Molecular Genetics of Uterine Sarcomas


Uterine sarcomas are a heterogeneous group of rare mesenchymal cancers, which includes tumours originating in both the smooth muscle of the myometrium and the endometrial stroma. They have variable course, although they are clinically aggressive as a group. Differentiating between various uterine sarcoma entities based on morphology and immunohistochemistry is feasible in many cases, but some specimens are challenging. Considerable knowledge has been gained in recent years regarding the molecular characteristics of these cancers, which may improve their diagnosis and impact on prediction, prognostication and treatment. This body of research has highlighted the genetic differences between leiomyosarcomas and their benign counterparts, leiomyomas, and allowed for classification of endometrial stromal sarcomas as low‐ or high‐grade. The relevance of these molecular changes in the therapeutic setting awaits future studies.

Key Concepts

  • Uterine sarcomas are a heterogeneous group of rare malignant mesenchymal tumours.
  • The diagnosis of uterine sarcomas based on morphology and immunohistochemistry may be challenging.
  • Analysis of fusion genes aids in the differential diagnosis between low‐ and high‐grade endometrial stromal sarcoma.
  • Undifferentiated uterine sarcoma is currently regarded as an aggressive variant of endometrial stromal sarcoma.
  • Uterine leiomyosarcomas have mutations in key cancer‐associated genes.
  • Leiomyomatosis tumours of uncertain malignant potential may harbour the molecular changes which characterise leiomyosarcomas.

Keywords: leiomyosarcoma; leiomyoma; endometrial stromal sarcoma; undifferentiated uterine sarcoma; uterus; molecular classification; diagnosis; prognosis

Figure 1. (a) Endometrial stromal cells with low‐grade atypia and multiple small vessels. (b) Endometrial stromal cells with higher mitotic activity compared to LG‐ESS and fewer vessels. (c) Tumour cells with more overt atypia and with high mitotic activity, lacking endometrial stromal differentiation. (d) Tumour cells with smooth muscle morphology, atypia and high mitotic activity, including atypical mitosis.
Figure 2. (a) CD10 in LG‐ESS. (b) Actin in LMS. (c) Desmin in LMS. (d) Caldesmon in LMS. (e) Smooth muscle actin in LMS.


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Further Reading

Davidson B and Micci F (2017) Molecular characteristics of uterine sarcomas. Expert Review of Molecular Diagnostics 17 (5): 515–522.

Ferreira J , Félix A , Lennerz JK , et al. (2018) Recent advances in the histological and molecular classification of endometrial stromal neoplasms. Virchows Archiv 473 (6): 665–678.

Hoang L , Chiang S and Lee CH (2018) Endometrial stromal sarcomas and related neoplasms: new developments and diagnostic considerations. Pathology 50 (2): 162–177.

Oliva E (2016) Practical issues in uterine pathology from banal to bewildering: the remarkable spectrum of smooth muscle neoplasia. Modern Pathology 29 (Suppl 1): S104–S120.

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Micci, Francesca, and Davidson, Ben(Mar 2019) Molecular Genetics of Uterine Sarcomas. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0028464]