Bone tumours

Metastatic bone tumours

• Commonest form of skeletal malignancy
• Are generally carcinomas
• In adults, 80% can be accounted for by the following primaries;
  • Breast
  • Bronchus
  • Prostate
  • Thyroid
  • Kidney
• In children the following cause bone secondaries;
  • Neuroblastoma
  • Wilms tumour
  • Ewing’s tumour
  • Rhabdomyosarcoma
• Most deposits cause osteolysis but prostate can cause osteosclerosis, they do this by stimulating either osteoclasts or osteoblasts
• Most common cause of hypercalcaemia in the middle aged and elderly
• Generally multifocal but kidney and thyroid can produce solitary lesions
• May occur in any bone but most involve the axial skeleton, femur and humerus
• Metastases to small bones of the hands and feet are uncommon and generally originate from cancers of the kidney, lung or colon
• Frequent cause of pathological fractures
• Pathways of metastatic spread include;
  • Direct extension
  • Lymphatic of haematogenous dissemination
  • Intraspinal seeding (Batson plexus of veins)

Primary bone tumours

• Uncommon – account for 0.5% of cancer deaths
• Predisposing factors;
  • Paget’s disease
  • Fibrous dysplasia
  • Exposure to ionising radiation
• Can present with pain (all the time), swelling, a lump, lymphadenopathy
• Do an x-ray, MRI, bone scan
• Biopsy can be open or closed
• Can be divided into;
  • Bone forming
  • Cartilage forming
  • Fibrous and fibro-osseous
  • Miscellaneous

• Most common benign primary bone tumours
  • Osteochondroma
  • Chondroma
• Most common malignant primary bone tumours (after those of bone marrow origin)
  • Osteosarcoma (20% of primary bone cancers)
  • Chondrosarcoma
  • Ewing’s tumour

• Staging- via the Enneking grading
  • 1 – low grade
  • 2- high grade
  • 3- mets
    • a – intracompartmental
    • b – extracompartmental

Bone forming tumour

1) OSTEOMA

Affects middle aged

Painless, dense overgrowth of cortical bone particularly in skull and mandible

Affects flat bones of jaw, skull and face

Generally solitary but can be multiple when associated with Gardner’s syndrome (mutations in APC result in intestinal polyps, epidermal cysts, fibromatosis and osteomas)

Generally slow growing but can obstruct the sinuses, impinge brain or eye or cause problems with the oral cavity

2) OSTEOID OSTEOMA

• Mainly affects males between 10-30
• Less than 2cm in dimension
• Can develop in any bone but generally involves the appendicular skeleton – femur and tibia
• Causes pain at rest which is dramatically relieved by asprin as the pain is caused by release of PGE2 by osteoblasts. Pain disproportionate for the small size
• On x-ray they are well circumscribed lesions with sclerosis around a small lucent nidus
• Treated by resection

3) OSTEOBLASTOMA

• Looks the same histologically as osteoid osteoma but is bigger (>2cm)
• Can occur at any age but is more common in male teens
• More commonly affects the spine
• The pain is dull and achy and doesn’t respond to asprin
• On x-ray it produces a lucent defect surrounded by active bone
• Treated by resection, can reoccur if not fully removed

4) OSTEOSARCOMA

• Malignant mesenchymal tumour in which the cancerous cells produce bone matrix
• Obeys Phemister’s law which states where there is growing bone you are more likely to get a tumour. Therefore occur in the metaphyseal region of long bones
• More commonly occur around knee
• 10-20% will have lung mets at presentation
• Most occurs in male teens
• 25% occur in the elderly and are associated with Pagets disease, bone infarct and ionising radiation
• Patients with hereditary retinoblastoma are 1000 times more likely to develop osteosarcoma – attributed to mutations in Rb
• Fatal if untreated, now 75% with early disease survive
• Morphology
  • Bulky tumours which can have haemorrhagic and cystic inclusions
  • Frequently produce soft tissue masses
  • Spread extensively in the medullary canal
  • May penetrate epiphyseal plate and enter the joint
  • Generally spindle shaped neoplasms
  • Produce osteoid (characteristic)
  • Radiologically there is a ‘sunray’ speculation around the bone and lifting of the periosteum (Codman’s triangle). Patchy osteolysis and osteosclerosis.
• Additional subtypes;
  • Parosteal osteosarcoma
  • Periosteal osteosarcoma
  • Telangiectatic

