[Leiomyoma]

• Benign mesenchymal tumor of uterine smooth muscle cells
• Most common uterine neoplasm affecting middle-aged women
• Usually asymptomatic, w/ no treatment required
• May cause abnormal bleeding /anemia, pain, menstrual disorder, subfertility, and bulk symptoms related to mass effects (constipation, frequent urination)
• Hormonally dependent: develops after menarche; regresses after menopause; may rapidly grow and bleed during pregnancy
• Often multiple (> 75%)
• Well-circumscribed mass w/ bulging, firm, whorled, white cut surface
• Composed of spindle cells arranged in intersecting fascicles

[Typical Imaging]

• Plain X-P/CT: Soft tissue mass; Often w/ mulberry-like calcification
• US: Solid, well-defined, concentric mass
• T1WI: homogeneous iso to myometrium; T1-high hemorrhage (rare)
• T2WI: homogeneous low; Signal increase due to degeneration; Speckled pattern due to hyalinization w/ edema
• DWI: low w/ low ADC (T2 blackout); Signal increase due to degeneration w/ high ADC (T2 shine-through)
• CE: Various, typically hypervascular on DCE-MRI
• MRS: bimodal choline and creatine peaks

Fig 1: Typical leiomyoma: Imaging findings

Fig 2: Typical leiomyoma: MR Imaging findings

[Location]

• FIGO Location-based Subclassification: Submucosal (FIGO 0-2), or others including intramural (FIGO 3, 4), subserosal (FIGO 5-7), or extra-uterine myometrium (FIGO 8): Cervical, Parasitic (Broad /Round ligaments)

Fig 3: FIGO Location-based Subclassification

Fig 4: FIGO-associated clinical symptoms

Fig 5: FIGO Location-based Subclassification

Fig 6: FIGO Location-based Subclassification

Subserosal leiomyomas:

• Bulky symptoms (Large lesions)
• FIGO 6-7 lesions may mimic ovarian tumors
• Beak sign (Claw sign): Edge of the adjacent uterus becomes beak-shaped
• Bridging vascular sign: Multiple curvilinear tortuous signal voids reflecting feeding vessels along the interface indicating uterine origin
• Myogenic Creatine peak is helpful in distinguishing T2-low fibrous ovarian tumors
• Pedunculated mass may cause torsion, and detachment into the peritoneum

Fig 7: Subserosal leiomyomas (FIGO 5-7)

Submucosal leiomyomas:

• Uncommon (5%)
• Abnormal bleeding, infertility, and recurrent pregnancy loss
• Originates from myometrium underlying the endometrium
• May appear as polypoid intra-cavitary mass, or prolapse through ext. os into the vagina (myoma delivery) w/ narrow stalk, composed of vascular connections and connective tissue as “Broccoli sign”
• Should be differentiated from cervical leiomyoma for adequate surgery
• May be edematous, T2-high mimicking epithelial tumors

Fig 8: Submucosal leiomyomas (FIGO 0-2)

Fig 9: Submucosal leiomyomas (FIGO 0-2)

Fig 10: Submucosal myoma delivery w/ “Broccoli sign”

Cervical leiomyoma

• Rare, and should be differentiated from delivered submucosal leiomyomas because surgical procedure may be different
• Large lesions may partially obstruct the urinary tract
• UAE may be ineffective due to alternate blood supply

Fig 11: Cervical leiomyomas (FIGO 8)

Broad ligament leiomyoma

• Subserosal leiomyomas may extend into the broad ligament
• Removal is feasible but difficult as there are many blood vessels
• Occasionally may become parasitic by developing a secondary blood supply
• The uterine artery and ureter are displaced and are therefore easily damaged during surgery, so preoperative diagnosis is important

Fig 12: Broad ligament leiomyomas

Parasitic leiomyoma

• Pedunculated subserosal leiomyoma which undergoes torsion, detaches from the uterus, and sustains its growth through neovascularization from adjacent tissues (e.g. broad ligament)

Diffuse /Disseminated peritoneal leiomyomatosis

• Usually in high-estrogen settings (pregnancy and oral contraceptive use) and spontaneous regression after hormone use has stopped
• Probably develop de novo after peritoneal metaplasia
• May arise postoperatively after morcellation during laparoscopic myomectomy

