Mesenchymal Neoplasms of the Female Genital Tract
Case 6 -
Deep (Aggressive) Angiomyxoma
Teri Longacre, Esther Oliva and Robert Soslow
Deep (aggressive) angiomyxoma (AAM) is a distinctive soft tissue neoplasm occurring in the pelvis and
perineum with a propensity for local-regional recurrence. Initially described by Steeper and Rosai in
1983 as a female gynecologic tumor, this uncommon specialized genital stromal tumor has also been
recognized to occur in the inguinoscrotal region in men, and is characterized by a paucicellular spindle
cell proliferation separated by loose myxoid stroma with a prominent thick-walled, hyalinized vascular
component. Despite the bland histologic appearance, AAM is an infiltrative tumor with a propensity for
aggressive local and regional recurrences, especially when incompletely excised. Due to involvement of
the deep pelvic soft tissues and retroperitoneal regions, these tumors often attain a large size and may
not be amenable to complete surgical excision.
While deep (aggressive) angiomyxoma can be very difficult to distinguish histologically from other
myxoid soft tissue lesions of the vulvovaginal region, especially from benign angiomyofibroblastoma,
differences in the clinical behavior between these various neoplasms requires accurate diagnosis to
ensure proper treatment. A variety of immunohistologic strategies have been proposed to be of value in
differentiating these various tumors, but in many instances their relative contribution is
overemphasized. In problematic cases, careful evaluation of a few key histologic features in concert
with attention to a series of practical considerations, including patient age, determination of adequacy
of biopsy and tumor sectioning, tumor size, borders and location (superficial versus deep) should permit
Deep (aggressive) angiomyxoma is a predominantly non-metastazing, locally infiltrative soft tissue
neoplasm that is most commonly encountered in the vulvovaginal region of reproductively aged women during
the third to fifth decades.
In men, the tumor occurs in analogous sites, but in a
slightly older age group with peak incidence in the sixth to seventh decade.
common site is the scrotum followed by the inguinal region, spermatic cord and perineum. Patients often
present with vague symptoms secondary to pressure effects on the adjacent urogenital or anorectal tracts.
The clinical impression frequently includes Bartholin's gland cyst or hernia and often underestimates the
extent of disease.
AAM is typically large (> 5 cm; range 3-60 cm), poorly circumscribed and has a tendency to recur when
incompletely excised. Reported recurrence rates vary from 36 to 72%, depending on size, anatomical
location, and amenability to wide resection. The higher reported recurrence rates have been attributed
to an enrichment of consultation cases. Most AAM are more superficially located and amenable to wide
excision; recurrences, when they occur are effectively treated by a single re-exicison. Recurrence is
uncommon in men, presumably due to improved surgical control. Most recurrences occur within 5 years
after excision, but recurrences have been described as late as 14 years following initial diagnosis.
Re-excision is usually successful provided the margins are free of involvement, but
patients with surgically inaccessible tumors may experience multiple recurrences with invasion into
adjacent tissue structures, which may rarely include bone.  Rapid growth during pregnancy
has been observed.
AAM is considered to be non-metastasizing; however two reports have
documented metastases to the lungs without apparent dedifferentiation and both patients died of their
Deep (aggressive) angiomyxoma typically has a macroscopic grey-colored, nonencapsulated gelatinous or
myxoid appearance and is characterized microscopically by bland, spindle shaped cells with moderate
pale-staining cytoplasm and round to oval nuclei. The vascular component is composed of small to
medium-sized vessels, which may be thick-walled or hyalinized; areas of perivascular microhemorrhages may
be present. Condensation of fibrillar collagenous material and bundles of smooth muscle may be seen
around the blood vessels. Almost all AAM are paucicellular at initial presentation, but recurrent AAM
may be more densely cellular and fibrotic.
Although once thought to be desmin negative, the stromal cells in AAM are now known to variably
express actin, vimentin, CD34 and desmin, as well as estrogen and progesterone receptors, and are
considered to be specialized genital myofibroblasts.
Although fewer cases have been
studied, expression of estrogen and progesterone receptors, as well as androgen receptors have also been
reported in AAM in men.
Expression of CD44, a cell surface receptor to hyaluronan in the
extracellular matrix has also been recently detected in AAM.
