Leiomyosarcoma
Leiomyosarcoma is a malignant tumour of smooth muscle. In the abdomen it arises most characteristically from the wall of a blood vessel — above all the inferior vena cava — and from the retroperitoneum and the uterus. It is the second commonest retroperitoneal sarcoma after liposarcoma, and it behaves quite differently from it: where liposarcoma threatens through relentless local regrowth, leiomyosarcoma carries a genuine and early risk of spreading through the bloodstream, principally to the liver and lungs. That difference shapes the whole approach to treatment.
How it forms
Smooth muscle is present throughout the body — in the walls of blood vessels, in the gut, in the uterus, and in the erector pili muscles of the skin — and leiomyosarcoma can arise anywhere it is found.
In the retroperitoneum, the tumour most often originates from the smooth muscle of the media of a vein, and the inferior vena cava is the classical site. Tumours arising from a vessel wall may grow outward into the retroperitoneum, inward into the lumen, or both. This has direct consequences: an intraluminal tumour obstructs venous return, and tumour thrombus can extend along the vein, occasionally as far as the right atrium.
Genetically, leiomyosarcoma is a complex karyotype sarcoma. Unlike liposarcoma with its characteristic MDM2 amplification, or the fusion-gene sarcomas, it has no single defining abnormality. Instead it shows chaotic chromosomal rearrangement with frequent loss of TP53, RB1 and PTEN. This genomic chaos explains two things: the absence of a targeted therapy, and the aggressive behaviour of high-grade tumours.
A proportion show defects in homologous recombination repair, including BRCA2 loss, which is a subject of current therapeutic interest since such tumours may be sensitive to PARP inhibition.
Most arise sporadically. Recognised associations include previous radiotherapy and, rarely, hereditary retinoblastoma and Li-Fraumeni syndrome.
It is worth distinguishing gastrointestinal leiomyosarcoma, which is genuinely rare, from GIST, which arises from the interstitial cells of Cajal and was historically misclassified as leiomyosarcoma. The distinction is made by immunohistochemistry — leiomyosarcoma is desmin and smooth muscle actin positive and CD117 negative — and it matters enormously, because GIST responds to imatinib and leiomyosarcoma does not.
Symptoms
As with other retroperitoneal tumours, symptoms appear late.
- an enlarging abdominal mass, often painless
- abdominal or back pain
- leg swelling — particularly with inferior vena cava involvement; may be bilateral
- dilated superficial abdominal wall veins, indicating venous obstruction with collateral flow
- deep vein thrombosis, sometimes the presenting feature and sometimes unexplained in an otherwise well patient
- Budd-Chiari features — ascites, liver enlargement — where the hepatic veins are involved
- renal impairment or hypertension where the renal veins are involved
- weight loss and fatigue in advanced disease
- Uterine leiomyosarcoma presents with abnormal uterine bleeding, pelvic pain and a rapidly enlarging uterine mass — frequently assumed to be a fibroid, which is a recognised diagnostic problem
How the diagnosis is made
- CT of chest, abdomen and pelvis with contrast — defines the tumour, its vascular relationships and any tumour thrombus, and assesses the lungs and liver, which must be imaged because of the metastatic pattern.
- MRI — superior for defining the relationship to vessels, the extent of intraluminal tumour, and involvement of nerve roots and muscle.
- Venography or CT venography where caval involvement is suspected, to plan reconstruction.
- Image-guided core biopsy — through a retroperitoneal route, in a specialist centre, to establish the diagnosis and grade before treatment. Distinguishing leiomyosarcoma from liposarcoma and from other retroperitoneal masses changes management substantially, including whether radiotherapy is considered.
- Immunohistochemistry — desmin, smooth muscle actin, h-caldesmon positive; CD117 and DOG1 negative, excluding GIST.
- Grading by the FNCLCC system — differentiation, mitotic count and necrosis — which is the strongest predictor of metastasis.
A note on uterine masses: distinguishing a leiomyosarcoma from a benign fibroid before surgery remains genuinely difficult. Features that raise suspicion are rapid growth (particularly after the menopause), an irregular or heterogeneous appearance on MRI with restricted diffusion, and raised LDH. This uncertainty is the reason that power morcellation of uterine masses is now avoided or performed only within a containment bag, since morcellating an unsuspected sarcoma disseminates it through the peritoneal cavity and markedly worsens the outlook.
Treatment
Surgery
Complete resection with clear margins is the only curative treatment.
For retroperitoneal disease, resection follows the same principles as for liposarcoma — en bloc removal with adjacent structures where necessary — though the surrounding fat is less often involved and the resection may be somewhat less extensive.
Where the inferior vena cava is involved, the operation is a specialist vascular undertaking:
- Where the cava is already occluded and collateral circulation is well developed, the segment may sometimes be resected and simply ligated.
- Where flow is preserved, the cava is reconstructed — with a prosthetic graft, a patch, or primary repair — to avoid severe leg and renal venous congestion.
- Involvement of the renal veins may require nephrectomy or renal vein reconstruction; involvement at the level of the hepatic veins requires hepatic vascular control and is undertaken only in centres equipped for it.
