Keywords
extragenital müllerian adenosarcoma - computed tomography - pelvic mass - uterine
sarcoma
Palavras-chave
adenosarcoma mülleriano extragenital - tomografia computadorizada - massa pélvica
- sarcoma uterino
Introduction
Müllerian adenosarcoma is an uncommon variant of the Müllerian mixed tumor of the
uterus.[1] Uterine adenosarcomas make up 5% of all uterine sarcomas and tend to occur in postmenopausal
women but may also be diagnosed in adolescents and young women.[2] The uterus is the most common site of origin, but, even though rarer, it may also
arise in extrauterine locations, including the ovary, vagina, fallopian tube, gastrointestinal
tract, bladder and peritoneal sites, such as the pouch of Douglas and the intestinal
serosa.[3]
[4]
[5] There are no specific risks or etiologic factors, but extrauterine adenosarcoma
has been reported to arise in association with endometriosis.[6] There are also few cases of adenosarcoma arising in women on tamoxifen, and those
with endogenous hyperestrogenism or prior pelvic radiation.[7]
[8]
[9] Adenosarcoma is characterized by a biphasic cellular differentiation, its essential
features include benign appearing epithelial component and malignant mesenchymal component.[3]
[4]
[10]
[11] The epithelial component is usually characterized by endometrioid type; the malignant
stromal component is typically low grade.[3]
[6] The most common symptom of uterine adenosarcoma is vaginal bleeding; some patients
complain of pelvic pain, vaginal discharge or symptoms related to uterine enlargement.[9] Upon examination, the patients often have a polypoid mass protruding through a dilated
cervical os.[6] Extrauterine adenosarcomas have no specific clinical presentation: abdominal discomfort
is the most common symptom.[3]
[6]
[12] Müllerian adenosarcomas have a good prognosis, with the exception of deeply invasive
tumors or those with high grade sarcomatous overgrowth; extrauterine adenosarcomas
also have a higher risk of recurrence.[9] Risk factors associated with recurrence and metastases include deep myometrial or
lymph-vascular space invasion and sarcomatous overgrowth.[6]
[10] We report a very interesting case of extrauterine Müllerian adenosarcoma demonstrated
on ultrasound and computer tomography (CT) imaging. According to our knowledge, this
is the first case described in the literature of extragenital Müllerian adenosarcoma
with full and exhaustive images not associated with known risk factors and/or comorbidities.
Case Description
A 27-year-old woman refers to our hospital complaining of dyspepsia and abdominal
distension for a few months. Her past medical history is silent. Her blood exams show
an elevated CA 125 of 1,309 UI/ml. Upon physical examination, she presents considerable
abdominal distension and obtuseness to the lower abdominal quadrants as for the presence
of ascites. A transabdominal ultrasound, performed using a Philips C5–2 MHz USB curved
array transducer (Philips Healthcare, Best, Netherlands) confirms the ascites in all
peritoneal recesses ([Fig. 1A]) and reveals a bulky mass, which occupies almost entirely the abdominal cavity and
the pelvis. It appears predominantly solid, with few cystic components and heterogeneous
echotexture ([Fig. 2A]). Internal blood flow is demonstrated on ultrasound color Doppler ([Fig. 3A]). A 246-CT (Philips Healthcare, Best, Netherlands) of the abdomen and pelvis is
performed after a few hours for further evaluation. The protocol used is as follows:
precontrast phase and postcontrast tri-phase scan (arterial phase, portal/venous phase
and delayed phase). The CT confirms the findings highlighted on the ultrasound: diffused
ascites ([Fig. 1B]) and a multiloculated, voluminous solid mass with definite margins measuring 20 × 10
cm on the axial view, with cranio-caudal extension of 23 cm. The mass occupies partially
the abdomen and entirely the pelvis, and presents contextual cystic components, the
largest of which was 6 × 4 cm, and calcifications, the largest of which measured 14 mm
([Fig. 2B-C]). It shows heterogeneous vascularity during the arterial phase ([Fig. 3B-C]) and presents few septa and pseudosepta, which have a lively enhancement on postcontrast
images, especially during the portal/venous phase ([Fig. 3D]). The mass dislocates the intestinal loops but does not show signs of local invasion.
There are no enlarged lymphnodes. The uterus is normal; the ovaries are not viewable.
The patient undergoes surgery with the presumed diagnosis of an adnexal cancer. The
mass is described as 30 cm in size, with irregular surface and cerebroid appearance.
The uterus and the ovaries are normal. Intraoperative pathological consultation reveals
borderline tumor of the fallopian tube. Bilateral salpingectomy and total omentectomy
are performed. The definitive histological examination shows normal fallopian tubes
and Müllerian adenosarcoma arising from the peritoneum. The peritoneal fluid presents
no pathological features. The patient is discharged without medical therapy and the
hospital stay is uneventful. One month after the surgery, hysteroscopy is performed
to obtain endometrial sample, which results negative for neoplasia. Two months after
the surgery, the patient undergoes a whole-body CT scan, which shows neither signs
of recurrence nor metastasis.
