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Magnetic Resonance Imaging of Benign andMalignant Uterine NeoplasmsGustavo Leursen, MD,* Carly Susan Gardner, MD,† Tara Sagebiel, MD,‡

Madhavi Patnana, MD,‡ Silvana de CastroFaria, MD, PhD,‡

Catherine E. Devine, MD,‡ and Priya R. Bhosale, MD‡

x.doi.org/10.1071/Published

ted in part byrd no.: P30CA

ment of Abdore, Rio Grandestic Imaging, Ustic Radiology

ss reprint requeter, 1400 Presssale@mdander

Benign and malignant uterine masses can be seen in the women. Some of these areasymptomatic and incidentally discovered, whereas others can be symptomatic.With the softtissue contrast resolution magnetic resonance imaging can render a definitive diagnosis,which can further help streamline patient management. In this article we show magneticresonance imagingexamplesof benignandmalignantmassesof theuterus and their treatmentstrategies.Semin Ultrasound CT MRI ]:]]]-]]] Published by Elsevier Inc.

Introduction

Amyriad of tumors occur in the uterus. In this article wewill discuss the benign and malignant uterine tumors,

with a focus on magnetic resonance imaging (MRI) features,pathology, and treatment.

BenignFibroidsUterine fibroids (leiomyomas or myomas) are the mostcommon pelvic tumors in women, seen predominantly inAfrican-Americans.1-3 Fibroids appear, grow, and regress duringlife, especially during reproductive age, pregnancy, and post-partum period, and are seen in 35% ofmenstruatingwomen.2,3

Associated risk factors include early menarche age, nulliparity,old age at first pregnancy, obesity, diabetes, hypertension, andfamily history. Although generally asymptomatic, fibroids maycause abnormal bleeding, pelvic pain, pressure, and infertility,which often reduce or disappear after menopause.2

53/j.sult.2015.05.003by Elsevier Inc.

NIH/NCI, USA Cancer Center Support Grant under016672.

minal Radiology, Hospital Moinhos de Vento, Portodo Sul, Brazil.T MD Anderson Cancer Center, Houston, TX., UT MD Anderson Cancer Center, Houston, TX.

sts to Priya R. Bhosale, MD, UT MD Anderson Cancerler St, Unit 1473, Houston, TX 77030. E-mail: Priya.son.org

Fibroids arise from uterine smooth muscle myometrium,composed of disordered smooth muscle cells and abundantextracellular matrix. Grossly, fibroids vary in size and num-ber.1,2 They are classified as (1) submucosal (adjacent to or inthe uterine cavity), (2) intramural (entirely within the myome-trium), and (3) subserosal (distort the outer contour or surfaceof the uterus). Moreover, subserosal and submucosal fibroidscan be pedunculated (attached to the uterus by a stalk),extending from the external uterine surface or within theuterine cavity (intracavitary); pedunculated fibroids can rarelytorse, leading to infarction (Fig. 1).3-5

Themyometrium, exposed to repeated hormonal influencesduring reproductive years, is vulnerable to mutations. In fact,the single-gene somatic defect (MED12 mutation) is seen inmost fibroids. Chromosomal rearrangements are often com-plex and diverse, explaining the variable growth, dormancy,and regression, and also the heterogeneous response tomedical therapy. Fibroids commonly undergo degeneration,particularly if they outgrow their blood supply. Types ofdegeneration include hyaline, myxoid, cystic, red (carneous orhemorrhagic), and sarcomatous.1,2

MRI is the most accurate imaging technique for fibroiddetection and localization. Nondegenerated fibroids classicallyappear as well-defined, rounded homogeneous masses, withdecreased T2-weighted signal intensity and intermediate T1-weighted signal intensity comparedwith normalmyometrium.Cellular fibroids (with more cellular compound and lessextracellular matrix) have high T2 signal intensity and greaterenhancement.1-4 Somefibroids have a rimof T2hyperintensityrelated to dilated lymphatics, veins, or edema that may

1

Figure 1 A 31-year-old woman presenting with acute pelvic painsecondary to an infarcted fibroid. Sagittal T2-weighted (A) MR imageshows intermediate to hyperintensefibroid (black asterisk) protrudinginto the rectouterine space, connected posteriorly to the lower uterusby a stalk (arrow). Large hypointense fibroid superiorly (whiteasterisk) should be noted. (B) Contrast-enhanced MR image showsabsent enhancement of the posterior pedunculated fibroid (blackasterisk) compatible with infarction in the context of acute torsion,found on laparoscopy.

Figure 2 A 45-year-old woman with large subserosal fibroid. SagittalT2-weighted MR image shows the hypointense fibroid (asterisk) withT2 hyperintense rim (arrow), attributed to dilated vessels, andlymphatics and edema or both.

Figure 3 A 41-year-old woman with submucosal fibroid with cysticdegeneration. Sagittal T2-weighted MR image shows heterogeneouspredominant T2 hyperintense signal in keeping with cystic degenera-tion (asterisk).

