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