|Year : 2016 | Volume
| Issue : 1 | Page : 105-108
Malignant mixed Mullerian tumor: A rare case report
Prasmit Amit Shah, Vikas Shyamraj Singh, Prakash M Roplekar, S Sudhamani, Surekha Bhalekar
Department of Pathology, School of Medicine, DY Patil University, Nerul, Navi Mumbai, Maharashtra, India
|Date of Web Publication||2-Jun-2016|
Prasmit Amit Shah
Department of Pathology, School of Medicine, DY Patil University, Nerul, Navi Mumbai - 400 706, Maharashtra
Source of Support: None, Conflict of Interest: None
Malignant mixed Mullerian tumor of the uterus, also called carcinosarcoma, is a very rare and aggressive type of malignancy with epithelial and mesenchymal components. Therefore, it is considered a metaplastic carcinoma. Predominantly these carcinomas are found in postmenopausal women presenting with uterine bleeding and uterine enlargement. We represent a case of a 60-year-old female with complaints of pain in the abdomen and bleeding per vaginum. Hysterectomy with bilateral salpingo-oophorectomy was performed and a diagnosis of malignant mixed Mullerian tumor of the uterus was made.
Keywords: Carcinosarcoma, malignant mixed Mullerian tumor, uterus
|How to cite this article:|
Shah PA, Singh VS, Roplekar PM, Sudhamani S, Bhalekar S. Malignant mixed Mullerian tumor: A rare case report. Arch Med Health Sci 2016;4:105-8
| Introduction|| |
Malignant mixed Mullerian tumors of the uterus are rare, high-grade neoplasms accounting for 2-5% of tumors derived from the body of the uterus. These tumors are most commonly seen in postmenopausal females. A higher incidence of these tumors is found in black women as compared to white. Synonyms include carcinosarcoma and metaplastic carcinoma. It is a biphasic neoplasm as it has both epithelial and mesenchymal components. It is divided into two types, homologous type and heterologous type: the homologous type, where the sarcomatous component is made up of endometrial stroma and fibrous or smooth muscle tissue, and the heterologous type, where the sarcomatous component is made up of cartilage, skeletal muscle, and/or bone. Here we report a rare case of malignant mixed Mullerian tumor of the uterus with homologous elements.
| Case Report|| |
A 60-year-old diabetic, postmenopausal woman appeared with history of pain in the abdomen since 5-6 months and bleeding per vaginum since 2 months.
Per speculum and per vaginal examination showed high-up, displaced cervix. Mild tenderness was noted. Bilateral fornices were free. Chest x-ray revealed only mild cardiomegaly. Ultrasonography showed a large anechoic cyst measuring 15 × 12.3 cm 2 in the right adnexa suggestive of right adnexal complex cyst. Contrast-enhanced computed tomography scan showed right ovarian cystic lesion with thick, irregularly enhancing walls, suggestive of neoplastic etiology. The alpha-fetoprotein level was 3.8 ng/mL (<5 ng/mL), the carcinoembryonic antigen level was 4 ng/mL (0-5 ng/mL), and the cancer antigen (CA)-125 level was 24.32 U/mL (0-35 U/mL). All of them were within normal limits.
Hysterectomy with bilateral salpingo-oophorectomy was advised. Preoperatively, the ovaries were normal and the uterus showed enlargement with cystic areas.
The gross specimen showed already-cut open uterus with separated cervix (uterus 12 × 11 × 8 cm 3, cervix 5 cm). The cut section of the uterus showed irregular, solid, multiple cystic and variegated areas distorting the endometrial cavity. Cysts showed straw-colored fluid. Yellowish, friable, and fleshy areas were also noted. Gross features of the bilateral adnexae and cervix were unremarkable. Lymph nodes were not received [Figure 1].
|Figure 1: Gross picture showing multiple cystic, solid and friable fleshy areas|
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Microscopy showed malignant tumor consisting of the admixture of epithelial and mesenchymal components. The epithelial component consisted of cells arranged in glandular pattern with round to oval pleomorphic vesicular nuclei, prominent nucleoli, and a moderate amount of eosinophilic cytoplasm [Figure 2]. The mesenchymal component consisted of sarcomatous spindle cells arranged diffusely. Individual tumor cells were elongated, with large pleomorphic vesicular nuclei, indistinct nucleoli, irregular nuclear membrane, and scant cytoplasm [Figure 3]. The tumor cells were invading the myometrium to about less than one-third of its thickness. No angiolymphatic invasion was noted. Extensive areas of necrosis, hemorrhage, and myxoid change were seen. The cervix showed features of chronic papillary endocervicitis. Bilateral ovaries, Fallopian tube More Detailss, and parametrium were unremarkable.
