Mesenchymal Neoplasms of the Female Genital Tract
Case 2 -
Mesodermal (Mullerian) Adenosarcoma
Teri Longacre, Esther Oliva and Robert Soslow
Adenosarcoma is an uncommon, predominantly low-grade malignant biphasic tumor that is composed of
sarcomatous stroma and benign epithelial elements. This tumor often represents a challenge for the
pathologist due to significant overlap with adenofibroma and other forms of benign polyp on the one hand
and with carcinosarcoma and sarcoma entrapping benign glands on the other. Indeed, the low-grade forms
of adenosarcoma account for a significant proportion of malignant lesions within the female genital tract
and peritoneum that are underdiagnosed by pathologists. 
Most adenosarcomas arise in the uterine corpus, but cervical, vaginal, tubal, ovarian and primary
peritoneal adenosarcomas also occur. Although almost all adenosarcomas occur in women, mesodermal
adenosarcoma has been reported in a boy with persistent mullerian duct syndrome and rarely, in the
testis, seminal vesicle and prostate.
Involvement of additional extragenital
sites in women has been linked to endometriosis. An association with unopposed estrogen and tamoxifen
therapy has also been reported in uterine adenosarcoma.
As with carcinosarcoma, a prior
history of pelvic radiation has been implicated in a few cases.
Adenosarcomas are typically slowly growing, indolent tumors, but recurrences at five or more years
following diagnosis are not unusual. In some instances, recurrence may not occur until 13 years or more
years following definitive therapy. Recurrences tend to be local, with distant metastases following
initial local recurrence(s). It has been suggested that these hematogenous metastases almost always
contain only sarcomatous elements.  A subset of tumors may exhibit a more aggressive
clinical course; these tumors often have stromal overgrowth or other features of a high-grade sarcoma and
may resemble carcinosarcoma in their clinical behavior. In contrast, adenofibromas are considered to be
clinically benign with little risk for recurrence once they are completely excised.
The adenofibroma-adenosarcoma-carcinosarcoma spectrum of biphasic mullerian tumors in the female
gynecological tract resembles the fibroadenoma-phyllodes-metaplastic carcinoma spectrum in the breast.
As in the breast, zones of histologic overlap exist and on occasion, areas of adenofibromatous,
adenosarcomatous and/or carcinosarcomatous differentiation may be seen in the same neoplasm.
Transformation of some adenosarcomas into carcinosarcomas has also been proposed. 
Classification of each of these tumors is ultimately based on the most histologically malignant area, but
it should not be surprising that just as there are gradations of histologic malignancy amongst these
tumors, gradations of clinical behavior may also occur. Gradations of clinical behavior are also
observed, depending on the site of origin (e.g., adenosarcomas arising in the ovary and peritoneum tend
to behave more aggressively than those arising in the uterine corpus or cervix).
Since adenosarcomas most commonly occur in the uterine corpus, most of the available clinical data
reflects uterine tumors. However, since differences in clinical presentation, clinical behavior, and (in
some instances) differential diagnosis do occur when adenosarcomas present at other sites, they are
Most patients with uterine corpus adenosarcoma are postmenopausal, although this neoplasm may occur
during the reproductive years. When they occur in the uterine body, adenosarcomas present as polyps or
polypoid lesions which may protrude through the cervical os or appear to arise from the cervix or lower
uterine segment with uterine enlargement; often there is a history of recurrent polyps, which on
retrospect may represent early or subtle forms of adenosarcoma. The polyps vary in size from 1 to 17 cm
(mean, 5 cm) and often exhibit microcystic architecture on cut section.
Approximately one-fourth of uterine corpus adenosarcomas are myoinvasive. Most patients with uterine
adenosarcoma are cured by hysterectomy. However, deep myoinvasion, lymphovascular invasion, high-grade
heterologous stroma, stromal overgrowth and extrauterine spread are associated with disease recurrence.
The overall recurrence rate is 15-25% for tumors without stromal overgrowth and 45-70% for those with
stromal overgrowth. Recurrent disease typically appears in the pelvis, although distant recurrences may
develop many years after pelvic recurrence(s). Approximately 10-25% of patients with uterine
adenosarcoma die of their disease. This figure rises to 54% for those whose tumors contain stromal
Surgery, including complete staging is the mainstay of therapy for uterine adenosarcoma with or
without sarcomatous overgrowth. Additional therapy in the form of radiation, chemotherapy, or both has
been reported; however, the superiority of any one modality has not been determined. Hormonal therapy
has also been tried in the adjuvant setting in low stage disease.
Cervical adenosarcomas tend to occur at a younger age than their uterine counterparts.
