Bone tumors – causes, symptoms, diagnosis, treatment, pathology

Bone tumors – causes, symptoms, diagnosis, treatment, pathology

Learning medicine is hard work! Osmosis makes it easy. It takes your lectures and notes to create
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much more. Try it free today! Bone tumors form when a bone cell divides
uncontrollably and forms a mass or tumor. If the tumor remains confined and doesn’t
spread into surrounding tissues, then it’s considered benign. But if the tumor invades into surrounding
tissues and metastasizes or spreads through blood or lymph, then it’s considered malignant. Malignant tumors can either be primary which
is when they arise from the bone cells, or secondary, which is when a tumor developed
somewhere else in the body, metastasized, and spread to the bones. The most common sources of tumor cells that
affect the bones but start somewhere else in the body, are the breast, prostate, the
lungs, the thyroid, and the kidneys. Now, even though the bones vary in size and
shape, they are all made of the same types of cells, and chief among them are osteoblasts
which build up new bone, and osteoclasts which help with bone breakdown or resorption. Now in addition to these, there are some more
primitive cells in the bone marrow called human mesenchymal stem cells and neuroectodermal
cells, which have the ability to differentiate into many cell types including nerve, fat,
bone, and cartilage cells. Now, in terms of anatomy, looking at a long-
bone like the femur – it has two epiphyses, which are the ends that contribute to joints
with other bones. Between the two epiphyses, is the diaphysis,
also called the bone shaft. In children and adolescents, there is an additional
narrow portion between the epiphysis and the diaphysis called the metaphysis. The metaphysis contains the growth plate,
the part of the bone that grows during childhood. In adults the growth plate has ossified and
fused with the diaphysis and the epiphysis. Now, there are genes that promote normal cell
growth called proto-oncogenes. With mutations, proto-oncogenes become oncogenes,
and these overstimulate the cell growth. To balance out cell growth, there are other
genes called tumor suppressor genes which promote apoptosis or cell death of mutated
cells. So oncogenes or mutated tumor suppressor genes
allow cells to keep growing uncontrollably resulting into tumors. Alright, primary bone tumors can be divided
up into ones that are most often benign, and those that are more often malignant. Let’s start with the most common benign
tumor, which is an osteochondroma and commonly affects males under 25 years. Osteochondroma is thought to arise from mutations
in the Exostosin 1, or EXT1 and Exostosin 2 or EXT2 genes, which encode the Exostosin
1 and 2 proteins. These proteins help to synthesize heparin
sulfate, which is a protein that regulates the growth of the growth plate. So in osteochondroma, a tumor arises from
the growth plate, and it typically results in a lateral bony projection. This bony stalk is called an exostosis, and
it has a cap, made mostly of hyaline cartilage. Now, osteochondromas typically develop in
the metaphysis of long bones, most usually the distal femur and the proximal tibia, around
the knee joint, but they can also occur in flat bones like the ilium, one of the hip
bones, as well as the scapula. Another benign tumor is the giant- cell tumor
of the bone – quite a name! A risk factor for giant cell tumors is having
a bony trauma like a fracture or radiation exposure. The tumor cells arises from osteoclasts cells,
but then develop into cells that have numerous nuclei – typically over 50 nuclei – so you
can think of them as destructive little giants. The giant cell tumor typically arises in the
epiphysis of the long bones, like the distal femur and the proximal tibia. On rare occasions, this tumor can become malignant,
especially in elderly individuals. Other benign tumors are osteoblastomas and
osteoid osteomas, both of which arise from osteoblasts. Both of these tumors classically form a nidus
– which is a disorganized mix of small blood vessels, tiny rods of bone called trabeculae,
and unmineralized bony tissue called osteoid. In osteoblastomas, the nidi – which is plural
for nidus – are large with a diameter of over 1.5 cm. In osteoid osteomas, the nidi are smaller
than 1.5cm in diameter and are often surrounded by a ring of sclerotic bone tissue. That ring of sclerotic tissue often produces
prostaglandins, which are small molecules that trigger the sensation of pain. Osteoblastomas also tend to affect the bones
of the axial skeleton, usually the mandible, and erode the surrounding bone. In comparison, osteoid osteomas typically
affect the diaphysis of long bones like the tibia, and don’t usually erode the surrounding
