Myxofibrosarcoma

Myxofibrosarcomas are soft tissue malignant tumours that are grossly and microscopically nodular and mucoid in appearance. They tend to occupy subcutaneous sites, that characteristically have a large vascular network with rapid circulation (Kindblom et al., 1977, Fletcher et al., 2002).  The differential diagnosis includes other soft tissue sarcomas such as leiomyosarcoma and liposarcoma (Mutter et al., 2011).

These tumours tend to occur in the elderly population, commonly affecting the extremities (lower > upper), and are typically prevalent in male patients aged sixty to eighty years (Fletcher et al., 2002, Sanfilippo et al., 2011).  Their presentation is often that of a painless slowly growing mass.

The risk of distant metastases is generally lower than for other soft tissue sarcomas.  Metastatic sites include lung, bone and lymph nodes, with histological grade being the main risk factor for metastasis (Mentzel, 2011, Sanfilippo et al., 2011).

Myxofibrosarcomas tend to grow by tracking along fascial planes, which can be manifested on MRI by a high signal “tail” which contains tumour (Kaya et al., 2008). Even in the absence of this appearance, these tumours tend to grow in an infiltrative fashion. The risk of local recurrence is consequently high compared to other sarcomas (31% in one series (Haglund et al., 2010)). When it occurs, local recurrence is associated with more chromosomal aberrations and a higher histological grade, so increasing the likelihood of invading distant sites; overall survival at five years has been reported as being 60-77% (Fletcher et al., 2002, Willems et al., 2006, Sanfilippo et al., 2011).

Management should be multidisciplinary, with a surgical approach emphasising negative margins. As with other soft tissue sarcomas, adjuvant radiotherapy may be useful  (Mutter et al., 2011, Sanfilippo et al., 2011).

 

Christopher Ghazala, Craig Gerrand

References

Fletcher C, Unni K, Mertens F (2002) World Health Organization classification of tumours. Pathology and genetics of tumours of soft tissue and bone. Lyon, France: IARC Press.

Haglund K,  Raut CP,  Nascimento AF, Wang Q, George S, Baldini EH (2010)  Recurrence Patterns and Survival for Patients with Intermediate- and High-Grade Myxofibrosarcoma. International journal of radiation oncology, biology, physics 18 October 2010 (Article in Press DOI: 10.1016/j.ijrobp.2010.08.042)

Kindblom LG, Merck C, Svendsen P (1977) Myxofibrosarcoma: a pathologico-anatomical, microangiographic and angiographic correlative study of eight cases. Br J Radiol 50:876-887.

Kaya M, Wada T, Nagoya S, Sasaki M, Matsumura T (2008)  MRI and histological evaluation of the infiltrative growth pattern of myxofibrosarcoma. Skeletal Radiol (2008) 37: 1085.

Mentzel T (2011) Sarcomas of the skin in the elderly. Clinics in Dermatology 29:80-90.

Mutter RW, Singer S, Zhang Z, Brennan MF, Alektiar KM (2011) The enigma of myxofibrosarcoma of the extremity. Cancer.

Sanfilippo R, Miceli R, Grosso F, Fiore M, Puma E, Pennacchioli E, Barisella M, Sangalli C, Mariani L, Casali P, Gronchi A (2011) Myxofibrosarcoma: Prognostic Factors and Survival in a Series of Patients Treated at a Single Institution. Annals of Surgical Oncology 18:720-725.

Willems SM, Debiec-Rychter M, Szuhai K, Hogendoorn PCW, Sciot R (2006) Local recurrence of myxofibrosarcoma is associated with increase in tumour grade and cytogenetic aberrations, suggesting a multistep tumour progression model. Mod Pathol 19:407-416.

Aseptic loosening of massive tumour endoprostheses

Reconstruction of the limb with a massive endoprosthesis after tumour resection is associated with a risk of aseptic loosening. A number of factors influence this risk. These include:

  • anatomical site
  • length of resection
  • muscle resection
  • possibly the use of a fixed hinge knee rather than a rotating hinge knee
  • the use of a hydroxyapatite collar

The risk of aseptic loosening is likely highest in the distal femur (13.6%) compared with the proximal femur (11%) and pelvis (7%), but in this paper, implants were also revised for other reasons, including deep infection (1).

Reference
(1) Endoprosthetic Reconstruction for the Treatment of Musculoskeletal Tumours of the Appendicular Skeleton and Pelvis.Jeys LM, Kulkarni A, Grimer RJ, Carter SR, Tillman R, Abudu A.  J Bone Joint Surg Am. 2008; 90: 1265-1271.

Infection after major tumour resection and endoprosthetic reconstruction

Infection remains a major problem after major tumour resection and endoprosthetic reconstruction.  Placing a large metal implant into a wound which has typically been open for several hours, in an immunocompromised patient is associated with higher infection rates than for other procedures.

In the paper by Jeys et al. , the overall rate of infection was 11.0%, most frequently with a coagulase negative staphylococcus. The risk varies significantly with anatomical site. For example, because of the limited skin cover, resection of the proximal tibia has traditionally been associated with high infection rates. The routine use of a gastrocnemius pedicled flap to improve soft tissue cover has improved this risk. Reconstruction of the pelvis has also traditionally been associated with a high infection rate (23%) compared with other sites (proximal femur 6.7%, distal femur 10.3%). Other risk factors include the use of radiotherapy, secondary patellar resurfacing, and the use of an extendable implant. Deep infection may require a secondary amputation.

Interestingly, there is evidence that deep infection is associated with improved survival in patients with osteosarcoma, likely through stimulation of the immune system. Jeys et al showed a 10-year survival for patients with osteosarcoma who had a deep infection within the first year post-resection of 84.5% compared to 62.3% in the non-infected group. Improved survival has also been shown in osteosarcoma with the use of Mifamurtide (a synthetic immune stimulant). Read more about Mifamurtide.