G. Leursen et al.2

enhance on postcontrast images (Fig. 2).1,2 It should be notedthat this T2 signal is not considered degeneration.2

The presence of degeneration may alter the appearance ofthe fibroid in MRI.5,6 Hyaline degeneration is the mostcommon, occurring in more than 60% of the fibroids. OnMRI, hyalinizationwithin thefibroid is characterized by diffusedicreased T2 signal. Cystic degeneration, found in 4% offibroids, is seen on MRI as well-defined areas of internal fluid(high T2 signal intensity, Fig. 3). Myxoid degenerationrepresents cystic foci of gelatinous material, either abundantor interspersed between smoothmuscle cells.OnMRI,myxoiddegeneration also shows low T1 signal and high T2 signal

intensity, but in postcontrast images it may have minimalenhancement around themucinous lakes or clefts (Fig. 4). Reddegeneration is related to massive hemorrhagic infarction,resulting in coagulative necrosis, and it is most often foundduring pregnancy or is related to oral contraceptives. OnMRI,red degeneration has variable signal intensity, with diffuse T1hyperintensity and variable T2 signal intensity or even aperipheral halo of T1 hyperintensity and T2 hypointensity.Calcifications are found in 4% of fibroids and appear ashypointense, nonenhancing areas on all MRI sequences.5,6

Figure 4 A 36-year-old woman with fibroid with myxoid degenera-tion. Axial T2-weighted MR image shows predominantly T2 hypoin-tense mass (asterisk) with cystic spaces (arrows). Contrast-enhancedaxial fat-suppressed T1-weightedMR image (B) shows intense stromalenhancement of themass (asterisk) and nonenhancement of the cysticspaces representative of myxoid degeneration (arrows).

Figure 5 A38-year-oldwomanwith lipoleiomyoma. Axial T1- andT2-weighted MR images show hyperintense signal (asterisk) indicativeof fat.

MRI of uterine neoplasms 3

Lipoleiomyomas, rare and seen only in 0.8% patients, arethought to reflect a variant of fibroids containing macroscopicfat. On MRI, these tumors follow fat signal on all sequences,characterized by T1 and T2 hyperintensity, signal loss on fat-saturated sequences, and India ink artifact on out-of-phaseimaging (Fig. 5).6 Currently, there are no reliable imagingcriteria for accurate diagnosis of degeneration into or de novoleiomyosarcoma.Rare and unusual fibroid growth patterns, such as atypical

extrauterine locations and aggressive invasive growth, havebeen described: intravenous leiomyomatosis (growth intoveins); metastasizing leiomyoma (spread to distant organs,especially lung); diffuse leiomyomatosis (diffuse growththroughout the uterine parenchyma, usually innumerablesmall nodules symmetrically enlarging the uterus); peritonealdisseminated leiomyomatosis (dissemination throughout theperitoneal cavity); retroperitoneal leiomyomatosis (growth in

the retroperitoneum, usually broad ligament); and parasiticleiomyomatosis (when a pedunculated leiomyoma loses itsconnection by torsion and attaches to other structure withparasitic vessels).2,5

Therapeutic approaches for uterine fibroids include expect-antmanagement,medical treatment, surgery (myomectomy orhysterectomy), uterine artery ligation or uterine artery embo-lization (UAE), and high-intensity focused ultrasound abla-tion.6-8 Management depends on many factors, includingfibroid size; number and location, as well as the presence ofsymptoms; patient age; and childbearing desire.7,8 Hysterec-tomy is the definitive treatment of fibroids, though minimallyinvasive procedures such as embolization and ablation arebecoming useful, uterine-sparing alternatives.6-8

MRI is important in pretreatment and posttreatment fibroidevaluation.3 For example, cervical fibroids may not respond toUAE because of alternate blood supply; nonenhancing fibroidsare also less likely to respond. Treatment of pedunculatedfibroids should be avoided particularly if the stalk is less than2 cm, as they can detach after treatment. Following therapy,a decrease in uterine and fibroid volume and coagulative

G. Leursen et al.4

necrosis of fibroids indicate response (Fig. 6). OnMRI, treatedfibroids become smaller, with well-defined T1 signal ofincreased intensity, andmore homogeneous T2 signal withoutenhancement in the intensity. Continued growth after treat-ment raises a concern of malignancy.3

PolypsEndometrial polyps, seen in 10%-40%ofwomen, are themostcommon pathologic lesions of the uterine corpus.9 They oftenpresent with abnormal premenopausal or postmenopausalbleeding.10

Endometrial polyps are benign localized overgrowths of theendometrium; they consist of stroma of dense fibrous tissue orsmooth muscle cells, thick-walled vessels, and endometrialglands.9-11 The endometrial polyps vary in size and can bemultiple in 20% of the cases. Patients treated with tamoxifenhave an increased incidence (8%-36%) of polyps.11,12 Mostpolyps are small and incidental, but can be can be associatedwith endometrial hyperplasia and carcinoma.9,10,12

On MRI, polyps are generally well-circumscribed (70%),isointense on T1 signals, and hypointense on T2 signals (80%)relative to normal endometrium.11 Polyps typically have rapidearly and persistent enhancement or gradually increasingenhancement, though the degree of enhancement varies withrespect to the outer myometrium (strong ¼ 17.5%, moderate¼ 52.5%, andweak¼ 30%).11 In few cases, a stalk can be seen,particularly when outlined by intracavitary fluid (Fig. 7).9,12,13

