Tumors of Bone and Cartilage Flashcards
Osteoma
• What is this?
• Where is it typically found?
• who is typicall affected?
This is a bone forming tumor of compact and trabecular bone that most often forms in crainial/facial bones. Often times it involves the paranasal sinuses.
• Women are slightly more affected at a 3:2 M:F ratio
Osteoid Osteoma/Osteoblastoma
• Describe the typical presentation of someone with an osteoid osteoma.
• What are some key features that differentiate these two tumors?
Osteoid Osteoma:
This most often presents in a male in his 20’s with a small mass (less than 2cm) in his appendicular skeleton with nocturnal pain that is caused by OSTEOBLAST secretion of PGE2. Because this pain is produced by products of COX the pain can be attenuated by NSAIDs.
Osteoblastoma:
• These are typically larger than 2cm and found in the posterior spine. Additionally, females are slightly more likely to get this disease than males and patients are usually younger. IMPORTANTLY, this pain is dull and not responsive to asprin.
Osteosarcoma
• Describe the patient that normally gets this and why they present.
• Where is this tumor most likely to be found?
Age distribution of this disease is bimodal with 75% of cases occuring in people under 20 years of age. The 25% of cases in older patients are likely secondary to radiation or Paget’s disease. These people typically present because they experience a pathologic bone fracture.
Most often these tumors are found in the knee but also may found in the proximal and axillary skeleton as shown below.
What might you want to check for in someone that presents with a osteoma?
• what other features accompanying the osteoma would lead you to this diagnosis?
You need to determine if its associated with Gardner Syndrome.
This syndrome has characterisitic features including COLON POLYPS, osteomas of the skull, thyroid cancer, epidermal cysts, and fibromas, Desmoid tumors (15% of the time).
What gene mutation is associated with Gardner’s syndrome (include chromosome number)?
• Is it inherited? If so, how?
This is a variant of FAP (familial adenomatous polyposis) so the APC gene is involved. This gene is found on chromosome 5q21 and it is inherited in an AUTOSOMAL DOMINANT fashion.
What is this most likely to be?
• why?
Osteoma because its a single bone tumor on the facial bones.
What are you looking for on histology of an osteoma?
Dense compact bone with a paucicellular (sparse cells) stroma
This is a biopsy of a tumor taken from the facial bones of a patient.
• What is the tumor type?
• Key features of this histology?
This is an osteoma as indicated by the stroma that has few cells and an areas dense bone
How do Osteomas typically appear grossly?
They may be flat or sessile (polyp-like) and are typically around 3 cm
• The tumor shown below was taken from the underside of the skull cap
What cells are responsible for the formation of an Osteoid Osteoma?
• How does this benign tumor present radiographically?
• what does it look like grossly?
Osteoblasts are responsible for the formation of osteoid osteomas. These tumors are characterized radiographically by a CENTRAL NIDUS surrounded by a bright white ring of reactive bone. On gross inspection these appear as oval masses of gritty, tan tissue that is surrounded by dilated and congested arteries.
**Remember the pain resloves with asprin
What are the key histological features of an osteoid osteoma?
What is this?
• key histological features?
Osteoid Osteoma or Osteoblastoma- key features are random trabeculations with a single layer of osteoblasts surrounding the trabeculae. They stoma consists of loose CT with dilated and congested capillaries (not shown here).
What is this tumor?
• how do you know?
Histology indicates that with random trabeculations and osteoblasts surrounding trabeculae with loose CT stroma this could be either osteoid osteoma or osteoblastoma. This is an osteoblastoma, not an osteoid osteoma becuase the spine is involved.
What are some key radiologic findings in osteosarcoma?
• is this diagnostic?
Codman triangle is often seen in the patients. The Codman triangle is really only indicative of aggressive tumors in the bone, but is most often associated with osteosarcoma. Note that the bone shown here is radiolucent, this is because Osteosarcoma forms OSTEOID so there is lots of unmineralized bone hangining around.
What is this?
• describe key features.
Shown here is osteosarcoma invading normal bone (see bright pink edges with osteocytes in lacunae). The tumor is producing bone spicules in a hypercellular osteoid matrix that has a lace-like appearance. It is this lace-like malignant osteoid that is DIAGNOSTIC. Additionally, you can see lots of hyperchromatic dark cells in the matrix.
Where is osteosarcoma most likely to metastasize?
• why?
• How often do we see matastasis at diagnosis?
