Dedifferentiated liposarcoma

A dedifferentiated liposarcoma is a soft tissue tumour which shows progression either in the primary tumour or after local recurrence to a sarcoma of variable histological grade, often not lipogenic. Dedifferentiated liposarcoma occurs in up to 10% of well-differentiated liposarcomas, although the risk is higher in the retroperitoneum and lower in the extremities, likely reflecting the longer time taken to detect tumours in the former location.

Dedifferentiated liposarcomas are most common in the retroperitoneum, but can occur in the spermatic cord or rarely head and neck and trunk. They are extremely rare in subcutaneous tissues. These tumours usually present as a painless mass, with both lipomatous and non-lipomatous elements on MRI scanning. Some present with an increase in size of a long-standing tumour, suggestive of dedifferentiation.

Dedifferentiated areas are variable histologically, but can resemble undifferentiated pleomorphic sarcoma or myxofibrosarcoma. Tumours most often contain ring or giant marker chromosomes.

After treatment, local recurrence can occur in up to 40% of cases, particularly in the retroperitoneum. Tumours exhibit a less aggressive clinical course than other types of high grade pleomorphic sarcoma, with metastases in 15-20% of cases and a overall mortality of 28-30% at 5 years.

 

1. WHO Classification of Tumours of Soft Tissue and Bone. 4th Edition, 2013.

Atypical lipomatous tumour

An atypical lipomatous tumour is a locally aggressive mesenchymal neoplasm in which the adipocytes show significant variation in cell size and have some nuclear atypia. These tumours are at risk of local recurrence. In the extremities or trunk the term atypical lipomatous tumour is justified as complete excision is usually curative and local recurrence manageable. In the retroperitoneum or mediastinum however, tumours with the same biological composition are difficult to completely remove and can recur with disastrous consequences for the patient. In these locations, the term “well-differentiated liposarcoma” may therefore be more appropriate.

Atypical lipomatous tumours account for 40-45% of all liposarcomas and occur predominantly in middle aged adults, peaking in the sixth decade. They most frequently occur in the deep soft tissues of the limbs, especially the thigh, but may also occur in the retroperitoneum or paratesticular area. Tumours often grow slowly, are painless and can achieve significant sizes.

Anatomical location is the most important prognostic factor. Lesions in surgically resectable sites tend not to recur after complete excision. In more difficult anatomic sites, incomplete excision is associated with local recurrence, which in turn can lead to loss of local control, or be associated with dedifferentiation and death. The risk of dedifferentiation is said to be over 20% in the retroperitoneum, but <2% in the limbs.

1. WHO Classification of Tumours of Soft Tissue and Bone. 4th Edition, 2013.

Lipoma

Lipomas are benign soft tissue tumours composed of mature adipocytes. Lipomas are the most common mesenchymal tumour in adults and are most common between the ages of 40 and 60 years. 5% of patients have multiple lipomas.

Lipomas typically occur in the subcutaneous soft tissues, but can also present in deeper locations, for example within or between muscles, or on the surface of bones.

Lipomas usually present as a painless soft tissue mass. On histological examination they can contain bone (osteolipoma), cartilage (chondrolipoma) or fibrous tissue (fibrolipoma). Deep intramuscular lipomas often encase muscle fibres – this can be seen on MRI scanning and these tumours have a higher rate of local recurrence.

Angiolipoma is a lipoma variant containing small capillary walled vessels. 5% of cases are inherited as an autosomal dominant. These usually present as tender subcutaneous masses. Angiolipomas are always benign and show no tendency to recur.

A large lipoma with stranding of muscle fibres

A large intramuscular lipoma of thigh with stranding caused by muscle fibres

1. WHO Classification of Tumours of Soft Tissue and Bone, 4th Edition.

 

Information for patients:

A good summary from NHS Choices.

Guide to trainees for the orthopaedic oncology rotation

We have compiled the following unofficial guide to trainees coming to an Orthopaedic Oncology attachment. It contains key topics in the curriculum to which you may get exposure in the attachment, competence levels for surgical procedures and other useful information.

