by Andrew Hughes
February 2018

Andy Hughes

The 2017-2018 Rein in Sarcoma Scholars are each writing a detailed article about a particular sarcoma cancer sub-type. Andrew is a second year medical student at the University of Minnesota. A longtime Minnesota resident, Andrew graduated from the University of Minnesota in 2014 with a degree in Biology. As an undergraduate, he was actively involved with Camp Kesem Minnesota, a week-long summer camp for children whose lives have been affected by a parent’s cancer. This experience provided an opportunity to honor his father who passed away from Leiomyosarcoma when Andrew was twelve years old. In his free time, he enjoys fishing, golfing, and spending time outdoors.

Leiomyosarcoma (LMS) is a malignant neoplasm with smooth muscle differentiation. The uterus is most frequently affected by LMS, but it can develop in a variety of soft tissue sites. There are only 1,700 new cases of LMS diagnosed annually in the United States. However, among soft tissue sarcomas, LMS is a relatively common subtype (up to 24%).

Older adults, age 60 – 80, are most commonly diagnosed with LMS as the risk of tumor development increases with age, but LMS has also been documented in children and young adults. Uterine LMS has an especially high incidence in younger females, age 30 – 60.

Retroperitoneal and inferior vena cava LMS are more commonly diagnosed in females, while LMS of the skin is more frequent in males.

Potential Tumor Locations

Leiomyosarcoma can develop anywhere, but the retroperitoneum is the anatomical region with the greatest propensity for LMS formation. The retroperitoneum is a large space that is located deep within the abdomen and abuts several structures including kidneys, pancreas, colon, major blood vessels, bladder, and various reproductive organs (i.e. uterus). In particular, the uterus comprises the majority of pelvic smooth muscle, thereby increasing its susceptibility to LMS formation.

Blood vessels can also give rise to LMS with the majority of tumors arising in venous structures. Veins are the low-pressure vessels that return blood to the heart, and LMS tends to develop in the large-caliber veins (inferior vena cava or leg veins). LMS may also develop within the soft tissue (i.e. muscle) of the extremities, and the thigh is most frequently affected by extremity lesions. Finally, it is possible to develop LMS of the skin, and these tend to arise within the dermis. The dermis represents the portion of the skin that contains the blood vessels, nerves, glands, and connective tissue.

Causes of Leiomyosarcoma

The majority of leiomyosarcomas seem to develop randomly with no relation to previous environmental exposures, lifestyle choices (i.e. exercise, diet, smoking, etc.), or inherited genetic defects (rare exceptions elaborated below). Given the sporadic onset of these tumors, patients and their families should recognize that previous choices or behaviors did not impact the development of the tumor.

There are two genetic conditions, Hereditary Retinoblastoma and Li Fraumeni Syndrome, where affected individuals are more likely to develop cancer. Individuals with these conditions have an increased predisposition to tumor formation due to defective tumor suppressor proteins. Tumor suppressor proteins normally inhibit proliferation and growth of cancer cells at an early stage; therefore, loss of these proteins results in the uncontrolled cell proliferation characteristic of cancer.

Ionizing radiation utilized in the treatment of cancer may, years later, result in the formation of sarcoma. The sarcoma generally arises within the area that received the radiation therapy.

Signs/Symptoms of Leiomyosarcoma

Leiomyosarcoma generally presents with non-specific symptoms because it can develop nearly anywhere in the body. This often contributes to a delayed diagnosis with an increased likelihood that the tumor will be detected at an advanced stage.

Possible Symptoms of Leiomyosarcoma:
  • Pain:
    • The pain may be diffuse/generalized throughout the abdomen/pelvis or it may be a localized tender nodule.
  • Palpable subcutaneous mass
    • Commonly detected in the arms, legs, or trunk
    • Especially concerning if the mass is enlarging and/or larger than 5 cm
  • Vaginal discharge or post-menopausal bleeding
  • Weight Loss
  • Ascites
  • Increased fluid in the abdomen
  • Diffuse swelling of the legs
  • Shortness of breath

Symptoms may be present for variable lengths of time ranging from weeks, months, or even years. Given the non-specific nature of the symptoms, they have the potential to resemble other medical conditions. Always consult with a physician regarding any concerning symptoms to receive a comprehensive work-up and formal diagnosis.

Establishing the Diagnosis of Leiomyosarcoma

The diagnosis may be established during the work-up of presenting symptoms or the tumor may be incidentally identified on imaging studies for unrelated symptoms/conditions. CT scans and MRIs are useful at delineating the size and location of a suspicious soft tissue mass, and its relationship to nearby organs, nerves, and blood vessels. The preferred diagnostic imaging study depends on the tumor location. A biopsy is then necessary to make the definitive diagnosis.

Tumor Biopsy:

Once the imaging studies identify the tumor, a biopsy is required to confirm the diagnosis and establish a treatment strategy. There are several biopsy methods available, and your physician will decide the preferred biopsy approach.