AAM do not stain for S100 or
Deregulation of the HMGA2 (high mobility group A) protein, has been reported in AAM. HMGA2 is an
architectural transcription factor that is expressed predominantly during embryogenesis and is activated
by rearrangements of chromosome 12q13-15.
Rearrangements affecting the HMGA2 gene
have been implicated in a variety of other gynecologic mesenchymal neoplasms, including uterine
leiomyomas, intravenous leiomyomatosis, endometrial polyps, as well as in lipomas, chondroid tumors, and
fibroadenomas of the breast. HGMA2 transcripts have also been identified in at least one
angiomyofibroblastoma.  High mobility proteins are believed to affect transcription by
bending the DNA and by interacting with other transcription factors, influencing chromatin changes during
the cell cycle. Normally, HMGA2 is expressed at low levels or not at all in adult tissue. The presence
of overexpression in some AAM has led to the suggestion that immunostaining with this marker may assist
in diagnosis or margin assessment, but this deserves further study. The role of HMGA2 deregulation in
AAM and these other neoplasms is not known.
Given the propensity for local recurrences and the isolated case reports of lung and in one case,
lymph node metastasis, AAM should be classified with the group of soft tissue tumors that exhibit
clinically intermediate behavior – i.e., risk of local recurrence but rarely metastasizes (Table 1).
The traditional treatment of choice is wide local excision with attention to margins, but the recent
literature suggests a more conservative approach based on a combination of surgical excision, arterial
embolization and hormonal therapy with or without adjuvant radiation.  Lymphadenectomy is
currently not indicated. Successful treatment with gonadotropin-releasing hormone agonists for small
primary disease, residual disease and recurrent disease has been reported.
the risk of local recurrence, long-term follow-up with MRI or CT scan is recommended.
Because of its locally aggressive, but predominantly non-metastasizing clinical behavior, AAM should
be distinguished from clinically benign genital stromal tumors with very low risk of recurrence (e.g.,
fibroepithelial stromal polyp, angiomyofibroblastoma, and cellular angiofibroma) on the one hand, and
from clinically malignant tumors with significant metastatic potential of more general distribution
(e.g., leiomyosarcoma, myxoid liposarcoma and low grade myxofibrosarcoma) on the other (Table 1). The
vast majority of the clinically malignant neoplasms that occur in the vulvovaginal region exhibit
substantially different demographic and histologic features from AAM and these neoplasms do not usually
pose a significant differential diagnostic dilemma. In contrast, most of the clinically benign lesions
that can potentially be confused with AAM are 1) also relatively site-specific, 2) uncommon, and 3) share
similar histologic and immunohistologic features, and the differential diagnosis of these lesions can be
quite challenging (Table 2).
Angiomyofibroblastoma vs Deep (Aggressive) Angiomyxoma
Angiomyofibroblastoma, one of the specialized genital stromal lesions most commonly confused with AAM,
typically occurs in reproductively aged women and like AAM, may also occur in the inguinoscrotal region
It presents clinically as a slowly growing mass, simulating a
Bartholin gland cyst or hernia. Unlike AAM, this tumor is well circumscribed, non-recurring and
characterized histologically by the presence of spindled and plump epithelioid or plasmacytoid cells that
may be multinucleate and tend to cluster around the numerous small to medium caliber blood vessels. The
vasculature is randomly arranged and may feature areas of perivascular fibrosis and thick walled vessels
similar to AAM. Alternating hypocellular and hypercellular areas is considered to be one of the
distinguishing features of this unusual neoplasm. Like AAM, angiomyofibroblastomas may exhibit
immunoreactivity for actin, desmin, CD34, and estrogen and progesterone receptors.
Although large lesions have been reported, most are less than 5 cm (range, 0.5-12 cm) and mitoses are not
prominent.  Occasionally, these tumors may contain abundant mature adipose tissue, raising
the consideration for an infiltrative process, but the borders of the tumor itself are circumspect, the
tumor is usually located in the superficial soft tissue and local excision is usually curative.
Recurrence has been observed in a case with sarcomatous transformation. 
Despite the apparent clinical and histological differences between AAM and angiomyofibroblastoma,
overlap cases may occur.  There is limited clinical experience with these hybrid tumors,
but they should probably be managed as if they had at least some potential for locally aggressive
behavior, since local recurrence has been observed with at least one such tumor.