Patients with primary cervical adenosarcomas range in age from 13 to 67 years
(mean, 37 years). Most present during the reproductive years with abnormal bleeding, which is initially
attributed to benign endocervical polyps. The polyps may be ectocervical or endocervical and range in
size from 2 to 8 cm or more. A sarcoma botryoides appearance has been reported. 
The numbers are few and data is limited, but most cases appear to be cured by hysterectomy, possibly
due to the early detection of low stage disease in the majority of patients. To date, less than 25
patients have been reported with endocervical adenosarcoma; recurrences have been reported in 18% while
deaths due to disease occurred in 12%.
As in uterine corpus tumors, depth of
invasion and sarcomatous overgrowth are adverse prognostic indicators.
It has been suggested that complete resection of the polyp alone may be adequate initial therapy for
cervical adenosarcoma when it occurs in younger women, provided there is a stalk that is clearly
uninvolved and there is no histologic evidence of invasion.  Although this is controversial
and there is little supporting data, conservation of reproduction and/or hormonal function should always
be considered in such cases. Adenosarcomas may be hormonally responsive, but there appears to be no
justification for oophorectomy in the younger patients at this time. 
Ovarian adenosarcoma occurs in reproductive and postmenopausal women from 30 to 84 years of age (mean,
55 years). Almost half occur in women <50 years of age.  Patients present with the
usual signs and symptoms of an ovarian tumor mass, most commonly abdominal discomfort and distention.
Most are unilateral, even when presenting at high stage disease. The tumors range in size from 5.5 to 50
cm (mean, 14 cm) and are more solid and cystic than polypoid. An association with endometriosis may be
present in some cases, but this is not as firmly established as in extragenital sites.
In contrast to the cervical and uterine corpus tumors, adenosarcomas arising in the ovary often have a
worse prognosis, presumably due to the greater ease of peritoneal spread at this location. In the
Eichhorn series, the overall recurrence rate for ovarian adenosarcomas was 77% at five or more years, and
the 5-, 10-, and 15-year survival rates were 64%, 46%, and 30%, respectively.  As in the
uterine tumors, high-grade sarcoma, high-grade sarcomatous stromal overgrowth, and advanced stage,
including tumor rupture are adverse prognostic factors. Age <53 years at diagnosis is also a risk
factor for disease recurrence, possibly due to increased likelihood of hormonal stimulation. Mitotic
index and low grade stromal overgrowth do not predict recurrence in stage I tumors. Synchronous uterine
or extragenital adenosarcomas may occur in some patients. 
Primary Peritoneal and Extragenital Sites
Adenosarcoma arising within the peritoneum and other extragenital sites is uncommon. In many of the
reported cases, a history of hysterectomy many years prior to presentation clouds the picture, and it is
not clear how many of these cases represent true de novo tumors or metastases from previously
unrecognized adenosarcomas. At least some cases appear to be primary, most of which are associated with
The pluripotent mesothelial and mesenchymal cells of the
pelvic/abdominal cavity have been cited as the site of origin for those cases in which no endometriotic
or other primary foci can be identified.
Sites of involvement include bladder, colon
or rectum, omentum, recto-vaginal septum, pouch of Douglas, liver, retroperitoneum and vaginal wall.
Multiple sites of peritoneal involvement may be present at initial presentation. 
A recent literature review by Murugasu and colleagues suggests that extragenital and peritoneal tumors
occur at a slightly younger age than uterine adenosarcomas (mean age, 41 years) with a significant
proportion developing in women less than 30 years of age.  Data is limited, but the
presence of adenosarcoma in the peritoneum appears to be an adverse risk factor regardless of histology.
 The reported overall rate of recurrence is 60% and death due to tumor occurs in almost 40%
of patients.  It is not clear why the extragenital tumors behave more aggressively, but
local complications due to bowel obstruction, larger tumor size at presentation, inability to achieve
complete surgical excision and exposure to the entire peritoneum have all been proposed as possible
Most adenosarcomas feature uniformly distributed, often cystic and irregularly contoured glandular
elements, often with internal papillations scattered throughout a variably cellular stroma. The stroma
forms a characteristic hypercellular collar or cuff (so called "cambium layer") around the glands, which
often exhibit mixed differentiation, including endometrioid, endocervical, ciliated, eosinophilic and
squamous. The epithelium typically appears benign or less often, atypical, simulating complex
hyperplasia or adenocarcinoma in situ. Asymmetric growth of stroma may compress the epithelial component
to produce irregular stellate glandular configurations; sometimes, when this asymmetry is extreme,
polypoid invaginations are produced. Stromal foam cells may be present. The classic adenosarcoma
exhibits a frondlike growth pattern, resembling phyllodes tumor of the breast. Adenosarcomas fall into
three general groups, depending on the atypicality of the stroma and the presence of stromal overgrowth:
Group 1: The first and most common type of adenosarcoma resembles
adenofibroma, but possesses more cellular and more mitotically active stroma (= low-grade adenosarcoma).
