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CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 997-999

Uterine malignant mixed müllerian tumor camouflaging as pelvic sarcoma


1 Department of Pathology, Kasturba Medical College, Manipal University, Manipal, Karnataka, India
2 Department of Pathology, Melaka Manipal Medical College, Manipal University, Manipal, Karnataka, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Roumina Hasan
179, B Type Quarters, KMC Quarters, Kasturba Medical College Campus, Manipal - 576 104, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.157325

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 > Abstract 

Malignant mixed Mllerian tumors (MMMTs) of the uterus are rare, aggressive tumors that present at an advanced stage and are associated with poor prognosis. They arise as a result of divergent carcinomatous and mesenchymal differentiation of tumor stem cells. Rarely one of the components may predominate contributing to diagnostic confusion. We present a rare case of uterine MMMT arising in endometrial adenocarcinoma, camouflaging as pelvic sarcoma with a major sarcomatous component. This case report highlights the importance of thorough tissue sampling and the role of immunohistochemistry (IHC) in arriving at an accurate diagnosis. This case also demonstrates the conversion theory of histogenesis of MMMTs.

Keywords: Carcinosarcoma, malignant mixed Müllerian tumor, uterus


How to cite this article:
Monappa V, Kudva R, Hasan R. Uterine malignant mixed müllerian tumor camouflaging as pelvic sarcoma. J Can Res Ther 2015;11:997-9

How to cite this URL:
Monappa V, Kudva R, Hasan R. Uterine malignant mixed müllerian tumor camouflaging as pelvic sarcoma. J Can Res Ther [serial online] 2015 [cited 2022 Dec 4];11:997-9. Available from: https://www.cancerjournal.net/text.asp?2015/11/4/997/157325


 > Introduction Top


Malignant mixed Müllerian tumor (MMMT) or carcinosarcomas are rare, aggressive, biphasic tumors of the female genital tract that exhibit both epithelial and mesenchymal components. [1] They occur in postmenopausal women both in genital and extragenital sites. [2],[3] In the uterus, they arise in the endometrium where the epithelial component usually predominates. [4]


 > Case report Top


A 57-year-old para-6 living-6, postmenopausal lady, known diabetic, presented with complaints of mass per abdomen and weight loss of 1 month's duration. Examination revealed a 20 weeks' size abdominopelvic mass. Laboratory investigations were normal except for elevated erythrocyte sedimentation rate (ESR: 101mm Hg) and CA125-(33.5U/l) levels. Ultrasonography (USG) showed a large abdomino-pelvic mass measuring 17 × 14 × 12cm probably arising from ovary with bilateral hydronephrosis.

At laparotomy, a large firm-to-hard polypoidal mass occupying the entire infraumbilical region, adherent to omentum, bowel wall, and the bladder was seen; uterus and bilateral ovaries appeared atrophic. No ascites or lymphadenopathy was noted. A peroperative diagnosis of malignant gastrointestinal stromal tumor (GIST) was considered. She underwent hysterectomy with bilateral salpingo-oophorectomy, infraumbilical omentectomy, and tumor debulking.

Pathological findings

The excision specimen together weighed 1,440g. Uterus with cervix measured 7 × 4× 2cm and revealed dilated endometrial cavity. Multiple grey-white nodules were seen in the parametrium, the largest measuring 6 × 3× 3cm. Separately sent pelvic tumor measuring 15 × 14 × 10 cm showed grey-white and yellow necrotic areas [Figure 1].
Figure 1: (a) Gross specimen showing uterus with dilated endometrial canal and bilateral parametria showing grey-white nodules; (b) Gross specimen of abdomino-pelvic mass with grey-white and yellow areas

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On histopathological examination, uterus showed features of atrophy [Figure 2]a]. The pelvic mass revealed a malignant tumor composed of pleomorphic spindle cells with enlarged nucleus, coarse chromatin, prominent nucleolus, and moderate eosinophilic cytoplasm arranged in a vague fascicular pattern with scattered bizarre cells, tumor giant cells, and a sprinkling of lymphocytes [Figure 2]b-d]. Initial impression was of a spindle cell sarcoma/malignant GIST.
Figure 2: (a) Atrophic endometrium, H and E, ×200. (b) Pleomorphic spindle cell sarcoma-like areas, H and E, ×200. (c and d) Pleomorphic spindle cells arranged in vague fascicular pattern with scattered bizarre cells, mitosis, and sprinkling of lymphocytes, H and E, ×400. H and E = Hematoxylin and eosin

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Immunohistochemistry (IHC) findings

Tumor cells were diffusely positive for vimentin, and negative for CD-117, CD-34, and desmin. Thus, IHC findings were suggestive of a sarcoma (? leiomyosarcoma). Malignant GIST was excluded by CD-117 and CD-34 negativity.

