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Mr Leiomyoma Vs Leiomyosarcoma 2 0 SCBT· MR 1 LEIOMYOMA VS LEIOMYOSARCOMA 5 Susan M. Ascher, MD Professor & Co-Director of Abdominal Imaging Georgetown University Hospital, Washington, DC T2-W MRI: Normal Uterus, Leiomyoma and Leiomyosarcoma NORMAL LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA LEIOMYOMA or LEIOMYOSARCOMA LEIOMYOMA LEIOMYOSARCOMA DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Distinguishing the two can be challenging Laparoscopic Power Morcellators • Hysterectomy • Myommectomy Prognosis is significantly worse in women who had leiomyosarcomas morcellated than women who underwent standard abdominal hysterectomy Park JY, et al. Gynecol Oncol 2011; 122:255-259. Perri T, et al. Int J Gyencol Cancer 2009; 19:257-260 DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Distinguishing the two can be challenging 4/17/14: FDA safety warning on LPM for hysterectomy & myomectomy • Prev of unsuspected uterine sarcoma: 1 in 352 • Prev of unsuspected uterine LMS: 1 in 498 • Upstaging sarcoma 1 in 7000 Pritts et al (open source) 7/10 -11/14: FDA OB-GYN Devices Panel FDA: Quantitative Assessment of the Prevalence of Unsuspected Uterine Sarcoma in Women undergoing Treatment of Uterine Fibroids. Summary and Key Findings http://www.fda.gov/downloads/MedicalDevices/Safety/AlertsandNotices/UCM393589. 7.11.14: “Fate of Uterine Device Now in Hands of FDA: Panel's Recommendations Run From Outright Ban to 'Black Box' Warning to Limited Use” Ethicon voluntarily suspend sales and recalls devices worldwide 9.22.14: “Gynecologists Resist FDA Over Popular Surgical Tool: Doctors Continue to Use Morcellators Months After Regulator Warned They Can Spread Undetected Cancer” 11.24.2014: FDA Black Box Warning & IIE “Warning Prompts Shift in Surgeries on Women” A Yale University study found that 84% of gynecological surgeons at large U.S. teaching hospitals changed hysterectomy techniques after a federal warning on a device called a power morcellator. 3.16.15 DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Thinking more broadly… Uterine conserving therapies exist • Uterine Artery/Fibroid Embolization (UAE/UFE) • High Frequency Ultrasound (HiFUS) • Gonadotropin-releasing Hormone Analogs Can imaging minimize risk? LEIOMYOSARCOMA 10-08-01 03-08-02 10-30-02 DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA Optimal pretreatment imaging to avoid misdx of (leiomyo)sarcoma Post treatment surveillance MODALITIES: Very Limited Data US: contrast & spatial resolution, operator dependent & body habitus limit CT: contrast resolution & ionizing rad PET: Promising for confirmation, metastasis and recurrence but FP MRI: Promising, but accuracy, sensitivity, specificity, PPV & NPV not established in large multicenter trial Radiology 1986; 158:385-391. Radiology 1988; 167:627-630. Obstet Gynecol Clin North Am 1995; 22:667-725. Gynecol Oncol 1995; 59:342-346. Fertil Steril 1998; 70:580-587. RadioGraphics 1999; 19:1179-1197. AJR 2001; 177:1307- 1311. Gynecol Oncol 2001; 80:372-377. Int J Gynecol Cancer 2002;12:354-361. JMRI 2004; 20:998- 1007. Eur Radiol 2008; 18:723-730. Eur Radiol 2009;19:2756-2764. Eur J Rad 2010; 74:241-249. Best