In most cases, the stromal component is nondescript, but in some instances the stromal cells are arranged
in cordlike patterns reminiscent of sex cord elements in uterine tumors resembling sex cord stromal
tumors. The recommended mitotic index thresholds for classifying a tumor as adenosarcoma vary between 2
MF/10 HPF to 4 MF/10 HPF.
The latter criterion is recommended, unless a particular
tumor exhibits prominent stromal cellularity or cytologic atypia, in which case the tumor should be
classified as uncertain malignant potential. An alternative approach is to classify these tumors as low
grade adenosarcoma (or low malignant potential) with the understanding that such tumors will probably
either not recur at all or may only recur many years after diagnosis. The distinction is most important
in women of reproductive age, for whom a hysterectomy may not be the treatment of choice.
Group 2: The second group features histologically malignant stroma (=
high-grade adenosarcoma), most often manifested by rhabdomyosarcomatous differentiation, but chondroid,
smooth muscle and undifferentiated sarcoma may also be seen. This group of tumors often contains
numerous mitotic figures, including atypical mitoses. Stromal overgrowth is not present.
Group 3: The third group features stromal overgrowth (= adenosarcoma with
stromal overgrowth). By definition, tumors with stromal overgrowth should contain pure stroma comprising
more than 25% of the tumor volume. Most, but not all of this group also contain high-grade sarcomatous
stroma, often with heterologous differentiation (typically rhabdomyosarcoma). These latter tumors are
associated with a uniformly poor prognosis. In some tumors, the stroma in the areas of stromal
overgrowth is low grade or bland as in the first type of adenosarcoma and these tumors, despite the
presence of stromal overgrowth may be associated with a more indolent disease course, with long disease
free intervals punctuated by intermittent localized recurrences. The mitotic count almost always exceeds
4 MF/10 HPF in tumors with stromal overgrowth, although exceptions do rarely occur, typically in the
group with low-grade sarcomatous overgrowth.
Recurrent adenosarcomas may continue to exhibit a biphasic phenotype or may be composed of stroma
only. In some instances, recurrences may transform to higher grade sarcoma or develop heterologous
elements that were not apparent in the primary tumor.  The transformation to higher grade
sarcoma or sarcomatous overgrowth is usually associated with increased tempo of disease with increased
frequency of recurrence and involvement of multiple sites. Hematogenous metastases, typically to the
lung, may occur and are often comprised only of stromal elements.
The immunophenotype of most adenosarcomas resembles that of endometrial stromal tumors (positive for
ER, PR, WT1, and CD10, with variable expression of muscle markers, androgen receptors and cytokeratin).
ER, PR, and CD10 expression are commonly lost in cases showing stromal overgrowth
stroma of adenosarcomas, particularly the low-grade tumors, is often CD10 positive and so this marker
cannot be used to differentiate endometrial stromal sarcoma with benign glands from a low-grade
A complex karyotype involving multiple chromosomes was identified by cytogenetic and molecular
cytogenetic analysis of an adenosarcoma from a 15-year-old girl.  Neither p53 nor HER-2/neu
appears to play a significant role in this disease.
The differential diagnosis of adenosarcoma includes adenofibroma and other clinically benign processes
with little or no recurrent potential at the benign end of the spectrum and carcinosarcoma and other
clinically malignant processes with significant recurrent and metastatic potential at the malignant end
of the spectrum.
Adenofibroma vs Adenosarcoma
Adenofibromas typically harbor paucicellular, fibromatous or fibrotic stroma and are distinguished
from adenosarcoma on the basis of low cellularity and low mitotic index. Adenosarcomas without stromal
overgrowth may have the typical low-power appearance of a benign adenofibroma but differ from that lesion
in that the stroma is more cellular (particularly the cambium-layer-like cuff immediately adjacent to the
epithelium) and is mitotically active. The presence of periglandular stromal condensation, increased
stromal cellularity and/or increased mitotic index distinguish adenosarcomas with recurring potential
from adenofibromas with little or no potential for recurrence. In the case of the uterine tumors, the
distinction can usually be made when the entire uterus is available for examination, although there is
some controversy concerning the level of mitotic activity that predicts potential for recurrence in the
absence of high-grade sarcomatous elements. Clement and Scully employ a threshold of 2 MF/10 HPF,
whereas Zaloudek and Norris present evidence to support a threshold of 4 MF/10 HPF.
This controversy largely reflects the observation that these predictors are far from perfect and
occasional adenofibromatous lesions, even with minimal or no mitotic activity, may demonstrate
myoinvasion or local recurrence on clinical follow-up.
