Uterine Sarkome

Mit einer Inzidenz von 1,5 – 3/100 000 Einwohnern treten uterine Sarkome sehr selten auf. Die operative Primärtherapie beinhaltet die totale Hysterektomie und Adnexektomie beidseits. Danach schließt sich adjuvant nur bei hormonabhängigen „Low-Grade“-Tumoren und dem endometrialen Stromasarkom eine endokrine Therapie an. Bei Metastasen ist beim Leiomyosarkom und undifferenzierten endometrialen Stromasarkom eine palliative Chemotherapie indiziert.

Kernaussagen

Uterine Sarkome sind mit 3% aller Uterusmalignome sehr seltene maligne Neoplasien der Uterusmuskulatur bzw. des uterinen Bindegewebes. Bei fehlenden spezifischen Symptomen sind ein schnell wachsender Uterus in der Postmenopause und Blutungsstörungen bzw. Postmenopausenblutung verdächtig. Die Primärtherapie besteht in der Regel aus der Hysterektomie mit Adnexektomie.

In der Adjuvanz ist eine Chemotherapie beim Leiomyosarkom nicht und beim undifferenzierten endometrialen Stromasarkom fraglich indiziert. Alternativ kann, vor allem bei hormonabhängigen „Low-Grade“-Tumoren und dem endometrialen Stromasarkom, eine endokrine Therapie mit MPA oder Aromatasehemmern erfolgen. Eine adjuvante Radiatio kommt in der Regel nicht zum Einsatz.

In der Rezidivsituation von uterinen Sarkomen sollte primär die operative Komplettresektion zur Prognoseverbesserung angestrebt werden. In der metastasierten Situation ist beim Leiomyosarkom und undifferenzierten endometrialen Stromasarkom eine palliative Chemotherapie indiziert.

In der im August 2015 publizierten S2k-Leitlinie für uterine Sarkome ist erstmals für Deutschland eine Leitlinie für diese heterogene Tumorentität erstellt worden.

Schlüsselwörter

Leiomyosarkom - endometriales Stromasarkom - undifferenziertes uterines Sarkom - Therapie - adjuvante Therapie - Radiatio

