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Primary Bone Tumors
Quick Review
Dpt. Aamir Memon
11/8/2013
Primary Bone Tumors
They are predominantly seen in the first three decades of life, during the ages of greatest
skeletal growth activity. Benign tumors are by far more common than malignant ones. The
most common benign tumors are osteochondroma, fibro-osseous lesions, and
enchondroma.
Some primary bone tumors are labeled as potentially malignant tumors as they show local
aggression but only rarely metastasize, e.g., giant cell tumor of bone.
Among primary malignant neoplasms, osteosarcoma and multiple myeloma have the highest
incidence, followed by chondrosarcoma and Ewing’s sarcoma.
The commonest sites for primary bone tumors, both benign and malignant, are in distal
femur and proximal tibia, which are the bones with highest growth rate.
Bone-forming tumors are neoplasms, in which neoplastic cells produce bones.
Classification:
 Benign
o Osteoma
o Osteoid osteoma
o Osteoblastoma
 Malignant
o Osteogenic sarcoma
Distribution of bone tumors in long bones
 Epiphyseal lesions:
o Chondroblastoma
o Giant cell tumor
 Metaphyseal intramedullary lesions:
o Osteosarcoma
o Chondrosarcoma
o Aneurysmal bone cyst
 Metaphyseal lesions centered in the cortex:
o Nonossifying fi broma (NOF)
o Osteoid osteoma
 Metaphyseal exostosis:
o Osteochondroma
 Diaphyseal intramedullary lesions:
o Ewing’s sarcoma
o Lymphoma
o Myeloma
o Fibrous dysplasia
o Enchondroma
 Diaphyseal lesions centered in the cortex:
o Adamantinoma
o Osteoid osteoma
Benign Tumors
Osteoma
Skeletal distribution:
 Involves flat bones of skull, face, and paranasal sinuses (especially frontal and
ethmoid).
Clinical features:
 Osteomas are often incidental with asymptomatic findings; they occur in middle age,
and are solitary and slow growing. They may lead to cosmetic deformity, obstruction
of sinus cavity, or impingement on brain and eye.
Gross morphology:
 Osteomas are mostly sessile, round-to-oval, and bosselated.
 They are seen projecting from subperiosteal/endosteal surface of cortex.
 Multiple osteomas may present with intestinal polyposis and soft tissue tumors
(Gardner syndrome).
Microscopy:
They are composed of compact, lamellar bone that is deposited in a cortical pattern with
Haversian-like systems. Rarely they may contain a component of trabecular bone in which
the intertrabecular spaces are filled with marrow material.
Treatment and prognosis:
Simple excision is the treatment of choice for symptomatic lesions. The lesion does not recur
after surgical excision and is not associated with malignant change.
Osteoid Osteoma
Skeletal distribution:
 Long bones (femur and tibia)
 Usually intracortical; less frequently arises from the medullary cavity
Clinical features:
 It is common in the age group of 10–30 years
 Presents with intense pain, which increases during night and is relieved by aspirin
(pain is thought to be due to excessive PGE2 production by proliferating osteoblasts).
 Also observed in most cases is localized swelling and tenderness.
X-ray:
It shows a central nidus smaller than 1.5 cm that is surrounded by sclerotic bone. The nidus
may be difficult to see on plain X-ray. CT is modality of choice to identify the nidus.
Bone scan always demonstrates intense focal uptake. The lesion can occur only in the cortex,
in both the cortex and medulla,or only the medulla. The four diagnostic features include
(1) A well-defined round-or-oval lesion,
(2) i.e., less than 2 cm in diameter,
(3) Has a homogeneous dense center, and
(4) A 1–2- mm peripheral radiolucent zone.
The radiologic differential includes osteoblastoma, osteomyelitis, arthritis, stress fracture,
and enostosis.
Gross morphology:
Appears as a well-defined round-to-oval mass of gritty tissue of less than 2 cm in size.