Fig. 1 Copious ascites on transabdominal ultrasound (A) and CECT (B).
Fig. 2 Transabdominal ultrasound (A) and axial CECT (B-C) images show a large solid, heterogeneous mass containing cystic spaces (▸). Note
the presence of calcifications (→) (C).
Fig. 3 Mass shows internal vascularity on ultrasound color Doppler (A) and axial computed tomography during arterial phase (B-C) (→). Enhancing on venous/portal phase of septa and pseudosepta (D) (→).
Discussion
Müllerian adenosarcoma is a very rare tumor and comprises only 5% of uterine sarcomas,
occurring in patients from 14 to 89 years old (median 58).[6]
[9] The extragenital locations are even rarer, and usually the patients affected by
this pathology present a history of endometriosis, tamoxifen therapy, hyperestrogenism
or prior pelvic radiation.[9] Other patients may have a history of recurrent endometrial or cervical polyps; however,
these may be coincidental associations without proven etiological factors.[6]
[9] In the literature, among the risk factors described, the majority of adenosarcomas
are associated with endometriosis.[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24] Symptoms may vary according to location. In uterine adenosarcoma, the most common
presenting symptom is abnormal vaginal bleeding, but some patients present pelvic
pain, abdominal mass or vaginal discharge.[9] In the extragenital locations, abdominal discomfort is the usual presenting symptom.[6] Histologically, the tumor is characterized by the presence of both epithelial and
stromal elements, with the latter predominating.[9] The epithelial elements usually consist of glands and, in most cases, the epithelium
is endometrioid and resembles proliferative endometrium; on the other hand, the malignant
stromal component is typical low grade.[6]
[9] Mesenchymal elements may also be observed.[9] Adenosarcomas with more than 25% of the tumor composed of pure high-grade sarcoma
are designated as adenosarcomas with sarcomatous overgrowth, and they may be associated
with deep myometrial and vascular invasion.[6]
In most adenosarcomas with a low-grade stromal component, the stromal element expresses
estrogen receptor, progesterone receptor, CD10, WT1, smooth muscle actin, low MIB1
proliferation index and is negative for P53.[6]
[9] The CD10 is diagnostically a useful marker for endometrial stromal tumors and can
also be used in establishing the diagnosis of uterine adenosarcomas.[6] Alterations in the PIK3CA/AKT/PTEN pathway were also found.[9] Immunohistochemistry of our patient presented high level of estrogen/progesterone
receptors, smooth muscle actin positivity and low MIB 1 proliferation index. Outside
the uterine cavity, the main locations of the cancer described are the ovary, peritoneum,
pelvis and, in patients who underwent hysterectomy, the vagina.[14]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
[25] Other sites where extragenital Müllerian adenosarcoma may be found are the rectum
and vaginal-rectum septum.[13]
[15]
[16] In 2001, Hirakawa et al[24] have interestingly reported for the first time the presence of tumor cells in the
ascitic fluid in a patient presenting adenosarcoma of the ovary.[24] In our patient, the peritoneal fluid presented no pathological cells. Only in one
case, it was described that a patient with history of endometriosis presented with
extragenital adenosarcoma and concomitant colon-rectal neoplasm, but the association
between the two tumors has not been studied yet.[15] Patients with Müllerian adenosarcoma have a generally good prognosis, unless the
tumor shows deep myometrial invasion or sarcomatous overgrowth.[9] Among the cases present in the literature, only a few have been reported with a
histologic description of “sarcomatous overgrowth,” a very rare condition with a worse
prognosis.[18]
[21]
[23] Recurrences, which occur in 20 to 30% of patients, are usually confined to the vagina,
pelvis or abdomen (44% recurrence rate of adenosarcomas with sarcomatous overgrowth
compared with 14% without sarcomatous overgrowth).[6]
[9] Anyway, long term follow-up is needed.[9] The treatment of uterine adenosarcoma is hysterectomy with bilateral salpingo-oophorectomy;
however, ovarian preservation can be considered in premenopausal women; treatment
decisions need to be individualized based on age and clinical/pathological parameters.[6] This is the first case reported in the literature, with a wide and complete imaging
description of this lesion, in a patient with a silent medical history, without known
risk factors and/or comorbidities, such as endometriosis. Interestingly, this is the
second case reported in Italy.[16]
Conclusion
Müllerian adenosarcoma should be included in the differential diagnosis of young patients
presenting with complex masses in. Although Müllerian adenosarcoma is a very rare
disease, more studies are needed to improve the knowledge of this condition to provide
its diagnostic, clinical and therapeutic management.