• Literatur

• 1 Brooks SE. et al. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989–1999. Gynecol Oncol 2004; 93: 204-208
• 2 Wittekind C, Meyer HJ. TNM-Klassifikation maligner Tumoren. Weinheim: Wiley-VHC; 2010: 184-187
• 3 Oliva E. et al. Mesenchymal Tumors of the Uterus. In: Kurman RJ. et al. eds. WHO Classification of Tumours of Female Reproductive Tract. Lyon: IARC Press; 2014: 135-147
• 4 Conklin CM, Longacre TA. Endometrial stromal tumors: the new WHO classification. Adv Anat Pathol 2014; 21: 383-393
• 5 Fletcher CDM. et al. WHO Classification of Soft Tissue and Bone. Lyon: IARC Press; 2013
• 6 DʼAngelo E, Prat J. Uterine sarcomas: a review. Gynecol Oncol 2010; 116: 131-139
• 7 McCluggage WG. Malignant biphasic uterine tumours: carcinosarcomas or metaplastic carcinomas?. J Clin Pathol 2002; 55: 321-325
• 8 Lopez-Garcia MA, Palacios J. Pathologic and molecular features of uterine carcinosarcomas. Semin Diagn Pathol 2010; 27: 274-286
• 9 Buttram jr. VC, Reiter RC. Uterine leiomyomata: etiology, symptomatology, and management. Fertil Steril 1981; 36: 433-445
• 10 Parker WH, Fu YS, Berek JS. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol 1994; 83: 414-418
• 11 Liao Q, Wang J, Han J. [Clinical and pathological analysis on 106 cases with uterine sarcoma]. Zhonghua Fu Chan Ke Za Zhi 2001; 36: 104-107
• 12 Sreenan JJ, Hart WR. Carcinosarcomas of the female genital tract. A pathologic study of 29 metastatic tumors: further evidence for the dominant role of the epithelial component and the conversion theory of histogenesis. Am J Surg Pathol 1995; 19: 666-674
• 13 Zaloudek CJ, Hendrickson MR, Soslow RA. Mesenchymal Tumors of the Uterus. In: Kurman RJ, Ellenson LH, Ronnett BM. eds. Blausteinʼs Pathology of the Female Genital Tract. New York, Dodrecht, Heidelberg, London: Springer; 2011
• 14 Park JY. et al. The impact of tumor morcellation during surgery on the prognosis of patients with apparently early uterine leiomyosarcoma. Gynecol Oncol 2011; 122: 255-259
• 15 Santos P, Cunha TM. Uterine sarcomas: clinical presentation and MRI features. Diagn Interv Radiol 2015; 21: 4-9
• 16 Sadeghi R. et al. Diagnostic performance of fluorine-18-fluorodeoxyglucose positron emission tomography imaging in uterine sarcomas: systematic review and meta-analysis of the literature. Int J Gynecol Cancer 2013; 23: 1349-1356
• 17 Sharma P. et al. Role of FDG PET-CT in detecting recurrence in patients with uterine sarcoma: comparison with conventional imaging. Nucl Med Commun 2012; 33: 185-190
• 18 Coffey D, Kaplan AL, Ramzy I. Intraoperative consultation in gynecologic pathology. Arch Pathol Lab Med 2005; 129: 1544-1557
• 19 Otis CN. et al. Protocol for the Examination of Specimens From Patients With Sarcoma. 2013;. Im Internet: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2013/UterineSarcomaProtocol_3000.pdf Stand: 01.07.2018
• 20 McCluggage WG, Fisher C, Hirschowitz L. Dataset for histological reporting of uterine sarcomas. London: Royal College of Pathologists; 2014
• 21 Ehdaivand S. et al. Incidental gynecologic neoplasms in morcellated uterine specimens: a case series with follow-up. Hum Pathol 2014; 45: 2311-2317
• 22 Amant F. et al. Clinical management of uterine sarcomas. Lancet Oncol 2009; 10: 1188-1198
• 23 Abeler VM. et al. Uterine sarcomas in Norway. A histopathological and prognostic survey of a total population from 1970 to 2000 including 419 patients. Histopathology 2009; 54: 355-364
• 24 Pelmus M. et al. Prognostic factors in early-stage leiomyosarcoma of the uterus. Int J Gynecol Cancer 2009; 19: 385-390
• 25 Iasonos A. et al. External validation of a prognostic nomogram for overall survival in women with uterine leiomyosarcoma. Cancer 2013; 119: 1816-1822
• 26 Garg G, Shah JP, Kumar S. et al. Ovarian and uterine carcinosarcomas: a comparative analysis of prognostic variables and survival outcomes. Int J Gynecol Cancer 2010; 20: 888-894
• 27 King ME, Dickersin GR, Scully RE. Myxoid leiomyosarcoma of the uterus. A report of six cases. Am J Surg Pathol 1982; 6: 589-598
• 28 Coindre JM. Grading and staging of sarcoma. In: Fletcher CDM. et al. eds. WHO Classification of Tumours of Soft Tissue and Bone. Lyon: IARC Press; 2013: 17-18
• 29 Guillou L. et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 adult patients with soft tissue sarcoma. J Clin Oncol 1997; 15: 350-362
• 30 Deyrup AT, Weiss SW. Grading of soft tissue sarcomas: the challenge of providing precise information in an imprecise world. Histopathology 2006; 48: 42-50
• 31 Coindre JM. Grading of soft tissue sarcomas: review and update. Arch Pathol Lab Med 2006; 130: 1448-1453
• 32 Kapp DS, Shin JY, Chan JK. Prognostic factors and survival in 1396 patients with uterine leiomyosarcomas: emphasis on impact of lymphadenectomy and oophorectomy. Cancer 2008; 112: 820-830