Microscopy:
There is a distinct demarcation between nidus and reactive bone. The central nidus is
comprised of randomly interconnecting trabeculae of woven bone prominently rimmed by
osteoblasts. Stroma surrounding tumor bone consists of loose connective tissue with many
dilated–congested capillaries.
The nidus is enveloped by sclerotic bone.
Treatment and prognosis:
Osteoid osteoma usually resolves without treatment over a period of time. If the patient does
not wish to endure the pain and prolonged use of nonsteroidal anti-inflammatory medications,
surgical removal, or percutaneous ablation of the nidus can be undertaken.
Osteoblastoma
Skeletal distribution:
 Osteoblastoma is a solitary, benign, bone-forming tumor that occurs in the spine and
long bones of young adults. Commonly involve sites include vertebrae, tibia, femur,
humerus, and pelvis.
 It is usually metaphyseal in location, and may be intracortical or intramedullary in
origin.
Clinical features:
Osteoblastoma and osteoid osteoma are histologically very similar, yet these two tumors are
very different in their presentation, localization, radiographic appearance, treatment, and
potential for recurrence. Osteoblastoma can be differentiated from the latter based on the
following features:
 It is larger than 2 cm (also called giant osteoid osteoma).
 It occurs in an older age group.
 Usually does not cause localized night pain and, when pain occurs, is not relieved by
NSAIDs.
 Does not present with an intense bony reaction unlike osteoid osteoma.
 Preferentially involves posterior elements of vertebrae, spine, femur, and bones of the
foot.
 An associated soft tissue mass may be seen in about 25% of patients.
Gross morphology:
On gross examination, osteoblastomas are red-to-tan in color with hemorrhagic areas. The
compact tissue is granular, friable, and gritty.
Microscopy:
The lesion is comprised of calcified osteoid growing within a highly vascularized connective
tissue and surrounded by minimal sclerosis. The vascular stroma is characterized by
pleomorphic spindle cells. The tumor cells diff erentiate into osteoblasts, which make varying
amounts of osteoid and woven bone. Cartilage production is a very rare finding in an
osteoblastoma, and should raise suspicion of osteosarcoma.
Treatment and prognosis:
Surgical resections by curettage, intralesional excision, or end block excision are all
treatment options depending on site.
Malignant Tumor (Osteogenic Sarcoma)
Osteogenic sarcoma is a malignant mesenchymal tumor in which neoplastic cells directly
lay down bone matrix (osteoid). It is the most common primary malignant bone tumor,
excluding myeloma and lymphoma.
Pathogenesis
Genetic contribution:
Mutations in tumor suppressor genes, e.g., P53 or RB1 are commonly associated. Germline
mutations in P53 gene induce multiple carcinomas and sarcomas (Li-Fraumeni syndrome).
Patients with hereditary retinoblastomas have a markedly increased risk of developing
osteosarcoma. Abnormalities in CDK4, P16, INK4A, cyclin D1, and MDM2 are also
implicated in nonhereditary osteosarcomas.
Environmental contribution:
Radiation, thorotrast, and therapeutic irradiation are all implicated. Children treated with
alkylating agents have an increased risk of osteosarcoma.
Classification
1. Based on affected age and presence of pre-existing bone pathology:
a) Primary (arise de novo): Common in the age group between 10 and 25 years.
b) Secondary (secondary to pre-existing bone pathology): Occurs in older patients
(more than 40 years), and constitutes about 6%–10% of all osteosarcomas.
Conditions predisposing to secondary osteosarcoma:
 Paget’s disease
 Exposure to radiation
 Chemotherapy (alkylating agents)
 Bone lesions like fibrous dysplasia, osteochondroma, enchondroma, and bone
infarcts.