Distinction between adenofibroma and adenosarcoma in the ovary and other extra-genital sites can be
more difficult, due to the exuberant stromal component that may accompany some of the epithelial
neoplasms in these sites. To compound this problem, adenosarcoma may occasionally develop as a mural
nodule in otherwise conventional serous or endometrioid cystadenoma.  Problems most often
arise when the adenosarcoma exhibits predominantly fibromatous stromal overgrowth, inconspicuous
periglandular cuffs or few, abortive intraglandular projections. To circumvent these problems, all cases
with any ambiguous histologic features falling within the endometrioid adenofibroma-adenosarcoma spectrum
should be thoroughly sampled when encountered in an extra-genital site. If the problematic lesion still
defies classification after thorough sectioning, consultation should be obtained.
Endometrial Polyp vs Adenosarcoma
Endometrial polyps may contain atypical stromal cells with cytologic features similar to the atypical
stromal cells observed in the vulva, vagina and cervix.  However, the characteristic
intra-glandular polypoid projections and periglandular stromal cuffs of adenosarcoma are not present in
benign polyps. Large endometrial polyps may harbor increased stromal mitotic figures (up to 5 MF/10
HPF), but these polyps do not have significant stromal atypia nor do they have a marked increase in
stromal cellularity. Such polyps are distinguished from adenofibromas on the basis of the characteristic
papillary or intraglandular polypoid projections in adenofibroma. 
Polypoid Adenomyoma/Atypical Polypoid Adenomyoma vs Adenosarcoma
Polypoid adenomyomas or adenomyofibromas (PA)
are circumscribed aggregates of fibromuscular tissue containing small, architecturally simple
glands without branching or budding.
The constituent cells are cytologically bland.
Morules may be present but they are usually not prominent and endometrial stroma may be present. They
uncommonly present as an exophytic or endophytic polypoid growth and are thought to represent endometrial
polyps or submucosal leiomyomas until they are examined histologically. These lesions are benign. They
usually do not pose a significant diagnostic problem unless they feature an especially prominent
fibromyomatous stroma or foci of alternate stromal differentiation.
Atypical polypoid adenomyomas or adenomyofibromas (APA) are characterized by a localized, polypoid endometrial proliferation with features
of complex atypical hyperplasia set in a stroma composed of smooth muscle or more commonly, smooth muscle
and fibrous tissue.
Trichrome stain often confirms the impression of a mixture of
spindled smooth muscle cells and collagen. In most cases, stromal mitotic figures do not exceed 2 MF/10
HPF; occasionally, focal increased stromal mitotic figures (3 to 5 MF/ 10 HPF) may be present, raising
the differential diagnosis of adenosarcoma.  The problem may be compounded by foci of
squamous epithelial differentiation, which are present in most cases. Unlike uterine adenosarcoma, most
PA and APA occur in premenopausal or perimenopausal women. Many of the patients are nulliparous and a
clinical history of infertility is not uncommon. Although tumors in the adenofibroma-adenosarcoma
spectrum may feature stromal smooth muscle, the stroma elsewhere is usually also either highly cellular
and resembles endometrial stroma or paucicellular and populated by spindled fibroblastic cells with
abundant collagen. Rarely, we have encountered adenosarcomas with a predominant low-grade smooth muscle
stroma, but even in these tumors, areas of classic periglandular stromal condensation and intraluminal
polypoid projections are seen.
Polypoid Endometriosis vs Adenosarcoma
Polypoid endometriosis is a rare manifestation of endometriosis that may simulate a neoplasm on
clinical, intraoperative, or pathologic assessment.  Some cases may be attributable to
exogenous hormones or hyperestrinism and, like conventional endometriosis, some may represent a
premalignant or neoplastic process. Unlike conventional endometriosis, polypoid endometriosis affects a
slightly older age group with 60% of cases occurring in women >50 years of age. Clinical follow up in
the largest series of cases reported to date indicates a benign course, although follow up is limited in
that only seven of the reported patients had >5 years follow up and only four had > 7 years.
Like adenosarcoma, polypoid endometriosis often features various types of epithelial metaplasia
(tubal, mucinous, squamous, papillary syncytial metaplasia), but unlike adenosarcoma, it usually does not
exhibit the characteristic stromal cellularity or stromal atypia of adenosarcoma. Some cases may feature
intraglandular stromal papillae and focal periglandular stromal hypercellularity and the point at which
these lesions cease to be polypoid endometriosis and warrant classification as adenosarcoma is not always
easy to define.  Because of this potential for histologic overlap, the distinction between
these two processes can be very difficult on frozen section as well as on permanent sections in some
Given the diagnostic difficulties and the limited data concerning the clinical
behavior of polypoid endometriosis, the possibility of adenosarcoma should be mentioned during
intraoperative consultation on any endometriotic lesion presenting as an unusual mass-like process.