• 33 Perri T. et al. Uterine leiomyosarcoma: does the primary surgical procedure matter?. Int J Gynecol Cancer 2009; 19: 257-260
• 34 Leitao MM. et al. Incidence of lymph node and ovarian metastases in leiomyosarcoma of the uterus. Gynecol Oncol 2003; 91: 209-912
• 35 Pautier P. et al. A randomized clinical trial of adjuvant chemotherapy with doxorubicin, ifosfamide, and cisplatin followed by radiotherapy versus radiotherapy alone in patients with localized uterine sarcomas (SARCGYN study). A study of the French Sarcoma Group. Ann Oncol 2013; 24: 1099-1104
• 36 Hensley ML. et al. Adjuvant gemcitabine plus docetaxel for completely resected stages I–IV high grade uterine leiomyosarcoma: Results of a prospective study. Gynecol Oncol 2009; 112: 563-567
• 37 Hensley ML. et al. Adjuvant therapy for high-grade, uterus-limited leiomyosarcoma: results of a phase 2 trial (SARC005). Cancer 2013; 119: 1555-1561
• 38 Reed NS, Mangioni C, Malmstrom H. et al. Phase III randomised study to evaluate the role of adjuvant pelvic radiotherapy in the treatment of uterine sarcomas stages I and II: an European Organisation for Research and Treatment of Cancer Gynaecological Cancer Group Study (protocol 55874). Eur J Cancer 2008; 44: 808-818
• 39 Bernstein-Molho R. et al. Metastatic uterine leiomyosarcomas: a single-institution experience. Int J Gynecol Cancer 2010; 20: 255-260
• 40 Leitao MM. et al. Surgical resection of pulmonary and extrapulmonary recurrences of uterine leiomyosarcoma. Gynecol Oncol 2002; 87: 287-294
• 41 Levenback C. et al. Resection of pulmonary metastases from uterine sarcomas. Gynecol Oncol 1992; 45: 202-205
• 42 Weiser MR. et al. Repeat resection of pulmonary metastases in patients with soft-tissue sarcoma. J Am Coll Surg 2000; 191: 184-190 discussion 190–191
• 43 Giuntoli 2nd RL. et al. Secondary cytoreduction in the management of recurrent uterine leiomyosarcoma. Gynecol Oncol 2007; 106: 82-88
• 44 Anraku M. et al. Pulmonary metastases from uterine malignancies: results of surgical resection in 133 patients. J Thorac Cardiovasc Surg 2004; 127: 1107-1112
• 45 Chen H. et al. Complete hepatic resection of metastases from leiomyosarcoma prolongs survival. J Gastrointest Surg 1998; 2: 151-155
• 46 Maki RG. et al. Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft tissue sarcomas: results of sarcoma alliance for research through collaboration study 002 [corrected]. J Clin Oncol 2007; 25: 2755-2763
• 47 Sutton G, Blessing JA, Malfetano JH. Ifosfamide and doxorubicin in the treatment of advanced leiomyosarcomas of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol 1996; 62: 226-229
• 48 Hensley ML. et al. Gemcitabine and docetaxel in patients with unresectable leiomyosarcoma: results of a phase II trial. J Clin Oncol 2002; 20: 2824-2831
• 49 Gupta AA. et al. Systematic chemotherapy for inoperable, locally advanced, recurrent, or metastatic uterine leiomyosarcoma: a systematic review. Clin Oncol (R Coll Radiol) 2013; 25: 346-355
• 50 Sutton GP. et al. Phase II trial of ifosfamide and mesna in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Am J Obstet Gynecol 1992; 166: 556-559
• 51 Look KY. et al. Phase II trial of gemcitabine as second-line chemotherapy of uterine leiomyosarcoma: a Gynecologic Oncology Group (GOG) Study. Gynecol Oncol 2004; 92: 644-647
• 52 Thigpen T. et al. Phase II trial of etoposide in leiomyosarcoma of the uterus: a Gynecologic Oncology Group study. Gynecol Oncol 1996; 63: 120-122
• 53 Rose PG. et al. Prolonged oral etoposide in recurrent or advanced leiomyosarcoma of the uterus: a gynecologic oncology group study. Gynecol Oncol 1998; 70: 267-271
• 54 Miller DS. et al. Phase II trial of topotecan in patients with advanced, persistent, or recurrent uterine leiomyosarcomas: a Gynecologic Oncology Group Study. Am J Clin Oncol 2000; 23: 355-357
• 55 Gallup DG. et al. Evaluation of paclitaxel in previously treated leiomyosarcoma of the uterus: a gynecologic oncology group study. Gynecol Oncol 2003; 89: 48-51
• 56 Seddon B. et al. Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): a randomised controlled phase 3 trial, 2017. Lancet Oncol 2017; 18: 1397-1410
• 57 Tap WD. et al. Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet 2016; 388: 488-497
• 58 Demetri GD. et al. Efficacy and safety of trabectedin in patients with advanced or metastatic liposarcoma or leiomyosarcoma after failure of prior anthracyclines and ifosfamide: results of a randomized phase II study of two different schedules. J Clin Oncol 2009; 27: 4188-4196
• 59 van der Graaf WT. et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet 2012; 379: 1879-1886
• 60 Dusenbery KE. et al. Limitations of adjuvant radiotherapy for uterine sarcomas spread beyond the uterus. Gynecol Oncol 2004; 94: 191-196