bone. Now, among malignant tumors, the most common
one is osteosarcoma. Osteosarcomas arise from osteoblasts of different
sizes – called pleomorphic – and these cells produce too much osteoid tissue. Osteosarcomas often form in the metaphysis
where there’s a lot of cell division occurring. They most commonly affect adolescents. Some known mutations that are linked to osteosarcomas
include mutations in the pRB protein, also seen in familial retinoblastoma, a childhood
malignant tumor of the eye, and the p53 protein which is also seen in Li-Fraumeni syndrome,
a condition in which there are a variety of cancers throughout the body. Another type of malignant bone tumor is Ewing’s
sarcoma, which is also common in adolescents, typically between the age of 10 to 20 years. Ewing sarcoma is thought to arise from neuroectodermal
cells, and which look like small, round, blue cells on microscopy. Ewing sarcoma is associated with chromosomal
mutations, specifically a translocation between the EWSR1 gene on chromosome 22 and FLI1 gene
on chromosome 11. You can remember this by 22+11=33, the jersey
number of the former basketball player Patrick Ewing. The EWSR1/FLI1 fusion results in the expression
of an abnormal protein called the EWSR1/FLI1 fusion protein or simply the Ewing sarcoma
protein. This protein causes defects in the differentiation
process of human mesenchymal stem cell and neuroectodermal cells, resulting in Ewing
sarcoma tumor cells. Ewing’s sarcoma can affect a number of different
bones, but most commonly affects the femur and the sacrum. Finally, there are chondrosarcomas which tends
to affect the elderly. Chondrosarcoma arises from the chondrocytes
which are cartilage-producing cells. Chondrosarcoma mainly affects bones of the
pelvis, but can also affect long bones like the proximal femur and proximal humerus. On imaging, the mass is typically within the
medullary cavity. Bone tumors commonly cause bone pain, swelling,
and fractures. Some unique symptoms are that the pain of
osteoid osteoma typically gets worse at night, while osteochondromas and osteoblastomas sometimes
press against spinal nerves, causing numbness and limb weakness. They can also cause avascular necrosis of
certain regions within the bone, if the tumor impinges on a major blood vessels. Malignant tumors typically cause a chronic
inflammatory response which leads to fever, night sweats, and weight loss. Bony tumors often metastasize to the lungs,
so in that setting, they can cause pulmonary symptoms like coughing and shortness of breath. The diagnosis of bone tumors starts with medical
imaging, like X-rays, CT-scans, and MRI imaging, or testing for serum tumor markers that are
specific for each type of tumor. Some tumors also have some classic X-ray findings. For example, osteochondroma cause exostoses,
while the giant cell tumor forms a multicystic bone lesions that look like soap bubbles. Osteosarcoma form lytic bone lesions, referred
to as a sunburst appearance, because the radiating tumor streaks look like sun rays. Osteosarcomas also cause the periosteum to
lift and that’s commonly called Codman’s triangle. In Ewing sarcoma, X-ray shows lytic bone lesions
referred to as onion skin appearance, because the periosteum looks like a sliced onion bulb. In Chondrosarcoma, there are patchy lytic
lesions that make the bone look like a “moth-eaten” piece of cloth. The treatment of bone tumors depends on whether
they are malignant or benign. Benign tumors can be surgically removed to
reduce pain and the risk of fractures, while malignant tumors are treated with radiotherapy,
chemotherapy, and surgery depending on the type and spread of the tumor. Alright, as a quick recap… benign tumors
include osteochondroma which presents with exostoses, giant-cell tumor which has giant
cells and looks like soap bubbles on X-ray, osteoid osteoma, characterized by a nidus
less than 1.5 cm, and osteoblastoma whose nidus is greater than 1.5 cm. The primary malignant tumors include osteosarcoma
that are made of large pleomorphic cells, and has a sunburst appearance on X-ray, Ewing
sarcoma that has round blue cells, and a sliced onion appearance on X-ray, and chondrosarcoma
which has large multinucleated chondrocytes and a moth-eaten appearance on X-ray. There are no known causes of the bone tumors,
but among risk factors, we have rapid bone growth, bone trauma, exposure to radiation,
and positive family history of bone tumors. Osteosarcoma is linked to RB1 and TP53 genes
mutations, while Ewing sarcoma is thought to arise when there are EWSR1, and FLI1 genes
mutation. Benign tumors can be surgically removed if
they’re causing symptoms, while the treatment for malignant tumors requires radiotherapy,
chemotherapy, and surgery.


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