AJR 2003; 181:1673-1675
© American Roentgen Ray Society
Sonography and MRI of Tamoxifen-Associated Müllerian Adenosarcoma of the Uterus
Danai Chourmouzi1,
Glykeria Boulogianni1,
Thomas Zarampoukas2 and
Antonios Drevelengas3
1 Interbalkan European Medical Center, Asklipiou 10 Str., 57001 Pylaia,
Thessaloniki, Greece.
2 Department of Pathology, AHEPA University Hospital, S Kyriakidi 1 Str.,
Thessaloniki, 54006 Greece.
3 Department of Diagnostic Radiology, AHEPA University Hospital, Thessaloniki,
54006 Greece.
Received October 15, 2002;
accepted after revision April 1, 2003.
Address correspondence to D. Chourmouzi.
Introduction
Müllerian adenosarcoma of the uterus is an uncommon biphasic tumor
consisting of epithelial and malignant stromal components. The terms
"malignant mixed mesodermal" or "malignant mixed
müllerian" tumor are also used. This rare tumor was first described
in 1974 and accounts for only 8% of all uterine sarcomas
[1]. It has been suggested that
primary müllerian adenosarcoma of the uterus may be associated with
tamoxifen therapy [2,
3].
Tamoxifen is used as adjuvant therapy for breast cancer. However, it has
been associated with many side effects, including endometrial hyperplasia,
endometrial polyps, and carcinoma. Müllerian adenosarcoma associated with
tamoxifen is rather uncommon. There are only 13 reported cases of uterine
adenosarcoma related to tamoxifen therapy and no adequate descriptions of
their imaging characteristics
[2–7].
We present a new case of this rare tumor in a woman who received long-term
tamoxifen therapy for breast carcinoma, and we describe imaging findings
obtained on sonography and MRI examinations.
Case Report
A 52-year-old woman was referred to our hospital because of abnormal
intermenstrual bleeding. She had a history of mastectomy for invasive ductal
carcinoma. The patient had been treated with 30 mg of tamoxifen daily for 50
months. Pelvic examination revealed an enlarged uterus. The patient underwent
transvaginal sonography (General Electric Medical Systems, Milwaukee, WI) with
a 7-MHz transducer. Sonographic examination revealed an expansion of the
endometrial cavity with a thickened heterogeneous endometrial echo complex
mass with small cystic spaces (Fig.
1A).
MRI was performed on a 0.5-T unit (Vectra, General Electric Medical
Systems). The imaging protocol consisted of spin-echo T1-weighted axial and
sagittal scans (TR/TE, 450/22) before and after IV administration of 0.1
µmol/kg body weight of gadopentetate dimeglumine (Magnevist, Shering,
Berlin, Germany) and spin-echo T2-weighted axial and sagittal scans
(5,200/100).
Findings of MRI revealed a significantly enlarged uterus with a thin
myometrium. The endometrial cavity was expanded by a heterogeneous mass
measuring 9.3 x 7.9 cm and extending to the internal os. The mass had
solid components with intermediate signal intensity on both sequences and
multiple well-defined cystic spaces with low signal intensity on T1-weighted
images and high signal intensity on T2-weighted images. Numerous thin septa
creating a lattice-like appearance were noted between cystic areas. After the
administration of gadolinium, we noted enhancement of the solid components and
septa. Areas of high signal intensity on T1-weighted images were also depicted
and presumed to represent hemorrhagic areas (Figs.
1B,
1C,
1D). On MRI, the tumor appeared
to be confined to the endometrium, although distortion of zonal anatomy with
absence of a junctional zone made it difficult to exclude the superficial
myometrium invasion.
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Fig. 1B. —52-year-old woman with müllerian adenosarcoma of uterus.
Axial unenhanced T1-weighted image (TR/TE, 450/22) shows uterine cavity
enlarged by mass measuring 9.3 x 7.9 cm. Note cystic areas
(arrows) of low-signal-intensity and intermediate-signal-intensity
septa and thin myometrium. Area of high signal intensity (arrowhead)
was presumed to represent hemorrhage.
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The patient underwent hysterectomy with bilateral oophorectomy. Results of
gross specimen pathology showed expansion of the uterine cavity by a large
polypoid tumor filling the endometrial cavity
(Fig. 1E). Microscopic
examination showed a neoplasm with glands of endometrial pattern and a
cellular stromal component. The condensed areas of stroma showed significant
atypia and mitotic activity without heterologous elements
(Fig. 1F). An area of
hemorrhage seen on MRI was not confirmed pathologically. A diagnosis of
müllerian adenosarcoma was made.
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Fig. 1F. —52-year-old woman with müllerian adenosarcoma of uterus.
Photomicrograph of histopathologic specimen shows mature endometrial glands
surrounded by elements of stromal sarcoma. (H and E, x10) Inset shows
stromal cells with significant atypia. (H and E, x40)
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Discussion
Tamoxifen has been used for the management of breast cancer for more than
30 years. Advanced and early breast cancer, ductal carcinoma in situ, and,
more recently, breast cancer prevention are considered indications for
tamoxifen treatment. Proliferative abnormalities of the endometrium such as
postmenopausal endometriosis, endometrial polyps, endometrial hyperplasia, and
endometrial carcinoma have been reported in patients receiving tamoxifen
therapy. The possible association between endometrial cancer and tamoxifen was
first recognized in 1985 [8].
