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Hysteroscopic Resection of Uterine Leiomyosarcoma: A Case Report and Literature Review
Hysteroscopic Resection of Uterine Leiomyosarcoma: A Case Report and Literature Review Luigi Nappi, MD, Attilio Di Spiezio Sardo, MD*, Ugo Indraccolo, MD, and Stefano Bettocchi, MD From the Department of Surgical Sciences, Unit of Obstetrics and Gynaecology, University of Foggia, Italy (Drs. Nappi, Indraccolo, and Bettocchi) and Department of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples “Federico II,” Italy (Dr. Di Spiezio Sardo).
ABSTRACT This case reports the hysteroscopic resection of an unsuspected leiomyosarcoma of the uterus in a 41-year-old multiparous woman with recurrent episodes of abnormal uterine bleeding. The available literature on this topic was reviewed and the potential implications of extrauterine spread after this procedure are discussed. Journal of Minimally Invasive Gynecology (2008) 15, 380 –383 © 2008 AAGL. All rights reserved.
Uterine sarcomas are uncommon tumors that account for less than 3% of all female genital tract malignancies and 3% to 5% of malignant tumors of the uterus [1,2]. These neoplasms carry a poor prognosis with an overall survival of less than 50% at 2 years, even when diagnosed at an early stage [3,4]. Unlike endometrial cancer, uterine sarcomas are not associated with well-known risk factors and also may affect young women. Abnormal uterine bleeding is the most common symptom of uterine sarcomas and diagnosis is often made incidentally at the time of myomectomy or hysterectomy for presumed benign condition [5,6]. In the last decades hysteroscopic transcervical resection of endometrial polyps and submucous myomas became a common treatment option as the occurrence of a malignant lesion not otherwise diagnosed is rare. A patient underwent hysteroscopic resection of an unsuspected leiomyosarcoma of the uterus. The available literature concerning this rare topic was reviewed and the potential implications of extrauterine spread after this procedure are discussed.
The authors have no commercial, proprietary, or financial interest in the products or companies described in this article. Corresponding author: Attilio Di Spiezio Sardo, MD, Unit of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples “Federico II,” Via Pansini 5, Naples, Italy. E-mail: [email protected] Submitted September 25, 2007. Accepted for publication February 8, 2008. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ -see front matter © 2008 AAGL. All rights reserved. doi:10.1016/j.jmig.2008.02.003
Case Report A 41-year-old woman, gravida 2 para 2, was referred to our unit for recurrent abnormal uterine bleeding. The patient provided an informed consent to perform the study. The study was eventually approved by our institutional review board. Her personal history was negative for genital neoplasia and medical diseases. Physical and bimanual pelvic examinations revealed normal findings. Transvaginal sonography showed an anteverted uterus with a greater than normal volume and the presence of multiple myomas, with the biggest being a submucous lesion of 41 ⫻ 32 mm. A vaginoscopic hysteroscopy was performed by means of a 4-mm continuous-flow operative office hysteroscope with a 2.9-mm rod lens (Bettocchi size 4; Karl Storz, Tuttlingen, Germany). A normal-appearing G1 myoma of nearly 4.5 cm was detected on the anterior wall of the uterus. Taking into account the young age of the patient and her desire for future fertility, a hysteroscopic myomectomy preceded by a 3-month preoperative treatment with gonadotropin-releasing hormone-analog (GnRH) was scheduled. During the treatment with GnRH agonist, the patient continued to experience abnormal uterine bleeding although repeated transvaginal sonography did not reveal any change in myoma size. Hysteroscopic resection of the myoma was performed by means of a continuous flow 9-mm resectoscope and sorbitol (5%) was used for distention and irrigation of the uterine cavity. A complete resection of the intracavitary portion of the myoma with no ablation of the endometrium was performed. A meticulous fluid-balance control was maintained.
Nappi et al.