2. Based on skeletal distribution/anatomical site:
a) Intramedullary: Conventional osteosarcoma (the most common type) is invariably
intramedullary and metaphyseal (zone of maximum bone growth) in origin. Long
bones like lower end of femur, upper end of tibia, and upper end of humerus are
involved in that order of frequency.
b) Intracortical
c) Surface
3. Based on morphology:
About 85% of osteosarcoma cases are of the “conventional intramedullary” type, and the
other 15% consists of several other subtypes, including telangiectatic, low-grade
intramedullary, and small cell, as well as, the surface subtypes parosteal, periosteal, and
high-grade surface osteosarcoma.
� Conventional intramedullary osteosarcoma can be further subdivided into the following
subtypes:
 Osteoblastic (shows a large amount of osteoid and bony trabeculae)
 Chondroblastic (malignant cartilage forms nearly 90% of the tumor)
 Fibroblastic (comprised of a large spindle cell/fibroblastic component)
� Surface osteosarcomas can be further subdivided into the following subtypes:
 Juxtacortical (parosteal) osteosarcoma
o Affects old age
o It is a slow-growing, low-grade tumor with a good prognosis.
o It is classically located on the posterior aspect of lower femur, where it
typically presents as a large lobulated mass encircling the bone.
 Periosteal osteosarcoma
o Grows on the surface of long bones
o Is usually limited to the cortex
o Has a prominent cartilaginous component
o Behaves more aggressively than a parosteal osteosarcoma, but less
aggressively as compared to a high-grade surface variant
 Osteosarcoma of jaw
o Affects older age
o Involves mandible and alveolar ridges of maxilla
o Has a prominent chondroblastic component
o Has a relatively good prognosis
 Osteosarcoma in Paget’s disease
o It is usually multicentric.
o Pelvis, humerus, and femur bones are involved in that order of frequency.
o Has a poor prognosis.
Clinical Features
Osteosarcomas present as painful, progressively enlarging masses with a large soft -tissue
component, sometimes associated with a pathological fracture. Levels of serum alkaline
phosphatase are raised.
X-ray
 On radiographs, conventional osteosarcoma is seen as a metaphyseal, large,
permeative, destructive, mixed sclerotic, and lytic lesion. Bone formation within the
tumor is characteristic of osteosarcoma, and is usually visible on the X-rays.
 Tumor breaks through the cortex, results in reactive periosteal bone formation, and lift
s the periosteum. Th e triangular shadow between cortex and raised periosteum is
radiographically called “Codman’s triangle.” The periosteal reaction is laid down to
the surface of the bone, and this is labeled as “sunray appearance.”
Morphology
Gross:
 Bulky, gritty, and gray–white tumor, often containing areas of hemorrhage and
necrosis
 Destruction of cortex and soft tissue extension are common
 Penetration of epiphyseal plate/entry into joint is infrequent
Microscopy:
 Frankly sarcomatous stroma comprised of large atypical spindle- shaped cells with
bizarre tumor giant cells and mitoses.
 Direct formation of tumor osteoid. In H&E sections, osteoid is seen as an
eosinophilic, glassy, homogenous material, produced by neoplastic cells and arranged
in a thin anastomosing lace-like pattern.
 Besides osteoid, chondroblastic and fibroblastic elements may be present. In the
presence of abundant malignant cartilage, tumor qualifies as a chondroblastic variant
of osteosarcoma.
 Spontaneous necrosis and vascular invasion are frequently seen.16
Diagnosis
 Imaging
 FNAC
 Open biopsy
Metastasis
 Lungs, other bones, pleura, and heart are common sites of metastasis.
 Regional lymph nodes are rarely involved.
Prognosis
Long-term survival rate is 60%–70% (with chemotherapy and limb salvage therapy).
