MBARARA UNIVERSITY OF SCIENCE

AND TECHNOLOGY
DEPARTMENT OF PATHOLOGY
ASSIGNMENT: BONE TUMORS

NAME: KASAGGA ASHRAF

REGISTRATION NUMBER:
2020/MBR/065/PS
INTRODUCTION
Bone cancer is an abnormal growth of tissue in the bone. It can be primary or
secondary. Primary bone sarcoma starts growing from the bone cells, while secondary
bone cancer starts from other organs of the body and then spread to the bone cells.
Pain, bone loss and hyper calcemia are the most common symptoms of a bone cancer.
Early bone cancer detection may lead to more efficient treatment and reduce the risk
of disabilities. However, bone cancer is usually misdiagnosed due to difficulties
encoountered by radiologists while interpreting medical images. Image processing
techniques can offer accurate interpretation tools for medical imaging and assist
radiologists in done cancer diagnosis

CLASSIFICATION
Bone tumors are classified into two main categories that is;
 Primary bone tumors
 Secondary bone tumors (metastatic bone tumors)

Primary bone tumors: These originate directly within the bone tissue they can be
benign (non cancerous) or malignant (cancerous).
The classification of primary bone tumors is based on the type of cells involved and
their behavior. These are;
a. Benign primary bone tumors.
Osteoma
Osteoid osteoma
Osteoblastoma
Enchondroma
Giant cell tumor of the bone
Fibrous dysplasia
Chondroblastoma
Non ossifying fibroma
Aneurysmal bone cyst
Osteochondroma
b. Malignant primary bone tumors.
Osteosarcoma
 Chondrosarcoma
Ewing sarcoma
Adamantinoma
Fibrosarcoma
Malignant fibrous histiocytoma
Chordoma
According to their cell of orign and histologic features, primary bone tumors can be
classified as being composed of:
 Bone-forming cells (e.g. osteoma, osteoblastoma and osteosarcoma)
 Cartilage-forming cells (e.g. chordoma and chondrosarcoma)
 Osteoclastic cells (e.g. giant cell tumor)
 Fibroblastic cells (e.g. fibrosarcoma and malignant fibrous histiocytoma)
 Undifferentiated cells (e.g. Ewing sarcoma)
 Hematopoietic and lymphoid cells (e.g. multiple myeloma, leukemia, and
lymphoma)
See tables below
Secondary (metastatic) bone tumors: These are cancers that have spread
(metastasized) to the bone from other parts of the body. The most common primary
cancers that metastasize to the bone include breast, lung, prostate, kidney, and thyroid
cancers. The classification of secondary bone cancer is based on the primary cancer
type rather than specific bone-related characteristics.
EPIDEMIOLOGY
The American cancer society’s estimates for primary cancer of bones and joints for
2023 are:
About 3970 new cases diagnosed (2,160 in males; 1,810 in females)
About 2,140 deaths (1,200 in males; 940 in females)
This includes cancers in both children and adults.

Primary bone cancers (cancers that start in the bones) are uncommon accounting for
less than 1% of all cancers. In adults, cancers that spread to the bones from other
organs ( known as bone metastasis) are much more common than primary bone
cancers.

Osteosacroma is the most common primary bone cancers overall, followed by

chondrosaarcoma and Ewing tumors ( Ewing sarcomas). but this varies by age group.

In adults, the most common primary bone cancer is chondrosarcoma. This is followed
by osteosarcoma, chordomas and Ewing tumors. Other types of bone cancer are much
less common.
In children and teens, osteosarcoma and Ewing tumors are much more common than
chondrosarcoma or other types of bone cancers.

The prognosis (outlook) for people with bonecancer depends on many factors,
including the type of bone cancer, the location of the tumor, whether the cancer has
spread (metastasised) when it’s first found, the person’s age and overall health, and
how well the cancer responds to treatment.