Polyps can also have a central fibrous core (low T2 signalintensity), intratumoral cysts (discrete smooth-walled cysticstructure of highT2 signal intensity), andhemorrhage (highT1signal intensity), described by Hase et al11 in 75%, 55%, and35%, respectively.9,11 Central fibrous core and intratumoralcysts favor benign polyps, whereas endometrial invasion,necrosis, and irregular internal “cystic” areas suggest endome-trial cancer.9 Polyps, in contrast to endometrial cancer,typically enhance avidly.11,14 Polyps demonstrate lessrestricted diffusion than malignant lesions; Fujii et al15

reported a mean apparent diffusion coefficient value of 1.44� 0.34 for benign lesions and 0.98 � 0.19 for malignantlesions with an accuracy of 92%.15-18

Endometrial polyps are typically removed to alleviatesymptoms and to evaluate for atypical hyperplasia or carci-noma or both.10-12 The risk of malignancy is related to polypsize and patient age. In the past, treatment was hysterectomy,but today, minimally invasive procedures such as hystero-scopic polypectomy, endometrial ablation, and postoperativeinsertion of a levonorgestrel intrauterine device are used.10

Figure 6 A 43-year-old woman before and after uterine arteryembolization. Sagittal T2-weighted MR images: (A) preuterine and(B) postuterine artery embolizations showmarked reduction in uterusandfibroid size. It should be noted that the individualfibroids becomesmaller, more well defined, and homogenous in signal intensity afterembolization (asterisk).

AdenomyosisAdenomyosis, seen in 21%-47%, is more common in pre-menopausal multiparous women.19-22 Two-thirds of patientsare symptomatic, experiencing menometrorrhagia, dysmenor-rhea, and pelvic pain.19,21,22 Associationswith endouterinesurgery, multiparity, and tamoxifen are reported.19,21,22

MRI of uterine neoplasms 5

Adenomyosis is defined as ectopic endometrial mucosawith-in the myometrium and adjacent smooth muscle hypertrophy.It often coexists with other hormone-dependent pelvic lesions,

namely fibroids, deep pelvic endometriosis, polyps, and endo-metrial hyperplasia.19 Adenomyosis can be focal (with one orseveral foci) or diffuse (with numerous foci spread throughoutthe myometrium), superficial or deep (penetrating more thanone-third of the myometrium), and is often asymmetric.19,21,23

Adenomyoma represents a nodular aggregate of endometrialglands with compensatory hypertrophy of surroundingmyometrium.20,23

MRI has a sensitivity of 70%-88%, specificity of 86%-93%,and accuracy of 85%-90% for diagnosis of adenomyosis.20-26

Findings include (1) globular uterus with regular contours;(2) asymmetric myometrial thickening (more common of theposterior wall); (3) focal or diffuse junctional zone (JZ)thicknessZ12 mm; (4) greatest JZ to myometrium thicknessratio440%-50%; and (5) myometrium foci of high T2 signalintensity and sometimes T1 signal intensity.19-21,23-26 JZthickening more than 12 mm is highly predictive of adeno-myosis (Fig. 8); JZo 8 mmpractically excludes the diagnosis.A thickness between 8 and 12 mm is indeterminate andadditional findings should be evaluated.19-21,23 The high-T2-signal-intensity foci reflect dilated fluid-filled endometrialglands (Fig. 8).19,24 This sign is highly specific, but seen inonly approximately half of the cases.21,23

JZ thickness varies in response to several conditions that needto be considered to avoid misdiagnosis.19-21,24 The JZ thickenswith age up to approximately 50 years and then starts to thin,being thinner or absent during themenopause.During themen-strual cycle, JZ thickness is variable; it is the thickest between8 and 16 days. Pregnancy, contraceptive pills, and gonado-tropin-releasinghormone agonist cause the JZ to get thinor evendisappear. Myometrial contractions, focal wedge-shaped areasof low T2 signal intensity, which bulge the uterine cavity, causepseudothickening of the JZ and mimic adenomyosis, thoughthey can be differentiated by their transient nature.19-21,24

Adenomyoma is seen on MRI as a poorly defined mass-likelesion of low T2 signal intensity containing internal high T2signal intensity (and occasionally T1 signal) foci (Fig. 8).Like fibroids, adenomyomas can be intramyometrial, subser-osal, and submucosal, including intracavitary growth (polypoidadenomyoma).19-21 Hemorrhagic cystic adenomyosis(adenomyotic cyst) is related to bleeding of adenomyosis,characterized on MRI by high T1 signal intensity reflectinghemorrhage or even fluid-fluid levels.19,21

Treatment of adenomyosis depends on the presence ofsymptoms, patient age, and future childbearing desire.19,21

Asymptomatic women do not require treatment.19 Medicaltreatment consists of hormonal therapy or nonsteroidalanti-inflammatory drugs or both.19,21,22 Surgical optionsinclude hysterectomy, myometrial or adenomyoma excision,

Figure 7 A 37-year-old woman with endometrial polyp. (A) SagittalT2-weighted MR image shows the polyp (asterisk) with stalk arisingfrom the endometrium (arrow). Axial T2-weighted (B) and fat-suppressed contrast-enhanced (C) MR images show the avidlyenhancing polyp with stalk arising from the endometrium (arrow).Well-circumscribed T2 hypointense fibroid with heterogeneousenhancement (asterisk) should be noted. The patient also incidentallyhas diffuse infiltrating rectal cancer.