Whenever possible, complete conservative excision is probably warranted. In problematic cases,
examination of multiple sections and consultation should be performed.
Conventional endometriosis can give rise to a number of malignant processes. Ovarian clear cell
carcinoma and endometrioid adenocarcinoma are the most notable examples of tumors arising in association
with endometriosis in the ovary. In extragenital sites, adenosarcoma and endometrial stromal sarcoma are
A significant proportion of extragenital adenosarcomas that have
been reported in the literature are diagnosed only after repeated biopsies and/or multiple clinical
recurrences of endometriosis. While it is likely that some of these cases are histologically
non-informative and possibly responsible for the historic designation of "aggressive endometriosis", it
is also possible that at least some cases may contain more diagnostic foci that can only be identified
when extensively sampled. Adenosarcoma should be given strong consideration in the differential
diagnosis of any new pelvic or abdominal mass in a patient with a history of endometriosis and such
masses should be subjected to extensive sectioning and histologic evaluation.
Carcinosarcoma vs Adenosarcoma
This distinction is based on the epithelial component. The malignant epithelial component in
carcinosarcoma is typically high grade and is usually not confused with the atypical glands that may
occur in adenosarcoma. Uncertainty in a curettage or biopsy specimen may occur due to inadequate
sampling, and many of these ambiguous cases can be resolved on hysterectomy. However, foci of atypical
glands and even well differentiated adenocarcinoma may rarely occur in tumors that are otherwise
indistinguishable from adenosarcomas. Since the clinical behavior of virtually all biphasic mullerian
tumors can be predicted on the basis of the most histologically malignant areas, the behavior of
adenosarcomas with focal low grade adenocarcinoma is probably closer to that of an adenosarcoma than a
carcinosarcoma, provided the foci are relatively small. Recent data suggests that the distinction
between uterine carcinosarcoma and adenosarcoma with high-grade sarcomatous overgrowth may be moot, given
the observed equivalent poor prognosis. 
Sarcoma Entrapping Benign Glands vs Adenosarcoma
In adenosarcoma, the glands are typically scattered throughout the tumor and they are large, irregular
and cystic in contour with stromal cuffing. Often, they feature papillations and various types of
metaplastic epithelium. In contrast, glands that are entrapped by a sarcomatous proliferation are
typically small and inconspicuous or form focal aggregates of residual glands surrounded by sarcoma.
Obviously, adenosarcomas with stromal overgrowth may also entrap benign glands in the areas of stromal
overgrowth. The key to the diagnosis is the presence elsewhere of typical adenosarcoma.
Endometrial Stroma Sarcoma with Glandular Elements vs Adenosarcoma
Adenosarcoma and rarely, adenofibroma, may exhibit overlapping histologic features with that of
endometrial stromal sarcoma with prominent glandular elements. Over a certain range of appearances there
is no sharp distinction between the two, but features favoring adenosarcoma include dilated, irregularly
shaped glands with intraluminal polypoid protrusions, a variety of mullerian epithelial types and the
characteristic periglandular stromal condensation.
If epithelium is present in endometrial stromal sarcoma, it usually takes the form of poorly
circumscribed, but regularly contoured small tubular glands or cords of epithelial-like cells. The
epithelial type in stromal sarcoma is almost always endometrioid, while a variety of epithelial types
with mucinous, squamous and syncytial metaplasia are often present in adenosarcoma. The stroma in
endometrial stromal sarcoma is also more monomorphous and does not exhibit the periglandular condensation
around glands that is so characteristic of adenosarcoma. Sex cord elements may be seen in both.
Embryonal Rhabdomyosarcoma vs Adenosarcoma with Heterologous Rhabdomyosarcomatous Differentiation
Adenosarcomas tend to occur in the uterine cervix of reproductive aged women, as well as in
postmenopausal women. The predilection for these tumors to occur in the cervix of postmenarchal
teenagers often poses a clinical differential diagnosis of embryonal rhabdomyosarcoma (sarcoma
botryoides). This differential diagnosis may continue at the macroscopic level, since a botryoides
appearance has been reported in some cases of cervical adenosarcoma. Furthermore, when these cervical
adenosarcomas feature microscopic rhabdomyosarcomatous differentiation, they can be especially difficult
to distinguish from embryonal rhabdomyosarcoma.  Since the treatment and prognosis of
cervical embryonal rhabdomyosarcomas may differ substantially from that of an adenosarcoma, the diagnosis
of adenosarcoma in this setting should be made with caution and only after complete histologic evaluation
and consultation. Embryonal rhabdomyosarcoma usually occurs in a younger premenarchal age group as
opposed to the postmenarchal age group.
