Introduction: Uterine adenosarcoma mostly seen in elderly and there are limited data on appropriate approach in premenopausal patient and the accurate prognosis. Herein we aimed to present a young case of Müllerian adenosarcoma of uterus which had only 9 years old. Case report: A 9year old pre pubertal girl presented to the gynecology department of Isfahan University of Medical Sciences-Iran with the vaginal bleeding. An intrauterine mass was noted via hysteroscopic examination as the reason of abnormal bleeding. The final pathology revealed Müllerian adenosarcoma of uterus. Subsequently hysterectomy was done due to persistent perfused vaginal bleeding; with ovarian preservation. Conclusion: Due to rarity of Müllerian adenosarcoma, the gynecologists and pathologists should be reminded about the possibility of the diagnosis in young patients too.
Uterine Müllerian adenosarcoma (MA) is typically a variant of endometrial stromal sarcoma with benign epithelial component which reported first in 1974 . Uterine MA is relatively rare and account less than 5% of uterine sarcoma which is only less than 3% of all uterine neoplasm Based on this rarity the FIGO classification had classified this group of uterine cancer in a different manner [2,3].
In general, the clinical behavior of uterine sarcomas is unfavorable but it supposed that the polypoid MA behave as a low grade tumor most of the time and the prognosis depends on the sarcomatous component growth rate [3-5]. The standard treatment in uterine sarcomas is total hysterectomy and bilateral salpingoophorectomy (BSO) [1,3]. While the safety of ovarian preservation in uterine limited leiomyosarcoma had been derived from population based database, due to small case series of adenosarcoma there is no consensus on oncologic outcome of this approach in reproductive age [6,7].
Here we decided to define the optimal management in Müllerian adenosarcoma with evaluating the oncologic outcome of similar FIGO subtype cases report and describe possibly the youngest case of uterine Müllerian adenosarcoma in the world.
A 9 year old previously healthy girl presented in November 2018 with chief complaint of vaginal bleeding started 2months before attending the hospital. The pubertal development was rejected because there was no sign of breast maturation or hair growing on the pubic and axillary area. There was no sign in favor of sexual abuse and the hymen was intact. In assessing the source of abnormal vaginal bleeding, hormonal function test and pelvic ultrasonography was requested. The FSH & LH was reported lower than normal and the elevated ESR was the lone finding; in about 102.
An enlarged uterus approximately 78*56*40 mm with thick heterogeneous endometrial thickness near 16 mm with multiple cystic area was shown on sonography. The patient subsequently underwent vaginoscopy and hysteroscopic examination. The vagina and cervix appeared normal but surprisingly a huge polypoid mass which occupied intra-uterine cavity was noted with no endometrial hyperplasia in regards (Figure 1-A). The mass had resected totally (Figure 1-B) and the histological examination of the mass revealed Müllerian adenosarcoma(Figure 1-C).The hysteroscopic sample was reviewed with another gyneco-pathologist and low grade polypoid Müllerian adenosarcoma with mild to moderate atypia, hemorrhagic necrosis and few mitosis was confirmed.
- Hysteroscopic view of endometrial mass (A) which was resected completely (B), The pathologic examination of the sample was suggestive of Adenosarcoma (C: 400× HPF).
A further investigation, such as chest radiography and Abdomino/pelvic magnetic resonance imaging (MRI) of the pelvis was done preoperatively. Unfortunately MRI of pelvis which had performed 2 weeks after hysteroscopic resection of the uterine mass again showed a polypoid nodule (3*2.5 cm) with no obvious myometrial invasion (Figure 2). There was no evidence of distant metastasis on other imaging.
- MRI shows a normal endometrium and myometrium with a mass originating in the corpus body (sagittal, coronal, axial view in T1 & T2 gradient slice; A, B, C).
After a thorough evaluation of the literature, the patient and her parents were discussed by the multidisciplinary team about the disease prognosis, The standard treatment and the other possible options. Complete staging laparotomy with ovarian preservation was the final decision. They declined the less aggressive approach due to non-documented safety based on limited prior case reports and the patient persistent symptom of abnormal vaginal bleeding. The procedure was performed uneventful in December 2018. On gross examination the uterus was larger than normal size and there was no signs of macroscopic involvement of other organs. Pathologic examination documented the polypoid low grade uterine MA in about 4*4*2 cm with near 2mm myometrial invasion; (Figure 3), the tumor was characterized by benign epithelial component and malignant sarcomatous stromal component with more than 2mitosis/HPF based on WHO criteria ; the other sample was free of malignancy (Figure 4). She was discharged well two days after surgery and is currently disease free after four months.