Figure 8 A 35-year-old woman with adenomyosis and focal adeno-myoma. Sagittal and axial T2-weighted (A) MR image showsthickening of the junctional zone greater than 12 mm (white line)and more focal mass-like area compatible with an adenomyoma(asterisk) containing characteristic T2 hyperintense foci (arrow).

G. Leursen et al.6

myometrial reduction, and endometrial ablation or resec-tion.19,21,22 UAE may improve or resolve symptoms, especiallythe short-term ones, though with increased risk of recur-rence.19,22 Recently, high-intensity focused ultrasound ablationhas shown promising results for adenomyosis treatment.22 OnMRI, reduction of uterine size, decrease in JZ thickness, andinfarction of focal lesions can be seen following treatment.19

Figure 9 A 51-year-old woman with tamoxifen-induced endometrialhyperplasia and diffuse polyps. Sagittal T2-weightedMR image showsheterogeneous thickening of the endometrium related to hyperplasiaand polyps in a patient treated with tamoxifen.

Endometrial Hyperplasia>Endometrial hyperplasia has an incidence of 133 per100,000 woman-years, and 389 per 100,000 woman-years

in women aged between 50 and 54 years. In patients withnormal menstrual cycle, endometrial hyperplasia is seen in0.5%-5%.27 In patients with abnormal bleeding, endometrialhyperplasia is found in 2.5% and most of them arepostmenopausal.28 It commonly results from unopposedestrogen or sequential estrogen-progesterone hormonereplacement therapy. Endometrial hyperplasia can occur inpremenopausal women with polycystic ovary disease andanovulatory cycles. Obesity and tamoxifen therapy are knownrisk factors (Fig. 9).12,29,30

Endometrial hyperplasia is characterized by excessive endo-metrial gland proliferation, with an increased glands to stromaratio.12,29 Endometrial hyperplasia is a precursor to endome-trial carcinoma.28-30 The most widely used histologic classi-fication system (World Health Organization) evaluatesarchitectural features and cytologic atypia to identify precursorlesions: 1—simple hyperplasia; 2—complex hyperplasia; 3—simple hyperplasia with atypia; and 4—complex hyperplasiawith atypia.12,27,29,30. Progression rates to carcinoma are 1%,3%, 8%, and 29% for the 4 precursor classifications, respec-tively.29 In women undergoing hysterectomy for biopsy-proven atypical endometrial hyperplasia, approximately 40%have concomitant carcinoma on surgical pathology.29,30

MRI is generally used only for problem solving, to excludeother diagnoses, like adenomyosis. The imaging appearance isnonspecific and may parallel early endometrial carcinoma,cystic atrophy, and endometrial polyps.12 In postmenopausalwomen, an endometrial thickness of 5 mm or more identifies95% of all carcinomas and an endometrial thickness less than4 mm has a 1% probability of cancer. In premenopausalwomen, there are no reliable criteria for differentiating benignand malignant endometrial hyperplasia.18,30

MRI of uterine neoplasms 7

OnMRI, endometrial hyperplasia is typically diffuse, with awell-defined endometrial-myometrial interface (Fig. 9). Thethickened endometrium is isointense or slightly hypointenseon T2 relative to normal endometrium (Fig. 9).12,18 Ondynamic contrast-enhanced (DCE)-MRI, endometrial hyper-plasia shows progressive enhancement, enhancing similar to orgreater than adjacentmyometrium.12-14 Sometimes, small low-signal-intensity cystic foci (cystic glandular dilatations) can beseen on delayed contrast-enhanced images.12,13 Diffusionweighted imaging (DWI) has been shown to be helpful indifferentiating malignant from benign lesions, including endo-metrial hyperplasia, with reported sensitivity and specificity of96% and 95%, respectively.16-18

Endometrial thickening is evaluated by curettage or biopsy.Management options can be surgical and nonsurgical.12,29,30

Simple and complex hyperplasia without atypia is usuallytreatedwith hormonal therapy (progesterone) and followed byimaging or endometrial sampling or both.12 Total hysterec-tomy is the current treatment of atypical endometrial hyper-plasia or endometrial intraepithelial neoplasia.30

Figure 10 A 30-year-old woman with endometrioid adenocarcinoma.Sagittal T2-weighted MR image shows solid tumor (asterisk) andsurrounding cystic hyperplasia.