Cartilage  forming tumours

1) OSTEOCHONDROMA (EXOTOSIS)

• Benign cartilage capped out growth, attached to the underlying skeleton by a bony stalk
• Common
• Can be solitary or multiple
• Solitary osteochondromas are diagnosed in early adulthood M>F
• Develop in bones only of endochrondral origin and arise in the metaphysis of long bones, especially around the knee
• Morphology
  • Range in size from 1cm to 20 cm
  • Cap is composed of hyaline cartilage and is surrounded by perichondrium
  • Medullary cavity is in continuity with that of the bone
• Generally present as slow growing masses which can cause pain if the impinge on a nerve or the stalk gets fractured
• Patients with multiple hereditary exostosis have a mutation in the EXT gene (autosomal dominant) and develop multiple osteochondromas. They are at higher risk of developing an oestosarcoma

2) CHONDROMA

• Benign tumours of the hyaline cartilage arising from remnants of epiphyseal pain
• If they arise from the medullary cavity they are called endochondromas (most common)
• If they arise from the surface of the bone they are called (sub)periosteal chondromas
• Cause pain, fracture and deformity
• Endochondromas can be solitary or multiple
• Located in the metaphyseal area of tubular bones – hands, feet, humerus and femur
• Multiple endochondromas or endochondromatosis is called Ollier disease
• If endochondromatosis is associated with tissue hemangiomas it is called Maffucci syndrome (also at risk of ovarian tumours and gliomas)
• Morphology
  • Small, nodular configuration
  • At the periphery of the nodules the cartilage can ossify and the centre can calcify and die
  • On x-ray they consist of well circumscribed lesions confined to the medulla – O ring sign
• Periosteal chondromas are rare and usually involve the proximal humerus and distal femar

3) CHONDROBLASTOMA

• Rare cartilaginous tumour in teens M>F
• Predilection for epiphyses
• Most arise near the knee and the small bones of feet
• Clinically very painful and because of their location can cause effusions and restrict mobility
• Well circumscribed and radio-lucent on x-ray
• Morphology
  • Very cellular, composed of sheets of polyhedral chondroblasts
  • Hyaline matrix calcifies producing a ‘chicken-wire’ pattern of mineralization
  • Scattered throughout the lesion are osteoclast-type giant cells

4) CHONDROMYXOID FIBROMA

• Rarest cartilage tumour – can be mistaken for a chondrosarcoma
• Affect young adults M>F
• Tumours arise most frequently from the metaphysis of tubular bones – around knee and bones of foot
• Patients complain of dull localised pain
• Radiolucent on x-ray with adjacent sclerosis of cortex
• Occasionally tumour can expand the surrounding cortex
• Morphology
  • Well circumscribed and glistening
  • Composed of poorly organised hyaline cartilage
  • Greatest cellularity at the peripheries

5)CHONDROSARCOMA

• Produce neoplastic cartilage
• Commonly arise secondary to benign cartilage tumours
• Patient >40, M>F
• Commonly arise in the central portions of the skeleton – rarely involves distal extremities
• Present as painful, rapidly progressive lumps
• Radiologically scalloping is seen and bone destruction – foci of flocculent density
• Preferentially metastase to lungs and skeleton
• Morphology
  • Composed of malignant hyaline or myxoid cartilage
  • Central necrosis may result in cystic spaces
  • Tumour can push into the surrounding soft tissues
  • Malignant cartilage infiltrates the marrow space
  • Prognosis depends on the grade and whether it was resected completely during initial stages

Fibrous and fibro-osseous bone tumours

• Tumours composed predominantly of fibrous elements are diverse and include some of the most common lesions of the skeleton

1) FIBROUS CORTICAL DEFECT/NONOSSIFYING FIBROMA

• Common, found in almost have of children over age 2
• Believed to be developmental defects rather than neoplasms
• Most arise from the metaphysis of the distal femur or proximal tibia
• Can be bilateral or multiple
• If they are greater than 5cm they are called non-ossifying fibroma
• Generally asymptomatic and spontaneously resolve although the ones that develop into non-ossifying fibromas may present with pathological fracture
• Morphology
  • Produce elongated sharply demarcated radiolucencies that are surrounded by a thin layer of sclerosis
  • Cellularly consist of fibroblasts and activated macrophages (Histiocytes)
  • Fibroblasts are arranged in a storiform pattern (pinwheel)
  • Histocytes may be present as giant cells or clusters of foamy macrophages