Hysteroscopy and Uterine Sarcomas
No intraoperative or postoperative complications occurred. All the resected tissue chips were microscopically examined by a pathologist who posed the diagnosis of leiomyosarcoma. After such diagnosis, the patient was extensively staged by ultrasound pelvic examination and total-body computed tomography scan, which revealed only the presence of a residual intrauterine mass of 1.9 ⫻ 1.9 cm. Carcino-embrionary antigen 125 dosage was 49 IU/mL (normal values: 0 –35 U/mL). The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy, and peritoneal washings. Pathologic examination revealed the presence of a 2.2-mm, intramural uterine tumor. The borders between tumor growth and the surrounding myometrium were disease free (1.5 cm). Microscopic examination revealed spindle-shaped cells with cytologic atypia and multiple nucleoli. Diagnosis of uterine leiomyosarcoma was confirmed and mitotic count was 20 ⫻ 10 high power field. Lymphatic and vascular invasion were found. Peritoneal cytology was negative and no sites of disease were detected. The patient received 6 courses of adjuvant chemotherapy with doxorubicin (30 mg/m2), ifosfamide (3 g/m2), plus mesna on days 1, 2, and 3, repeated every 21 days. At 3 years of follow-up the patient has no sign of recurrent disease.
Discussion Mesenchymal uterine tumors are rare malignancies, occurring in only 17 per million women annually, thus representing fewer than 5% of all uterine malignancies [7]. The 3 most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma, and malignant mixed mullerian tumor [8]. Less than 1% of women believed to have a leiomyoma actually have a sarcoma at hysterectomy. The incidence of leiomyosarcoma arising on a leiomyoma is less than 1% [9]. Other types of tumor including angiosarcomas, rhabdomyosarcomas, and malignant fibrous histiocytomas are rarer and not specific to the uterine site [10]. In general, 2 distinct tissue components give rise to malignant mesenchymal tumors; myometrial muscle (smooth) is the tissue component for leiomyosarcoma and endometrial stromal sarcoma, whereas both muscle and stromal tissue types give rise to malignant mixed mullerian tumor, even called carcinosarcoma [7,9]. In addition, uterine sarcomas are classified into homologous (consisting of cells native to the uterus) or heterologous (cells usually not found in the uterus). A review of 141 patients with uterine sarcoma [11] reported a histologic diagnosis of leiomyosarcoma to predict the worse prognosis of uterine sarcomas, followed by mixed mullerian tumors and endometrial stromal sarcoma. An earlier exposure to pelvic radiotherapy is the only known causal factor for uterine sarcomas. The most common symptoms are vaginal bleeding and pain [9].
381
The diagnosis of such tumors is often made postoperatively for a presumed benign condition. A vaginal digital and speculum examination should be performed, together with a smear. A transvaginal ultrasound examination, hysteroscopy, and endometrial biopsy are usually performed as part of the general investigative procedure but are seldom useful in the diagnosis of leiomyosarcoma. Blind endometrial biopsy misses the diagnosis of leiomyosarcoma in 40% to 80% and endometrial stromal sarcoma in 20% [9]. Hysteroscopic reports of uterine sarcomatous tumors are not frequent [12]: two studies [13,14] reported 3 cases of mixed mullerian tumors stating that it is possible to misdiagnose sarcomatous tissue for a benign endometrial polyp or submucous myoma at hysteroscopic view. Two studies [15,16] described 3 cases of unsuspected leiomyosarcoma in 2 series of hysteroscopic resections for presumed uterine submucous myomas, asserting that hysteroscopic diagnosis of uterine sarcomas might be very difficult. Several authors [17–22] have reported some cases of endometrial stromal sarcoma diagnosed after hysteroscopic endometrial resection. Particularly, 1 study [17] reported the case of a young woman (26 years old) who underwent operative hysteroscopy to remove a polypoid lesion, responsible for recurrent abnormal bleeding. This lesion was 4-cm long with no atypical features with the exception of dilated vessels. In that patient, 2 negative dilatation and curettages were performed before the hysteroscopy, revealing the poor diagnostic accuracy of blind dilatation and curettage. Another report [22] described the case of a 33-year-old woman who had a benign submucous myoma diagnosed at diagnostic hysteroscopy and underwent a resectoscopic surgery after 3 months of treatment with GnRH agonist, which did not reduce the size of the lesion. Recently, 6 cases of malignant mesenchymal tumors diagnosed after pathologic analysis of specimens obtained at hysteroscopy were reported, suggesting that at least a target biopsy should be always performed in all symptomatic intrauterine lesions, even if their appearance suggests a typical submucosal myoma or polyp [23]. Taken