References
American Cancer Society. Facts and figures2023. American Cancer Society. Atlanta, Ga. 2023.
National Cancer Institute. SEER Cancer Stat Facts: Bone and joint Cancer. Accessed at
https://seer.cancer.gov/statfacts/html/bones on 8 July 2023
National Comprehensive Cancer Network (NCCN). Practice Guidelines in Oncology: Bone Cancer.
Version 1. Accessed at www.nccn.org/proffesionals/physician_gls/pdf/bone.pdf/ on 8 July 202
 OSTEOSARCOMA
Oteosarcoma is a malignant tumor in which the cancerous cells produce osteoid
matrix or mineralized bone. It is the most common primary malignat tumor of the
bone, exclusive of myeloma and lymphoma, and accounts approximately 20% of
primary bone cancers.
Osteosarcoma occurs in all age groups but has a bimodaal age distribution, 75% occur
in persons younger than 20 years of age. The second peak occurs in older adults, who
frequently suffer from conditions known to predispose to osteosarcoma and these
include Paget disease, bone infarcts, and prior radiation.
Overall, men are more commonly affected than women (1.6 : 1). Any bone can be
involved. The tumors usually arise in the metaphyseal region of the long bones of the
extremities, and almost 50% occur about the knee that is distal femur or proximal
tibia.

CLINICAL PRESENTATION.
Osteosarcoma typically presents as painful, progressively enlarging massesaround the
knee or other involved site.
The involved area is swollen and tender and the function of adjacent joint becomes
reduced
Serum alkaline phosphatase is increased

Radiography appearance: Shows a large destructive, mixed lytic (bone

destruction) and blastic mass (neoplastic bone formation) with infiltrative margins.
The tumor frequently breaks through the cortex and lifts the periosteum, and produces
a space between the cortex and lifted ends of periosteum. Radiologically, this space
appears as triangular shadow and is known as Codman triangle (characteristic but not
diagnostic of this tumor). The space mainly contains reactive new bone, which is
arranged perpendicular to the bone surface, but it may also contain malignant tumor.
When the malignant tumor extends into soft tissue, parallel lines of mineral deposition
in the periosteal region gives an appearance of rays of sun called as “sunburst”
appearance

PATHOGENESIS
Based on the pathogenesis, OS is divided into primary and secondary.
Primary Osteosarcomas
In this type, the underlying bone is unremarkable. About 70% of OS have acquired
genetic abnormalities, such as ploidy changes and chromosomal aberrations.

Mutations in tumor suppressor gene:

RB, the retinoblastoma gene (a cell cycle regulator) mutations is associated with
1000-fold increased risk of osteosarcoma and its mutation is found in about two-thirds
of patients .
Patients with Li-Fraumeni syndrome (germline TP53 mutations) have a greater
incidence of osteosarcoma and abnormalities that interfere with p53 function are
common in sporadic tumors. TP53, a gene whose product functions as the guardian of
genomic integrity by promoting DNA repair and apoptosis of irreversibly damaged
cells.
Inactivation of INK4a, which codes p16 (a negative regulator of cyclin-dependent
kinases) and p14 (it augments the function of tumor suppressor gene p53). have also
been found in osteosarcoma.
MDM2 and CDK4: They are cell cycle regulators that inhibit functions of p53 and
RB, respectively. They are overexpressed in many low-grade osteosarcomas, often
through chromosomal amplification of regional 12q13-q15.

Peak incidence of osteosarcomas is during the time of the adolescent growth spurt. It
occur mostly in the growth plate region of the bones with the fastest growth. The
increased proliferation at these sites may predispose to osteosarcoma.

Secondary Osteosarcoma
Osteosarcomas in older persons almost always develop in association with pre-
existing bone disorders. These include:
Paget disease of bone.
Radiation exposure:
Following therapeutic radiation for tumor, such as lymphoma.
Radium watch dial painters, who wetted their brushes by licking them, developed
osteosarcoma many years later.
Chemotherapy: Children treated with alkylating agents (other malignancies) have an
increased risk.
Pre-existing benign bone lesions. For example, fibrous dysplasia, osteomyelitis, and
bone marrow infarcts. Trauma may call attention to an existing osteosarcoma rather
than causing the tumor.
CLASSIFICATION
It can be classified in different ways:
1. Anatomic site of origin;
Conventional (classical, medullary, intramedullary, textbook)
Intracortical
Surface osteosarcoma
– Parosteal (juxtacortical): They arise on the surface of the cortex.
– Periosteal: They arise on the surface of periosteum.
2. Degree of differentiation:
Well differentiated
Moderately differentiated
Poorly differentiated.
3. Number of tumors
Solitary
Multicentric
– Synchronous
– Metachronous.
4. Pathogenesis (described above)
Primary
Secondary to pre-existing disorders.
5. Histologic features (described below).