Multiple resections from the pelvic mass, parametrial nodules, and uterus were studied. Endometrium showed evidence of a high-grade endometrial adenocarcinoma; parametrial nodules showed lymphatic emboli and multiple tumor deposits surrounded by the sarcomatous spindle cell proliferation. On further IHC, cytokeratin (CK) was found to be positive in both the carcinomatous cells and spindle cell sarcomatous components [Figure 3].
Figure 3: (a) Focus of endometrial adenocarcinoma, H and E, ×200. (b) Parametrial nodules showing metastatic endometrial carcinoma surrounded by spindle cell sarcomatous stroma, H and E, ×200. (c) Parametrium showing lymphatic tumor emboli, H and E, ×200. (d) CK positive in carcinoma (left) and sarcomatous (right) areas. CK, ×200 (left), ×400 (right). CK = Cytokeratin

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A final diagnosis of uterine MMMT (homologous type) arising in a high-grade endometrial adenocarcinoma, International Federation of Gynecology and Obstetrics (FIGO) stage-IIIa with deposits in the parametrium and pelvic peritoneum was made.


 > Discussion Top


MMMTs comprise 2-5% of all malignant uterine tumors. [2],[4] The most common site of origin of genital MMMTs is the uterine corpus followed by vagina, cervix, ovary, and fallopian tubes. They commonly occur in elderly females presenting with vaginal bleeding, pain, weight loss, and abdominal mass. [4],[5]

The unusual finding in our case was the absence of vaginal bleeding. A localized aggressive endometrial tumor which rapidly metastasized and flourished at the metastatic site may be the probable explanation for this finding. This also explains why the lesion was not picked up in the initial tissue sections. The carcinomatous component is considered to be the 'driving force', while the sarcomatous component is a marker for 'aggressiveness'. [6]

The risk factors for MMMTs are similar to that of endometrial carcinoma and include diabetes, hypertension, obesity, advanced age, nulliparity, exogenous estrogen exposure, and long-term tamoxifen use. [5]

Histogenesis of MMMT is still not clear. The most popular theories proposed are (i) collision, (ii) combination, and (iii) conversion theories. [5] According to the conversion theory, the epithelial component transforms into mesenchymal component by metaplastic differentiation. [1],[5] Our case camouflaged as a pelvic sarcoma having possibly originated from metastatic endometrial adenocarcinoma with subsequent sarcomatous transformation. This case supports the conversion theory of histogenesis of MMMTs.

USG features are nonspecific and MMMT appears as heterogeneous uterine mass with internal vascularity. On computed tomography (CT), they appear as large heterogeneously enhancing broad-based uterine masses. Due to its multiplanar imaging and excellent soft tissue resolution, magnetic resonance imaging (MRI) has become the preferred imaging modality in evaluation of suspected uterine MMMTs. On MRI, they are isointense to normal endometrium and myometrium on T1-weighted sequences, with 33% showing some heterogeneity, while on T2-weighted images they show heterogeneous signals, being predominantly hyperintense to myometrium and either isointense or hypointense to endometrium. [7]

Grossly, uterine MMMTs are bulky, fleshy tumors compared to endometrial adenocarcinomas and present at an advanced stage with extrauterine extension, as was observed in this case.

Microscopically MMMTs are characteristically biphasic, composed of an admixture of variable proportions of malignant epithelial and stromal components. Based on the sarcomatous elements, they are further categorized into homologous and heterologous types. The homologous type is composed of the tissues native to the uterus (endometrial stromal sarcoma, leiomyosarcoma, and fibrosarcoma), while the heterologous type is composed of the sarcomatous components such as rhabdomyosarcoma, chondrosarcoma, osteosarcoma, liposarcoma, etc. The carcinomatous element in either type is mostly endometrioid type; nonetheless, serous, clear cell, or mucinous types can also be seen. [4],[5]

On immunohistochemistry, the epithelial component is positive for CK and epithelial membrane antigen (EMA) and variably positive for vimentin. The mesenchymal component also shows CK positivity in more than 50% of cases in addition to vimentin and variable SMA positivity and other stromal lineage markers as per their histological appearance. Other markers like CD-10(considered to be a marker for Müllerian derived mesenchymal cells), HER2/neu, and epidermal growth factor receptor (EGFR) also have a role. [8] In our case the microscopy and IHC pattern were consistent with homologous MMMT (carcinosarcoma). Further, CD117 negativity excluded the possibility of malignant GIST, which was the other radiological differential diagnosis.

