic in small biopsies. Distinction is
crucial as surgical treatment of the two lesions is very different with AMF-like tumour necessitating
only local excision, while AA needs wide resection. AA occurs most often in the pelvic soft tissues and
perineum in relatively young females, and rarely occurs in males. In contrast to AMF-like tumour,
aggressive angiomyxoma is an often poorly demarcated infiltrating poorly cellular tumour with less
vascularity, more stromal mucin and red cell extravasation. Foci of increased cellularity have been
reported in these cases. Immunohistochemical staining is not useful in the distinction between these
tumours as both display myofibroblastic differentiation and myofibroblastic markers. 
Superficial angiomyxoma is another lesion occurring in this location which may recur. The usually
dermal location and absence of thick walled blood vessels are helpful in this distinction.
A focal fascicular pattern with wavy spindle cells suggests the possibility of a neural tumour. AMF-
like tumour lacks the typical lamellar or whorled pattern of a perineurioma and is EMA negative. Myxoid
neurofibroma and neurilemmoma display S-100 protein staining. The prominent vascular component seen in
angiomyofibroblastoma is also not seen in neural tumours. Solitary fibrous tumour can be distinguished
from AMF- like tumour by its "patternless " architecture, marked variation in cellularity, keloidal
hyalinisation and a frequent hemangiopericytomatous vascular pattern. CD 34 is not useful to distinguish
between these lesions as solitary fibrous tumour is invariably positive, and most cases of AMF-like
tumour are positive.
Spindle cell lipoma is another differential diagnostic consideration due to the presence of mature
adipocytes and bland spindle cells. Presence of numerous blood vessels with hyalinized walls and wispy
delicate collagen are not typical of spindle cell lipoma, which tends to have more eosinophilic ropy
refractile collagen bundles. Unlike AMF-like tumour, most spindle cell lipomas occur in the head and
neck region. Smooth muscle tumours are rare in genitalia. In contrast to AMF-like tumours, these are
composed of intersecting fascicles of cells with abundant eosinophilic cytoplasm and cigar shaped nuclei.
Histogenesis of these tumours is uncertain. Lesional cells display fibroblastic and sometimes
myofibroblastic differentiation. Given the immunohistochemical expression of oestrogen and progesterone
receptors in some cases, hormones may have influence in the pathogenesis of these tumours. AMF- like
tumour is a benign neoplasm, with no evidence of metastatic disease and only one case reported to recur
A complete local excision with clear margins appears to be adequate treatment of these
- Fletcher CD et al. Angiomyofibroblastoma of the vulva. A benign neoplasm distinct from aggressive angiomyxoma. Am J Surg Pathol 1992; 16(4):373-82.
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- Laskin WB et al. Angiomyofibroblastoma of the female genital tract Hum Pathol 1997; 28:1046-1055
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