Classification of primary tumors involving bones have been given in Table
Histological types Benign Malignant
Hematopoietic (40%) --- Myeloma
Maligant lymphoma
Chondrogenic (22%) Osteochondroma
Chondroma
Chondromyxioid fibroma
Chondrosarcoma
(Differentiated, Messenchymal)
Osteogenic (20%) Osteoid Osteoma
Osteoblastoma
Osteosarcoma
Unknown origin (10%) Giant cell tumor
Unicameral bone cyst
Aneurysmal bone cyst
Fibrogenic Metaphyseal fibrous defect
(fibroma)
Fibrous histiocytoma
Desmoplastic fibroma
Notochordal Benign notochordal tumor Chordoma
Neuroectodermal Ewing’s Sarcoma

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Primary bone tumors

  • 1. Primary Bone Tumors Quick Review Dpt. Aamir Memon 11/8/2013
  • 2. Primary Bone Tumors They are predominantly seen in the first three decades of life, during the ages of greatest skeletal growth activity. Benign tumors are by far more common than malignant ones. The most common benign tumors are osteochondroma, fibro-osseous lesions, and enchondroma. Some primary bone tumors are labeled as potentially malignant tumors as they show local aggression but only rarely metastasize, e.g., giant cell tumor of bone. Among primary malignant neoplasms, osteosarcoma and multiple myeloma have the highest incidence, followed by chondrosarcoma and Ewing’s sarcoma. The commonest sites for primary bone tumors, both benign and malignant, are in distal femur and proximal tibia, which are the bones with highest growth rate. Bone-forming tumors are neoplasms, in which neoplastic cells produce bones. Classification:  Benign o Osteoma o Osteoid osteoma o Osteoblastoma  Malignant o Osteogenic sarcoma Distribution of bone tumors in long bones  Epiphyseal lesions: o Chondroblastoma o Giant cell tumor  Metaphyseal intramedullary lesions: o Osteosarcoma o Chondrosarcoma o Aneurysmal bone cyst  Metaphyseal lesions centered in the cortex: o Nonossifying fi broma (NOF) o Osteoid osteoma  Metaphyseal exostosis: o Osteochondroma  Diaphyseal intramedullary lesions: o Ewing’s sarcoma o Lymphoma o Myeloma o Fibrous dysplasia o Enchondroma  Diaphyseal lesions centered in the cortex: o Adamantinoma o Osteoid osteoma
  • 3. Benign Tumors Osteoma Skeletal distribution:  Involves flat bones of skull, face, and paranasal sinuses (especially frontal and ethmoid). Clinical features:  Osteomas are often incidental with asymptomatic findings; they occur in middle age, and are solitary and slow growing. They may lead to cosmetic deformity, obstruction of sinus cavity, or impingement on brain and eye. Gross morphology:  Osteomas are mostly sessile, round-to-oval, and bosselated.  They are seen projecting from subperiosteal/endosteal surface of cortex.  Multiple osteomas may present with intestinal polyposis and soft tissue tumors (Gardner syndrome). Microscopy: They are composed of compact, lamellar bone that is deposited in a cortical pattern with Haversian-like systems. Rarely they may contain a component of trabecular bone in which the intertrabecular spaces are filled with marrow material. Treatment and prognosis: Simple excision is the treatment of choice for symptomatic lesions. The lesion does not recur after surgical excision and is not associated with malignant change. Osteoid Osteoma Skeletal distribution:  Long bones (femur and tibia)  Usually intracortical; less frequently arises from the medullary cavity Clinical features:  It is common in the age group of 10–30 years  Presents with intense pain, which increases during night and is relieved by aspirin (pain is thought to be due to excessive PGE2 production by proliferating osteoblasts).  Also observed in most cases is localized swelling and tenderness. X-ray: It shows a central nidus smaller than 1.5 cm that is surrounded by sclerotic bone. The nidus may be difficult to see on plain X-ray. CT is modality of choice to identify the nidus. Bone scan always demonstrates intense focal uptake. The lesion can occur only in the cortex, in both the cortex and medulla,or only the medulla. The four diagnostic features include (1) A well-defined round-or-oval lesion, (2) i.e., less than 2 cm in diameter, (3) Has a homogeneous dense center, and (4) A 1–2- mm peripheral radiolucent zone. The radiologic differential includes osteoblastoma, osteomyelitis, arthritis, stress fracture, and enostosis. Gross morphology: Appears as a well-defined round-to-oval mass of gritty tissue of less than 2 cm in size.