• 61 Chew I, Oliva E. Endometrial stromal sarcomas: a review of potential prognostic factors. Adv Anat Pathol 2010; 17: 113-121
• 62 Chang KL. et al. Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases. Am J Surg Pathol 1990; 14: 415-438
• 63 Barney B. et al. Does radiotherapy or lymphadenectomy improve survival in endometrial stromal sarcoma?. Int J Gynecol Cancer 2009; 19: 1232-1238
• 64 Einstein MH. et al. Management of uterine malignancy found incidentally after supracervical hysterectomy or uterine morcellation for presumed benign disease. Int J Gynecol Cancer 2008; 18: 1065-1070
• 65 Shah JP. et al. Lymphadenectomy and ovarian preservation in low-grade endometrial stromal sarcoma. Obstet Gynecol 2008; 112: 1102-1108
• 66 Chan JK, Kawar NM, Shin JY. et al. Endometrial stromal sarcoma: a population-based analysis. Br J Cancer 2008; 99: 1210-1215
• 67 Bai H. et al. Ovary and Uterus-sparing procedures for low-grade endometrial stromal sarcoma: a retrospective study of 153 cases. Gynecol Oncol 2014; 3: 654-660
• 68 Amant F, De Knijf A, Van Calster B. et al. Clinical study investigating the role of lymphadenectomy, surgical castration and adjuvant hormonal treatment in endometrial stromal sarcoma. Br J Cancer 2007; 97: 1194-1199
• 69 Beck TL, Singhal PK, Ehrenberg HM. et al. Endometrial stromal sarcoma: analysis of recurrence following adjuvant treatment. Gynecol Oncol 2012; 125: 141-144
• 70 Chu MC, Mor G, Lim C. et al. Low-grade endometrial stromal sarcoma: hormonal aspects. Gynecol Oncol 2003; 90: 170-176
• 71 Leath CA 3rd et al. A multi-institutional review of outcomes of endometrial stromal sarcoma. Gynecol Oncol 2007; 105: 630-634
• 72 Gadducci A, Cosio S, Romanini A. et al. The management of patients with uterine sarcoma: a debated clinical challenge. Crit Rev Oncol Hematol 2008; 65: 129-142
• 73 Sampath S. et al. The role of adjuvant radiation in uterine sarcomas. Int J Radiat Oncol Biol Phys 2010; 76: 728-734
• 74 Nam JH. Surgical treatment of uterine sarcoma. Best Pract Res Clin Obstet Gynaecol 2011; 25: 751-760
• 75 Piver MS. et al. Uterine endolymphatic stromal myosis: a collaborative study. Obstet Gynecol 1984; 64: 173-178
• 76 Weitmann HD. et al. Radiation therapy in the treatment of endometrial stromal sarcoma. Int J Radiat Oncol Biol Phys 2001; 49: 739-748
• 77 Kortmann B. et al. Concurrent radiochemotherapy of locally recurrent or advanced sarcomas of the uterus. Strahlenther Onkol 2006; 182: 318-324
• 78 Cheng X. et al. Recurrence patterns and prognosis of endometrial stromal sarcoma and the potential of tyrosine kinase-inhibiting therapy. Gynecol Oncol 2011; 121: 323-327
• 79 Dahhan T. et al. The efficacy of hormonal treatment for residual or recurrent low-grade endometrial stromal sarcoma. A retrospective study. Eur J Obstet Gynecol Reprod Biol 2009; 144: 80-84
• 80 Maluf FC. et al. Endometrial stromal sarcoma: objective response to letrozole. Gynecol Oncol 2001; 82: 384-388
• 81 Pink D. et al. Harm or benefit of hormonal treatment in metastatic low-grade endometrial stromal sarcoma: single center experience with 10 cases and review of the literature. Gynecol Oncol 2006; 101: 464-469
• 82 Harter P. et al. Pegylated liposomal doxorubicin and carboplatin in malignant mixed epithelial mesenchymal and mesenchymal gynecologic tumors: A phase II trial of the AGO study group. J Clin Oncol 2011; 29 (Suppl) Abstr.. 5093
• 83 du Bois A. et al. Combination therapy with pegylated liposomal doxorubicin and carboplatin in gynecologic malignancies: a prospective phase II study of the Arbeitsgemeinschaft Gynaekologische Onkologie Studiengruppe Ovarialkarzinom (AGO-OVAR) and Kommission Uterus (AGO-K-Ut). Gynecol Oncol 2007; 107: 518-525
• 84 Malouf GG. et al. Prognostic factors and outcome of undifferentiated endometrial sarcoma treated by multimodal therapy. Int J Gynaecol Obstet 2013; 122: 57-61
• 85 Tanner EJ. et al. High grade undifferentiated uterine sarcoma: surgery, treatment, and survival outcomes. Gynecol Oncol 2012; 127: 27-31
• 86 Schick U. et al. Outcome and prognostic factors in endometrial stromal tumors: a Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2012; 82: e757-e763
• 87 Oliva E. Cellular mesenchymal tumors of the uterus: a review emphasizing recent observations. Int J Gynecol Pathol 2014; 33: 374-384
• 88 Hendrickson MA. et al. Mesenchymal tumors and related lesions. In: Tavassoli FA, Devilee P. eds. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: World Health Organization Classification of Tumours. IARC Press; 2003: 233-249
• 89 Beckmann MW. et al. Surgical methods for the treatment of uterine fibroids – risk of uterine sarcoma and problems of morcellation: Position Paper of the DGGG. Geburtshilfe Frauenheilkd 2015; 75: 148-164