|Year : 2011 | Volume
| Issue : 1 | Page : 88-91
Malignant mixed Mullerian tumor of broad ligament with synchronous ovarian and endometrial carcinoma: A rare association
Prerna Arora1, Seema Rao1, Nita Khurana1, Divya Talwar2, Renu Tanwar2
1 Department of Pathology, Maulana Azad Medical College, New Delhi -110 002, India
2 Department of Obstetrics and Gynecology, Maulana Azad Medical College, New Delhi -110 002, India
|Date of Web Publication||5-May-2011|
Department of Pathology, Maulana Azad Medical College, New Delhi 110 002
Extragenital malignant mixed Mullerian tumor (MMMT) is a rare tumor in females, and it is even more rarely encountered among the multiple genital malignancies. There are some reports of extragenital MMMTs associated with synchronous or metachronous gynecologic tumors of Mullerian duct origin. We recently encountered an MMMT of broad ligament which is associated with papillary serous cystadenocarcinoma of the ovary and endometrioid adenocarcinoma arising in atypical polypoid adenomyoma endometrium in a 76-year-old woman. This case is presented for its rarity and unique presentation. To our knowledge, ours is the first reported case of this unique combination of multiple synchronous genital malignancies.
Keywords: Broad ligament malignant mixed Mullerian tumor, extragenital malignant mixed Mullerian tumor, synchronous tumors
|How to cite this article:|
Arora P, Rao S, Khurana N, Talwar D, Tanwar R. Malignant mixed Mullerian tumor of broad ligament with synchronous ovarian and endometrial carcinoma: A rare association. J Can Res Ther 2011;7:88-91
|How to cite this URL:|
Arora P, Rao S, Khurana N, Talwar D, Tanwar R. Malignant mixed Mullerian tumor of broad ligament with synchronous ovarian and endometrial carcinoma: A rare association. J Can Res Ther [serial online] 2011 [cited 2014 Sep 18];7:88-91. Available from: http://www.cancerjournal.net/text.asp?2011/7/1/88/80460
| > Introduction|| |
Malignant mixed Mullerian tumor (MMMT) is a biphasic neoplasm of female genital tract.  Broad ligament cancers of Mullerian origin occur in women of reproductive age, most of whom are infertile or nulliparous.  Extragenital MMMTs can occur in association with metachronous or synchronous gynecologic carcinomas which suggest that multifocal tumorigenesis within the tissues of same embryologic origin can have a role in the pathogenesis.  The presence of a multiple gynecologic tumor involving uterus, ovary and broad ligament synchronously is a rarity.We report a case of MMMT of broad ligament in association with endometriod adenocarcinoma arising in atypical polypoid adenomyoma along with papillary serous carcinoma of the ovary, which is the first case of its kind, to the best of our knowledge.
| > Case Report|| |
A 76-year-old (G 4 P 4 L 4 ) postmenopausal woman presented with complaints of pain and lump in lower abdomen. There was no past history of previous surgery for any other tumors, previous irradiation, chemotherapy, exogenous estrogen, or tamoxifen use.
On abdominal examination, a large hard mass was palpated in lower abdomen. Biochemical findings showed elevated CA-125 levels to 211 U/ml. Ultrasound examination revealed a large solid cystic mass in lower abdomen and pelvis, posterior to bladder with anteriorly displaced uterus. Contrast enhanced computed tomography (CECT) of the pelvis revealed a large heterogeneous solid-cystic abdominopelvic mass which measured 13 × 9 × 6 cm 3 and extended behind the uterus into rectouterine pouch, suggesting adenocarcinoma of the ovary. Patient underwent exploratory laparotomy. Preoperatively, there was no focus of extragenital endometriosis and large solid-cystic mass which was densely adhered to the fundus of the uterus, right ovary and bladder was visualized in the broad ligament. There were extensive adhesions and the tissues were very friable, hence, subtotal hysterectomy was performed along with bilateral salpingoopherectomy, infracolic omentectomy, appendectomy, pelvic lymphadenectomy and was sent for histopathological examination.
Gross: The specimen consisted of uterus with attached left sided adnexa. A 14 × 10 × 5 cm 3 mass was attached to posterior uterine wall and grew in broad ligament, which was bosselated and predominantly solid with focal cystic areas intermingling with areas of hemorrhage [Figure 1]a. Endometrial cavity revealed a polypoidal mass measuring 3 × 1.2 × 1 cm 3 , which was solid grey white with small cystic areas [Figure 1]b. Left sided adenexa was unremarkable. The right-sided ovarian cyst which was sent separately measured 8 × 5 × 2 cm 3 in size. The cut section of this mass consisted of solid and cystic components with friable papillary projections [Figure 1]c. Right tube was unremarkable. Specimen of appendix showed thickening of the wall. Ten pelvic lymph nodes received were submitted for microscopic examination.
