Moving Toward Individualized Medicine for Uterine Leiomyomas

Abstract

Uterine leiomyomas are common and life-altering for many women. Despite a wide range of symptoms, varying characteristics of the uterus and the leiomyomas themselves, and many alternatives, hysterectomy accounts for almost three fourths of all surgical therapy, yet there is increasing evidence for a variety of procedural therapies for symptomatic leiomyomas and a new generation of medical therapies under development. With increasing evidence of long-term risk from hysterectomy and new data regarding leiomyoma biology, individualized medical approaches to leiomyomas are likely in the near future. Key biological attributes that influence this disease process are common driver mutations and the new appreciation of the interaction of smooth muscle cells and fibroblasts. Additionally, the interaction between cell types and steroid hormone responsiveness likely plays a role in pathogenesis that can be leveraged in individualized therapy. However, given the independent clonal nature of leiomyomas within the same uterus, moving in the direction of biopsies for individual leiomyomas to understand the biology is unlikely to be fruitful. Use of advanced imaging will likely continue to evolve not only to accurately predict malignant disease, including sarcomas, but to predict leiomyoma subtypes, response to therapy, or both. We predict the continued evolution of therapy from excisional or interventional therapies to medical therapies and ultimately prediction of at-risk individuals. Ideally, individualized therapies will offer primary prevention for women at high risk of leiomyomas and secondary prevention after initial treatment.

Figure 1.

Risks and benefits associated with hysterectomy with bilateral ovarian conservation at any age.^-,-*Although symptoms may be alleviated with other less invasive treatment options.

Figure 2.

FIGO classification system labels leiomyoma types 0 through 7 (A). FIGO classification can be more difficult to implement in patients with large (B) or multiple leiomyomas (C). BI, bladder; BW, bowel. Figure 2A used with permission of Mayo Foundation for Medical Education and Research. All rights reserved.

Figure 3.

Use of T2-weighted images, dynamic magnetic resonance imaging with contrast enhancement, and diffusion weighted imaging (with inset apparent diffusion coefficient map) for leiomyoma or leiomyosarcoma diagnosis. Benign leiomyoma: mildly heterogeneous low T2 signal (A), early and heterogeneous avid enhancement (B) no significant restricted diffusion (C). Degenerated leiomyoma: heterogeneous high T2-weighted signal (D) T1-weighted imaging with fat saturation shows homogeneous hypoenhancement (E) heterogeneous diffusion restriction (F). Leiomyosarcoma: infiltrative, ill-defined mass with intermediate T2 signal (G) enhancement of the viable tumoral tissue (H) and hyperintense on high B-value imaging with subsequent restricted dark signal on the apparent diffusion coefficient map (I).

Figure 4.

Typical leiomyoma demonstrates contrast enhancement on T1-weighted imaging (A) and has average stiffness (C). After uterine artery embolization, leiomyoma no longer enhances (B) and has increased stiffness (D).