together, these reports suggest that there are no specific hysteroscopic characteristics to identify uterine sarcomas before tissue being sent for pathological review [6,13–23]. A focal area of malignancy might be missed by targeteye biopsy as it is impossible to examine the entire lesion, mostly in case of large ones. Furthermore, the biopsy of myometrial lesions by means of conventional instruments (i.e., grasping forceps, scissors) might pose notable difficulties because of the high consistency of these lesions. Because of that, the removal of the whole myomatous lesion represents the only method to definitively rule out the presence of sarcomatous tissue. Resectoscopic slicing should be preferred to laser or electrosurgical vaporization as it has the great advantage of offering the pathologist the possibility to analyze the tumor entirely. The main disadvantage of vaporizing electrodes is the lack of tissue sample
382
Journal of Minimally Invasive Gynecology, Vol 15, No 3, May/June 2008
for pathology. When vaporizing electrodes are used, it is mandatory that no myoma be vaporized in its entirety but that substantial portions are retrieved for microscopic examination [24,25]. In our patient, because of the notable size of the lesion and the severity of her symptoms, the complete resectoscopic removal of the lesion was scheduled right after the outpatient diagnostic hysteroscopy. The endoscopic approach to uterine lesions hiding a sarcoma may pose other practical issues besides the need for a histologic specimen to reach a definitive diagnosis. The use of preoperative GnRh agonist before the removal of a normal-appearing submucous myoma [26,27] may delay the final tissue diagnosis [28], as it occurred in our patient. Furthermore, we cannot exclude that retrograde dissemination of disease through the fallopian tubes may occur during diagnostic or operative hysteroscopy, thus changing the prognosis. All studies available in literature on this issue regard to endometrial adenocarcinoma [29 –37]. They have substantially shown that although there might be an increased risk of peritoneal contamination by cancer cells after diagnostic hysteroscopy, there is no evidence that these patients have a worse prognosis than those who have undergone other diagnostic procedures (i.e., dilatation and curettage). Furthermore the cancer cells found in the peritoneal cavity usually disappear within a short period of time and seem to have a low viability potential [37]. Currently, no studies evaluating either the risk of peritoneal spread of malignant mesenchymal cells at diagnostic hysteroscopy or the viability and capability of such disseminated cells to implant are available in the international literature. Such studies are mandatory to address these issues. Meanwhile, taking into account the aggressive nature of mesenchymal tumors (with an early pattern of local recurrence and widespread dissemination), a particularly careful attitude to avoid the spread of mesenchymal cells during hysteroscopy should be recommended. Furthermore, it should be emphasized that the higher intrauterine pressures (around 100 –120 mm Hg) conventionally reached during resectoscopic surgery potentially carries a major risk of peritoneal dissemination. An electronically controlled system for irrigation and aspiration (Endomat; Karl Storz) can be helpful to maintain a correct low intrauterine pressure (⬍70 mm Hg) in case of suspicion of neoplastic lesion avoiding or at least reducing the spread of malignant cells through the fallopian tubes. A more serious concern might be represented by the dissemination of malignant cells into deeper myometrial tissue. Indeed, whether intravascular or lymphatic penetration of malignant cells might be increased by endoscopic endomyometrial resection is still uncertain. However, some authors suggest that the intense radiofrequency energy effect on tumor cells and surrounding tissue (including the microvasculature) would tend to fur-
ther reduce the viability of local malignant cells and their potential for intravascular dissemination and subsequent metastatic invasion [20]. In our patient, neither metastasis nor positive peritoneal washing were found. Conclusions According to our experience and the available literature reviewed, the removal of the whole myomatosus lesion, even if its appearance suggests a typical submucosal myoma, represents the only method to definitively rule out the presence of sarcomatous tissue. A preoperative target biopsy under hysteroscopic view could be useful, but it could miss focal areas of malignancy. Whether a uterine sarcoma is diagnosed, total abdominal hysterectomy and bilateral salpingo-oophorectomy are considered the standard therapy [4]; the role of conservative, fertility-sparing surgery in young women still needs to be ascertained as a limited number of anecdotal cases were reported so far in the literature [38 – 41].