MalignantEndometrial CancerEndometrial carcinoma is the most common gynecologic and10th most commonmalignancy, with an incidence of 24.6 per100,000women per year.31 It is most common inwomen aged45-74 years, withmedian age at diagnosis of 62 years.31Most ofthe endometrial cancers are diagnosed at an early stage (68%)with 5-year survival rate of 81.5% overall, 17.5% for metastaticdisease, and 95.1% for localized disease.31 Symptoms includeabnormal uterine bleeding and vaginal discharge.32 The mainrisk factor is exposure to unopposed estrogen, exogenous(hormone replacement) or endogenous (anovulation inpolycystic ovary syndrome, estrogen-producing tumors, andexcessive peripheral conversion in adipose tissue in obesity).Tamoxifen, nulliparity, infertility, early menarche, and latemenopause are also known risk factors.12,32 Combined orprogesterone-based oral contraceptive pills are protective.Lynch syndrome (hereditary nonpolyposis colon cancer) andCowden syndromehave increased risk of endometrial cancer.32

Endometrial carcinomas are classified into 2 major types(type I and type II). Type I tumors comprise 80% and includegrade 1 or 2 endometrioid histology. These tumors arehormone responsive and have favorable prognosis. Type IItumors comprise 10%-20% and include grade 3 endometrioidand nonendometrioid carcinomas (serous, clear cell,mucinous, squamous, transitional cell, mesonephric, andundifferentiated). These tumors are of higher grade and havepoor prognosis, without clear association to estrogen stim-ulus.33 Endometrioid carcinoma has a different genetic profilefrom that of nonendometrioid neoplasms. The former showsmicrosatellite instability and specificmutations of PTEN,K-ras,and β-catenin genes, whereas in the latter, p53 mutationspredominate.33

MRI in diagnosis and staging of endometrial carcinomauses a multiparametric approach, including high-resolution

T2-weighted, DW, and DCE image acquisitions.34,35 Thetumor shows intermediate T2 signal intensity relative tonormal endometrium, and mildly T2 hyperintesity comparedwith myometrium, the latter of which helps determine thedepth of myometrial invasion (Figs. 10 and 11).34-36

Onquantitative evaluation, apparent diffusion coefficient valueis lower in endometrial carcinoma (0.86-0.98) than innormal endometrium (1.28-1.65), indicating restricteddiffusion.15-18,34,35,37-40 Contrast-enhanced images distinguishtumor from blood products and tumor from normal myome-trium; tumor enhances to a lesser degree than both endome-trium and myometrium in equilibrium and delayed contrast-enhanced images (Fig. 11).14,34-36,41,42

The staging of endometrial cancer is based on InternationalFederation of Gynecology and Obstetrics (FIGO). The mostimportant factors of local staging on MRI are depth ofmyometrial invasion and cervical stromal involvement.34,35

Depth of myometrial invasion, defined as less than or greaterthan 50% thickness of the myometrium, is best assessed onDCE images, as JZ thinning in postmenopausal patients, andunderlying adenomyosis or fibroids can confound assessmenton T2-weighted images alone.12,34,35 Cervical stromal involve-ment is characterized by extension into the cervix, best seen inT2-weighted (sagittal) or DCE images. High-resolution T2-weighted imaging has a 55%-77% accuracy for staging.34 Theaddition of DCE improves accuracy to 83%-98%.12,34-36,40,42

DWI has shown high accuracy for tumor staging (62%-90%)and may be helpful in noncontrast examinations.34,35,37,43

Endometrial cancer spreads via different routes (direct,lymphatic, transtubal peritoneal seeding, or hematogenous).Metastases to paraaortic lymph nodes before pelvic lymphnodes can occur via gonadal vessels.12 The involvement oflymph nodes based on size criteria has substantial limitations.

Figure 11 A 67-year-old woman with endometrial cancer. Sagittal T2-weighted (A) and contrast-enhanced fat-suppressed T1-weighted(B) images show disruption of the junction zone (arrow in A) andgreater than 50% tumor invasion into the myometrium (arrow in B).

G. Leursen et al.8

Incorporation of morphologic features (internal heterogeneity,spiculated margins, necrosis, and signal intensity comparableto that of the primary tumor) improves lymph node evalua-tion.34,35 The incidence of nodal involvement correlates withdepth of myometrial invasion: 3% if less than 50%myometrialinvasion, 46% if greater than 50%.12,34,35

The management of endometrial cancer is based on stage ofthe disease. The International Federation of Gynecology andObstetrics (FIGO) recommendation is total hysterectomy,bilateral salpingo-oophorectomy, bilateral pelvic and paraaorticlymphadenectomy, peritoneal washing, and omentalbiopsy.32,35 However, in patients with early stage disease, therole of lymphadenectomy is controversial and these womenmay be appropriately treated with minimally invasive laparo-scopic hysterectomy and bilateral salpingo-oophorectomy,

decreasing morbidity and hospital stay.32,35 In selected patientswith cervical or vaginal involvement, adjuvant radiation therapymay be used. Chemotherapy is reserved for advanced disease.44