Cellular Angiofibroma vs Deep (Aggressive) Angiomyxoma
Cellular angiofibroma is a rare, recently described soft tissue neoplasm resembling spindle cell
lipoma with an apparent predilection for the vulvovaginal region in middle-aged women. 
Like AAM and angiomyofibroblastoma, this lesion can also present in the inguinoscrotal region of men;
rarely, it occurs in extravulvar sites.
When occurring in the vulva, the tumor is
distinguished by its small size (<5 cm), circumscription, and a uniformly cellular, mitotically active
proliferation of bland spindle cells arranged in short fascicles, admixed wispy bundles of collagen and
numerous small to medium-sized thick-walled and often hyalinized blood vessels.
Occasionally, scattered multinucleate cells may be present. Entrapment of nerves and fat may be seen at
the periphery of the tumors, but aggressive infiltration into adjacent structures has not been observed.
Mast cells are often abundant and several cases have featured prominent perivascular lymphoid aggregates.
Cellular angiofibroma is typically more cellular than AAM and does not feature elongated bundles of
smooth muscle aggregated around blood vessels.
The histologic distinction between cellular angiofibroma and angiomyofibroblastoma is more
controversial, but cellular angiofibroma is characterized by more spindled cells set in a collagenous
stroma, whereas angiomyofibroblastoma has larger, more epithelioid cells aggregated around blood vessels.
Fibroepithelial stromal polyp is typically less cellular and features more enlarged, atypical and
multinucleate cells than cellular angiofibroma. The constituent cells of cellular angiofibroma can
express CD34, estrogen and progesterone receptor, and occasionally, actin and desmin.
Few cases have been reported and follow-up information is limited, but complete excision
with clear margins appears to be curative therapy for cellular angiofibroma in most instances.
One local recurrence has been reported, suggesting that cellular angiofibroma may have
limited potential for local recurrence. 
Superficial Cervicovaginal Myofibroblastoma (Myofibroblastoma) vs Deep (Aggressive) Angiomyxoma
This lesion occurs more frequently in the vagina, but may be seen in the cervix and vulva.
Initially identified only in the cervix and vagina (hence the term, superficial
cervicovaginal myofibroblastoma), this lesion is thought to arise from hormonally responsive mesenchymal
cells in the subepithelial stromal layer normally present throughout the endocervix and vulva of adult
women. Myofibroblastoma is small (< 5cm; range 0.2 to 6.5 cm), superficial, polypoid and well
circumscribed but unencapsulated. The cells are ovoid or spindled and dispersed in a finely collagenized
stroma. Lace-like, seive-like and fascicular patterns are often present within the same lesion.
Thick-walled vessels may be distributed along the center of the lesion. Because of its small size and
superficial location, myofibroblastoma is almost never mistaken for aggressive angiomyxoma.
Unlike the fibroepithelial polyp, a distinct uninvolved Grenz zone often separates the lesion from the
overlying surface epithelium. Immunohistologic features do not differ significantly from other
vulvovaginal lesions. Although metachronous lesions have been observed in one patient, no recurrences
have been reported. An association with tamoxifen has been suggested. 
Superficial Angiomyxoma vs Deep (Aggressive) Angiomyxoma
Although superficial angiomyxoma should always be considered in the histologic differential diagnosis
of AAM, this lesion is superficial, small (< 5cm), lacks infiltrative borders and is almost always
Superficial angiomyxomas often exhibit a multilobulated growth
pattern and have a significant potential for local, but nondestructive recurrence (up to 40%). These
lesions are centered in the dermis and superficial subcutaneous tissue, feature abundant myxoid stroma
with bland fibroblasts, and scattered neutrophilic inflammatory cells. Up to a third contain an
epithelial or adnexal component secondary to entrapment.  Necrosis is absent. Superficial
angiomyxomas may arise in a wide variety of anatomic regions; when multiple or presenting in the external
ear, an association with Carney's complex should be considered. 