  • Core Needle Biopsy:
    • The core needle biopsy is minimally invasive (may be performed in clinic) and it yields intact tissue structures thereby improving the pathology assessment. Core needle biopsies may require imaging guidance (i.e. ultrasound) if the tumor is deep within the abdomen/pelvis or if the initial biopsy did not generate definitive results.
  • Open Incisional Biopsy:
    • A portion of the tumor is surgically removed for pathological assessment.
  • Excisional Biopsy:
    • The entire tumor is removed with an excisional biopsy, and this may be performed for small (< 3cm) superficial tumors.
Biopsy Findings:

An experienced pathologist plays a critical role in establishing the diagnosis as they are able to identify microscopic features and lab markers (immunostains) that are characteristic of LMS

  • Macroscopic Appearance (without magnification):
    • White/Gray Mass with a “whorled” (spiral) appearance.
    • May demonstrate evidence of hemorrhage (bleeding) or necrosis (tissue death).
    • The borders of the tumor may be sharp and well-circumscribed, or the tumor may be poorly defined and infiltrating nearby structures.
  • Microscopic Appearance:
    • When the tumor is evaluated with a microscope, there will be bundles of intersecting spindle-shaped cells with dark and elongated nuclei.
  • Immunophenotype:
    • The pathologist is able to apply particular immunostains to the biopsy sample to help identify LMS. LMS should be positive for at least one of the following three immunostains: smooth muscle actin, desmin, or h-caldesmon. The certainty of the LMS diagnosis increases when multiple immunostains are positive. However, it is important to recognize that these immunostains are only suggestive of LMS and they must be combined with other findings to establish a definitive diagnosis. Specifically, the diagnosis of LMS should integrate the macroscopic and microscopic features of the tumor, imaging findings, and the immunophenotype.
    • One goal of future therapies is to utilize this molecular “fingerprint” to develop individualized treatment strategies.
Tumor Grade:

Tumors are “graded” by pathologists to help predict prognosis. A combination of pathologic factors contributes to the tumor grade including:

  • Degree of similarity between the cancer cells and the tissue of origin
  • Number of actively dividing cells (mitotic cells)
  • Presence/Absence of necrosis (dead cells)
  • Overall pattern of growth
Tumor Staging:

Once the diagnosis is established, a series of staging tests are ordered to determine whether the LMS has spread beyond the primary organ. The main imaging studies used for staging are CT or PET scans. The tumor stage is based on 4 factors:

  • Size of the tumor
  • Degree of invasion (i.e. how deep does the tumor extend within the primary organ?)
  • Tumor grade (as described above)
  • Evidence of distant metastatic spread (i.e. to lymph nodes, lungs, etc.)


Localized Disease (stage I – III):

  • Surgical Resection:
    • This is the first-line treatment for ALL patients who have resectable, localized disease regardless of the tumor location.
    • The goal is an R0 resection where the surgeon achieves wide negative margins and complete tumor removal. R0 resection represents the approach with the greatest potential for cure.
      • Of note, retroperitoneal tumors are especially challenging to attain negative margins because the tumors are generally large and closely associated with vital structures.
    • When LMS is localized to the uterus, the surgical approach is usually complete hysterectomy.
  • Radiation Therapy:
    • The main goal of radiation therapy is to reduce localized recurrence and allow the surgeon to perform a less radical surgery (removal of less surrounding tissue). Radiation may be performed pre- or postoperatively.
    • Radiation therapy prior to surgery should be considered for tumors where a large margin around the mass is not possible without morbidity.
    • If complete surgical resection is not achieved, post-operative radiation therapy should be considered.
  • Chemotherapy:
    • Current research into the exact role of chemotherapy is ongoing. In most cases, there are no clear recommendations for chemotherapy use as an adjuvant therapy for localized disease. As a result, the use of adjuvant chemotherapy will depend on the site of the LMS as well as the institutional and provider preferences. Since current evidence shows that many patients with LMS will suffer a recurrence despite complete surgical resection, adjuvant chemotherapy is sometimes considered to potentially to reduce recurrence risk.

Metastatic Disease (Stage IV):

  • Surgery:
    • Surgical removal of the metastatic disease (metastasectomy) is generally recommended when there is one single site of metastatic disease that developed following a long disease-free period.
  • Palliative Management:
    • If the LMS is metastatic, the goal is to slow disease progression to prolong survival and/or improve symptoms (palliation). Options for palliation may include one or more of the following methods:
      • Chemotherapy (exact regimen depends on many factors)
          Generally, involves a multi-drug regimen that is either doxorubicin or gemcitabine based. However, there are several other new agents available too. The effectiveness will be assessed after several “cycles” of chemotherapy.
      • Radiation Therapy
      • Surgery
      • Supportive Care (treatment of symptoms only)
      • Ablation or Embolization procedures


The prognosis of LMS depends on several factors:

  • Tumor Size and Location
    • Smaller tumors have a better prognosis than larger tumors.
    • Tumors in the extremities carry a better prognosis compared to retroperitoneal or large vessel tumors.
  • Tumor Grade
    • High grade tumors have very abnormal cells and a poorer prognosis.
  • Surgical Resectability
  • Presence of Metastatic Disease
  • Tumor’s response to therapy (i.e. radiation therapy or chemotherapy)
  • Microscopic features of the tumor

The majority of local recurrences and metastatic lesions develop within two to three years of the initial diagnosis, but it is possible for tumors to develop much later (even 10 years or more). It is important to recognize that prognosis and long-term outlook are predicted on an individualized basis by your physician. Immediate medical attention for concerning symptoms yields the best possible prognosis because it increases the likelihood that therapy can be implemented during the early stages of the disease.


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