References 1. Olah KS, Gree H, Blunt S, et al. Retrospective analysis of 318 cases of uterine sarcoma. Eur J Cancer. 1991;27:1095–1099. 2. Marchese MJ, Liskow AS, Crum CP, McCaffrey RM, Frick HC II. Uterine sarcomas: a clinicopathologic study, 1965–1981. Gynecol Oncol. 1984;18:299 –312. 3. Zaloudek C, Norris HJ. Mesenchymal tumors of the uterus. In: Kurman RJ (ed). Blausteins Pathology of Female Genital Tract. New York: Springer-Verlag, 1994, p. 478 –528. 4. Berchhuck A, Rubin SC, Hoskins WJ, Saigo PE, Pierce VK, Lewis JL Jr. Treatment of uterine leiomyosarcoma. Obstet Gynecol. 1988;71: 845– 850. 5. Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma. Obstet Gynecol. 1994;83:414 – 418. 6. Schwartz PE, Kelly MG. Malignant transformation of myomas: myth or reality? Obstet Gynecol Clin North Am. 2006;33:183–198. 7. Denschlag D, Masoud I, Stanimir G, Gilbert L. Prognostic factors and outcome in women with uterine sarcoma. Eur J Surg Oncol. 2007; 33:91–95. 8. Braly PS. Disease of the uterus. In: Scott JR, Di Saia PJ, Hammond CB, Spellacy WN (eds). Danforth’s Obstetrics and Gynecology. Philadelphia: Lippincott Williams and Wilkins; 1999, p. 837– 857. 9. Papadopoulos AJ, Kenney A. Solid malignant uterine tumors. Curr Obstet Gynecol. 2001;11:296 –301. 10. Benoit L, Arnould L, Cheynel N, et al. The role of surgery and treatment trends in uterine sarcoma. Eur J Surg Oncol. 2005;31:434 – 442. 11. Livi L, Paiar F, Shah N, et al. Uterine sarcoma: twenty-seven years of experience. Int J Radiat Oncol Biol Phys. 2003;57:1366 –1373. 12. Takamizawa S, Minakami H, Usui R, et al. Risk of complications and uterine malignancies in women undergoing hysterectomy for presumed benign leiomyomas. Gynecol Obstet Invest. 1999;48:193–196. 13. Suzuki A, Tahara H, Okamura H. Hysteroscopic diagnosis of malignant mixed mullerian tumor of the corpus uteri. Gynecol Oncol. 1983;15:350 –356. 14. Benifla JL, Filippini F, Darai E, et al. Operative hysteroscopy procedure on an unsuspected mixed mullerian tumor of the uterus. Gynecol Endosc. 1997;6:147–149.