SUBTYPES
Most Common Subtype
• Primary
• Solitary
• Conventional/Intramedullary
• Poorly differentiated.

The subtypes of osteosarcoma are recognized and are grouped according to:
 Site of origin (intramedullary, intracortical, or surface)
 Histologic grade (low, high)
 Primary (underlying bone is unremarkable) or secondary to preexisting
disorders (benign tumors, Paget disease, bone infarcts, previous radiation
 Histologic features (osteoblastic, chondroblastic, fibroblastic, telangiectatic,
small cell, and giant cell)

MORPHOLOGY

Gross morphology
Gross appearance varies depending on the proportions of bone, cartilage, stroma and
blood
Size: Usually big bulky tumors.
Cut surface: Gray-white in color, gritty, shows areas of hemorrhage and cystic
degeneration.
The tumors frequently destroy the surrounding cortices and produce soft tissue
masses. They spread extensively in the medullary canal, infiltrating and replacing
hematopoietic marrow. Infrequently, they penetrate the epiphyseal plate or enter th
joint. When the invasion occurs, the tumor grows into along tendinous structures or
through the attachment site of the joint capsule.

Microscopic morphology

Malignant Tumor Cells

Tumor cells vary in size and shape
Nucleus: Usually show large hyperchromatic nuclei and often shows mitotic figures
Bizarre tumor giant cells are common as are mitoses, some of them abnormal
forexample tripolar.
Vascular invasion is usually conspicuous, and some tumors also exhibit
extensive necrosis.

Matrix Component
Production of osteoid (unmineralized/noncalcified) or bone (calcified osteoid) by
malignant tumor cells is the single diagnostic feature of conventional osteosarcoma.
Osteoid: It appears as a dense, uniform, eosinophilic glassy intercellular material.
Neoplastic bone: It usually has a fine, lace-like architecture but also may be deposited
in broad sheets or as primitive trabeculae. In addition to bone, tumor cells may
produce cartilage or fibrous tissue, but these are not required for diagnosis. When
malignant cartilage is abundant, the tumor is called chondroblastic sarcoma.

Histological Subtypes
Most tumors contain a mixture of cells with varying amounts of matrices mentioned
below. Depending on the one predominant matrix, conventional osteosarcoma is
divided into:
• Osteoblastic: Large amount of osteoid and bony trabeculae.
• Chondroblastic: Abundant malignant cartilage.
• Fibroblastic/fibrohistiocytic: They appear similar to malignant fibrous histiocytoma.
• Telangiectatic: Large cavernous dilated vascular channels and it is more aggressive.
• Small cell: The tumor cells are small in size, uniform and simulate the appearance of
Ewing’s sarcoma and malignant lymphoma.
• Giant cell: This subtype contains numerous giant cells.
Vascular invasion and necrotic area may be conspicuous.

Immunohistochemistry:
The malignant tumor cells stain prominently for alkaline phosphatase and osteonectin.

SPREAD
Local Spread
Invasion of the adjacent cortex and destroys the nearby cortex
Elevation or perforation of the periosteum by tumor tissue
Spread along the medullary (marrow) cavity
Extension into epiphysis
Articular end of the bone is generally not involved in the initial stage
Later, it may infiltrate the epiphyseal plate and may even involve the joint s[ace
Extension into the soft tissues and may involve skin.

Blood spread
It is an aggressive tumor which may spread through the bloodstream to the lungs.
Less commonly, it may metastasize to other bones, pleura, brain and the heart.
CASE STUDY QUESTION
An 18 year old presented to orthopedic department with a complaint of pain and
progressive swelling around his right knee for the past 3months. Physical findings
showed a diffuse hard swelling with local pain over the area of the distal right femur.
An X-ray of the right knee showed an ill-defined mass involving the metaphyseal
region of th distal right femur with elevationof the adjacent periosteum. A bone
biopsy specimen was obtained and it comfirmed the provisional clinical diagnosis.
What is the probable diagnosis
Ans. Osteosarcoma lower end of femur

References
Robbins and Cotran PATHOLOGIC BASIS OF DISEASE NINTH EDITION
Exam Preparatory Manual For Undergraduates PATHOLOGY 4th Edition