A variety of pure sarcomas have been reported in the female genital tract but they are all quite
rare. These include osteosarcoma, chondrosarcoma, rhabdomyosarcoma, liposarcomas, malignant schwannoma,
and angiosarcomas.  The chief differential diagnostic consideration in all of these tumors
is a carcinosarcoma or adenosarcoma with stromal overgrowth and an inconspicuous epithelial component.
Since each of these sarcomas is high grade and treated similarly the distinction may not be of great
importance. This might change if it becomes apparent that carcinosarcomas respond more like carcinomas
A Managerial Approach
Although authorities differ on the appropriate mitotic index conventions for distinguishing
adenofibroma from adenosarcoma, uterine tumors with particularly cellular stroma, more than minimal
stromal cell atypia and/or borderline mitotic counts should be considered as being of at least uncertain
malignant potential, particularly if subepithelial condensation is present. When such tumors are
encountered in the ovary and extra-genital sites, they should be classified as adenosarcomas due to the
higher risk of recurrent disease at these sites. Other benign proliferations featuring a mixture of
glands and stroma (endometrial polyps, polypoid adenomyoma - both typical and atypical - and polypoid
endometriosis) typically lack the characteristic peri-glandular cuffing and the polypoid invaginations
seen in adenosarcoma, but may require additional sectioning or sampling in order to exclude the latter
It can be especially difficult to distinguish adenofibroma from adenosarcoma on a limited endometrial
sampling. The difficulty is heightened by the rare reported instances of lesions that otherwise resemble
a typical adenofibroma, but have demonstrated myometrial invasion in the hysterectomy specimen. When
this differential diagnosis occurs in the post-reproductive years, the distinction is mostly of
prognostic significance. However, when it occurs in women during the reproductive years, the distinction
may carry significant therapeutic implications, since an adenofibroma can be treated by polypectomy
whereas adenosarcoma is treated by hysterectomy. In these latter cases, imaging studies and repeat
hysteroscopic directed sampling with consultation should be sought.
The distinction between adenosarcoma with sarcomatous stromal overgrowth and pure uterine sarcoma or
carcinosarcoma depends on identifying neoplastic glands in some part of the tumor – benign in
adenosarcoma and malignant in the case of carcinosarcoma.
Most malignant mixed mullerian neoplasms (carcinosarcoma) are easily recognized as high-grade biphasic
malignant neoplasms, whether the tumor is initially encountered in an endometrial sampling or a
hysterectomy specimen. On occasion, adenosarcomas may contain foci of glandular atypia that meet
criteria for carcinoma in situ or even focal adenocarcinoma, raising the differential diagnosis of
carcinosarcoma. If the remaining glandular pattern is consistent with an adenosarcoma, the lesion should
be diagnosed as such with a comment in the report that there are areas featuring carcinomatous
epithelium. Such tumors are uncommon and so there is no outcome data (other than anecdotal) that
supports this classification, but one would expect that such tumors would behave more like typical
adenosarcoma unless there is associated high grade carcinoma, high grade sarcoma, or stromal overgrowth.
Differential Diagnosis of Adenosarcoma
| ||Benign glands ||Malignant glands|
|Benign stroma ||Adenofibroma|
Atypical polypoid adenomyoma
|Malignant stroma ||Adenosarcoma|
with sarcomatous stroma
with stromal overgrowth
Endometrial stromal sarcoma with glandular elements
Sarcoma entrapping benign glands
* Carcinofibroma, a term reported in the older literature to describe the presence of adenocarcinoma
in an adenofibromatous process, is not currently considered to be a standard diagnostic entity.
- Amant F, Schurmans K, Steenkiste E, et al. Immunohistochemical determination of estrogen and progesterone receptor positivity in uterine adenosarcoma. Gynecol Oncol 2004;93:680-685.
- Amant F, Steenkiste E, Schurmans K, et al. Immunohistochemical expression of CD10 antigen in uterine adenosarcoma. Int J Gynecol Cancer 2004;14:1118-1121.
- Anderson J, Behbakht K, De Geest K, et al. Adenosarcoma in a patient with vaginal endometriosis. Obstet Gynecol 2001;98:964-966.
- Arenas M, Rovirosa A, Hernandez V, et al. Uterine sarcomas in breast cancer patients treated with tamoxifen. Int J Gynecol Cancer 2006;16:861-865.
- Benda JA, Veronezi-Gurwell A, Wilcox M, et al. An unusual extrauterine variant of adenosarcoma with multiple recurrences over 16 years. Gynecol Oncol 1994;53:131-137.
- Blom R, Guerrieri C. Adenosarcoma of the uterus: a clinicopathologic, DNA flow cytometric, p53 and mdm-2 analysis of 11 cases. Int J Gynecol Cancer 1999;9:37-43.
- Chen KT. Rhabdomyosarcomatous uterine adenosarcoma. Int J Gynecol Pathol 1985;4:146-152.
