Sarcoma Pathology

This is a drama of many characters: meet some of the cast. The names alone can be intimidating – like a soup of random syllables. Names of tumours usually follow the tissue that they resemble, + oma for benign, and + sarcoma for malignant. (Lipoma = Fat + oma, Liposarcoma = Fat + sarcoma, Rhabdomyosarcoma = Skeletal Muscle + sarcoma, etc). But there are historical accidents – synovial sarcoma does not arise from synovium!

Here is collected some general information of the most common and important tumours. At medical student level we do not expect you to have more than a passing knowledge, once in residency you will learn more as is relevant to your area of practice.

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Bone Tumours: Benign

Benign bone tumours display a broad range of behaviour. They can be incidental lesions, e.g. enchondromas, or require simple surgery, e.g. osteochondromas. Others, such as Giant Cell Tumours of Bone require subspecialist management.

Osteochondroma

Osteochondromas are a benign developmental defect of growth, and the most common benign bone tumour. They are often asymptomatic and become bothersome in adolescence. Multiple Hereditary Exostoses (MHE) is an autosomal dominant condition resulting in the development of multiple osteochondromas. Osteochondromas can very occasionally become malignant, and a lesion that shows growth or pain in adulthood should be considered for specialist referral.

Biology

  • A portion of the epiphyseal plate breaks away and grows perpendicular to the normal physis on the side of the bone
    • Cartilage in the cap responds to the same growth signals as normal growth plate cartilage
    • Will grow as child grows, growth stops at skeletal maturity
  • Gross:
    • Cauliflower-like appearance with a cartilage cap
  • Histopathology
    • Moderately cellular cartilage, with chondrocytes in columns
  • Malignant transformation can occur, usually to a low grade chondrosarcoma
    • Risk = 1 in 1000 for sporadic, 1-25% in MHE

Imaging

  • Plain X-ray usually diagnostic
    • Metaphyseal location
    • Lesion and the underlying bone have continuous cortex and medullary space
  • MRI will show the cartilage cap thickness and reveal malignant transformation
  • A cartilage cap thicker than 2 cm is generally diagnostic for malignant change

Clinical

  • Asymptomatic: observe
  • Local irritation, snapping tendons, impact on surrounding neurovascular structures, or cosmesis are indications for removal
  • A growing or painful lesion, especially in an adult, is suspicious for malignant change
    • Refer to subspecialist multidisciplinary team

Giant Cell Tumour

Giant Cell Tumour of Bone is a benign, locally aggressive tumour. It usually occurs in individuals between the ages of 20 and 40, and very rarely in children. It is an unusual benign tumour as a small group of them (1%) do metastasize and behave in a systemically aggressive manner. Treatment usually consists of curettage and reconstruction of the defect.

Biology

  • Stroma contains mononuclear cells with large multinucleated giant cells present
  • 20% of all benign bone tumours
  • Location
    • Epiphyseal or apophyseal
    • Most common in fast growing sites: distal femur, proximal tibia, distal radius, proximal humerus, but can occur elsewhere
  • Brown tumour of hyperparathyroidism can be indistinguishable histologically
  • 1% behave in a malignant fashion – for those, 5 year survival is less than 30%

Imaging

  • Plain X-ray
    • Epiphyseal, eccentric lytic lesion
    • Usually associated with a joint
    • 'Neocortex’ evident
  • MRI
    • Dark on T1 and T2 sequences. May have fluid-fluid levels.

Clinical

  • Intralesional curettage
    • Combine with adjuvant, e.g. Liquid N, Phenol, Extensive burring
    • Recurrence rate 15-20%
  • Reconstruct with bone graft and/or bone cement
  • Some will require joint replacement
  • Important to follow for local or systemic recurrence
  • New agents such as denosumab are being explored for difficult or recurrent lesions

Aneurysmal Bone Cyst

Aneurysmal Bone Cysts are benign tumours of bone that are similar to giant cell tumours in their appearance and clinical presentation. They are also managed similarly, with curettage and bone grafting the most common treatment. They are, however, distinct pathologic entities, with a specific translocation identified for aneurysmal bone cysts. Many types of tumours can undergo cystic change, so it is important to differentiate true aneurysmal bone cysts from other entities with secondary cystic change.

Biology

  • Translocation at t(16;17)(q22;p13) demonstrated
  • Slight female predisposition, age < 25years (younger than GCT of bone)
  • Metaphyseal or metadiaphyseal lesion of long bones

Imaging

  • Plain X-ray looks very similar to a Giant Cell Tumour of Bone
    • Metaphyseal lytic lesion which expands the cortex
    • Well defined margins with a neocortex
  • MRI
    • Fluid-Fluid levels where the cellular components of the blood have settled out

Clinical

  • Curettage and grafting of the defect
    • Allograft, autograft, synthetic bone substitutes
    • Pre-operative embolization or tourniquet use as can be haemorrhagic
  • May resect if in a relatively expendable location (metatarsal, proximal fibula)
  • Angio-embolization for spinal or sacral locations

Bone Tumours: Malignant

Primary malignant tumours of bone are important as they require early referral for subspecialist workup by a multidisciplinary team. This has been shown to lead to higher rates of cure and lower rates of amputation. Treatment involves chemotherapy, radiation therapy and surgery or some combination thereof.