Because it is a sarcoma osteosarcoma is most likely to be angioinvasive with deposition of malignant cells in the lungs. 20% of the time the cancer has already metastasized at the time of diagnosis giving a poor prognosis.
Note: the 5 year survival of osteosarcoma is 70%, but this is very much reduced in patients with secondary underlying conditions.
What gene mutations are associated with osteosarcoma?
• How often is one of these gene mutations present?
• syndromes that may predispose you to this disease?
• describe some of the normal functions of these genes.
4 main gene mutations present in 70% of cases:
• RB - pts. have 1000X risk of getting osteosarcoma. Remember that RB blocks G1/S transition by preventing Elongation Factor-2 (EF-2) from dimerizing with dimerizing protein (DP) to got to the nucleus. The inhibitory RB-EF2 complex may also suppress cell cycle progression by activating Histone Deacetylases (HDACs)
• p53 - Li-Fraumeni Syndrome kids are predisposed to OS. Remebmer p53 is a gaurdian gene that promotes p21 and works with BAX to induce apoptosis.
• MDM2 and CDK4 - regulate p53 and RB - mutations here may seal the diagnosis of OS.
• INK4a - controls transcription of p16 and p14 that augment p53 function
What is this?
• what are some key features?
Chondroma
• How does this typically present?
• Where are these often found?
These are asymptomatic cartilage tumors that arise most often between the ages of 20 and 50. Tumors may arise in diaphyseal medullary cavity (enchondroma), Juxtacortical/subperiosteal or soft tissue chondroma.
Osteochrondroma
• How does this disease typically present?
• Where does it usually occur?
Osteochondromas typically present in MALE patients between 10 and 20 years old and are most often asymptomatic unless they impinge on surrounding structures. The tumor typically arises at the epiphyseal (growth) plate. It appears as a pedunculated mass.
Chrondosarcoma
• How does this patient typically present?
• Where is the tumor usually located?
This tumor usually presents in the axial skeleton or proximal appendicular skeleton in a male that is 40 years or older. Some clear cell variants may arise in males in their 20s (in the epiphysis). These tumors may be juxtacortical but are most often intramedullary. These lesions are PAINFUL.
Very important that you DO NOT SEE OSTEOID in this tumor, if you do then its a osteosarcoma
How can age alone be an indicator of whether or not a tumor is benign?
If a person is under 30 then their bone tumor is likely to be benign. If the patient is over 50 the tumor is more likely to be malignant.
How do we usually treat osteosarcoma?
Neoadjuvant therapy with tumor removal is the most common method of treating osteosarcoma
What gene mutation is often associated with chondromas?
• what other disorders are caused by a similar mutation?
Isocitrate Dehydrogenase (IDH) 1 or 2 is often mutated in several cells within the tumor. IDH 1/2 mutations can lead to the formation of 2-hydroxyglutarate (instead of alpha-ketoglutarate). 2-hydroxyglutarate promotes DNA methylation preventing cells from maturing.
• This mutation is also seen in gliomas and acute myeloid leukaemia (AML)
What gross features indicate that this is a chrondroma?
Chondromas typically appear grossly as gray-white masses with a consistency similar to normal cartilage
What is this?
• Key features?
Chondroma:
• numerous chondrocytes that are closely packed near the periphery in a pink ground substance that vaguely resembles normal cartilage. Remember normal cartilage has light blue ground substance.
Osteochondromas are typically slow growing tumors, what typically stops the growth of these tumors?
• How common are these?
• KEY GROSS FEATURE?
• Treatment?
Closure of the growth plate typically causes the cessation of osteochondroma growth. A key feature to look for is that the tumor is CONTINUOUS with the bone it arises from and has a cartilage cap. Treatment can typically be performed by simple excision.
What is the risk of an osteochondroma turing into someting malignant?
5-10% of patients will have a progression to osteosarcoma
*Note the cartilage cap on the osteosarcoma shown below
According to Robbins some osteochondromas may have a hereditary component related to mutations in the EXT 1/2 genes
What tumor is shown here?
• Key radiographical freatures.
Enchondroma (found in small bones of hands and feet) shows up as a radiolucent nodule of hyaline cartilage with scalloped endosteal surface.
What cancer is this most likely?
This is chondrosarcoma
What type of tumor is this? Is it malignant or benign?
• what are the key characterisitics?
This is a chondrosarcoma.
Key Characteristics:
• Cells that mimic normal chondrocytes in that they appear to float in a chrondriod-like matrix.