|Figure 1: (a) Mass in broad ligament with uterus and left-sided adenexa, showing predominantly solid areas with few cystic areas (single arrow), and areas of hemorrhage (block arrow), (b) Endometrial cavity showing polypoidal mass (arrow head), (c) Right ovarian cyst showing papillary projections (arrow head)|
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Microscopy: Broad ligament mass showed a malignant tumor composed of mixture of carcinomatous and sarcomatous elements [Figure 2]a. The malignant epithelial component was formed of papillary serous carcinoma, while the stromal component was heterologous with rhabdomyosarcomatous [Figure 2]b, cartilaginous [Figure 2]c, and osseous differentiation [Figure 2]d along with large areas of necrosis. The findings were confirmed by relevant immunohistochemical markers (IHC) by avidin-biotin-complex (ABC) method using antibodies; vimentin (Vim), epithelial membrane antigen (EMA), and myoglobin (Myo) [Figure 3]a-c. Endometrial polypoidal mass showed features of atypical polypoidal adenomyoma with a focus of moderately differentiated endometrioid adenocarcinoma minimally invading the myometrium [Figure 4]a. The right-sided ovarian mass revealed moderately differentiated papillary serous cystadenocarcinoma [Figure 4]b which infiltrated the capsule. Omentum, appendicular wall as well as periappendicular tissue showed deposits of papillary serous adenocarcinoma. All pelvic lymph nodes showed reactive change.
|Figure 2: (a) Mixture of carcinomatous and sarcomatous components in broad ligament mass (H&E, ×100),(b) Stromal component showing rhabdomyosarcomatous differentiation (H&E, ×100), (c) Stromal component showing cartilaginous differentiation (H&E, ×400),(d) Stromal component showing osseous differentiation (H&E, ×200)|
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|Figure 3: (a) Epithelial component showing positivity with epithelial membrane antigen (EMA), (b) Stromal component showing positivity with vimentin (Vim), (c) Rhabdomyosarcomatous differentiation in stromal areas showing positivity with myoglobin (myo)|
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|Figure 4: (a) Atypical polypoidal adenomyoma with a focus of moderately differentiated endometriod adenocarcinoma (arrow) (H&E, ×200), (b) Right side ovarian cyst showing papillary projections (H&E, ×200)|
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| > Discussion|| |
MMMTs are highly aggressive biphasic neoplasms most commonly arising from the endometrium, less frequently, in the ovaries, fallopian tubes, cervix and vagina.  The risk factors for MMMT include obesity, nulliparity, exogenous estrogen and long-term tamoxifen use.  Uterine endometrial carcinoma is also known to be associated with excess estrogen exposure, which hypothesizes that the pathogenesis of these two histological types of tumors may be similar.
Extragenital MMMTs are rare; usually occur in older women and are most commonly located in the pelvic peritoneum, followed by serosal surface of colon, retroperitoneum, abdominal peritoneum, and omentum.  These tumors are known to be associated with previous radiation, chemotherapy, extragenital endometriosis and have been described in association with synchronous or metachronous colonic cancer and gynecologic tumors.  The presence of synchronous / metachronous genital carcinomas suggests multifocal tumorigenesis from the tissue of the same embryologic origin. Broad ligament MMMT are very unusual. The patient in the present case was postmenopausal and had extragenital heterologous MMMT in broad ligament associated with synchronous endometrial carcinoma and ovarian malignancy.
MMMTs are classified into homologous type and heterologous type based on the mesenchymal component; however, no apparent relationship exists between the outcome and the presence or absence of a heterologous component in extragenital MMMT. 
According to Clement et al. atypical polypoid adenomyoma (APA) is considered as a type of uterine MMMT.  APA is a rare entity which presents as an endometrial polyp in premenopausal women and follows a benign course with low malignant potential. Few case reports in literature describes APA developing into endometrial adenocarcinoma, especially in postmenopausal women.  The patient n the present case was postmenopausal who had APA with a focus of well-differentiated endometriod adenocarcinoma minimally invading the myometrium. In addition, there was presence of synchronous papillary serous cystadenocarcinoma ovary.
Most common synchronous cancers involve endometrium and ovary. Synchronous genital malignancies are considered to be metastatic lesions arising from either organ. However, such simultaneous involvement of both organs may occasionally represent independent primaries; a fact often overlooked. We report a case with triple primary cancer occurring in ovary, endometrium and broad ligament with different histology. Extensive literature search, does not describe occurrence of such a rare association, as seen in our case. This coexistence may be incidental, but it may also imply a possible linkage between these tumors. Several theories have been proposed regarding histogenesis of MMMT, the most important of which is the "collision" (a mixture of two distinct neoplastic populations, a carcinoma and sarcoma), the "combination" (both populations originate from a common stem cell precursor), and "conversion" hypothesis (a metaplastic transformation of one neoplastic cell type into another).  The phenotypical diversity of extragenital MMMTs suggests origin from progenitor cells within the mesothelium, with multidirectional differentiation. However, the "conversion hypothesis," supports the occurrence of metachronous/ synchronous ovarian and uterine carcinoma. According to Singh et al. owing to the common occurrence of mixed tumors in female genital tract, these need careful evaluation, as tumors of apparently different histologies may still represent metastases with a minor component being missed at the primary site. 
In summary, we report an extremely rare case of triple synchronous genital and extragenital malignancies with tumor deposits of metastatic papillary adenocarcinoma in the Appendix. The finding that MMMT had similar epithelial component as that of serous papillary adenocarcinoma ovary lends support to the possibility of conversion hypothesis. Metastasis with epithelial-to-mesenchymal transformation seems a defendable explanation in our case and much more likely than the co-occurrence of independent malignant collision tumors.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]