  • 4. Microscopy: There is a distinct demarcation between nidus and reactive bone. The central nidus is comprised of randomly interconnecting trabeculae of woven bone prominently rimmed by osteoblasts. Stroma surrounding tumor bone consists of loose connective tissue with many dilated–congested capillaries. The nidus is enveloped by sclerotic bone. Treatment and prognosis: Osteoid osteoma usually resolves without treatment over a period of time. If the patient does not wish to endure the pain and prolonged use of nonsteroidal anti-inflammatory medications, surgical removal, or percutaneous ablation of the nidus can be undertaken. Osteoblastoma Skeletal distribution:  Osteoblastoma is a solitary, benign, bone-forming tumor that occurs in the spine and long bones of young adults. Commonly involve sites include vertebrae, tibia, femur, humerus, and pelvis.  It is usually metaphyseal in location, and may be intracortical or intramedullary in origin. Clinical features: Osteoblastoma and osteoid osteoma are histologically very similar, yet these two tumors are very different in their presentation, localization, radiographic appearance, treatment, and potential for recurrence. Osteoblastoma can be differentiated from the latter based on the following features:  It is larger than 2 cm (also called giant osteoid osteoma).  It occurs in an older age group.  Usually does not cause localized night pain and, when pain occurs, is not relieved by NSAIDs.  Does not present with an intense bony reaction unlike osteoid osteoma.  Preferentially involves posterior elements of vertebrae, spine, femur, and bones of the foot.  An associated soft tissue mass may be seen in about 25% of patients. Gross morphology: On gross examination, osteoblastomas are red-to-tan in color with hemorrhagic areas. The compact tissue is granular, friable, and gritty. Microscopy: The lesion is comprised of calcified osteoid growing within a highly vascularized connective tissue and surrounded by minimal sclerosis. The vascular stroma is characterized by pleomorphic spindle cells. The tumor cells diff erentiate into osteoblasts, which make varying amounts of osteoid and woven bone. Cartilage production is a very rare finding in an osteoblastoma, and should raise suspicion of osteosarcoma. Treatment and prognosis: Surgical resections by curettage, intralesional excision, or end block excision are all treatment options depending on site.
  • 5. Malignant Tumor (Osteogenic Sarcoma) Osteogenic sarcoma is a malignant mesenchymal tumor in which neoplastic cells directly lay down bone matrix (osteoid). It is the most common primary malignant bone tumor, excluding myeloma and lymphoma. Pathogenesis Genetic contribution: Mutations in tumor suppressor genes, e.g., P53 or RB1 are commonly associated. Germline mutations in P53 gene induce multiple carcinomas and sarcomas (Li-Fraumeni syndrome). Patients with hereditary retinoblastomas have a markedly increased risk of developing osteosarcoma. Abnormalities in CDK4, P16, INK4A, cyclin D1, and MDM2 are also implicated in nonhereditary osteosarcomas. Environmental contribution: Radiation, thorotrast, and therapeutic irradiation are all implicated. Children treated with alkylating agents have an increased risk of osteosarcoma. Classification 1. Based on affected age and presence of pre-existing bone pathology: a) Primary (arise de novo): Common in the age group between 10 and 25 years. b) Secondary (secondary to pre-existing bone pathology): Occurs in older patients (more than 40 years), and constitutes about 6%–10% of all osteosarcomas. Conditions predisposing to secondary osteosarcoma:  Paget’s disease  Exposure to radiation  Chemotherapy (alkylating agents)  Bone lesions like fibrous dysplasia, osteochondroma, enchondroma, and bone infarcts. 