Clinically, uterine MMMTs are aggressive tumors and usually are detected at advanced stage, carrying a poor prognosis. Pathologic stage at initial presentation is the most relevant prognostic factor. Other prognosticators being depth of myometrial invasion, lymphnode metastasis, positive peritoneal cytology, histologic nature of carcinomatous and sarcomatous components, lymphovascular invasion, expression of p53, and other cell cycle regulatory proteins. [4],[5],[6]

Surgery in the form of total abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, paraaortic lymph node dissection is the standard treatment option. As a part of staging procedure, peritoneal/pelvic washings and the omental biopsy are subjected to pathological examination. [5] Presence of epithelial elements in the tumor improves the success rates of adjuvant chemotherapy. Recently, ifosfamide and cisplatin have been identified as the most effective therapeutic agents in genital MMMTs. [9] Adjuvant pelvic radiotherapy after surgery has been found to delay the appearance of distant metastasis with decreased local recurrence, without any recognizable effect on long-term survival. [10]

In the present case, the patient underwent optimal tumor debulking followed by adjuvant chemotherapy with cisplatin and ifosfamide. Follow-up after 10 months revealed no signs of tumor recurrence. Subsequently, the patient was lost to follow-up.

To conclude, uterine MMMTs are uncommon, aggressive tumors; the preoperative diagnosis of which is always elusive. In the present case (which camouflaged as a sarcoma on initial histological sections), the accurate diagnosis was possible only on a careful and thorough sampling of the primary uterine tumor and metastatic parametrial nodule. Thus, our case highlights the importance of proper tissue sampling in order to pick up any minor epithelial component, and hence not to miss out the actual diagnosis.

 
 > References Top

1.
Kurshumliu F, Rung-Hansen H, Skovlund VR, Gashi-Luci L, Horn T. Primary malignant mixed müllerian tumor of the peritoneum a case report with review of the literature. World J Surg Oncol 2011;9:17.  Back to cited text no. 1
    
2.
Naniwadekar MR, Desai SR, Ranade RG, Kanetkar SR. Extra genital heterologous malignant mixed mullerian tumor of primary peritoneal origin. Indian J Pathol Microbiol 2009;52:88-90.  Back to cited text no. 2
[PUBMED]  Medknow Journal  
3.
Ko ML, Jeng CJ, Huang SH, Shen J, Tzeng CR, Chen SC. Primary peritoneal carcinosarcoma (malignant mixed mullerian tumor): Report of a case with five-year disease free survival after surgery and chemoradiation and a review of literature. Acta Oncol 2005;44:756-60.  Back to cited text no. 3
    
4.
Ho SP, Ho TH. Malignant mixed Mullerian tumours of the uterus-a ten-year experience. Singapore Med J 2002;43:452-6.  Back to cited text no. 4
    
5.
Kanthan R, Senger JL. uterine carcinosarcomas (malignant mixed müllerian tumours): A review with special emphasis on the controversies in management. Obstet Gynecol Int 2011;2011:470795.  Back to cited text no. 5
    
6.
Gonzalez Bosquet J, Terstriep SA, Cliby WA, Brown-Jones M, Kaur JS, Podratz KC, et al. The impact of multi-modal therapy on survival for uterine carcinosarcomas. Gynecol Oncol 2010;116:419-23.  Back to cited text no. 6
    
7.
Bharwani N, Newland A, Tunariu N, Babar S, Sahdev A, Rockall AG, et al. MRI appearances of uterine malignant mixed müllerian tumors. AJR Am J Roentgenol 2010;195:1268-75.  Back to cited text no. 7
    
8.
Costa MJ, Walls J. Epidermal growth factor receptor and c-erbB-2 oncoprotein expression in female genital tract carcinosarcomas (Malignant mixed müllerian tumors): Clinicopathologic study of 82 cases. Cancer 1996;77:533-42.  Back to cited text no. 8
    
9.
Thigpen JT, Blessing JA, Beecham J, Homesley H, Yordan E. Phase II trial of cisplatin as first-line chemotherapy in patients with advanced or recurrent uterine sarcomas: A Gynecologic Oncology Group study. J Clin Oncol 1991;9:1962-6.  Back to cited text no. 9
    
10.
Callister M, Ramondetta LM, Jhingran A, Burke TW, Eifel PJ. Malignant mixed Müllerian tumors of the uterus: Analysis of patterns of failure, prognostic factors, and treatment outcome. Int J Radiat Oncol Biol Phys 2004;58:786-96.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]



 

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