1. Interesting Case October 2012

2. 2 Interesting Case View the following cytology images and then think about your diagnosis. Slides 12 onwards provide the answer and follow up with corresponding histology

3. 3 Case submitted by Nick Dudding FIBMS, Biomedical Scientist, Sheffield, UK. Assistant Director. East Pennine Cytology Training Centre. Callum Bowler FIBMS. Advanced Biomedical Scientist. James Cook University Hospital. Middlesbrough. UK

4. 4 Case history 67 year old Female. SurePath™ LBC sample Modified Papanicoloau staining All photomicrographs are x400

5. 5 Figure 1.

6. 6 Figure 2.

7. 7 Figure 3.

8. 8 Figure 4.

9. 9 Figure 5.

10. 10 Figure 6.

11. 11 What do you think this represents ? Tissue repair Clear cell carcinoma Decidual change Squamous cell carcinoma Carcinosarcoma (mixed mullerian carcinoma)

12. 12 Answer It is E Carcinosarcoma or mixed mullerian carcinoma

13. 13 Cytomorphology Figure 1 shows one exfoliated ball of cells with slightly eccentric nuclear placement and prominent nucleoli. This would represent the carcinomatous elements. Figure 2 shows a single, but highly abnormal looking cell with multiple nucleoli contained within two enlarged nuclei. The remaining figures show a variety of enlarged or elongated cells, all with nucleoli, but also presenting with plentiful cyanophilic cytoplasm. These almost certainly represent the sarcomatous elements.

14. 14 Histopathology The uterus showed a high grade carcinosarcoma composed predominantly of sarcoma (Figures b – c) with rhabdomyoblasts and a minor component of serous adenocarcinoma (Figure a). The carcinosarcoma infiltrated a leiomyoma but not the myometrium and hence is probably best regarded as FIGO IB. Focal vascular invasion was seen. The cervix, omentum and right and left ovaries and tubes showed no significant histological abnormalities.

15. 15 Figure A.

16. 16 Figure B.

17. 17 Figure C.

18. 18 Disease Fact Sheet Malignant mixed Müllerian tumor, also known as malignant mixed mesodermal tumor, MMMT and carcinosarcoma, is a malignant neoplasm arising in the uterus. (Barwick KW, Livolski VA. Malignant mixed Müllerian tumours of the uterus. Am J Surg Pathol 1979, 3: 125 – 135). carcinosarcomamalignantneoplasm uterus Although MMMT can be picked up by cytology it generally presents in a postmenopausal patient being investigated for uterine bleeding, and found to have an enlarged uterus

19. 19 They are usually large, soft polypoid tumours occuring in the endometrium and myometrium. They are composed of a mixture of carcinomatous and sarcomatous elements. (Silverberg SG, Major FJ,Blessing JA, Fetter B, Askin FB, Liao sy, Miller A. Carcinosarcoma (malignant mixed mesodermal tumour) of the uterus. A gynecologic Oncology Group pathologic study of 203 cases. Int J Gynecol Pathol1990, 9: 647 – 651). The appearance of the sarcomatous elements divides the entity into two types, homologous and heterologous. In the homologous type, the sarcomatous component resembles tissues found in the uterus such as endometrial stromal sarcoma or leiomyosarcoma. In the heterologous type the sarcomatous element comprises tissues not found in the uterus, such as cartilage, skeletal muscle and/or bonehomologousendometrialcartilageskeletal musclebone

20. 20 MMMT account for between two and five percent of all tumors derived from the body of the uterus, and are found predominantly in postmenopausal women with an average age of 66 years. (Chuang JT, Van Velden DJJ, Graham JB Carcinosarcoma and mixed mesodermal tumour of the uterine corpus. Review of 49 cases. Obstet Gynecol 1970, 35: 769 -780). Risk factors are similar to those of adenocarcinomas and include obesity, exogenous estrogen therapies, and nulliparity. Less well- understood but potential risk factors include tamoxifen therapy and pelvic irradiation(1)postmenopausaladenocarcinomasobesity exogenousnulliparitytamoxifen

21. 21 Outcome of MMMTs is determined primarily by depth of invasion and stage. As with endometrial carcinomas, the prognosis is influenced by the grade and type of the adenocarcinoma, being poorest with serous differentiation. MMMTs are highly malignant; a stage I tumor has an expected five-year survival rate of 50%, while the overall five-year survival rate is less than 20%.[1][1]

22. 22 References Siegal GP; Chhieng DC (2005). Updates in diagnostic pathology. Berlin: Springer. pp. 12–14. ISBN 0-387- 25357-212–14ISBN0-387- 25357-2