- The hysterectomy specimen (A), The histologic examination of the uterus showed a 8*5*3 cm corpus uteri (B) with a 4*4*2 cm polypoid mass with 2 mm invasion to myometrium (C).
- The microscopic examination confirmed the low grade mullerian adenosarcoma with spindle & papillary like structure with mild to moderate pleomorphism and nuclear atypia (3/10 HPF) (A, B: 40×, 100× HPF).
Low grade uterine Müllerian adenosarcoma (MA) as an biphasic neoplasm are expected to have good prognosis in the absence of myometrial deep invasion and sarcomatous over growth [1,3]. The commonest presenting symptom is vaginal bleeding . There is no proven etiology for MA; the lone possible risk factor based on previous study is prior pelvic radiation history, hormone or tamoxifen therapy [3,8] which was not found in our case at all.
Fortunately most of the time these neoplasm presented in early stage and the prognosis is based on sarcomatous stromal architecture . The absence of sarcomatous overgrowth, lymphovascular and deep myometrial invasion lead to 5-years survival of 100 % [1,5]. Adenofibroma as a benign polypoid lesion must be differentiated from the diagnosis of uterine MA with caution; whit marked atypia in mesenchymal cells and more than 1 mitotic figure per 10HPF . The other differential diagnoses are Müllerian mesenchymal malignant tumor and rhabdomyosarcoma .
The commonest age of MA presentation is postmenopausal patient, it seems that cervical MA is more common in younger age than uterine originated tumor . Based on previous case reports the youngest age for low grade uterine MA was 15 years . So there is limited data concerning the prognosis of fertility preservation in reproductive age patient [3,5]. The gold standard of treatment is surgical staging but there is some studies that showed no adverse oncologic outcome in regards of local excision or at least ovarian preservation in reproductive age [3,4,9]. Also there is no consensus on the rule of lymph node dissection (LND) in MA .
Ovarian preservation is based on the low probability of ovarian metastasis but to the best of our knowledge mesenchymal element of MA have Estrogen receptor expression so evidence on the safety of ovarian preservation is limited and there are some studies on the high possibility of recurrence by conservative surgery . Furthermore there is less than 5 cases with successful pregnancy after MA fertility preservation approach . It must emphasis on the long term follow-up for this patient due to the possibility of late recurrences even after 11 years [2,9]. Table 1 shows the youngest stage 1 Müllerian adenosarcoma (uterine& cervical) in literature.
|Reference||Location||Case (age)||Chief complaint||Primary treatment||Prognosis||Disease free period|
||Uterine||21||Menorrhagia & anemia||Local excision||Normal delivery and local recurrences||3 years|
||7 had local excision||1 Normal delivery,
||Cervix||10 y||Vaginal bleeding and cervical mass||TAH-BSO-staging||-|
||Uterine||15 y||With heterologous component||TAH-BSO-ChT-RT||-|
||Cervix||11- 25Y||With heterologous component||metrorrhagia||TAH(simple or radical) ± BSO-RT-ChT||1.5-3.5 years|
||Cervix||15||With heterologous component||metrorrhagia||Local excision||4 years|
||Cervix||23||With heterologous component||Local excision||Lost follow up!|
||Cervix||26||With heterologous component||Pelvic pain and bleeding||TAH||No follow-up|
TAH: total abdominal hysterectomy, RT: radiotherapy adjuvant, ChT: chemotherapy adjuvant, BSO: bilateral salpingoophorectomy.
Based on favorable pathologic criteria of present young case; lack of gross abnormalities via intraoperative inspection, absence of lymphovascular invasion and heterologous or sarcomatous overgrowth component; the poor prognostic characteristic of MA; BSO and LND was omitted from surgical planning [4,2]. Adjuvant therapy was not done for present patient because of absence of sarcomatous overgrowth or heterologous tissue and no residue of tumor after surgery .
Due to rarity of Müllerian adenosarcoma (MA), The gynecologists and pathologists should be reminded about the possibility of this diagnosis. The optimal management of MA is uncertain and the safety of either uterine or ovary preservation is still under exploration and so should be individualized, Long term surveillance is warranted to provide more information about these unusual neoplasm behavior and the significance of genetic and race on the age of MA presentation.
We would like to aknowledge Dr Zahrasadat Allameh for her review.
All authors declare that there is no conflict of interests regarding the publication of this article.