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15. Corson S, Brooks P. Resectoscopic myomectomy. Fertil Steril. 1991; 55:1041–1044. 16. Emanuel MH, Wamsteker K, Eastham WN, et al. Leiomyosarcoma or cellular leiomyoma diagnosed after hysteroscopical transcervical resection of presumed leiomyoma. Gynecol Endosc. 1992;1:161–164. 17. Marabini A, Gubbini G, De Jaco P, et al. A case of unsuspected endometrial stromal sarcoma removed by operative hysteroscopy. Gynecol Oncol. 1995;59:409 – 411. 18. Hansen UD, Lund CO. Finding of an unsuspected endometrial stromal sarcoma by hysteroscopic endometrial resection. Gynecol Endosc. 1998;7:279 –280. 19. Sinervo K, Martyn P. Endometrial stromal sarcoma diagnosed after hysteroscopic endometrial resection. J Am Assoc Gynecol Laparosc. 2000;7:257–259. 20. Vilos GA, Harding PG, Sugimoto AK, et al. Hysteroscopic endometrial resection of three uterine sarcomas. J Am Assoc Gynecol Laparosc. 2001;8:545–551. 21. Amant F, Moerman P, Cadron I, et al. The diagnostic problem of endometrial stromal sarcoma: report of six cases. Gynecol Oncol. 2003;90:37– 43. 22. Flam F, Radestad A. Endometrial stroma sarcoma diagnosed by operative hysteroscopy. Hum Reprod. 1996;11:2797–2798 23. Shveiky D, Revel A, Rojansky N, Benshushan A, Shushan A. Diagnosis of malignant mesenchymal uterine tumors by hysteroscopic excisional biopsy. J Minim Invasive Gynecol. 2005;12:29 –33. 24. Glasser MH. Endometrial ablation and hysteroscopic myomectomy by electrosurgical vaporization. J Am Assoc Gynecol Laparosc. 1997; 4:369 –374. 25. Isaacson K. Hysteroscopic myomectomy: fertility-preserving yet underutilized. OBG Manage. 2003;15:69 – 83. 26. Friedman AJ, Lobel SM, Rein MS, Barbieri RL. Efficacy and safety considerations in women with uterine leiomyomas treated with gonadotropin-releasing hormone agonist: the estrogen threshold hypothesis. Am J Obstet Gynecol. 1990;163:1114 –1119. 27. Strovall TG, Ling FW, Henry LC, Woodruff MR. A randomized trial evaluating leuprolide acetate before hysterectomy as treatment for leiomyomas. Am J Obstet Gynecol. 1991;164:1420 –1425.
383 28. Milman D, Zalel Y, Biran H, et al. Unsuspected uterine leiomyosarcoma discovered during treatment with a gonadotropin-releasing hormone analogue: a case report and literature review. Eur J Obstet Gynecol Reprod Biol. 1998;76:237–240. 29. Romano S, Chimoni Y, Muralee D, et al. Retrograde seeding of endometrial cancer during hysteroscopy. Gynecol Oncol. 1992;44: 116 –118. 30. Schmitz MJ, Nahhas WA. Hysteroscopy may transport malignant cells into the peritoneal cavity. Eur J Gynecol Oncol. 1994;15:121– 124. 31. Egarter C, Krestan C, Kurz C. Abdominal dissemination of malignant cells with hysteroscopy. Gynecol Oncol. 1996;63:143–144. 32. Zerbe MJ, Zhang J, Bristow RE, et al. Retrograde seeding of malignant cells during hysteroscopy in presumed early endometrial cancer. Gynecol Oncol. 2000;79:55–58. 33. Obermair A, Geramou M, Gucer F, et al. Does hysteroscopy facilitate tumor cell dissemination? Cancer. 2000;88:139 –143. 34. Gu M, Shi W, Huang J, et al. Association between initial diagnostic procedure and hysteroscopy and abnormal peritoneal washing in patients with endometrial carcinoma. Cancer. 2000;96:143–147. 35. Kudela M, Pilka R. Is there a real risk in patients with endometrial carcinoma undergoing diagnostic hysteroscopy? Eur J Gynecol Oncol. 2001;22:342–344. 36. Kudela M, Pilka R Dzvincuk P, et al. Risks in hysteroscopy in patients with endometrial carcinoma a prospective clinical study. Ceska Gynekol. 2002;67:74 –78. 37. Selvaggi L, Cormio G, Ceci O, et al. Hysteroscopy does not increase the risk of microscopic extrauterine spread in endometrial carcinoma. Int J Gynecol Cancer 2003;13:223–227. 38. Davis AM. Myomectomy: surgical technique and results in a series of 1,150 cases. Am J Obstet Gynecol. 1952;63:592– 604. 39. Van Dinth T, Woodruff JD. Leiomyosarcoma of the uterus. Am J Obstet Gynecol. 1982;144:817– 823. 40. Madej J, Bocian J, Basta A. On the possibility of sparing surgical treatment of leiomyosarcoma in young women. Ginekol Pol. 1985; 51:9 –12. 41. Lissoni A, Cormio G, Bonazzi C, et al. Fertility-sparing surgery in uterine leiomyosarcoma. Gynecol Oncol. 1998;70:348 –350.