Uterine SarcomasUterine sarcomas are a rare and heterogeneous group oftumors that account for 5%-8% of all uterine malignancies,and include leiomyosarcoma, endometrial stromal sarcoma(ESS), and malignant mixed epithelial and mesenchymaltumors (MEMTs). ESS and leiomyosarcoma are composed ofpurely nonepithelial components, whereas MEMTs are com-posed of epithelial andmesenchymal components. The clinicalpresentation is nonspecific but these tumors classically presentas rapidly growing masses, which may be accompanied byvaginal bleeding and abdominal or pelvic pain.45-49 Associa-tions include African-American ethnicity, long-term tamoxifentherapy, and previous pelvic irradiation.47

Leiomyosarcomas are a common subtype, representing40%, and arising from the myometrial smooth muscle.46-48

Diagnosis is based on atypia, mitosis, and tumor necrosis.46,48

They are usually solitary intramural masses and may ariserarely from a fibroid.46-48 Less than 0.5% of uteri removed forpresumed fibroids have incidental leiomyosarcoma. Patholog-ically, it can be difficult to distinguish leiomyomas withabundant mitosis from well-differentiated leiomyosarcomas.46

ESSs arise from endometrial stroma, accounting for 10%-15% of uterine sarcomas and are characterized by resemblanceto endometrial stroma with cells of varying atypia (well differ-entiated or low grade to undifferentiated or high grade).46-48

Extrauterine ESS may originate in endometriosis.46 Associationwith tamoxifen and estrogen use has been reported.47

MEMTs can be benign (adenofibromas and adenomyomas)or malignant (adenosarcomas, carcinosarcomas, and carcinofi-bromas). In adenosarcomas, the epithelial component isbenign and mesenchymal component malignant; in carcinofi-bromas the epithelial component is malignant and mesenchy-mal component benign; in carcinosarcomas both componentsare malignant. The mesenchymal aspect of MEMTs can havehomologous (elements normally found within the uterus) orheterologous components (elements not usually seen withinthe uterus, including benign or malignant cartilage, fat, bone,and rhabdoid tissues).46,49

Carcinosarcoma, formerly calledmalignantmixedmülleriantumor, is the most common uterine sarcoma, representingnearly 50% of all uterine sarcomas and 2%-3% of all uterinemalignancies.45,46,48-50 This tumor behaves more like endo-metroid adenocarcinoma than like sarcoma, with commonrisk factors and similar patterns of clonality, lymphaticmetastases, and recurrence; however, the prognosis is generallypoor.46,48 It is accepted that carcinosarcoma represents meta-plastic transformation of carcinoma to sarcoma; someresearches argue that the carcinosarcoma represents an aggres-sive form of endometrial carcinoma.45,46,49 Associations tolong-term tamoxifen therapy and previous pelvic irradiationhave been reported.12,45,49

The 5-year survival rates vary according to the histologictype. Leiomyosarcomas for example, range from 18.8%-68%,

MRI of uterine neoplasms 9

ESSs from 25%-98%, and MEMTs from 22%-39% (carcino-sarcomas) to more than 80% (adenosarcomas).47,50,51

Imaging differentiation of leiomyosarcomas from leiomyo-mas is difficult. The most common MRI appearance is a largeinfiltratingmyometrialmasswith irregular, ill-definedmargins;heterogeneous T1 signal; intermediate- to high-intensity T2signal; and heterogeneous enhancement owing to areas ofnecrosis and hemorrhage (Fig. 12).47,48 These characteristicsdo not differentiate it from benign degenerating fibroids.48,52

Rapid growth remains suspicious for leiomyosarcoma thoughnot reliable.47,48,53 In a large retrospective study (n¼ 580), lessthan 3% of leiomyosarcomas showed rapid growth and

Figure 12 A 63-year-old woman with rapidly growing pelvic mass,diagnosed with leiomyosarcoma in the context of multiple fibroids.Sagittal T2-weighted (A) and contrast-enhanced fat-suppressed T1-weighted (B) images showmarkedly heterogeneous appearing fibroid(arrow in A) containing irregularly enhancing internal soft tissue(arrow in B).

leiomyosarcoma was discovered in just 1 woman among 371women with rapidly growing masses (presumed fibroids).53

Restricted diffusion and T2 signal of the mass have shownpotential for differentiating benign from malignant tumors.54

ESS frequently appears as a polypoid endometrial mass onMRI, with low-intensity T1 and heterogeneous T2 signals.These tumors involve the myometrium and have a tendencyfor lymphatic and vascular invasion, appearing as worm-likebands of low-intensity T2 signal within areas of myometrialinvolvement.47,48 Compared with endometrial carcinoma,ESS is larger with more delayed contrast enhancement,irregular nodular margins, and nodular extension into themyometrium.47,48

Malignant mixed müllerian tumors have similar imagingcharacteristics to those of endometrial carcinoma.45,47,48 MRIfindings of carcinosarcoma have been describedmainly in caseseries; these tumors are generally well defined with the tumorepicenter in the endometrium (88%), cervix (8%), or myome-trium (4%), and can present even as prolapsed uterine tumors(Fig. 13).45,49,50,55,56 The tumor typically has high-intensity orheterogeneous T2 signal relative to myometrium and can haveintratumoral T1 hyperintensity related to hemorrhage.Enhancement pattern varies, though delayed heterogeneousenhancement contrasts with the relative hypoenhancement ofmore common endometrial carcinomas.45

The primary treatment of uterine sarcoma is surgery. Pelviclymphadenectomy and adjuvant radiotherapy are usuallyperformed, even in early stage disease, owing to the highincidence of lymph node involvement and pelvic recurrence.Chemotherapy may be indicated, especially in MEMTs, owingto the epithelial component.48,50

Figure 13 A 61-year-old woman with uterine carcinosarcoma. SagittalT2-weighted MR image shows the classic prolapse of a polypoiduterine mass (arrow) into the vagina or vulva, known as the “broccolisign.” Abnormal heterogeneous thickening of the endometrial cavityrelated to combined tumor and blood products (asterisk) should benoted.