Practice & Research Clin Obstet and Gynaecol 2011; 25:681-689. Am J Obstet Gynecol 2014; 210:368 e1-8. Est’d MRI Features Usual Leiomyomas (UL) Whorls of SM cells w/ intervening collagen T1-W: ↔ SI T2-W: SI • Well defined • Round/oval Gd-T1-W: Viable T1-W T2-W Gd T1-W Est’d MRI Features Usual Leiomyomas (UL) Whorls of SM cells w/ intervening collagen T1-W: ↔ SI T2-W: SI • Well defined • Round/oval T1-W T1-W w/ Fat Sat Gd-T1-W: Viable T2-W Gd T1-W DIFFUSION WEIGHTED IMAGING Info water mobility & tissue cellularity Exploits Brownian motion: Random H2O motion Describes water diffusibilty • Intact cell membranes • Cellular density Qualitative (DWI) & Quant (ADC) Restricted Diff & Malig ( cells impede motion) • DWI: High SI on High Bo image • Low ADC Map SI & ADC value • Overlap with benign fibrosis, abscess, cytotoxic edema Qayyum A. Radiographics 2009; 29:1797-1810 Est’d MRI Features Usual Leiomyomas (UL) Whorls of SM cells w/ intervening collagen T1-W: ↔ SI T2-W: SI DWI Gd-T1-W: Viable T2-W DWI/ADC: ↓SI/↓SI (blackout) ADC DEGENERATED LEIOMYOMAS (DLM) Up to 2/3 with degeneration • More common if > 5-8 cm Etiology: Outgrow blood supply • Rapid growth, preg, trauma & PM atrophy Type: Degree & rapidity of insufficiency Hyaline (60%), cystic/liq necrosis (4%), myxoid, red/carneous, hemorrhagic, calcific, coagulative necrosis & sarcomatous “Cellular” LM: Compact SM cells, little collagen MRI OF UL, DML and LMS RadioGraphics 1999;19:1179-1197 & S131-S145 TYPE Overall T1-W SI T2-W SI Enhance DWI LDH & Morph (early) /ADC LDH3 Usual Round/Oval Low-Iso Low Variable Does not Not Restrict Elevated Hyaline/ Round/oval Low-Iso Low Min-None (Calcific) Cystic or Round Oval Low High None in Liq. Necrosis cysts Myxoid Round/Oval Very High Min-None Red/ Round/Oval Peripheral or Variable w/ or None Carneous Diffuse High w/o Low Rim (coag nec) (Cellular) Round/Oval Variable High Marked Restrict Elevated Sarcoma (coag nec) ? ? ? ? ? ? Degenerated Leiomyoma (Red) T2-W T1-W FS DCE T1-W FS DWI ADC “Degenerated” Leiomyoma (Cellular) Compact SM cells with little or no collagen DCE Gd T1-W FS T2-W T1-W FS DWI ADC LEIOMYOMA or LEIOMYOSARCOMA T2-W T1-W FS 3D Gd T1-W FS T2-W DWI ADC Degenerated Leiomyoma (Coag Necrosis & Carneous Degen) DEGENERATED LEIOMYOMA vs LEIOMYOSARCOMA No large prospective studies No large retrospective studies LEIOMYOMA vs LEIOMYOSARCOMA: Studies surveyed: 60 cases of LMS Grouped w/ other sarcomas Different imaging protocols -Magnet strength -Sequences performed -IV contrast to include image acquisition Different parameters assessed -T1-W & T2-W, DCE, DWI/ADC, PWI -”Serum LDH” PUBLISHED STUDIES Study Criteria/Findings Acc Sens Spec PPV NPV Schwartz et al Morphology 69% 1998 T1 & T2 to ID subtypes overall 4 LMS/45 (uncomplicated, cellular, for sub- Retrospective hemorrhagic, cystic, LMS) type Sahdev et al T2 Heterogeneous (68%) 2001 T1 Variable 11 LMS/5MMT/ Enhancing 2 Rhab/4ESS Retrospective Goto et al T1 & T2 97.1 100 96.9 71.4 100 2002 DCE MRI (40-60 sec) 90.5 100 87.5 71.4 100 10/140 DCE MRI & LDH 99.3 100 99.2 90.9 100 Prospective (absent enhancement in DLM) Tanaka et al T2 > 50% 87 72.7 100 100 80 2004 T1 9LMS/3UMP/24 WD non-viable area Retrospective 3 criteria