ABSTRACT This case reports the hysteroscopic resection of an unsuspected leiomyosarcoma of the uterus in a 41-year-old multiparous woman with recurrent episodes of abnormal uterine bleeding. The available literature on this topic was reviewed and the potential implications of extrauterine spread after this procedure are discussed. Journal of Minimally Invasive Gynecology (2008) 15, 380 –383 © 2008 AAGL. All rights reserved.
Uterine sarcomas are uncommon tumors that account for less than 3% of all female genital tract malignancies and 3% to 5% of malignant tumors of the uterus [1,2]. These neoplasms carry a poor prognosis with an overall survival of less than 50% at 2 years, even when diagnosed at an early stage [3,4]. Unlike endometrial cancer, uterine sarcomas are not associated with well-known risk factors and also may affect young women. Abnormal uterine bleeding is the most common symptom of uterine sarcomas and diagnosis is often made incidentally at the time of myomectomy or hysterectomy for presumed benign condition [5,6]. In the last decades hysteroscopic transcervical resection of endometrial polyps and submucous myomas became a common treatment option as the occurrence of a malignant lesion not otherwise diagnosed is rare. A patient underwent hysteroscopic resection of an unsuspected leiomyosarcoma of the uterus. The available literature concerning this rare topic was reviewed and the potential implications of extrauterine spread after this procedure are discussed.
The authors have no commercial, proprietary, or financial interest in the products or companies described in this article. Corresponding author: Attilio Di Spiezio Sardo, MD, Unit of Gynecology and Obstetrics, and Pathophysiology of Human Reproduction, University of Naples “Federico II,” Via Pansini 5, Naples, Italy. E-mail: [email protected] Submitted September 25, 2007. Accepted for publication February 8, 2008. Available at www.sciencedirect.com and www.jmig.org 1553-4650/$ -see front matter © 2008 AAGL. All rights reserved. doi:10.1016/j.jmig.2008.02.003
Case Report A 41-year-old woman, gravida 2 para 2, was referred to our unit for recurrent abnormal uterine bleeding. The patient provided an informed consent to perform the study. The study was eventually approved by our institutional review board. Her personal history was negative for genital neoplasia and medical diseases. Physical and bimanual pelvic examinations revealed normal findings. Transvaginal sonography showed an anteverted uterus with a greater than normal volume and the presence of multiple myomas, with the biggest being a submucous lesion of 41 ⫻ 32 mm. A vaginoscopic hysteroscopy was performed by means of a 4-mm continuous-flow operative office hysteroscope with a 2.9-mm rod lens (Bettocchi size 4; Karl Storz, Tuttlingen, Germany). A normal-appearing G1 myoma of nearly 4.5 cm was detected on the anterior wall of the uterus. Taking into account the young age of the patient and her desire for future fertility, a hysteroscopic myomectomy preceded by a 3-month preoperative treatment with gonadotropin-releasing hormone-analog (GnRH) was scheduled. During the treatment with GnRH agonist, the patient continued to experience abnormal uterine bleeding although repeated transvaginal sonography did not reveal any change in myoma size. Hysteroscopic resection of the myoma was performed by means of a continuous flow 9-mm resectoscope and sorbitol (5%) was used for distention and irrigation of the uterine cavity. A complete resection of the intracavitary portion of the myoma with no ablation of the endometrium was performed. A meticulous fluid-balance control was maintained.
Nappi et al.
Hysteroscopy and Uterine Sarcomas
No intraoperative or postoperative complications occurred. All the resected tissue chips were microscopically examined by a pathologist who posed the diagnosis of leiomyosarcoma. After such diagnosis, the patient was extensively staged by ultrasound pelvic examination and total-body computed tomography scan, which revealed only the presence of a residual intrauterine mass of 1.9 ⫻ 1.9 cm. Carcino-embrionary antigen 125 dosage was 49 IU/mL (normal values: 0 –35 U/mL). The patient underwent a total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic lymphadenectomy, and peritoneal washings. Pathologic examination revealed the presence of a 2.2-mm, intramural uterine tumor. The borders between tumor growth and the surrounding myometrium were disease free (1.5 cm). Microscopic examination revealed spindle-shaped cells with cytologic atypia and multiple nucleoli. Diagnosis of uterine leiomyosarcoma was confirmed and mitotic count was 20 ⫻ 10 high power field. Lymphatic and vascular invasion were found. Peritoneal cytology was negative and no sites of disease were detected. The patient received 6 courses of adjuvant chemotherapy with doxorubicin (30 mg/m2), ifosfamide (3 g/m2), plus mesna on days 1, 2, and 3, repeated every 21 days. At 3 years of follow-up the patient has no sign of recurrent disease.