Osteosarcoma

Osteosarcoma is the most common primary bone sarcoma. Canadian Terry Fox, who ran his Marathon of Hope to raise funds for cancer research, succumbed to this disease in 1981. Prompt diagnosis and careful management by a specialized multidisciplinary team can result in good cure rates (60-75%). Treatment involves chemotherapy and wide resection surgery, which today usually involves limb salvage surgery.

Biology

  • Characterized by the presence of malignant spindle cells that produce osteoid, the primitive matrix of bone
  • Several sub-types
  • Two peaks of incidence (60% are <25 years, 30% are >40 years)
  • Some rare hereditary conditions associated
  • Metastases occur from haematogenous spread
    • Most common site is lung, second is bone
    • 20% present with detectable metastases

Imaging

  • Plain X-ray
    • Metaphyseal site most common: distal femur/proximal tibia/proximal humerus
    • Poorly defined margins
    • Mixed osteoblastic and osteolytic appearance
    • Cortical disruption and soft tissue mass
  • MRI
    • Invasion of soft tissue, neurovascular involvement, skip lesions

Clinical

  • Presentation
    • Pain and swelling around a joint
      • Unexplained pain for >6 weeks warrants an X-ray
    • Visible or palpable mass
  • Biopsy
    • Should be performed by the surgeon who will perform the definitive resection
  • Treatment
    • Chemotherapy - Doxorubicin, Cisplatin, Methotrexate, Ifosfamide
    • Surgery
      • Wide margin resection
      • Limb Salvage usually feasible

Chondrosarcoma

Chondrosarcoma is a malignant cartilage forming tumour of bone. It can arise de novo or from pre-existing benign lesions such as enchondromas or osteochondromas. The six subtypes vary in aggressiveness from very low grade tumours that almost never metastasize to higher grade tumours that almost always do. Most commonly it is a disease of adulthood. Urgent surgical referral to a specialist unit with expertise in treating this difficult cancer is required.

Biology

  • Can occur in any bone
  • Gross
    • Chondroid matrix: pearl-grey, translucent, shiny, firm, rubbery
    • Calcified tissue and cystic degeneration
  • Histopathology
    • Low Grade, hard to distinguish from normal cartilage
    • High Grade
      • Hypercellularity and atypia
      • Prominent myxoid stroma
      • Areas of necrosis

Imaging

  • Plain X-ray
    • High grade lesions
      • Large, destructive, radiolucent lesion
      • Stippled calcification, seen well on CT
    • Low grade lesions
      • Intraosseous, no soft tissue mass
      • If arising from osteochondroma – bony erosion of the underlying lesion
  • MRI
    • High signal in areas of cartilage
    • If arising from osteochondroma – thickened cartilage cap >2 cm

Clinical

  • Presentation
    • Pain, slowly enlarging mass, sometimes fracture
    • May have a history of Multiple Hereditary Exostoses
  • Biopsy should only be performed by an experienced surgeon
  • Treatment
    • High grade
      • Wide resection with wide margins, may require amputation
    • Low grade
      • Controversial, wide resection generally recommended
    • Chemotherapy and radiotherapy not usually effective

Ewing Family Tumour

Ewing Family Tumour refers to a collection of tumours previously described separately, including Ewing’s Sarcoma, Askin Tumour and primitive neuroectodermal tumours (PNET). These are characterized by small round blue cells with specific translocations. They occur spontaneously in younger people. The most striking part of their presentation is the large soft tissue mass often associated with them. Treatment involves radiation therapy, chemotherapy and surgery.

Biology

  • 3% of all paediatric malignancies, 10% of all malignant bone tumours
  • Age 5-30 yrs
  • Male predisposition, 3:2
  • Occur in axial and appendicular skeleton
  • Histopathology
    • Simple chromosomal translocation: EWS on chromosome 22 to FLI-1 on chromosome 11 (80-95%)
    • Sheets of small round blue cells with high nuclear-to-cytoplasmic ratio
    • CD99+ immunoreactivity in 95%

Imaging

  • Plain X-ray
    • Diffuse permeative lytic destruction
    • Large soft tissue mass
    • Periosteal reaction looks like a cut onion
  • Bone scan detects skip lesions or distant metastases
  • MRI shows large soft tissue mass

Clinical

  • Presentation
    • Pain, swelling, warmth
    • Large soft tissue mass
    • Constitutional symptoms such as fever and weight loss are common
  • Refer urgently to multidisciplinary team
  • Treatment
    • Chemotherapy
    • Roles of Radiation and Surgery for local control remain controversial

Soft Tissue Tumours: Benign

The vast majority of soft tissue tumours encountered by family physicians are benign. The challenge is distinguishing which of the many “lumps and bumps” that present need to be considered for referral. Although most can be managed with observation or simple excision, there are some such as fibromatosis or tenosynovial giant cell tumour that may warrant subspecialist referral in their own right.