These operations require a team comprising sarcoma, vascular and hepatobiliary surgeons, and should not be attempted outside such a setting.
Radiotherapy
Its role is limited in leiomyosarcoma. The STRASS trial of preoperative radiotherapy for retroperitoneal sarcoma found no benefit in leiomyosarcoma, and subgroup analysis suggested possible harm. It is not routinely used for retroperitoneal leiomyosarcoma, though it has a clearer role in extremity and trunk disease.
Systemic therapy
Leiomyosarcoma is among the more chemosensitive of the sarcomas, which is relevant given its metastatic tendency.
- Doxorubicin, alone or with ifosfamide, is the standard first-line treatment for advanced disease.
- Gemcitabine with docetaxel is particularly active in leiomyosarcoma and is widely used, especially in uterine disease.
- Trabectedin, pazopanib and eribulin are established later-line options.
- Adjuvant chemotherapy after complete resection remains of uncertain benefit and is discussed individually, typically for high-grade tumours in fit patients.
- PARP inhibitors in homologous recombination-deficient tumours are under active investigation.
Metastatic disease
Resection of isolated lung metastases (metastasectomy) is worthwhile in selected patients with limited disease, a long disease-free interval and good performance status, and can achieve prolonged survival. Liver metastases may similarly be treated surgically or with ablation in selected cases.
Recovery
Recovery depends on the extent of the operation. A retroperitoneal resection with vascular reconstruction involves one to two weeks in hospital, usually with critical care, and two to three months to full activity. Where the cava has been reconstructed or ligated, leg swelling is common in the early months and compression stockings are used; anticoagulation is generally given for a defined period after graft reconstruction.
Follow-up
More intensive than for liposarcoma because of the metastatic risk: CT of chest, abdomen and pelvis at three to six monthly intervals initially, extending over at least ten years. The lungs are the commonest site of metastasis and are imaged at every review.
When to seek an opinion
Any retroperitoneal mass should be referred to a specialist sarcoma centre before biopsy or surgery. Unexplained leg swelling with an abdominal mass, or an unexplained deep vein thrombosis in a patient who is otherwise well, warrants abdominal imaging. A uterine mass growing rapidly, particularly after the menopause, needs specialist assessment before any procedure involving morcellation.
Common questions
How is this different from the fatty type of sarcoma?
The fatty type mainly causes trouble by coming back in the same place and rarely spreads elsewhere. Leiomyosarcoma carries a real risk of spreading through the bloodstream to the lungs and liver. This means the follow-up scans are more frequent and include the chest, and chemotherapy has a larger role.
My tumour is growing from a major vein. Can that be operated on?
Yes, in a centre equipped for it. The affected segment of vein is removed with the tumour and then either repaired, replaced with a graft, or — if the vein is already blocked and your body has developed alternative routes for the blood — simply tied off. This is specialised surgery requiring a vascular surgeon alongside the sarcoma surgeon.
Why do my legs swell?
Because the tumour is obstructing the large vein returning blood from your legs to the heart. Your body gradually develops alternative routes, which is why you may also see prominent veins on the abdominal wall. Swelling often improves over the months after surgery, and compression stockings help in the meantime.
Do I need chemotherapy?
For disease that has spread, yes — this type responds better to chemotherapy than most sarcomas, and several effective drugs are available. After complete removal of a localised tumour the benefit of chemotherapy is less clear, and it is discussed individually, usually for higher-grade tumours in patients fit enough for it.
Do I need radiotherapy?
Generally not for this type in the abdomen. A large trial found no benefit from radiotherapy before surgery in leiomyosarcoma specifically, unlike some other sarcoma types, so it is not routinely offered.
I was told my uterine tumour was a fibroid. How could this be missed?
Because fibroids are extremely common and sarcomas of the uterus are rare, and the two can look very similar on scans. Features that raise concern are rapid growth, especially after the menopause, and particular appearances on MRI. It is a recognised difficulty rather than an oversight, and it is the reason techniques that cut up a uterine mass inside the abdomen are now avoided or done inside a protective bag.
It has spread to my lungs. Is anything possible?
Yes. Where the deposits are few, removing them surgically is worthwhile and can give long periods of disease-free survival, particularly if a long time passed between the original operation and their appearance. Where they are more numerous, chemotherapy can control the disease for considerable periods. This is not a situation where treatment options run out quickly.
Is it inherited?
Almost always no. The genetic changes occur within the tumour rather than being inherited. Rare inherited conditions are associated with sarcomas, and genetic assessment is considered where there is a strong family history of cancer or where the tumour occurs at an unusually young age.
Related conditions
Other conditions of the sarcoma & retroperitoneal covered on this site:
- Retroperitoneal liposarcoma
- Soft tissue sarcoma of the trunk and abdominal wall
- Desmoid tumour (aggressive fibromatosis)
- Benign retroperitoneal tumours and masses
This page provides general information and does not replace an individual medical consultation. Sarcoma should be assessed in a specialist sarcoma centre before biopsy or surgery.