Discussion Mesenchymal uterine tumors are rare malignancies, occurring in only 17 per million women annually, thus representing fewer than 5% of all uterine malignancies [7]. The 3 most common variants of uterine sarcoma are endometrial stromal sarcoma, leiomyosarcoma, and malignant mixed mullerian tumor [8]. Less than 1% of women believed to have a leiomyoma actually have a sarcoma at hysterectomy. The incidence of leiomyosarcoma arising on a leiomyoma is less than 1% [9]. Other types of tumor including angiosarcomas, rhabdomyosarcomas, and malignant fibrous histiocytomas are rarer and not specific to the uterine site [10]. In general, 2 distinct tissue components give rise to malignant mesenchymal tumors; myometrial muscle (smooth) is the tissue component for leiomyosarcoma and endometrial stromal sarcoma, whereas both muscle and stromal tissue types give rise to malignant mixed mullerian tumor, even called carcinosarcoma [7,9]. In addition, uterine sarcomas are classified into homologous (consisting of cells native to the uterus) or heterologous (cells usually not found in the uterus). A review of 141 patients with uterine sarcoma [11] reported a histologic diagnosis of leiomyosarcoma to predict the worse prognosis of uterine sarcomas, followed by mixed mullerian tumors and endometrial stromal sarcoma. An earlier exposure to pelvic radiotherapy is the only known causal factor for uterine sarcomas. The most common symptoms are vaginal bleeding and pain [9].
381
The diagnosis of such tumors is often made postoperatively for a presumed benign condition. A vaginal digital and speculum examination should be performed, together with a smear. A transvaginal ultrasound examination, hysteroscopy, and endometrial biopsy are usually performed as part of the general investigative procedure but are seldom useful in the diagnosis of leiomyosarcoma. Blind endometrial biopsy misses the diagnosis of leiomyosarcoma in 40% to 80% and endometrial stromal sarcoma in 20% [9]. Hysteroscopic reports of uterine sarcomatous tumors are not frequent [12]: two studies [13,14] reported 3 cases of mixed mullerian tumors stating that it is possible to misdiagnose sarcomatous tissue for a benign endometrial polyp or submucous myoma at hysteroscopic view. Two studies [15,16] described 3 cases of unsuspected leiomyosarcoma in 2 series of hysteroscopic resections for presumed uterine submucous myomas, asserting that hysteroscopic diagnosis of uterine sarcomas might be very difficult. Several authors [17–22] have reported some cases of endometrial stromal sarcoma diagnosed after hysteroscopic endometrial resection. Particularly, 1 study [17] reported the case of a young woman (26 years old) who underwent operative hysteroscopy to remove a polypoid lesion, responsible for recurrent abnormal bleeding. This lesion was 4-cm long with no atypical features with the exception of dilated vessels. In that patient, 2 negative dilatation and curettages were performed before the hysteroscopy, revealing the poor diagnostic accuracy of blind dilatation and curettage. Another report [22] described the case of a 33-year-old woman who had a benign submucous myoma diagnosed at diagnostic hysteroscopy and underwent a resectoscopic surgery after 3 months of treatment with GnRH agonist, which did not reduce the size of the lesion. Recently, 6 cases of malignant mesenchymal tumors diagnosed after pathologic analysis of specimens obtained at hysteroscopy were reported, suggesting that at least a target biopsy should be always performed in all symptomatic intrauterine lesions, even if their appearance suggests a typical submucosal myoma or polyp [23]. Taken together, these reports suggest that there are no specific hysteroscopic characteristics to identify uterine sarcomas before tissue being sent for pathological review [6,13–23]. A focal area of malignancy might be missed by targeteye biopsy as it is impossible to examine the entire lesion, mostly in case of large ones. Furthermore, the biopsy of myometrial lesions by means of conventional instruments (i.e., grasping forceps, scissors) might pose notable difficulties because of the high consistency of these lesions. Because of that, the removal of the whole myomatous lesion represents the only method to definitively rule out the presence of sarcomatous tissue. Resectoscopic slicing should be preferred to laser or electrosurgical vaporization as it has the great advantage of offering the pathologist the possibility to analyze the tumor entirely. The main disadvantage of vaporizing electrodes is the lack of tissue sample