- Chen Z, Hong B, Drozd-Borysiuk E, et al. Molecular cytogenetic characterization of a case of Mullerian adenosarcoma. Cancer Genet Cytogenet 2004;148:129-132.
- Clement PB, Oliva E, Young RH. Mullerian adenosarcoma of the uterine corpus associated with tamoxifen therapy: a report of six cases and a review of tamoxifen-associated endometrial lesions. Int J Gynecol Pathol 1996;15:222-229.
- Clement PB, Scully RE. Mullerian adenofibroma of the uterus with invasion of myometrium and pelvic veins. Int J Gynecol Pathol 1990;9:363-371.
- Clement PB, Scully RE. Mullerian adenosarcoma of the uterus: a clinicopathologic analysis of 100 cases with a review of the literature. Hum Pathol 1990;21:363-381.
- Czernobilsky B, Hohlweg-Majert P, Dallenbach-Hellweg G. Uterine adenosarcoma: a clinicopathologic study of 11 cases with a reevaluation of histologic criteria. Arch Gynecol 1983;233:281-294.
- Dincer AD, Timmins P, Pietrocola D, et al. Primary peritoneal mullerian adenosarcoma with sarcomatous overgrowth associated with endometriosis: a case report. Int J Gynecol Pathol 2002;21:65-68.
- Eichhorn JH, Young RH, Clement PB, et al. Mesodermal (mullerian) adenosarcoma of the ovary: a clinicopathologic analysis of 40 cases and a review of the literature. Am J Surg Pathol 2002;26:1243-1258.
- Feroze M, Aravindan KP, Thomas M. Mullerian adenosarcoma of the uterine cervix. Indian J Cancer 1997;34:68-72.
- Fleshman RL, Wasman JK, Bodner DG, et al. Mesodermal adenosarcoma of the testis. Am J Surg Pathol 2005;29:420-423.
- Gast MJ, Radkins LV, Jacobs AJ, et al. Mullerian adenosarcoma of the cervix with heterologous elements: diagnostic and therapeutic approach. Gynecol Oncol 1989;32:381-384.
- Gilks CB, Clement PB, Hart WR, et al. Uterine adenomyomas excluding atypical polypoid adenomyomas and adenomyomas of endocervical type: a clinicopathologic study of 30 cases of an underemphasized lesion that may cause diagnostic problems with brief consideration of adenomyomas of other female genital tract sites. Int J Gynecol Pathol 2000;19:195-205.
- Hattab EM, Allam-Nandyala P, Rhatigan RM. The stromal component of large endometrial polyps. Int J Gynecol Pathol 1999;18:332-337.
- Hendrickson MR, Longacre TA, Kempson RL. Pathology of uterine sarcomas. In: Rubin SC, Coukos E, eds. Cancer of the Uterus. New York: Publishers Domain, 2004.
- Inoue M, Fukuda H, Tanizawa O. Adenosarcomas originating from sites other than uterine endometrium. Int J Gynaecol Obstet 1995;48:299-306.
- Jelovsek JE, Winans C, Brainard J, et al. Endometriosis of the liver containing mullerian adenosarcoma: case report. Am J Obstet Gynecol 2004;191:1725-1727.
- Jones MW, Lefkowitz M. Adenosarcoma of the uterine cervix: a clinicopathological study of 12 cases. Int J Gynecol Pathol 1995;14:223-229.
- Judson PL, Temple AM, Fowler WC, Jr., et al. Vaginal adenosarcoma arising from endometriosis. Gynecol Oncol 2000;76:123-125.
- Kanngurn S, Somran J, Art-Ong C, et al. Primary peritoneal adenosarcoma with stromal overgrowth and fetal type cartilage: a case report and literature review. J Med Assoc Thai 2005;88:849-854.
- Krivak TC, Seidman JD, McBroom JW, et al. Uterine adenosarcoma with sarcomatous overgrowth versus uterine carcinosarcoma: comparison of treatment and survival. Gynecol Oncol 2001;83:89-94.
- Laurila P, Leivo I, Makisalo H, et al. Mullerian adenosarcomalike tumor of the seminal vesicle. A case report with immunohistochemical and ultrastructural observations. Arch Pathol Lab Med 1992;116:1072-1076.
- Liu L, Davidson S, Singh M. Mullerian adenosarcoma of vagina arising in persistent endometriosis: report of a case and review of the literature. Gynecol Oncol 2003;90:486-490.
- Longacre T, Hendrickson M. Mesenchymal tumors. In: Goff B, ed. Gynecologic Pathology. Philadelphia, PA: Current Medicine, 1997:6.1-6.17.
- Longacre TA, Chung MH, Rouse RV, et al. Atypical polypoid adenomyofibromas (atypical polypoid adenomyomas) of the uterus. A clinicopathologic study of 55 cases. Am J Surg Pathol 1996;20:1-20.
