Leiomyosarcoma (LMS)

Leiomyosarcoma (LMS) is a smooth muscle tumor that can occur in almost any part of the body.^1,2 Despite being a common type of soft tissue sarcoma (STS), LMS is a rare type of cancer that is resistant, unpredictable, and often recurs later in life.¹

LMS accounts for 10%–20% of all new STSs.² LMS originates in either smooth muscle cells or the precursor mesenchymal stem cells that differentiate into smooth muscle cells.³ For this reason, LMS shows a predilection for soft tissues and the adominopelvic organs and can arise in the abdomen, retroperitoneum, larger blood vessels and the uterus.^1,2

LMS is less likely to be found in the extremities, where it accounts for 10–15% of limb sarcomas.² Uterine LMS is the most common type of uterine sarcoma and is the largest site-specific group of LMS.²

The cause of LMS is not clearly defined; however, genomic profiles of LMS tumors often show loss of chromosomes that are involved in cell proliferation pathways or tumor suppressor genes.⁴ 

Research shows that the most frequently mutated genes are TP53, RB1, and ATRX. Mutations in other genes involved in apoptosis, cell-cycle regulation, angiogenesis and growth factor signaling have been proposed to potentially have a role in LMS carcinogenesis.⁴

In the majority of cases, LMS is driven by a perturbed tumor suppressor network, giving rise to whole-genome duplication and large-scale genomic instability. This accelerates tumor evolution.⁵ 

LMS typically presents with non-specific symptoms that result from the displacement of structures in specific anatomic locations of the primary tumor and metastases, rather than invasion.² 

Generally, if the tumor is present only at the cutaneous level, then it may appear as small nodules, but a deep tumor may arise near medium to large veins.⁶ In some cases, LMS can be found near large, vascularized structures where there is a risk that the tumor may obstruct the vessel, leading to decreased blood flow.⁶ 

As LMS is commonly found in the abdominopelvic organs, patients with uterine LMS may present with abnormal uterine bleeding or abnormal uterine growth.^3,4 

LMS has an incidence rate of 1.2 cases per 100,000 person-years.⁷ The annual incidence of LMS is less than 2 women per 100,000.⁸ Approximately 4,000 patients are diagnosed with LMS annually in the United States.⁹ 

As in STSs in general, the overall incidence of LMS increases with age and peaks in people’s 70s.² Uterine LMS, however, appears earlier, presenting from the 30s into old age, being most prevalent in perimenopausal women – typically in their 50s.² The incidence according to sex depends on tumor location, with a greater predominance of women among patients with retroperitoneal and inferior vena cava LMS.² In contrast, men show a mild prevalence among patients with noncutaneous soft tissue sites and cutaneous LMS.² 

At present, no specific laboratory or radiographic tests are clinically available to assist with LMS diagnosis.³ 

The gold standard for LMS diagnosis is morphologic diagnosis based on microscopic examination.³ Microscopic examination is supported by immunohistochemistry, classical cytogenetics, and molecular testing.³ Diagnosing LMS can be complicated by overlapping features of other benign or malignant neoplasms.¹⁰ 

One such overlapping condition is leiomyoma, which is a common benign tumor of the uterus.¹¹ Computed tomography (CT), magnetic resonance imaging (MRI) and ultrasound can prove useful in distinguishing between LMS and leiomyoma.¹¹ As a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of LMS for a benign leiomyoma could potentially result in significant treatment delays and increase morbidity and mortality.¹¹

Imaging tests, including CT or MRI, are needed to stage the disease.³ CTs are used for retroperitaneal and visceral lesions while MRI is preferred for head, neck or limb tumors.³

Histologic grade, tumor size, and tumor depth are the three most important prognostic factors in patients diagnosed with LMS.³ Tumor depth is a strong prognostic factor for disease recurrence and mortality, with deep tumors associated with worse outcomes.¹²  

Evidence suggests that high-grade malignant soft tissue tumors have a low rate of survival for patients with LMS.¹³ Moreover, the Musculoskeletal Tumor Society (MSTS) stage, the presence of metastases, and the size of the primary lesion are closely and statistically related to patient death at a mean of 3 years after discovery.¹³ However, in patients with MSTS stages 1 or 2 (non-metastatic), the survival rate is improved.¹³ In addition, the survival rate is dependent on the tumor site; the 5-year survival rate may be 50% for upper limbs, 23% for lower limbs and 29% for the trunk wall.¹⁴ 

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3. Mangla A, Yadav U. Leiomyosarcoma. In: Leiomyosarcoma. Treasure Island Florida: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551667/. Last accessed September 2023.
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6. Mangla A, Yadav U. Leiomyosarcoma. In: Leiomyosarcoma. Treasure Island Florida: StatPearls Publishing; 2022. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551667/. Last accessed September 2023.
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14. Mestiri S, Elghali MA, Bourigua R, et al. Rare Tumors 2019;11:2036361318820171.