Orthopaedic Oncology Syllabus

Classic papers in Orthopaedic Oncology

We recently scratched our heads and put a list of classic orthopaedic oncology papers together for this book:

http://www.amazon.co.uk/Classic-Papers-Orthopaedics-Paul-Banaszkiewicz/dp/1447154509

We were looking for papers that made an impact on the specialty or inform daily practice, as well as those which are cited widely. The list we came up with was:

 

CADE, S. (1955). Osteogenic sarcoma; a study based on 133 patients. Journal of the Royal College of Surgeons of Edinburgh, 1(2), 79–111. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/13307660
Codman, E. A. (2009). The classic: the registry of bone sarcomas as an example of the end-result idea in hospital organization. 1924. Clinical Orthopaedics and Related Research, 467(11), 2766–70. doi:10.1007/s11999-009-1048-7
Dahlin, D. C., & Coventry, M. B. (1967). Osteogenic sarcoma. A study of six hundred cases. The Journal of Bone and Joint Surgery. American Volume, 49(1), 101–10. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/5225072
Enneking, W. F., Dunham, W., Gebhardt, M. C., Malawar, M., & Pritchard, D. J. (1993). A system for the functional evaluation of reconstructive procedures after surgical treatment of tumors of the musculoskeletal system. Clinical Orthopaedics and Related Research, (286), 241–6. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8425352
Enneking, W. F., Spanier, S. S., & Goodman, M. A. (2003). A system for the surgical staging of musculoskeletal sarcoma. Clinical Orthopaedics and Related Research, (153), 106–20. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/7449206
Mankin, H. J., Lange, T. A., & Spanier, S. S. (1982). The hazards of biopsy in patients with malignant primary bone and soft-tissue tumors. The Journal of Bone and Joint Surgery. American Volume, 64(8), 1121–7. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/16951637
Mirels, H. (1989). Metastatic disease in long bones. A proposed scoring system for diagnosing impending pathologic fractures. Clinical Orthopaedics and Related Research, (249), 256–64. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/2684463
O’Sullivan, B., Davis, A. M., Turcotte, R., Bell, R., Catton, C., Chabot, P., … Zee, B. (2002). Preoperative versus postoperative radiotherapy in soft-tissue sarcoma of the limbs: a randomised trial. Lancet, 359(9325), 2235–41. doi:10.1016/S0140-6736(02)09292-9
Rosen, G., Murphy, M. L., Huvos, A. G., Gutierrez, M., & Marcove, R. C. (1976). Chemotherapy, en bloc resection, and prosthetic bone replacement in the treatment of osteogenic sarcoma. Cancer, 37(1), 1–11. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1082364
Rosenberg, S. A., Tepper, J., Glatstein, E., Costa, J., Baker, A., Brennan, M., … Wesley, R. (1982). The Treatment of Soft-tissue Sarcomas of the Extremities. Prospective Randomized Evaluations of (1) Limb-sparing Surgery Plus Radiation Therapy Compared with Amputation and (2) the Role of Adjuvant Chemotherapy. Annals of Surgery, 196(3), 305–315. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1352604/pdf/annsurg00139-0081.pdf

What’s missing? Your comments welcomed.

Staging for soft tissue sarcoma

As well as the MSTS system for staging soft tissue sarcoma, there is an established American Joint Committee on Cancer Staging (AJCC) TNM system. This is in its seventh version.

Staging investigations typically involve local site imaging and CT of chest, possibly including the abdomen and pelvis. Nodal involvement is unusual, but may be more common in some types, such as clear cell sarcoma, epithelioid sarcoma and rhabdomyosarcoma.

The size cut off between T1 and T2 is 5cm, above which tumours are considered T2. Tumours above and not involving the deep fascia are considered superficial,  those involving or deep to the fascia are considered deep.

 

Definitions for staging

TX

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor ≤5 cm in greatest dimension. (Size should be regarded as a continuous variable, and the measurement should be provided.)

T1a

Superficial tumor.b

T1b

Deep tumor.b

T2

Tumor >5 cm in greatest dimension.b

T2a

Superficial tumor.b

T2b

Deep tumor.

 

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1b

Regional lymph node metastasis.

 

M0

No distant metastasis.

M1

Distant metastasis.

 

Stage IA

T1a

N0

M0

G1, GX

T1b

N0

M0

G1, GX

Stage IB

T2a

N0

M0

G1, GX

T2b

N0

M0

G1, GX

Stage IIA

T1a

N0

M0

G2, G3

T1b

N0

M0

G2, G3

Stage IIB

T2a

N0

M0

G2

T2b

N0

M0

G2

Stage III

T2a, T2b

N0

M0

G3

Any T

N1

M0

Any G

Stage IV

Any T

Any N

M1

Any G

 

Reference:

 AJCC: Soft tissue sarcoma. In: Edge SB, Byrd DR, Compton CC, et al., eds.: AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer, 2010, pp 291-8.