Fibroepithelial Stromal Polyp vs Deep (Aggressive) Angiomyxoma
Fibroepithelial stromal polyp (so called pseudosarcoma botyroides) of the genital tract is another
genital stromal lesion that may be misdiagnosed as a malignant process. Unlike AAM, this lesion is
relatively common and typically presents as a small exophytic and polypoid mass in reproductive aged
women, most commonly in the vagina, but also in the vulva and cervix.
they have a fronded appearance simulating a condyloma. These lesions have a propensity to occur during
pregnancy (many spontaneously regress following parturition) and may be single or occasionally, multiple.
 When they occur on the vulva, these lesions are commonly small, but may grow to large,
sometimes disfiguring proportions (up to12 cm). Histologically, they are characterized by variable
cellularity and a notoriously wide range of morphologic appearances. Cell types range from small spindle
cells to enlarged, bizarre angulated and multinucleated forms. The multinucleated atypical cells are
often enriched along the stromal-epithelial interface. The vascular component is also variable, but
medium thick-walled vessels, often coursing through the middle of the lesion are usually present.
Mitotic figures may be prominent (> 10 MF/10 HPF), including atypical forms and in these cases, the
lesion may be initially misinterpreted as malignant. The absence of a clear demarcation between the
lesional cells and the stromal-epithelial interface and the presence of characteristic stellate
multinucleate stromal cells facilitate the correct diagnosis. The stroma of these lesions is often pale
and edematous or myxoid, mimicking AAM. Similar to AAM, the stromal cells are variably reactive for
desmin, actin and estrogen and progesterone hormone receptors, but not S100. 
Fibroepithelial stromal polyps appear to represent a reactive process rather than a neoplasm. Although
occasional local, nondestructive recurrences have been documented, reexcision has been successful in all
Exuberant Angiomyofibroblastic Stromal Response vs Aggressive Angiomyxoma
A variety of other secondary or reactive myofibroblastic proliferations can occur in the vulvo-vaginal
soft tissue, giving rise to an inflamed and edematous or myxoid stroma, which on a small biopsy may be
misinterpreted as a neoplastic process. Two pseudosarcomatous proliferations that should be considered
in the differential diagnosis of AAM include nodular fasciitis and postoperative spindle cell nodule.
 Both may undergo focal myxoid change, but are distinguished from AAM by areas of greater
cellularity, plump spindle cells, numerous thin walled vessels, small size, and the presence of easily
found mitotic figures. A history of recent operative procedure may facilitate recognition of the
postoperative spindle cell nodule. The characteristic torn tissue paper pattern provides a clue to the
diagnosis of nodular fasciitis with myxoid change.
Fallopian tube prolapse, which may occur from 2 months to 30 years following vaginal hysterectomy is
especially prone to misdiagnosis.
Clinical history of prior surgery with imaging
studies may provide a clue to the underlying etiology of the process.
Vulvar hypertrophy with lymphedema may also mimic deep angiomyxoma. A history of prior surgery or
lymphatic obstruction and attention to the ectatic lymphatic spaces in vulvar lymphedema will provide the
correct diagnosis.  Lymphedema may also impart a verruciform or frondlike appearance to the
overlying skin, which may raise the differential diagnosis of condyloma.
Leiomyomas with Hydropic or Myxoid Change vs Deep (Aggressive) Angiomyxoma
Leiomyomas of the vulva or vagina may undergo hydropic or myxoid change, especially during pregnancy
and may be confused with AAM on a small biopsy. Tumors with epithelioid or myxohyaline features may also
be a source of confusion, but most genital smooth muscle tumors can be recognized by the presence
elsewhere of classic interlacing fascicles of elongate spindle cells with prominent eosinophilic
cytoplasm and blunt ended nuclei.
Rarely, smooth muscle tumors featuring the histologic features of myxoid leiomyosarcoma has been
reported in the vulva; as in other smooth muscle variants, these tumors can be recognized by the presence
of additional foci with typical smooth muscle histology.
features are the greater cellularity and nuclear atypia in the non-myxoid areas.
Vulvar smooth muscle tumors occur predominantly in premenopausal women and rarely present in women
over 50 years of age. They are considered to be malignant when they have three or all four of the
following features: 1) size > 5cm; 2) infiltrative margins; 3) moderate to severe cytologic atypia;
and 4) > 5 MF/10 HPF.  Most vulvar smooth muscle tumors recur locally; less than
one-fourth metastasize to the lungs or other distant sites causing death. However, long-term follow-up
is limited in most series and the rate of metastasis may be higher than is currently appreciated.