Based on these findings, the histopathological diagnosis given was malignant mixed Mullerian tumor (carcinosarcoma). Tumor-node-metastasis (TNM) staging was T1aNxMx Stage IA and the International Federation of Gynecology Obstetrics (FIGO) Stage IA. (T1a: Tumor limited to endometrium or invading less than half of myometrium. Nx: Regional lymph nodes cannot be assessed. Mx: Distant metastasis cannot be assessed.)
| Discussion|| |
Malignant uterine neoplasms containing both carcinomatous and sarcomatous components are classified by the World Health Organization (WHO) as carcinosarcoma. The first case was reported by Gerhardt in 1989, which was confirmed by Meyer with personal examination of the slides. Most of the patients present in the fifth decade of life but lowest age of presentation at 15-17 years has also been reported. In our case, the patient was a 60-year-old female.
The most common location for malignant mixed Mullerian tumor is the uterine corpus, but it can also be found in the cervix, ovaries, fallopian tubes, vagina, peritoneum, and extragenital sites. The usual location is the uterine body, particularly the posterior wall of the fundus, in concordance with our case.
Predisposing factors for malignant mixed Mullerian tumor are said to include nulliparity, diabetes, obesity, chronic estrogen stimulation, and history of pelvic radiation. Cases of tamoxifen-associated malignant mixed Mullerian tumor have also been reported. The classical symptom triad indicative of malignant mixed Mullerian tumor consists of pain, severe vaginal bleeding, and passing of necrotic tissue per vaginum. In this case, the patient presented with pain and postmenopausal bleeding.
Three main theories regarding the histogenesis of malignant mixed Mullerian tumor have been proposed: (A) The collision theory suggests that carcinoma and sarcoma are two independent neoplasms; (B) The combination theory suggests that both components are derived from a single stem cell that undergoes divergent differentiation; (C) The conversion theory suggests that the sarcomatous elements derive from the carcinoma during the evolution of the tumor. McCluggage suggested that the spindle cell component is a pseudosarcomatous stromal reaction in the presence of carcinoma.
Malignant mixed Mullerian tumors are further divided into two types, the homologous type and the heterologous type. The homologous tumor is one whose sarcomatous component is made up of endometrial stroma and fibrous or smooth muscle tissue. The heterologous type is one where the sarcomatous component is made up of tissue not found in the uterus, such as cartilage, skeletal muscle, and/or bone. The subtypes occur in equal frequency. The most common epithelial component is adenocarcinoma, but clear cell, mucinous, and papillary serous components can also occur. The most common mesodermal component is undifferentiated sarcoma in homologous tumors and rhabdomyosarcoma in heterologous tumors. In our case, endometrioid adenocarcinoma with homologous type was seen.
Grossly, the tumors present as large, soft, broad-based and polypoid masses involving the endometrium and myometrium with fleshy surfaces. Necrosis and hemorrhage are commonly noted, while extensive myometrial invasion can also be seen. Microscopy typically shows a mixture of carcinomatous and sarcomatous components. It may be homologous or heterologous. Angiolymphatic invasion is common and neuroectodermal differentiation is rarely seen.
Surgical management includes total abdominal hysterectomy with bilateral salpingo-oophorectomy, infracolicomentectomy, and bilateral pelvic and para-aortic lymphadenectomy. Multiple chemotherapeutic regimen have been studied, with response rates ranging 12-100%. Thus, up till now there is no consensus on optimal adjuvant chemotherapy.
Malignant mixed Mullerian tumors express epithelial markers such as epithelial membrane antigen and pancytokeratin as well as stromal lineage markers such as desmin and S-100. However, in our case the diagnosis was clear-cut on histopathological study.
Extension to pelvis, lymphatic and vascular permeation, distant lymph node, and blood-borne metastasis are common. In our case, there was no evidence of lymph node or distant metastasis. Recurrences are said to occur in over half of the patients after surgical and adjuvant therapy.
The average 5-year survival was 21%; 70-90% of tumor-related deaths occurred within 18 months of diagnosis. The most important prognostic factor is the extent of the tumor at the time of diagnosis. Some authors have described that malignant mixed Mullerian tumors with heterologous elements are worse than those with the homologous components.
In our case, total abdominal hysterectomy with bilateral salpingo-oophorectomy was done. Postoperatively, the patient did not receive any chemotherapy, and is being followed up for 3 months. Till now no recurrence has been noted.
| Conclusion|| |
Malignant mixed Mullerian tumors are extremely rare and aggressive tumors. The clinician should have a high index of suspicion for postmenopausal patients presenting with per vaginal bleeding and should consider the possibility of malignant mixed Mullerian tumor. The outcome depends on the stage of disease and the depth of invasion. Combination chemotherapy and radical surgery remains the mainstay of treatment.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]