382
Journal of Minimally Invasive Gynecology, Vol 15, No 3, May/June 2008
for pathology. When vaporizing electrodes are used, it is mandatory that no myoma be vaporized in its entirety but that substantial portions are retrieved for microscopic examination [24,25]. In our patient, because of the notable size of the lesion and the severity of her symptoms, the complete resectoscopic removal of the lesion was scheduled right after the outpatient diagnostic hysteroscopy. The endoscopic approach to uterine lesions hiding a sarcoma may pose other practical issues besides the need for a histologic specimen to reach a definitive diagnosis. The use of preoperative GnRh agonist before the removal of a normal-appearing submucous myoma [26,27] may delay the final tissue diagnosis [28], as it occurred in our patient. Furthermore, we cannot exclude that retrograde dissemination of disease through the fallopian tubes may occur during diagnostic or operative hysteroscopy, thus changing the prognosis. All studies available in literature on this issue regard to endometrial adenocarcinoma [29 –37]. They have substantially shown that although there might be an increased risk of peritoneal contamination by cancer cells after diagnostic hysteroscopy, there is no evidence that these patients have a worse prognosis than those who have undergone other diagnostic procedures (i.e., dilatation and curettage). Furthermore the cancer cells found in the peritoneal cavity usually disappear within a short period of time and seem to have a low viability potential [37]. Currently, no studies evaluating either the risk of peritoneal spread of malignant mesenchymal cells at diagnostic hysteroscopy or the viability and capability of such disseminated cells to implant are available in the international literature. Such studies are mandatory to address these issues. Meanwhile, taking into account the aggressive nature of mesenchymal tumors (with an early pattern of local recurrence and widespread dissemination), a particularly careful attitude to avoid the spread of mesenchymal cells during hysteroscopy should be recommended. Furthermore, it should be emphasized that the higher intrauterine pressures (around 100 –120 mm Hg) conventionally reached during resectoscopic surgery potentially carries a major risk of peritoneal dissemination. An electronically controlled system for irrigation and aspiration (Endomat; Karl Storz) can be helpful to maintain a correct low intrauterine pressure (⬍70 mm Hg) in case of suspicion of neoplastic lesion avoiding or at least reducing the spread of malignant cells through the fallopian tubes. A more serious concern might be represented by the dissemination of malignant cells into deeper myometrial tissue. Indeed, whether intravascular or lymphatic penetration of malignant cells might be increased by endoscopic endomyometrial resection is still uncertain. However, some authors suggest that the intense radiofrequency energy effect on tumor cells and surrounding tissue (including the microvasculature) would tend to fur-
ther reduce the viability of local malignant cells and their potential for intravascular dissemination and subsequent metastatic invasion [20]. In our patient, neither metastasis nor positive peritoneal washing were found. Conclusions According to our experience and the available literature reviewed, the removal of the whole myomatosus lesion, even if its appearance suggests a typical submucosal myoma, represents the only method to definitively rule out the presence of sarcomatous tissue. A preoperative target biopsy under hysteroscopic view could be useful, but it could miss focal areas of malignancy. Whether a uterine sarcoma is diagnosed, total abdominal hysterectomy and bilateral salpingo-oophorectomy are considered the standard therapy [4]; the role of conservative, fertility-sparing surgery in young women still needs to be ascertained as a limited number of anecdotal cases were reported so far in the literature [38 – 41].
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