Endometrial adenocarcinoma is the most common malignancy associated with
tamoxifen therapy. Both dosage and duration of treatment may be related to the
development of uterine malignancies; tamoxifen dosage as low as 20 mg/day has
been shown to increase cancer risk in patients
[9]. To our knowledge, primary
müllerian adenosarcoma of the uterus in association with tamoxifen
therapy has rarely been described. This side effect is consistent with the
fact that endometrial stromal cells also contain estrogen receptors
[3,
4].
Adenosarcomas are biphasic tumors consisting of a malignant stroma and a
benign glandular element. Histologically, adenosarcomas may be considered to
represent an intermediate state between adenofibromas and carcinosarcomas of
the endometrium. They are usually single lesions arising from uterine fundus
and projecting to the endometrial cavity. Gross pathologic examination reveals
a polypoid mass, which appears to contain necrotic soft areas.
Microscopically, the adenosarcoma presents a glandular epithelial component
lined by a benign-appearing epithelium. The sarcomatous component contains
oval to spindle-shaped cells with mild to moderate atypia
[7,
10]. To the best of our
knowledge, only 13 cases in which patients presented with müllerian
adenosarcomas after tamoxifen therapy have been reported in the
literature.
Ascher et al. [11,
12] described two distinct MRI
patterns in women receiving tamoxifen: homogeneous high signal intensity on
T2-weighted images and enhanced endometrial–myometrial interface, or
heterogeneous signal intensity on T2-weighted images and lattice-like
enhancement traversing the endometrial canal on contrast-enhanced images.
Correlation of these imaging patterns with histopathologic findings revealed
that the former was associated with degenerative or proliferative changes,
whereas the latter was associated with polyps. These polyps often have spaces
representing cystic atrophy and dilated glands, whereas lattice-like
morphology reflects the enhancing septa between the cysts in the polyp
[11,
12]. No distinct features were
found for endometrial carcinoma. Gynecologists are therefore advised to
perform a more aggressive sampling procedure to evaluate the entire
endometrial cavity in cases in which imaging findings match the second pattern
because there is the possibility of coincident carcinoma in a polyp.
To our knowledge, there are no distinct reported imaging findings of
müllerian adenosarcoma of the uterus associated with tamoxifen treatment.
The imaging features in this case fit the second radiographic pattern,
indicating the presence of a polyp. The endometrial cavity in our patient was
expanded by a large heterogeneous mass with many well-circumscribed cystic
spaces. A central area of high signal intensity on T1-weighted images,
representing subacute hemorrhage, was noted. The lattice-like enhancement
after the administration of gadolinium was similar to that noted in the
reported cases of endometrial polyps associated with tamoxifen treatment
[11,
12]. Our case suggests that
primary müllerian adenosarcoma should be considered in the differential
diagnosis in women undergoing long-term tamoxifen therapy when imaging
findings suggest the presence of an endometrial polyp.
References
- Clement PB, Scully RE. Müllerian adenosarcoma of the uterus: a
clinicopathologic analysis of 100 cases with a review of the literature.
Hum Pathol1990; 21:363
–381[Medline]
- Carvalho FM, Carvalho JP, Motta EV, Souen J. Müllerian
adenosarcoma of the uterus with sarcomatous overgrowth following tamoxifen
treatment for breast cancer. Rev Hosp Clin Fac Med Sao
Paulo 2000;55:17
–20[Medline]
- Clement PB, Oliva E, Young RH. Müllerian 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[Medline]
- Arici DS, Aker H, Yildiz E, Tasyurt A. Müllerian adenosaracoma
of the uterus associated with tamoxifen therapy. Arch Gynecol
Obstet 2000;264:105
–107[Medline]
- Bocklage T, Lee K, Belinson JL. Uterine müllerian adenosarcoma
following adenomyoma in a woman on tamoxifen therapy. Gynecol
Oncol 1992;44:104
–109[Medline]
- Jagavkar RS, Shakespeare TP, Stevens MJ. Endometrial adenosarcoma
with adjuvant tamoxifen therapy for primary breast carcinoma.
Australas Radiol1998; 42:157
–158[Medline]
- Jessop FA, Roberts PF. Müllerian adenosarcoma of the uterus in
association with tamoxifen therapy. Histopathology2000; 36:91
–92[Medline]
- Killackey MA, Hakes TB, Pierce VK. Endometrial adenocarcinoma in
breast cancer patients receiving antiestrogens. Cancer Treat
Rep 1985;69:237
–238[Medline]
- Oshima H, Miyagawa H, Sato Y, et al. Adenofibroma of the
endometrium after tamoxifen therapy for breast cancer: MR findings.
Abdom Imaging2002; 27:592
–594[Medline]
- Seidman JD, Wasserman CS, Aye LM, MacKoul PJ, O'Leary TJ. Cluster
of uterine müllerian adenosarcoma in the Washington, DC, metropolitan
area with high incidence of sarcomatous overgrowth. Am J Surg
Pathol 1999;23:809
–814[Medline]
- Ascher SM, Imaoka I, Lage JM. Tamoxifen-induced uterine
abnormalities: the role of imaging. Radiology2000; 214:29
–38[Abstract/Free Full Text]
- Ascher SM, Johnson JC, Barnes WA, Bae CJ, Patt RH, Zeman RK. MR
imaging appearance of the uterus in postmenopausal women receiving tamoxifen
therapy for breast cancer: histopathologic correlation.
Radiology1996; 200:105
–110[Abstract/Free Full Text]
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Introduction
Case Report