 

 

 

The Cade Regime for Osteosarcoma

Sir Stanford Cade was one of the pioneers of radiotherapy and worked at the Westminster Hospital between 1924 and 1960. Amongst his extraordinary output he published a thoughtful paper on the treatment of osteogenic sarcoma in the prechemotherapy era (1).  He reasoned that early amputation had no impact on survival in osteosarcoma, and therefore that early metastasis was the norm. Furthermore he argued that to amputate the limbs of patients with such a poor prognosis was unreasonable and mutilating. The Cade regime therefore involved high dose radiotherapy to the primary tumour site, followed by secondary amputation if the patient survived long enough. He was able to demonstrate clinical, radiological and pathological responses to radiotherapy in this relatively radioresistant tumour.  His description defined treatment for osteosarcoma in the prechemotherapy era.

Reference:

Journal of the Royal College of Surgeons of Edinburgh. 1955 Dec ;1(2):79–111.

Limb reconstruction in children

Limb reconstruction in children after the resection of bone tumours is associated with the following particular issues:

  • Growth – predicted final leg length discrepancies of more than 3cm are most often addressed using an extendible implant, eg the Stanmore Juvenile Tumour System. The paper by Cool et al suggests how to calculate the expected growth if bone age is known.
  • Longevity of reconstruction – endoprosthetic reconstructions in children are inevitably associated with the need for revision – biological reconstructions may be preferred
  • Adaptation – children may be more able to adapt to loss of function than adults
  • Amputation – amputation in a child can lead to disproportionate limb length discrepancy at skeletal maturity, and trans-osseous amputations can overgrow and require revision. For this reason, amputations through joints may be preferred.
  • Radiotherapy – adjuvant radiotherapy can affect growth plates
  • Acetabular deformity – hemiarthroplasty of the hip is associated with subluxation as growth occurs, particularly for children under 11 years of age (1). A Collona arthroplasty of the acetabulum in which the acetabulum is reamed to deepen the socket may help. Otherwise a shelf osteotomy may be needed in later life.

(1)  van Kampen M, Grimer RJ, Carter SR, Tillman RM, Abudu A. Replacement of the hip in children with a tumor in the proximal part of the femur. J Bone Joint Surg Am. 2008 Apr;90(4):785-95.

Primary lymphoma of bone in adults

Primary lymphoma of bone (PLB) is defined as malignant, lymphoid infiltrate within bone, without evidence of lymph nodes or other tissues at presentation. It arises from the medullary cavity and manifests as a localised, solitary lesion.

It is rare, accounting for only 3% of primary bone malignancies and 5% of extra nodal lymphomas(1). Bone lymphoma is not uncommon in advanced lymphoma originating from other sites, but PLB accounts for less than 2% of all lymphomas in adults (2).

To be defined as primary bone lymphoma there must be:

(i) a primary focus in a single bone

(ii) positive histological diagnosis

(iii) no evidence of distant soft tissue or distant lymph node involvement.

However this definition of PLB is controversial. Some studies have included patients with Ann Arbor stage 1 and 2 only, whereas others have also included patients with stage 4 disease (3).  Regional lymph node involvement at diagnosis is therefore accepted by some, as is involvement of multiple skeletal sites, as long as the other criteria are met (4).

The majority of PLB is Non-Hodgkin lymphoma, with large B-cell lymphoma being the most common subtype. Other types include follicular lymphoma and Burkitt lymphoma. Differential diagnosis includes Ewing’s sarcoma, neuroblastoma, and other round cell tumours. It can also be associated with AIDS, immunosuppression and Paget’s disease.

The most common presentations are bone pain not relieved by rest, a palpable mass, pathological fracture or cord compression. About 10% have systemic symptoms at presentation including night sweats, weight loss and fever. Common sites include the femur, humerus, tibia, spine, pelvis, sternum, ribs and skull.

PLB most often involves the diametaphysis of major long bones. Radiological findings are of an aggressive pattern of lytic bone destruction and associated soft tissue mass. CT or MRI will show a large soft tissue mass and abnormal marrow attenuation without extensive cortical destruction (5).