Biology

  • Benign masses
    • Grow slowly and do not metastasize
    • Low cellularity with infrequent, normal mitoses
    • Well-differentiated appearance, similar to normal tissue

Some Subtypes

Lipoma

  • Most common soft tissue tumour
  • Appears to arise from adipose cells
  • If deep to fascia, they are usually intra-muscular

Haemangioma

  • Appears to arise from endothelial cells
  • Managed with sclerotherapy

Schwannoma

  • Appears to arise from schwann cells in peripheral nerves
  • Stain positive for S100

Fibromatosis

  • Locally aggressive tumour, infiltrating adjacent tissue
  • Histological appearance of fibroblasts with no pleomorphism
  • Difficult tumours to manage as local recurrence is very problematic

Intra-articular Tumours

  • Tenosynovial Giant Cell Tumour (TGCT)
    • Formerly known as Pigmented Villonodular Synovitis (PVNS)
    • Proliferative synovial process containing haemosiderin and giant cells
    • Can behave in a locally aggressive manner
  • Synovial Chondromatosis
    • Metaplasia of hyaline cartilage within the synovium
    • Grossly can see osteocartilaginous loose bodies within the joint

Myositis Ossificans

  • Not a true neoplasm but a reactive process, typically following trauma
  • Matures into a bony mass in the soft tissues

Soft Tissue Tumours: Malignant

Soft tissue sarcomas are a group of malignant tumours that can affect any connective tissue. This group includes low grade tumours that frequently recur locally but hardly ever spread to other sites, and high grade tumours that have a high propensity to metastasize. They are easily transplantable, and so biopsy should be done by a subspecialist multidisciplinary team. Management involves a combination of surgery, radiation therapy and chemotherapy. Cure rates range from 45 to 95% depending on the subtype and stage.

Biology

  • Histology
    • Appear to re-capitulate different tissue types and are named accordingly
    • Show features of malignancy: hypercellularity, pleomorphism, atypia and abnormal mitoses
  • Most common site of metastases is the lung
    • Some types will spread to the lymph nodes

Some Subtypes

Liposarcoma

  • Several variants such as myxoid liposarcoma and dedifferentiated liposarcomas that behave very differently
  • Well-differentiated liposarcomas do not metastasize, but they often recur and can develop into dangerous de-differentiated liposarcoma
  • Can spread via lymphatics as well as haematogenously

Synovial Sarcoma

  • Most common soft tissue sarcoma in young adults
  • Occurs near joints, but has no relation to the synovium
  • Associated with a specific translocation
  • Can spread via lymphatics as well as haematogenously

Pleomorphic Undifferentiated Sarcoma

  • Known historically as Malignant Fibrous Histiocytoma (MFH)
  • High grade
  • More common in older patients
  • Occurs superficially as well as deep to the deep fascia

Metastatic Tumours

Metastatic lesions from other primary cancers frequently appear in the bones, and even in the soft tissues of the limbs. The most common tumours to metastasize to bones are prostate, thyroid, breast, lung and renal cell carcinomas. As the population ages, and as more patients live longer with their cancers, the problems of managing metastatic tumours are increasing. This is becoming a management challenge for all physicians involved in the care of these patients.

Biology

  • Tumour dissemination from a primary source to other organs
  • Skeleton is the third most common site of metastasis
    • 60-84% of all cases of metastatic disease involve bone
    • 70% of those with bone metastases report pain

Imaging

  • Plain X-ray: Aggressive, moth-eaten appearance

Clinical

Presentation

  • Pain - insidious onset, pain at rest, nocturnal pain
  • Pathologic fracture may be the first presentation
  • Hypercalcemia is the most common metabolic presentation

Work-Up (in brief)

  • History
    • Systemic/Constitutional symptoms
    • Risk factors
  • Examination
    • Lymphadenopathy
    • Thyroid, lungs, abdomen, breast, prostate
  • Investigations
    • Bloods
    • CXR or CT chest, CT or USS abdomen/pelvis
    • Plain X-ray of painful sites
    • Bone scan or skeletal survey

Treatment

  • Manage the primary tumour on its merits
  • Supportive therapy and pain control
  • Counselling and home care
  • Surgery
    • For fracture or impending fracture
    • Occasionally resection of a solitary metastasis is considered, especially for renal cell carcinomas