Vaginal smooth muscle tumors, which also occur in premenopausal women (mean age, 40 years), are mostly
benign and appear to be more common than their vulvar counterparts. Local recurrence is associated with
tumors exhibiting mitotic index > 5 MF/10HPF. 
Although smooth muscle tumors with myxoid features can potentially be confused with AAM, the major
difficulty in diagnosing smooth muscle tumors of the genital tract lies in predicting recurrent potential
with a reasonable degree of accuracy. Since the presence of any mitotic activity, nuclear atypia,
necrosis, or evidence of infiltration into adjacent tissue in a vulvar smooth muscle tumor may be
associated with recurrent potential, regardless of size, such lesions should probably be completely
excised with clear margins whenever possible.  Since almost all of these tumors express ER
and/or PR, they may respond to hormonal therapy. Adjuvant chemotherapy should probably be reserved for
those tumors exhibiting unequivocal sarcomatous features.
All tumors with unusual or atypical features should be fully evaluated using a broad
immunohistochemical panel in order to exclude spindle cell variants of melanoma, carcinoma and other soft
Other Clinically Benign Myxoid Mesenchymal Lesions
Clinically benign myxoid appearing neoplasms with a more generalized site distribution that can be
confused with AAM include myxoid neurofibroma and schwannoma, spindle cell lipoma, myxoma and hemangioma.
Myxoid neurofibroma is recognized by the characteristic darkly staining, wavy or buckled nuclei,
immunoreactivity for S100, and absence of a prominent vascular pattern. Schwannomas are also uniformly
and diffusely S100 positive. Because of its bland appearance, myxoma is often included in the
differential diagnosis of AAM, but myxomas occur in skeletal muscle (intramuscular myxoma) or immediately
adjacent to a large joint (juxta-articular myxoma), feature inconspicuous capillary-sized vessels and are
almost never serious differential diagnostic considerations. Although spindle cell lipoma more closely
resembles cellular angiofibroma, this lesion is also frequently mentioned in the list of differential
diagnoses for AAM. Spindle cell lipoma differs from AAM on the basis of its small size, location in the
dermis and subcutis and the presence of a denser spindle cell proliferation with eosinophilic ropy
collagen bundles.  Cellular angiofibroma possesses a more richly vascularized stroma with
wispy collagen as opposed to the classic ropy collagen in spindle cell lipoma. Additionally, the
pelviperineal region is generally considered to be an unusual site for spindle cell/pleomorphic lipoma.
The presence of a focally prominent vasculature and extravasation of red blood cells in AAM may suggest
hemangioma on a limited biopsy, but hemangiomas are small, typically unassociated with a prominent myxoid
stroma and do not commonly occur in the vulva. The recently described prepubertal vulval fibroma is
unlikely to be confused with any of the typical vulvar mesenchymal lesions due to its predilection for
prepubertal females (age range, 4-12 years; median, 8 years). This lesion, which most commonly involves
the labia majora, presents as a unilateral, ill defined and painless subcutaneous vulvar mass with
microscopic features that suggest a hamartomatous process. Histologic sections show a patternless,
mitotically inactive and bland spindle cell proliferation that extends around vessels, nerve and mature
fat with no clear interface. Mitotic activity is sparse. Recurrences may occur when incompletely
excised, which is probably not infrequent given the poor demarcation of the lesion from the surrounding
normal tissue. 
Other Clinically Intermediate Myxoid Mesenchymal Lesions
Other soft tissue neoplasms with clinically intermediate behavior that may be confused with AAM
include dermatofibrosarcoma protuberans, pelvic fibromatosis, atypical lipomatous tumor and low-grade
myxofibrosarcoma.  Dermatofibrosarcoma protuberans with paucicellular myxoid stroma can
cause difficulty because the myxoid areas may be indistinguishable from bland myxoid areas in AIM;
identification depends on finding the distinctive repetitive storiform pattern elsewhere in the tumor and
the absence of desmin reactivity. Pelvic fibromatosis features a more collagenous stroma and atypical
lipomatous tumor (well differentiated liposarcoma) with myxoid change is recognized by the presence of
atypical cells with angulated hyerchromatic and dense nuclei. Low-grade myxofibrosarcoma has thin
walled, curvilinear vessels and more nuclear atypia; it often exhibits a multinodular growth pattern and
is usually desmin negative. Like AAM, low-grade fibromyxoid sarcoma is capable of repeated and locally
aggressive recurrences, especially when incompletely excised. However, low-grade fibromyxoid sarcoma
occurs predominantly in the torso, thigh and shoulder areas of young adults and contains areas of fibrous
stroma arranged in a swirling or whorled pattern alternating with myxoid stroma. 