Because PLB is rare, there have been few randomised control trials to evaluate treatment. Traditionally radiotherapy has been used as treatment with or without chemotherapy. However more recently the standard treatment has consisted of chemotherapy (CHOP regime) with or without radiotherapy depending on the histological type and stage. Several studies have established that a combination of chemotherapy and radiotherapy is better than radiotherapy alone (6,7).

The evidence is conflicting as to which regimen produces the best survival rates. Most studies are of small sample size and are therefore limited in their value in identifying prognostic factors.

A study by Alencar et al recorded progression free survival at 83% at 4 years with no difference between treatment with chemotherapy and a combination of chemotherapy and radiotherapy (8).  Jawed et al, in a review of 1500 adults, estimated 5 year survival at 58% and 10 year survival at 45%, and the only positive prognostic indicators identified were localised disease and younger age (9).

Disease free and overall survival rates have also been reported to be 78% and 91% at 5 years and 73% and 87% at 10 years, respectively (10).

Surgical management is limited to biopsy, stabilisation of pathological fracture and decompression of spinal canal compromise. There is no clear role for debulking surgery or resection.

The introduction of rituximab in March 2001 for treatment of diffuse large cell lymphoma has shown increased survival rates compared to those treated without rituximab, for example 3 year progression free survival has been demonstrated at 88% verses 52% without rituximab (11).

Dr Ruth Blackwell MBBS

GPST1

Newcastle Upon Tyne

References:

1. Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
2 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.
3 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
4 Singh T, Satheesh CT, Lakshmaiah KC, Suresh TM, Babu GK, Lokanatha D, Jacob LA, Halkud R. Primary bone lymphoma: A report of two cases and review of the literature. J Can Res Ther 2010;6:296-8
5 Mulligan ME, McRae GA, Murphey MD. Imaging features of primary lymphoma of bone AJR Am J Roentgenol 1999;173:1691-7.
6 Dubey P, Ha CS, Besa PC et al. Localized primary malignant lymphoma of bone. Int J Radiat Oncol Biol Phys 1997;37:1087-1093.
7 Baar J, Burkes RL, Bell R, Blackstein ME, Fernandes B, Langer F. Primary non-Hodgkin’s lymphoma of bone. A clinicopathologic study. Cancer. Feb 15 1994;73(4):1194-9.
8 Alencar et al Primary bone lymphoma – the university of Miami experience. Leuk lymphoma. Jan 2010;51(1):39-49
9 Jawad et al. Primary Lymphoma of bone in adult patients. Cancer 2010;116(4):871
10 Fidias P, Spiro I, Sobczak ML, Nielsen GP, Ruffolo EF, Mankin H, et al. Long-term results of combined modality therapy in primary bone lymphomas. Int J Radiat Oncol Biol Phys 1999;45:1213-8.
11 Ramadan KM, Shenkier T, Sehn LH, Gascoyne RD, Connors JM. A clinicopathological retrospective study of 131 patients with primary bone lymphoma: A population-based study of successively treated cohorts from the British Columbia Cancer Agency. Ann Oncol 2007;18:129-35.

Osteosarcoma

An osteosarcoma is a malignant tumour containing cells of mesenchymal origin and which is characterised by the formation of malignant osteoid.  Osteosarcomas are the most common primary bone sarcoma, but osteosarcomas also (rarely) occur in bone – in other words the prefix “osteo-” relates to the production of osteoid matrix rather than an origin in bone.

  • Incidence is around 1-2 per million per annum, which is around 131 new cases in England per annum
  • Osteosarcomas have a peak incidence in the second decade of life, and a smaller peak in the elderly
  • They classically occur in the metaphyseal regions of long bones  where most growth occurs (ie distal femur, proximal tibia, proximal humerus)
The WHO histological classification of osteosarcoma recognises the following groups:
1. Central (Medullary) tumours
  • conventional central osteosarcomas (the most common type)
  • telangiectatic osteosarcoma
  • intraosseous well-differentiated (low-grade) osteosarcomas
  • small-cell osteosarcomas
2. Surface (peripheral) tumours
  • parosteal (juxtacortical) well-differentiated (low-grade) osteosarcomas
  • periosteal osteosarcoma: low to intermediate-grade osteosarcoma
  • high-grade surface osteosarcoma

References:

Bone Sarcomas: incidence and survival rates in England – NCIN Data Briefing. National Cancer Intelligence Network 2010.