Strategies for reducing the rate of infection include:

  • screening the patient for infection preoperatively (central lines have the potential to increase the rate of infection)
  • repeating the antibiotic dose during long procedures, especially where there has been significant blood loss
  • re-draping and re-gowning after tumour resection and before placing the implant
  • using silver coated implants
  • ensuring the implant  is well covered with muscle and fascia as well as skin, given the high risk of wound complications after tumour surgery.

Reference:

Periprosthetic infection in patients treated for an orthopaedic oncological condition. Jeys LM, Grimer RJ, Carter SR, Tillman RM. J Bone Joint Surg Am. 2005;87: (842-849).

Post operative infection and increased survival in osteosarcoma patients: are they associated? Jeys LM, Grimer RJ, Carter SR, Tillman RM, Abudu A. Ann Surg Oncol. 2007;14(10):2887-95.

 

Incidence and epidemiology of soft tissue sarcoma

Soft tissue sarcomas occur with an incidence of 30 per million and represent less than 1% of all malignancies. They can occur in almost any anatomic site, but tend to occur with a frequency that reflects the volume of mesechymal-derived tissue in that region.  For example, around 55% occur in the limbs. The type of tumour varies with age: rhabdomyosarcoma is a disease of early life, whereas leiomyosarcoma is more common in the elderly.

Environmental factors associated with sarcoma include:

  • Radiation (eg after therapeutic radiotherapy)
  • Immunodeficiency
  • Occupational (eg exposure to dioxins)

Genetic factors include

  • Li-Fraumeni syndrome (inherited p53 deficiency)
  • Neurofibromatosis.

Complications of endoprosthetic reconstruction

The major complications particular to endoprosthetic reconstruction of the limb following tumour resection include:

  • infection
  • aseptic loosening
  • dislocation
  • wear
  • implant fracture
These are in addition to other complications associated with major tumour resection, regardless of the kind of reconstruction, which include:
  • wound complications
  • thromboembolism
  • neurological injury
  • vascular injury
Local recurrence of tumour might be considered a failure of local therapy, rather than a complication.

Classification of soft tissue tumours

Soft tissue tumours are classified using the WHO classification, based on the morphological appearances of the tumour and whether or not it is benign or malignant. There are more than 50 variants of soft tissue sarcoma. The classification includes:

  • adipocytic tumours (eg lipoma, liposarcoma)
  • fibroblastic/myofibroblastic tumours (eg elastofibroma, adult fibrosarcoma)
  • so-called fibrohistiocytic tumours (eg GCT of tendon sheath, pleomorphic MFH)
  • smooth muscle tumours (eg angioleiomyoma, leiomyosarcoma)
  • pericytic tumours (eg glomus tumour)
  • skeletal muscle tumours (eg rahbdomyoma, rhabdomyosarcoma)
  • vascular tumours (eg haemangioma, angiosarcoma)
  • chondro-osseous tumours (eg soft tissue chondroma, extraskeletal osteosarcoma)
  • tumours of uncertain differentiation (eg intramuscular myxoma, synovial sarcoma)

Multidisciplinary team working

The principle of multidisciplinary team working has been enshrined in NHS culture since the publication of the NHS Cancer Plan in 2000.  It is particularly important that sarcomas are managed by specialist multidisciplinary teams because many aspects of diagnosis require discussion between clinicians, radiologists and pathologists, and the multi-modality nature of treatment for many sarcomas means that coordination is needed in order to tailor treatment to the needs of the individual patient. Sarcoma specialist multidisciplinary teams should include specialists in:

  • orthopaedic, plastic, general and thoracic surgery
  • medical (and paediatric) oncology
  • clinical (radiation) oncology
  • pathology
  • radiology
  • nursing
  • rehabilitation

Classification of primary bone tumours

Primary bone tumours can be classified according to the tissue of differentiation, using the WHO system. Tumours are classified as:

  • cartilage tumours (eg osteochondroma, chondrosarcoma)
  • osteogenic tumours (eg osteoid osteoma, osteosarcoma)
  • fibrogenic tumours (eg desmoplastic fibroma, fibrosarcoma)
  • fibrohistiocytic tumours (eg benign fibrous histiocytoma, malignant fibrous histiocytoma)
  • Ewing sarcoma/Primitive Neuroectodermal tumour (PNET)
  • Haemopoetic tumours (eg plasma cell myeloma)
  • Giant cell tumour of bone
  • Notochordal tumours (eg chordoma)
  • Vascular tumours (eg haemangioma)
  • Smooth muscle tumours (eg leiomyosarcoma)
  • Lipogenic tumours (eg lipoma, liposarcoma)
  • Neural tumours (eg neurilemmoma)
  • Miscellaneous tumours (eg adamantinoma)
  • Miscellaneous lesions (eg aneurysmal bone cyst)
  • Joint lesions (eg synovial chondromatosis)
For more information look here.
A simpler classification can also be helpful:
  • Cartilage forming tumours
  • Bone forming tumours
  • Fibrous tumours
  • Non-matrix producing tumours

Seven questions to ask when looking at an x-ray

A good approach to looking at an X-ray demonstrating an abnormality in the bone is to ask seven questions:
  1. Where is the lesion?
  2. How large is the lesion?
  3. What is the lesion doing to the bone?
  4. What is the bone doing in response?
  5. Is the lesion making matrix?
  6. Is the cortex eroded?
  7. Is there a soft tissue mass?
(from Levesque et al. A Clinical Guide to Primary Bone Tumours)