Figure 14 A 23-year-old womanwith gestational trophoblastic disease,rising beta-HCG after dilation, and curettage for molar pregnancy.Sagittal T2-weighted (A) and contrast-enhanced fat-suppressed T1-weighted (B) images show an avidly enhancing uterine mass (arrow)with invasion into the myometrium.

G. Leursen et al.10

Gestational trophoblastic diseaseGestational trophoblastic disease (GTD) has abnormal tropho-blastic proliferation and comprises a spectrum of lesions withvarying malignant potential.57-59 The trophoblast is a richlyvascular gestational tissue that provides nourishment betweenmaternal endometrium and developing embryo. This tissueproduces beta-human chorionic gonadotrophin (β-hCG),which is most frequently elevated in GTD.57,58 GTD is dividedinto 5 main types: (1) hydatidiform mole, (2) invasive mole,(3) choriocarcinoma, (4) placental-site trophoblastic disease(PSTD), and (5) epitheloid topoblastic disease.The clinical presentation, laboratory findings, and prognosis

vary among the different types of GTD, with moles mostcommonly manifesting as vaginal bleeding or as missed orincomplete abortions.59 Gestational hypertension in the firsttrimester is virtually diagnostic of hydatidiform mole.59 Over-all, 80%-85% of molar pregnancies follow a benign coursewithout local recurrences or metastases, 15%-20% locallyinvasive, and 3%-5%developingmetastases.59 Vaginal seedingis seen in up to 30% of the cases. Metastases are primarilyhematogeneous, most commonly to the lungs (76%-87%),liver (10%), and brain (10%), and tend to be hypervascularwith propensity to hemorrhage.57,59,60

Hydatidiform moles, either complete or partial, result fromaberrant fertilization and represent 80% of all GTDs, with anincidence of 0.6-1.1 per 1000 pregnancies.57-61 Both subtypesare premalignant, with 15% of complete moles and0.5%-1.0% of partial moles undergoingmalignant transforma-tion.57-59 The invasive lesions include invasive mole, chorio-carcinoma, and PSTD; epitheloid topoblastic disease is a rarevariant of PSTD. Hydatidiform moles and choriocarcinomaarise from villous trophoblast, which produces β-hCG,whereas PSTD arises from interstitial trophoblast.57-60 Theterm gestational trophoblastic neoplasia or persistent tropho-blastic neoplasia refers to invasive GTD, including invasivemole, choriocarcinoma, and PSTD.57,59

Complete moles are characterized by absence of an embryoand severe villous swelling and trophoblast hyperplasia,resembling a bunch of grapes. Partial moles usually havean embryo that may survive up to the second trimesterand exhibit less intense villous swelling and patchy hyper-plasia.57-60 Invasive moles extend into or beyond themyometrium, considered locally invasive nonmetastasizingneoplasm.57,61 Choriocarcinoma represents malignant troph-oblast proliferation, arising from any type of pregnancy (50%from moles, 25% term or preterm, and 25% aborted orectopic) and occurring in 1 of 20,000-50,000 pregnancies.58,59

It is highly malignant with extensive necrosis and hemorrhageand early vascular invasion resulting in metastases even if theprimary tumor is small.57,60

Diagnosis of GTD is based on clinical history and examina-tion, quantitative β-hCG titers, and pelvic ultrasonography.57

MRI does not play a role in routine evaluation butmay be usedfor problem solving and better delineating extent of myome-trial and extrauterine invasion in invasive mole and chorio-carcinoma.57,59,62,63 In 25%-40% of patients with completemoles, theca lutein cysts are seen, resulting in bilateral multi-cystic ovarian enlargement.59,60

MRI of molar pregnancy is nonspecific, and difficult to bedistinguished from those of retained products of concep-tion.57,61,62,64,65 Findings include expansion of the endome-trial cavity containing heterogeneous low-intensity T1 andhigh-intensity T2 signal with multiple cystic spaces represent-ing hydropic villi, with enhancement of tumor and surround-ing cystic spaces (Fig. 14).57,59-64 Invasive moles infiltrate anddisrupt the JZ and myometrium on T2-weighted and post-contrast images (Fig. 14).59,61-63 However, loss of zonalanatomy may also be observed after missed or incompleteabortions or recent curettage.62-65

The management of patients with GTD varies according tohistologic subtype. Molar pregnancies are treated preferably bysuction curettage. β-hCG, an excellent tumor biomarker, isuseful in tumor surveillance and recurrence.57-59 Invasivemoleand choriocarcinoma are treated primarily with chemotherapy(Fig. 15). Other recommendations for chemotherapy include

A

B

Figure 15 A 23-year old with gestational trophoblastic disease, aftertreatment with chemotherapy. Sagittal T2-weighted (A) and contrast-enhanced fat-suppressed T1-weighted (B) images show decrease insize and enhancement of the previously seen uterine mass (arrow)compatible with treatment response.

