How to Tell a Sarcoma from a Myoma?Gynecologist’s Point of View Ginger J. Gardner, MD Associate Professor, Weill Cornell Medical College Associate Member, Gynecology Service Director, Survivorship Program Department of Surgery Memorial Sloan-Kettering Cancer Center
Case 50yo undergoing work-up for newly diagnosed breast cancer, presents with increasing vaginal bleeding and associated dysmenorrhea. Pelvic exam consistent with an enlarged fibroid uterus. Endometrial biopsy benign. Pelvic imaging reveals…
Peri or Post-Menopausal Bleeding&Enlarging / Necrotic Uterine Mass…Think SARCOMA!
Uterine Leiomyosarcoma Histologic Features high mitotic rate atypia and necrosis SMA positive, h-caldesmon positive ER/PR positive 7-71% Multiple, complex chromosomal abnormalities No single specific translocation Clinical Features Median age 56 years 40-70% risk for recurrence in 2-5 years for uterus-limited disease Lung, liver, rarely bone Median survival after dx of metastatic disease is 1 year
Uterine LeiomyosarcomaDiagnosis Soslow RA. Diagn Histopathol 2008;14:175-188.
Uterine SarcomasDiagnosis • The vast majority are diagnosed incidentally after a procedure for presumed benign indications • No reliable method to detect these preoperatively • Myomectomy, SCH, morcellations for specimen removal are commonly performed • Patient counseling • What is the risk of malignancy? • What are the implications in patients ultimately diagnosed with sarcomas?
Uterine SarcomasIncidence SEER data
Surgery for Presumed LeiomyomaRisk of Malignancy *371 with “rapidly” enlarging – 1 (0.27%) LMS found ** 2 (0.2%) endometrial carcinomas also found “New” or enlarging symptomatic fibroids in postmenopausal women should raise some concerns?
Uterine morcellationResidual disease *1 LMS upstaged on imaging (lung nodules); 2/4 (50%) with residual at reoperation Eisenhauer MH, et al. Int J Gynecol Cancer 2008;18:1065-1070.
Uterine morcellationImpact on LMS outcome Perri T, et al. Int J Gynecol Cancer 2009;19:257-260.
Uterine morcellationRecommendations • Avoid in women with highly concerning pelvic imaging • Avoid in postmenopausal women with a newly diagnosed pelvic mass or an enlarging pelvic mass • If sarcoma encountered post morcellation, consider MIS re-evaluation to remove cervix if retained and careful peritoneal inspection
Post-Menopausal Bleeding&Enlarging / Necrotic Uterine Mass…Think SARCOMA!
Uterine Sarcomas: histologic types • 2000 cases/yr • 0.5-3.3 cases/100,000 women • Heterogenous group of tumors • Natural history, prognosis, treatment vary by histology and grade ESS 15% AS 5% CS 45% LMS 35%
International Society of Gynecologic Pathologists’ Classification of Uterine Sarcomas • Pure non-epithelial sarcomas • Leiomyosarcoma (LMS) • Endometrial stromal sarcoma (ESS) • Mixed ESS/LMS • Other homologous/heterologous tumors • Mixed epithelial and non-epithelial sarcomas • Carcinosarcoma (mixed malignant Mullerian tumor) • Adenofibroma • Carcinofibroma • Undifferentiated sarcomas
Uterine SarcomasGOG classification • Leiomyosarcoma • Smooth muscle tumor of uncertain malignant potential (STUMP) • Endometrial stromal sarcoma (low grade) • Undifferentiated sarcoma • Others: adenosarcoma, carcinofibroma • Carcinosarcoma (MMMT, metaplastic carcinoma) GOG Pathology Manual. Revised 2009
EORTC Radiation TrialAdjuvant Therapy for LMS • Uterine Sarcoma Stage I/II • Randomized to Pelvic RT vs Observation • Total patients 223 -Leiomyosarcoma 103 -Carcinosarcoma 91 -Endometrial Stromal Sarcoma 28
EORTC Radiation TrialAdjuvant Therapy for LMS In subset analysis, adjuvant RT did not improve local control or distant recurrence for LMS patients Reed, et al. Eur J Cancer 2008.
GOG 277Adjuvant Therapy for LMS Eligibility • High grade uterine LMS • Uterine limited disease (FIGO stage I) • >5 mitoses/hpf • <12 weeks since surgery • Negative preoperative imaging
Uterine SarcomasSummary • Uterine sarcomas can masquerade as benign uterine fibroids • Incidence is <0.5% among pts undergoing fibroid surgery • Peri- or Post-menopausal bleeding and an enlarging necrotic uterine mass are red flags for possible sarcoma • Avoid Morcellation for patients with these clinical characteristics • For early stage LMS, GOG277 is evaluating appropriate adjuvant management