- Manivel C, Shenoy BV, Wick MR, et al. Cystosarcoma phyllodes of the prostate. A pathologic and immunohistochemical study. Arch Pathol Lab Med 1986;110:534-538.
- Mazur MT. Atypical polypoid adenomyomas of the endometrium. Am J Surg Pathol 1981;5:473-482.
- Mazur MT, Myers JL, Maddox WA. Cystic epithelial-stromal tumor of the seminal vesicle. Am J Surg Pathol 1987;11:210-217.
- Mikami Y, Hata S, Kiyokawa T, et al. Expression of CD10 in malignant mullerian mixed tumors and adenosarcomas: an immunohistochemical study. Mod Pathol 2002;15:923-930.
- Murugasu A, Miller J, Proietto A, et al. Extragenital mullerian adenosarcoma with sarcomatous overgrowth arising in an endometriotic cyst in the pouch of Douglas. Int J Gynecol Cancer 2003;13:371-375.
- Park HM, Park MH, Kim YJ, et al. Mullerian adenosarcoma with sarcomatous overgrowth of the cervix presenting as cervical polyp: a case report and review of the literature. Int J Gynecol Cancer 2004;14:1024-1029.
- Parker RL, Dadmanesh F, Young RH, et al. Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature. Am J Surg Pathol 2004;28:285-297.
- Raffaelli R, Piazzola E, Zanconato G, et al. A rare case of extrauterine adenosarcoma arising in endometriosis of the rectovaginal septum. Fertil Steril 2004;81:1142-1144.
- Ramos P, Ruiz A, Carabias E, et al. Mullerian adenosarcoma of the cervix with heterologous elements: report of a case and review of the literature. Gynecol Oncol 2002;84:161-166.
- Rossi G, Cavazza A, Longo L, et al. Localized pleural metastatic adenosarcoma of the uterine cervix mimicking a malignant solitary fibrous tumour: CD10 has no value in differential diagnosis. Histopathology 2002;41:82-83.
- Seidman JD, Chauhan S. Evaluation of the relationship between adenosarcoma and carcinosarcoma and a hypothesis of the histogenesis of uterine sarcomas. Int J Gynecol Pathol 2003;22:75-82.
- Slavin RE, Krum R, Van Dinh T. Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature. Hum Pathol 2000;31:456-463.
- Soslow RA, Ali A, Oliva E. Mullerian adenosarcomas: an immunophenotypic analysis of 35 cases. Am J Surg Pathol, In press.
- Stern RC, Dash R, Bentley RC, et al. Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types. Int J Gynecol Pathol 2001;20:133-139.
- Swisher EM, Gown AM, Skelly M, et al. The expression of epidermal growth factor receptor, HER-2/Neu, p53, and Ki-67 antigen in uterine malignant mixed mesodermal tumors and adenosarcoma. Gynecol Oncol 1996;60:81-88.
- Tackin S, Bozaci EA, Sonmezer M, et al. Late recurrence of uterine Mullerian adenosarcoma as heterologous sarcoma: Three recurrences in 8 months increasing in number and grade of sarcomatous components. Gynecol Oncol 2006;101:179-182.
- Tahlan A, Nanda A, Mohan H. Uterine adenomyoma: a clinicopathologic review of 26 cases and a review of the literature. Int J Gynecol Pathol 2006;25:361-365.
- Tai LH, Tavassoli FA. Endometrial polyps with atypical (bizarre) stromal cells. Am J Surg Pathol 2002;26:505-509.
- Takeuchi K, Kitazawa S, Deguchi M, et al. Adenofibromasarcoma originating from a mural nodule of ovarian serous cystadenoma. Eur J Gynaecol Oncol 2005;26:511-513.
- Thiel DD, Erhard MJ. Uterine adenosarcoma in a boy with persistent mullerian duct syndrome: first reported case. J Pediatr Surg 2005;40:e29-31.
- Visvalingam S, Jaworski R, Blumenthal N, et al. Primary peritoneal mesodermal adenosarcoma: report of a case and review of the literature. Gynecol Oncol 2001;81:500-505.
- Yantiss RK, Clement PB, Young RH. Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis: a study of 17 cases. Am J Surg Pathol 2000;24:513-524.
- Young RH, Clement PB. Malignant lesions of the female genital tract and peritoneum that may be underdiagnosed. Semin Diagn Pathol 1995;12:14-29.
- Young RH, Treger T, Scully RE. Atypical polypoid adenomyoma of the uterus. A report of 27 cases. Am J Clin Pathol 1986;86:139-145.
- Zaloudek CJ, Norris HJ. Adenofibroma and adenosarcoma of the uterus: a clinicopathologic study of 35 cases. Cancer 1981;48:354-366.