MRI of uterine neoplasms 11

persistently elevated or rising hCG levels and metastaticdisease.57-59 Surgery and radiotherapy are reserved for high-risk patients.59

Other Uncommon Uterine Malignancies(Small Cell Cancer and Lymphoma)Neuroendocrine Tumor (Small Cell Cancer)Small cell carcinoma is a group of malignant neoplasmsshowing neuroendocrine differentiation, mainly arising in thelung and digestive tract.66-68 In the uterus, small cell carcino-mas are rare, accounting for less than 1% of all endometrialmalignancies.66-70 On pathology, these tumors are character-ized by sheets of small densely packed cells, hyperchromatic

nuclei, high nuclear-to-cytoplasmic ratio, and positivemarkersfor neuroendocrine differentiation on immunohistochemis-try.66,67,69-72 Uterine small cell carcinomas exhibit aggressivebehavior, local invasion, extrauterine spread, early lymph nodeinvolvement, and distant metastasis at diagnosis.66,67,71-73

Clinically, the most common symptoms include abnormalvaginal bleeding and pelvic pain.67,69,73 Uterine small cellcarcinomas may produce and secrete metabolically activeamines and peptides and cause paraneoplastic syndromes,including syndrome of inappropriate secretion of antidiuretichormone, retinopathy, Cushing syndrome, and membranousglomerulonephritis.66,68,69,71,73 These tumors have beendescribed in a wide age range of women (23-84 years), witha mean age of 60 years.67,69 The prognosis is poor and mostpatients present with advanced disease.67,69,72,73

MRI features of uterine small cell carcinoma are limited tocase reports, and generally speaking indistinguishable fromthose of other uterine neoplasms.66-73 Typically, the tumor isseen as an intracavitarymass, frequently associatedwith diffusemyometrium invasion and extrauterine spread.66,67,69 OnMRI, the tumor usually has low T1 and high T2 signalintensity.66-69,72,73 The tumor may demonstrate irregularheterogeneous enhancement because of tumor infiltration,hemorrhage, and necrosis,66,67,73 though a homogeneousenhancement resembling lymphoma has also beendescribed.68 Enlarged lymph nodes and distant metastasisare commonly found at diagnosis.66,67,73

The treatment of uterine small cell neuroendocrine carcino-mas includes chemotherapy along with local treatment, whichmay be surgery, radiotherapy, or both. The surgical approachtypically is total hysterectomy and pelvic lymphadenectomy.Hormonal therapy and octreotide are also sometimesused.69-72

LymphomaUterine lymphomamay be primary or secondary. Distinguish-ing primary from secondary lymphoma is important as theydiffer in treatment and prognosis.74 Involvement of the femalereproductive organs in secondary lymphoma has beenreported in 40% of cases in autopsy series, whereas primaryuterine lymphomas are rare, representing less than 1% ofextranodal lymphomas.74,75 Most of the primary uterinelymphomas are non-Hodgkin lymphomas , themost commonbeing diffuse large B-cell and follicular lymphoma.74 Bypathology, tumor is characterized by infiltrates of lymphocytesand plasma cells in the uterine stroma.74 These tumors aredifficult to detect on Papanicolaou test as they may not involvethe epithelium. For this reason, primary lymphoma usually is alarge lesion at diagnosis.74 Lymphoma infiltrates the uterus,causing diffuse enlargement without disruption of the uterinearchitecture; polypoid lesions are less common. Local spread ismost common to the vagina and bladder.74-76 The age range ofpresentation is broad (20-80 years) with a mean age of 40years, and most patients present with vaginal bleeding.74,75

MRI is a useful imaging modality to assess the extent ofuterine lymphoma.74 Lymphoma causes homogeneousenlargement of the uterus with preservation of the zonalarchitecture on T2-weighted images, though loss of zonal

G. Leursen et al.12

anatomy and endometrial disruption have also beendescribed.74,77,78 Typically, the lesion has a low to intermediateT1 signal and high T2 signal intensity.74-78 Thoughno imagingfindings have been described on DWI in uterine lymphoma,lymphomas in general show restricted diffusion because ofhypercellularity and little extracellular space.79 The tumortypically enhances homogenously, though it can be heteroge-neous.74,77,78 Differentiating lymphoma from other pelvicmalignancies is crucial to prevent unnecessary surgery. Stand-ard treatment is with chemotherapy or radiation therapy.74,75

ConclusionAwide spectrum of benign andmalignant pathologies occur inthe uterus. MRI is helpful in delineating the anatomy, extent ofgrowth in both benign and malignant diseases, staging ofcommon and uncommon primary uterine malignancies, andresponse to targeted and systemic treatment.

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