Fig 13: Parasitic leiomyomas Disseminated /Diffuse peritoneal leiomyomatosis

Intravenous leiomyomatosis

• Leiomyoma w/ intravenous growing
• Usually asymptomatic, however, may extend into IVC (>10%) w/ life-threatening symptoms
• Worm-like shape is characteristic
• Should be differentiated from endometrial stromal sarcoma which often involves adjacent vessels

Diffuse leiomyomatosis

• Symmetrically enlarged uterus w/ complete replacement of the myometrium by innumerable poorly defined, confluent leiomyomatous nodules
• Menorrhagia or dysmenorrhea, abdominal pain and infertility
• May be seen in patients w/ HLRCC
• Hormonal treatment fails to control the symptoms
• Hysterectomy is the standard treatment, and UAE is an effective alternative

Fig 14: Intravenous leiomyomatosis Diffuse leiomyomatosis

Various degenerations and subtypes of leiomyomas

According to WHO2020: Cellular; hydropic; apoplectic; lipo-; myxoid; dissecting leiomyomas and diffuse leiomyomatosis may show characteristic MR imaging findings. Other subtypes including leiomyoma with bizarre nuclei; fumarate hydratase–deficient; mitotically active; epithelioid leiomyomas may not show specific imaging findings

Cellular leiomyoma

• Benign hypercellular variant w/o mitosis and atypia, w/ less fibrotic tissue
• Less than 5%
• Occasionally w/ patchy hemorrhage, and w/ dilated intra-tumoral vessels as flow voids
• T2-high reflecting fluid-rich tissues w/ avid early enhancement; Mild diffusion restriction w/ low ADC reflecting hypercellularity

Fig 15: Cellular leiomyoma

Hydropic leiomyoma

• Edema is present in about 50% of leiomyomas
• Conspicuous zonal, watery edema, which separates tumor cells into thin and delicate cords or nests in hydropic leiomyoma
• T2-very high w/ CE

Myxoid leiomyoma (myxoid smooth muscle tumor)

• Extremely rare
• Gelatinous and sticky cut surface
• Cells widely separated by myxoid acid-mucin stroma. Lack atypia and mitotic activity
• May show clinically aggressive course including myxoid leiomyosarcoma
• T2-very high like hydropic leiomyoma, mucin (N-acetyl mucinous compounds) is revealed on MRS

Fig 16: Edema –Hydropic degeneration / Myxoid smooth muscle tumor

Apoplectic leiomyoma

• Hormonal therapy may induce multiple discrete hemorrhagic foci and hyalinization (apoplectic change)
• In pregnant patients or oral contraceptive use may cause hemorrhagic infarction (red degeneration) resulting from peripheral venous thrombus: T1-high and T2/SWI-low rim
• T1-high hyaline necrosis resulting from chronic infarction
• Calcification may occur in longstanding lesions

Fig 17: Apoplectic leiomyoma

Dissecting leiomyoma

• Irregular dissection by nodules of bland smooth muscle cells, often w/ conspicuous hydropic change
• May extend outside the uterus as cotyledonoid dissecting leiomyoma: distinctive gross features resembling cotyledon of the placenta
• Large lobulated mass: The intramural component dissects into the myometrium; The exophytic component tends to extend into the broad ligament
• T2-high due to edema and perinodular hydropic degeneration; DWI-slight high w/ high ADC (T2 shine-through)

Fig 18: Dissecting (cotyledonoid) leiomyoma

Lipoleiomyoma

• Small amount of fatty degeneration is not rare in leiomyomas
• Striking amount of mature adipocytes admixed with smooth muscle cells is lipoleiomyoma showing rapid growth after menopause due to fatty metaplasia of smooth muscle cells

Fig 19: Fatty degeneration -Lipoleiomyoma

STUMP (Smooth muscle tumors of uncertain malignant potential)

• Smooth muscle tumors that do not meet the criteria for either leiomyoma or leiomyosarcoma, and may actually contain both leiomyoma and difficult-to-diagnose leiomyosarcoma
• No comprehensive reports of imaging findings