2. Based on skeletal distribution/anatomical site: a) Intramedullary: Conventional osteosarcoma (the most common type) is invariably intramedullary and metaphyseal (zone of maximum bone growth) in origin. Long bones like lower end of femur, upper end of tibia, and upper end of humerus are involved in that order of frequency. b) Intracortical c) Surface 3. Based on morphology: About 85% of osteosarcoma cases are of the “conventional intramedullary” type, and the other 15% consists of several other subtypes, including telangiectatic, low-grade intramedullary, and small cell, as well as, the surface subtypes parosteal, periosteal, and high-grade surface osteosarcoma. � Conventional intramedullary osteosarcoma can be further subdivided into the following subtypes:  Osteoblastic (shows a large amount of osteoid and bony trabeculae)  Chondroblastic (malignant cartilage forms nearly 90% of the tumor)  Fibroblastic (comprised of a large spindle cell/fibroblastic component) � Surface osteosarcomas can be further subdivided into the following subtypes:  Juxtacortical (parosteal) osteosarcoma o Affects old age o It is a slow-growing, low-grade tumor with a good prognosis. o It is classically located on the posterior aspect of lower femur, where it typically presents as a large lobulated mass encircling the bone.  Periosteal osteosarcoma o Grows on the surface of long bones
  • 6. o Is usually limited to the cortex o Has a prominent cartilaginous component o Behaves more aggressively than a parosteal osteosarcoma, but less aggressively as compared to a high-grade surface variant  Osteosarcoma of jaw o Affects older age o Involves mandible and alveolar ridges of maxilla o Has a prominent chondroblastic component o Has a relatively good prognosis  Osteosarcoma in Paget’s disease o It is usually multicentric. o Pelvis, humerus, and femur bones are involved in that order of frequency. o Has a poor prognosis. Clinical Features Osteosarcomas present as painful, progressively enlarging masses with a large soft -tissue component, sometimes associated with a pathological fracture. Levels of serum alkaline phosphatase are raised. X-ray  On radiographs, conventional osteosarcoma is seen as a metaphyseal, large, permeative, destructive, mixed sclerotic, and lytic lesion. Bone formation within the tumor is characteristic of osteosarcoma, and is usually visible on the X-rays.  Tumor breaks through the cortex, results in reactive periosteal bone formation, and lift s the periosteum. Th e triangular shadow between cortex and raised periosteum is radiographically called “Codman’s triangle.” The periosteal reaction is laid down to the surface of the bone, and this is labeled as “sunray appearance.” Morphology Gross:  Bulky, gritty, and gray–white tumor, often containing areas of hemorrhage and necrosis  Destruction of cortex and soft tissue extension are common  Penetration of epiphyseal plate/entry into joint is infrequent Microscopy:  Frankly sarcomatous stroma comprised of large atypical spindle- shaped cells with bizarre tumor giant cells and mitoses.  Direct formation of tumor osteoid. In H&E sections, osteoid is seen as an eosinophilic, glassy, homogenous material, produced by neoplastic cells and arranged in a thin anastomosing lace-like pattern.  Besides osteoid, chondroblastic and fibroblastic elements may be present. In the presence of abundant malignant cartilage, tumor qualifies as a chondroblastic variant of osteosarcoma.  Spontaneous necrosis and vascular invasion are frequently seen.16 Diagnosis  Imaging  FNAC  Open biopsy Metastasis  Lungs, other bones, pleura, and heart are common sites of metastasis.  Regional lymph nodes are rarely involved.
  • 7. Prognosis Long-term survival rate is 60%–70% (with chemotherapy and limb salvage therapy). Classification of primary tumors involving bones have been given in Table Histological types Benign Malignant Hematopoietic (40%) --- Myeloma Maligant lymphoma Chondrogenic (22%) Osteochondroma Chondroma Chondromyxioid fibroma Chondrosarcoma (Differentiated, Messenchymal) Osteogenic (20%) Osteoid Osteoma Osteoblastoma Osteosarcoma Unknown origin (10%) Giant cell tumor Unicameral bone cyst Aneurysmal bone cyst Fibrogenic Metaphyseal fibrous defect (fibroma) Fibrous histiocytoma Desmoplastic fibroma Notochordal Benign notochordal tumor Chordoma Neuroectodermal Ewing’s Sarcoma