• because they are tumor cells that have LARGE NUCLEI with high N/C ratios and abundant mitotic figures on high power. (see below)
What is this lesion?
• what patient is this most likely to be found in?
• What would histology show?
This is a fibrous cortical defect. Key to knowing this is that the lesion in an INTRAMEDULLARY non-ossifying lesion. This would most likely be found in a teenager.
Histology would likely show spindle cells arranged in a storiform pattern with scattered giant cells, histiocytes, cholesterol clefts and hemosiderin (this is shown below)
Is this a cancerous lesion?
• key histological features?
This is a Fibrous cortical defect, not a cancerous lesion. It was most likely found in the knee area of a teenager. Histology shown here is typical of the defect with spindle cells in a storiform (spindled) pattern with lots of giant cells. Sometimes histiocytes, cholesterol clefts, and hemosiderin are also present.
Shown below is a gross picture indicating that this disease is INTRAMEDULLARY
What disease is indicated by this gross pathology and histology?
• Key features of each?
Fibrous Dysplasia
Gross:
• Variably sized, circumscribed, medullary, tan-white, gritty mass lesions
• Larger ones may distort the bone structure
Histology:
• Poorly formed islets and trabeculae of woven bone without a ring of osteoblasts (may resemle chinese characters)
• Instead of being surrounded by osteoblasts the trabeculae are surrounded by fibroblasts that deposit collagen
What is this disease?
Fibrous Dysplasia - notice the trabeculae is surrounded by lots of fibroblasts with collegen deposition taking place
What is Mazabraud Syndrome?
Fibrous Dysplasia + Soft Tissue Myxomas
What disease is shown here in this 35 year old male?
• what is the pathogenesis of this disease?
This is a Giant Cell Tumor of the Bone - this tumor has a classic soap bubble appearance on radiograph
NEOPLASTIC cells in this tumor are OSTEOBLASTS that upregulate RANKL leading to Osteoclastic stimulation. Note that osteoclasts will make up the majority of the cells in this neoplasm despite it being an osteoblastic disorder.
What disease is shown in this histology of the lesion that was biopsied from the epiphysis of a 25 year old female?
• Key characteristics?
Note that 40-60% of these tumors recur locally and 4% metastasize to the lung (mets often resolve spontaneously)
What is the gross appearance of an Ewing Sarcoma?
White, Fleshy (fish-flesh), ill-defined tumor with extensive involvment of medulla and cortex with periosteal elevation (seem at bottom of pic). May resemble pus or be necrotic.
What key characteristics are seen in the histology of this bone cancer?
• what in your differential?
• Key characteristics to look for on x-ray?
This is an Ewing Sarcoma (Primative neuroectodermal tumor - PNET) that is characterized by sheets of small round uniform BLUE cells. Indistinct cell membranes, and glycogen rich cytoplasm that may be clear.
**when you see this appearence, lymphomas should be in your differential
Sometimes the cells form Homer Wright rosettes that are characteristic of of neuroendocrine tumors (shown below).
What distict appearance is seen on radiographs of Ewing Sarcoma?
Onion skinning may be seen in the diaphysis of long bones
What genetic mutation is heavily associated with this disease?
• why is it so important?
• who is this usually seen in?
Ewing Sarcoma is associated with an 11:22 translocation*** that leads to formation of ***EWS-FLI1 fusion gene.
Its important to find this translocation via FISH to differentiate this from a lymphoma
We typically see this in white males that are under 15 years old
How is the cancer caused by the 11:22 translocation causing formation of the EWS-FLI1 fusion protein treated?
• what is an important prognostic finding?
These tumors are most often treated with neoadjuvant chemotherapy followed by surgical excision with or witout radiation.
• 75% five-year cure rates and 50% long-term cure is seen in these patients
• An important prognostic finding in these patients is the amount of chemotherapy induced necrosis
What is this fluid-filled cyst with a thin wall?
Solitary Bone Mass - patients who present with this are usually men in their 20s who have a fracture
What is this?
• what is the chance of it coming back?
• what does it look like grossly?
Aneurysmal bone cysts are just cysts that look like a sponge filled with blood. 20% will recur
**This a benign tumor but GROWS rapidly
What is this?
• how do you know?
You can see big cystic areas with hemorrhage and abundant capillary beds. When you zoom in you will see GIANT CELLS. The presence of capillary beds is what differentiates this disease from a giant cell tumor.