Fig 20: STUMP (Smooth muscle tumors of uncertain malignant potential)

Leiomyoma mimickers (benign)

• Ademomyotic lesions: Typical adenomyosis appears as ill-defined T2-low lesion, and some variants may mimic leiomyoma. Hemorrhagic foci are suggestive findings
• Physiological transient myometrial contraction may mimic leiomyoma or focal adenomyosis, but may disappear during the examination
• Rare intramural tumors such as adenomatoid tumor, endometrial stromal nodule and PEComa may appear as leiomyoma-like well-demarcated masses.

Fig 21: Leiomyoma mimickers (Benign: adenomyotic lesion)

Fig 22: Leiomyoma mimickers (Benign)

Leiomyoma mimickers (malignant)

• Uterine sarcomas may mimic leiomyoma as well-demarcated myometrial mass, and diffusion restriction is suggestive of malignancy
• Sarcoma w/ massive necrosis w/o diffusion restriction mimics degenerated leiomyoma, peripheral residual viable area is diagnostic
• Rarely, may cause red degeneration w/ massive hemorrhagic necrosis

Fig 23: Leiomyoma mimickers (Malignant)

Leiomyosarcoma

• Uncommon (1-2%) uterine malignancy (malignant smooth muscle tumor)
• Affecting older women (> 50 years), but 15% ≤ 40 years
• Genital bleeding, palpable pelvic mass, and pelvic pain (overlapped w/ leiomyoma)
• Large (mean 10cm), irregular shaped, ill-demarcated mass w/ hemorrhage and massive necrosis; Destruction of myometrial margin is suggestive
• T2-inhomogeneous, w/ T1-high/SWI-low hemorrhage and unenhanced massive necrosis
• DWI-high w/ low ADC reflecting hypercellularity (≤905 x 10^-3mm²/s, small ROI, sensitivity of 88% and specificity of 100%)
• ESUR guideline shows criteria for differentiation from leiomyoma

Fig 24: European Society of Urogenital Radiology (ESUR) Guidelines: Differentiation between leiomyoma and leiomyosarcoma

Fig 25: Atypical uterine mass evaluation at MRI

Malignant transformation

• Rarely, leiomyosarcoma may arise from benign leiomyoma
• Rapid-growing heterogeneous mass w/ hemorrhagic necrosis arising from T2-low leiomyoma is suggestive of malignant transformation

Fig 26: Malignant transformation (leiomyosarcomas arising from leiomyoma)

Advanced MR technique for differentiation

MR Spectroscopy (MRS) measures various metabolites:

• Choline (Cho) peak reflects metabolic activity of cell membrane in solid tumors. Malignant tumors tend to show higher peaks reflecting high cellular proliferating activity. However, high-grade sarcomas often show massive necrosis and may cause low Cho concentration due to the decrease of viable tumor cells
• High lipid (Lip) peak associated with necrosis is suggestive for high-grade malignancy

Computed DWI (cDWI):

• High b-value images w/ better SNRs, w/ less sensitivity to T2 shine-through effects
• Signal decrease on high b-value cDWI (b≥1500) may suggest benignity

Fig 27: Advanced MR technique: MR Spectroscopy (MRS)/ Computed DWI (cDWI)

Susceptibility-weighted sequence (SWS):

• SWS visualize the magnetic susceptibility effects generated by local inhomogeneity of the magnetic field caused by hemorrhagic contents as signal voids
• SWS may be helpful for the diagnosis of uterine sarcoma by detecting intra-tumoral hemorrhage w/ high sensitivity
• SWS is also useful in diagnosing acute red degeneration

Fig 28: Advanced MR technique: Susceptibility-weighted MR sequences (SWS)

[Management]

Hysterectomy is a definitive treatment

Uterine-sparing alternatives:

• Medications: GnRH analog
• Myomectomy: hysteroscopic, laparoscopic, and open resection approaches
• Uterine artery embolization (UAE)
• Focused ultrasound (FUS)

Fig 29: Management strategy for Leiomyomas

Fig 30: Non-Surgery Management