in combo to dx sarc Study Criteria/Findings Acc Sens Spec PPV NPV Tamai et al LMS ADC 1.17 +/- .15 2008 DL ADC 1.70 +/- .11 5 LMS/2 ESS/58 UL ADC 0.88 +/- .27 Retrospective Nl Myo ADC 1.62 +/-.11 LMS overlap with UL & cell Namimoto et al TCR > 0 100 100 2009 ADC < 1.05 +/- .11 4 LMS/2 ESS/ (3 Tesla magnet) 2 MMT/103 Retrospective Cornfeld et al Ill-defined margins 56 88-94 2010 Reader gestalt 4 LMS/2UMP/ (No DWI /ADC) 1ESS/2 mix/25 No obj crit to DDx unusal LM Retrospective from sig mesen. neos Thomassin-Naggara Intermediate T2 92.4 92 et al 2013 High DWI SI (high Bo) 47/51 4LMS/19Sarc/6UMP ADC 1.23 Correct 26 benign LM Age > 44.8 years classify Retrospective Sato et al Low risk DWI & ADC 1.1 94.6 100 94.0 66.7 100 2014 High risk DWI & ADC <1.1 10 LMS/93 lx Age of sarc pts: 55 years Retrospective Recurvsive Partition Model DDx Benign from Unknown & Mal tumors Unique Myometrial Tumor Low DWI SI High DWI SI Low T2 SI Intermed T2 SI ADC > 1.23 ADC 1.23 *Correctly classified tumors in 88% (28/32 tumors): 2 FN (recur LMS & stromal sarcoma); 2 FP (Leiom) **Age ~ 45+ years Thomassin-Naggara I, et al. Eur Radiol 2013;23:2306-2314 UNDIFFERENTIATED SARCOMA T2-W T1-W T1-W FS 3D Gd T1-W DWI ADC Thomassin-Naggara I, et al Eur Radiol 2013;23:2306-2314 SI on DWI & ADC Value CLASSIFICATION DWI: Intermediate to High SI HIGH RISK GROUP ADC < 1.1 LMS: 66.7% (10/15) 16.1% (15/93) FP: Cellular LM (4) & Atypical LM (1) 93 Uterine Tumors 1. DWI: Low SI or LOW RISK GROUP 2. Intermediate to High SI LMS: 0% (0/78) and an ADC 1.1 TN: Cellular LM (3) 83.9% (78/93) *Mean total LDH was not sig different between myomas & LMS **No correlation between DCE and DWI *** Mean age of sarcoma patients: 55 years Sato K, et al. Am J Obstet Gynecol 2014; 210:368.e1-8 MRI OF UL, DML and LMS RadioGraphics 1999;19:1179-1197 & S131-S145 TYPE Overall T1-W SI T2-W SI Enhance DWI LDH & Morph (early) /ADC LDH3 Usual Round/Oval Low-Iso Low Variable Does not Not Restrict Elevated Hyaline/ Round/oval Low-Iso Low Min-None (Calcific) Cystic or Round Oval Low High None in Liq. Necrosis cysts Myxoid Round/Oval Very High Min-None Red/ Round/Oval Peripheral or Variable w/ or None Carneous Diffuse High w/o Low Rim (coag nec) (Cellular) Round/Oval Variable High Marked Restrict Elevated Sarcoma Irregular Variable- Heterogen Variable Restrict Elevated (coag nec) Usually High (None- Marked) LEIOMYOSARCOMA T2-W 3D Gd T1-W T2-W T1-W FS LEIOMYOSARCOMA T2-W T1-W FS 3D T1-W FS 3D Gd T1-W LEIOMYOMA 9.27.2010 9.27.10 3D T1-W FS T2-W 3D Gd T1-W August 2015 LMS: Uterine Rupture! T2-W 3D Gd T1-W POTENTIAL AREAS OF INVESTIGATION Registry of (Leiomyo)sarcomas Imaging Lexicon: • Multiparametric features •Morphology, SI, DCE, DWI/ADC • “Leiomyoma Score” •1 definite UL 5 definite LMS Large Multicenter Prospective Trial • Uniform exam parameters CONCLUSIONS Features of UL are well established Florid LMS are routinely detected • Ill-defined, heterogeneous (intermed/high T2), necrotic, hemorrhagic, restricted diffusion/low ADC & elevated LDH Overlap between DL & LMS exists Radiology: Measured interpretations • Pre AND post UFE/UAE Close collaboration of stakeholders THANK YOU [email protected] .
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