Other Clinically Malignant Myxoid Mesenchymal Lesions
Unlike these clinically benign stromal lesions, most of the clinically malignant myxoid appearing
neoplasms that may be considered in the differential diagnosis of AAM either rarely occur in the
pelviperineal region or occur in the pelviperineal region but in a different age bracket from AAM, and do
not usually pose a significant differential diagnostic dilemma. Embryonal rhabdomyosarcoma (sarcoma
botryoides) can present in the vulvovaginal area either as a primary tumor or due to metastasis or direct
spread. Although it may contain myxoid, edematous and spindle cell areas, embryonal rhabdomyosarcoma is
recognized by the presence of a characteristic cambium layer, differentiating rhabdomyoblasts, and is
typically seen in a younger age group than AAM.  Myxoid liposarcoma is exceedingly rare in
the genital region, but may present there as a primary tumor or following spread from the adjacent pelvic
region through the inguinal canal or perirectal sheath.  Paucicellular variants may be
confused with AAM, but most myxoid liposarcomas can be recognized by the presence of areas containing the
characteristic 'chicken wire' arborizing vasculature and lipoblasts. Myxoid variants of malignant
melanoma (neurotropic or desmoplastic) and malignant peripheral nerve sheath tumor are identified by the
presence elsewhere of areas that are diagnostic of the respective tumors. Most melanomas can be excluded
by an S100 stain and malignant nerve sheath tumors exhibit substantially more cytologic atypia compared
to AAM. Primary or metastatic carcinoma with prominent myxoid and spindle cell change can be excluded by
a good clinical history and cytokeratin stains.
AAM is a distinctive soft tissue neoplasm of the pelviperineal region with a
proclivity for local recurrence and aggressive infiltration into adjacent deep organs and tissues. The
rate of local recurrence and sometimes unpredictable behavior associated with AAM merit the distinction
of this clinically intermediate tumor from the other clinically benign genital stromal tumors as well as
the less common, but clinically malignant tumors with significant metastatic potential that may also
occur in this site. Because of their relatively nonspecific mesenchymal features, significant
morphologic overlap exists among the specialized genital stromal tumors and precise classification may
not always be possible.
Since the distinction of these lesions usually makes little difference in terms of
clinical management as long as they are separated from AAM, a practical approach utilizing key histologic
features (Table 2) and the following clinical information is most useful in the individual case: 1)
tumor size; 2) depth of involvement (e.g., cutaneous, subcutaneous, deep soft tissue); 3) margins
(infiltrative versus well circumscribed); 4) imaging studies, if performed; and 5) history of prior
malignancy. Whether the lesion is reactive or neoplastic should be considered; if neoplastic, the
possibility of a metastasis or extension of a tumor from the nearby retroperitoneum or deep pelvic organs
should be excluded, since this could significantly alter management and prognosis. Immunohistochemical
studies should be utilized in a directed fashion. Since most specialized genital stromal tumors exhibit
similar immunophenotypic patterns, immunohistochemistry is most useful in exclusion of melanoma (S100)
and metastatic carcinomas with myxoid and/or spindle cell features (cytokeratin and EMA). Reactivity
with S100 also helps to exclude most nerve sheath tumors in this setting.
The difficulties encountered in distinguishing these various entities is compounded
by small biopsies, which may not be entirely representative, and/or inadequate sampling of the lesion.
This can be controlled to a certain extent by submission of the entire biopsy when it is small and by
adequate sectioning when the biopsy is large. In the problematic case, one section per cm should be
obtained. In all cases, sections should be taken in order to document the tumor interface and the
surgical margins; these should be obtained at right angles to the lesion (perpendicular margins), not
tangentially (shave margins). When in doubt, correlation with imaging studies and complete, conservative
excision with clinical follow up is warranted.