2) FIBROUS DYSPLASIA

• Rare and benign of fibro-osseous tissue. All the components of normal bone are present but in an immature form
• Can result in 3 clinical patterns;
  • Monostotic – involvement of a single bone
  • Polyostotic – involvement of several bones
  • McCune-Albright Syndrome – polyostotic disease associated with café au lait spots and endocrine abnormalities  due to G-protein mutation and excess cAMP
• Monostotic lesions account for 70% of cases
  • Affects males and female in early adolescence and often stops growing at the time of growth plate closure
  • Can cause enlargement and torsion of the bone and if craniofacial bones are involved, disfigurement
• Polyostotic disease without endocrine changes results in 27% of cases
  • Manifests earlier than monostotic disease and can continue into adulthood
  • Can cause crippling deformities and spontaneous and recurrent fractures
  • Small risk of development of malignancy
• McCune-Albright syndrome is associated with sexual precocity, hyperthyroidism, GH secreting pituitary adenomas an adrenal hyperplasia
  • Bone lesions are generally unilateral and café au lait spots affect the same side and are large and irregular
• Morphology
  • Well circumscribed
  • Trabeculae look like Chinese writing

3) FIBROSARCOMA/MALIGNANT FIBROUS HISTIOCYTOMA

• Fibroblastic collagen producing tumours of the bone
• Difficult to distinguish between the two
• Mostly affect middle aged and elderly
• Fibrosarcoma M=F
• Malignant histiocytoma M>F
• Present as painful enlarging masses usually arising at the metaphysic of long bones and pelvic flat bones. Often develop pathological fractures
• Radiologically lytic and penetrate into soft tissue
• High grade tumours have a poor prognosis

Miscellaneous Bone tumours

1) EWING SARCOMA

• Peripheral primitive neuroectodermal tumour. Histologically if lesion shows neuroectodermal differentiation it is called a Primitive Neuroectodermal tumour (PNET) and if it is undifferentiated it is called a Ewing sarcoma
• Accounts for 5-10% of primary bone tumours and typically affect children and young adults M>F. Whites more commonly affected than blacks
• Can affect all bones and patients present with localised pain and swelling and possibly pathological fractures
• Most commonly femur, pelvis, tibia, humerus and ribs
• Usually are at the diaphysis of long bones – site is tender, warm and swollen and may mimic infection
• Due to a 11-22 chromosome gene translocation which act as a dominant oncogene
• X-rays show a lytic destructive lesion that extends into the soft tissues with a distinctive periosteal reaction called onion-skinning
• Morphology
  • Arise from medulla and invade the cortex and periosteum producing a soft tissue mass
  • Contains areas of haemorrhage and necrosis
  • Tumour cells are arranged in circles with a central fibrillary space called Homer-Wright rosettes

2) Giant cell bone tumour

• Also called an osteoclastoma as it contains a profusion of multinucleated oestoclast giant cells
• Are believed to be of macrophage-monocyte lineage
• Relatively benign but very aggressive locally
• Arises in the epiphyses of adult (age 20-30) long bones F>M
• Majority arise around the knee – patients can complain of arthritic symptoms an can present as pathological fractures
• Radiologically they are large and lytic and can erode into the subchondral bone plate
• Can metastase to lungs
• Morphology
  • Frequently undergo cystic degeneration
  • Osteocytic giant cells can have up to 100 nuclei
  • Secondary features include haemorrhage, necrosis, reactive bone formation and hemosiderin deposition
  • Required to be distinguished from the brown tumour seen in hyperparathyroidism

3) Myeloma

• Affects middle aged and elderly M>F
• Causes 1% of cancer deaths
• Can be multiple or solitary (plasmacytoma)
• Plasmacytomas can progress to multiple myelomas
• Monoclonal proliferation of bone marrow plasma cells
• Widespread osteolytic lesions, bone pain, hypercalcaemia, monoclonal gammopathy and amyloidosis
• Complications include recurrent infections due to abnormal immunoglobulin suppression
• Hyperviscosity syndrome
• Renal insufficiency
• Neuropathy can result due to infiltration of nerve root trunks