Table 1. Managerial Classification of Vulvovaginal Soft Tissue Tumors* 
(= local excision curative, recurrences may occur but are not destructive
(= local recurrences common and may be destructive; metastases with or without dedifferentiation are rare
(= local recurrences common; metastases occur
|Angiomyofibroblastoma ||Deep (aggressive) angiomyxoma ||Myxoid carcinoma|
|Fibroepithelial stromal polyp ||Dermatofibrosarcoma protuberans, myxoid variant ||Myxoid leiomyosarcoma|
|Cellular angiofibroma ||Pelvic (desmoid) fibromatosis ||Myxoid liposarcoma|
|Superficial angiomyxoma ||Atypical lipomatous tumor ("well differentiated liposarcoma") ||Myxoid embryonal rhabdomyosarcoma|
|Superficial myofibroblastoma of the lower female genital tract ||Low grade myxofibrosarcoma ||Myxoid malignant melanoma|
|Myxoid neurofibroma ||Atypical myxoid smooth muscle tumor ||Myxoid malignant peripheral nerve sheath tumor|
|Myxoid smooth muscle tumor (leiomyoma with hydropic change) ||Low grade fibromyxoid sarcoma |
Postoperative spindle cell nodule
Prepubertal vulval fibromaasfdVulvar hypertrophy with lymphedema
*Tumor is used in a generic sense. Some of these processes may be hamartomatous or reactive (e.g. prepubertal vulval fibroma, vulvar hypertrophy with lymphedema, nodular fasciitis, postoperative spindle cell nodule, etc.
Table 2. Differential Diagnosis of Specialized Genital Stromal Tumors*
| ||FESP ||Cellular Angiofibroma ||Angiomyofibroblastoma ||Superficial Myofibroblastoma ||Deep (Aggressive) Angiomyxoma|
|Age (years) ||Reproductive, associated with pregnancy (16-75; mean 32) ||Late reproductive (20-77; mean 47) ||Reproductive (23-71; mean 42) ||Reproductive (23-80; mean 55) ||Reproductive (16-70; mean 36)|
|Site ||Cutaneous ||Cutaneous and subcutaneous ||Subcutaneous ||Cutaneous and/or mucosal ||Subcutaneous and deep soft tissue|
|Size ||Small (<5 cm) ||Small (<5 cm) ||Small (<5cm) ||Small (<5cm) ||Large (>5cm)|
|Behavior ||No recurrence ||No recurrence ||No recurrence ||No recurrence ||Recurrences (30%)|
|Cellularity ||Variable, large atypical and multinucleate cells common ||Cellular, rare multinucleate cells ||Hypocellular and hypercellular areas ||Multipatterned, moderately cellular ||Paucicellular|
|Vasculature ||Medium caliber thick walled vessels in fibrovascular cores ||Numerous thick walled vessels ||Numerous small caliber vessels with perivascular epithelioid and plasmacytoid cells ||Numerous small caliber vessels, focal hyalinized vessels ||Medium to large caliber thick walled, hyalinized vessels with perivascular bundles of smooth muscle|
|Mitotic index ||Can be high (>10/10 hpf) ||Can be high (>10/10 hpf) ||Low ||Low ||Low|
|Margins ||No Grenz zone ||Circumscribed, can be focally infiltrative ||Circumscribed ||Circumscribed, Grenz zone ||Infiltrative|
|Expression present ||Actin, desmin, CD34, ER, PR ||CD34, ER, PR ||Actin, desmin, CD34, ER, PR ||Actin, desmin, CD34, ER, PR ||Actin, desmin, CD34, ER, PR|
*Tumor is used in a generic sense. Fibroepithelial stromal polyp and possibly, cellular angiofibroma may not represent neoplasms in the strict sense of the term. Abbreviations: FESP, fibroepithelial stromal polyp; IHC, immunohistochemistry (Note: antibodies are listed if they have ever been reported to stain positively in lesional cells of the respective tumor. Most genital stromal tumors exhibit variable immunoreactivity with the markers listed); ER, estrogen receptor; PR, progesterone receptor.
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