Bone pain - Pathology Flashcards
What suffix do you generally use for benign tumours?
‘Oma’
What suffix do you use for malignant tumours?
‘Sarcoma’
What is the term used to describe a benign tumour of osteoblasts?
Osteoma
What is the term used to describe a malignant tumour of osteoblasts?
Osteosarcoma
What is the name given to a benign tumour of chondrocytes?
Chondroma
What is the name given to a malignant tumour of chondrocytes?
Chondrosarcoma
Lisst the 3 common benign primary bne tumours
- Osteochondroma
- Osteoid osteoma
- Giant cell tumour of bone
Osteochondroma
a) What is an osteochondroma and what is it composed with?
b) Which bones does it commonly affect?
c) Predominanace
d) Age diagnosed
e) Imaging features
f) Treatment
a) A benign tumour - overgrowth of cartilage and bone. It is composed with an overlying cap known as exostoses
b) Metaphysis of long bones
c) Male predominance - M:F = 3:1
d) Most commonly diagnosed in under 30s
e)
- Continuity of the cortex and medullary cavity of the lesion with that of the parent bone
- Pednucleated lesions typically point away from the nearest joint
f) Surical excision of symptomatic lesions or concerns of malignant transformation = curative if all cartilaginous cap is removed
What tumour is being shown on this x-ray? Describe the x-ray
This is pednucleated osteochondrama (often point away from the nearest joint as seen in this image)
There is continuity of the cortex and medullary cavity of the lesion with that of the parent bone.
Osteochondromas are composed with an overlying cap known as exostoses as seen in the images below. If the cap is irregular or excessively thick, especially in an adult, what must you exclude?
Secondary chondrosarcoma
Osteoid osteoma
a) What type of tumour is it? and what is it characterized by?
b) Which bones does it commonly affect?
c) Predominanace
d) Age diagnosed
e) Clinical presentation
f) Imaging features
g) Treatment
h) Prognosis
a) Benign tumour forming neoplasm of osteoblasts. It is characterized by a limited growth potential
b) Cortex of diaphysis or metaphysis of long bones, usually of the lower limb
c) Male predominance - M:F = 2:1
d) Most commmonly diagnosed in under 30s
e) Often presents with night pain and tenderness relieved by NSAIDs
f) Imaging (x-ray) shows a well-defined central radiolucent nidus surrounded by dense sclerosis
g) CT guided radiofrequency ablation (minimally invasive) or complete surgical excision of the nidus (curative)
h) Complete surgical excision of the nidus is curative
What tumour is being shown o this x-ray? Describe the x-ray
Osteoid osetoma
Central nidus surrounded by scelerotic bone
Osteoid osetoma and osteoblastoma have similar histologic features but differ clinically and radiologically. Describe 3 difference between the two
- Osteoid osteoma is <2 cm in size whereas osteoblastoma is >2cm in size
- Osteoid osteoma involves diaphysis and metaphysis of long bones usually in lower limb whereas osteoblastoma involves posterior components of the vertebrae (laminae and pedicles) more frequently
- Pain from osteoid osteoma is better with NSAIDs (Oooooh that’s better) where as pain in osteoblastoma is unresponsivenes to NSAIDs
Giant cell tumour
a) What type of tumour is it? Why is it called a giant cell tumour?
b) Which bones does it commonly affect?
c) Predominanace
d) Age diagnosed
e) Clinical presentation
f) Imaging features
g) Treatment
a) A locally agressive and rarely metasizing neoplasm. It is so called because muli-nucleated osteoclast type giant cells dominate the histological picture
b) Metaphysis and epihysis of long bones, usually femur, tibia and radius
c) Slight female predominance - M:F = 1:1.4
d) Middle age (Median age of diagnosis is 35 years)
e) Usually presents with pain, swelling and reduced ROM (can be similar to symptoms of arthritis)
f) ‘Soap bubble’ lytic lesion at the end of a long bone.
g) Curettage (defect filled with cement)/joint replacement/amputation
What tumour is being shown on this x-ray? Describe the x-ray
Giant cell tumour
X-ray of distal radius which contains a soap bubble lesion in the metaphysis and epiphysis of the distal radius
List the top 3 most common maligant bone tumours
- Osteosarcoma
- Chondrosarcoma
- Ewing sarcoma
Osteosarcoma
a) Desccribe the type of tumour it is
b) Which bones does it commonly affect?
c) Predominanace
d) Age diagnosed
e) Risk factors
f) Genetic features
g) Clinical presentation
h) Imaging features
i) Management
l) Prognosis
a) A tumour consisting of malignant proliferation of osteoblasts
b) Metaphysis of long bones
c) Slight male predominance- M:F = 1.6:1
d) Most common malignant bone tumour in children
e)
- Paget’s disease
- Previous history/chemotherapy
- Some inherited conditions (Familial retinoblastoma syndrome and Li-Freumeni syndrome)
f) Mutations of tumour supressor gene p53 and Rb are commonly seen
g) Commonly presents with pain, swelling, limping/limited ROM and it can present with metastatic symptoms
h)
- X-rays show combination of bone destruction and formation
- Soft tissue calcification produces ‘suburst’ appearance
- Lifting of periosteum known as ‘Codman’s triangle’
i) Surgical resection of all gross disease + chemotherapy
What is the tumour shown in the x-ray? Describe the x-ray
Osteosarcoma
The x-ray shows a case of osteosarcoma which involves a sunburst appearance of the metaphysis of the distal fibula extending onto the posterior aspect of the tibia and also involving the calcaneum below.
Chondrosarcoma
a) Which bones does it commonly affect?
b) Predominanace
c) Age diagnosed
d) Clinical presentation
e) Imaging features
f) Management
a) Commonly arises in the axial skeleton, especially the pelvis, shoulder, and ribs
b) Predominance in male - M:F = 2:1
c) Middle age to older adults (in 40’s)
d) Usually present as painful progessively enlarging masses
e) Flocculent or popcorn like calcifications - destory cortex & form tissue mass
f)
- Wide surgical excision
- Chemotherapy
What malignant tumour does this? Desribe the x-ray
Osteochondroma
The x-ray of the pelvis shows a large exophytic growth arising from the right iliac bone with a chondroid matrix. It shows the characteristic rings and arcs pattern of calcification.
Ewing sarcoma
a) Which bones does it commonly affect?
b) Predominanace
c) Age diagnosed
d) Clinical presentation
e) Imaging features
f) Treatment
a) Diaphysis of long bones
b) Slight male predominance - M:F = 1.5:1
c) 80% less than 20 years of age
d) Localised, painfull mass or swelling, commonly in the long bones of the arms and lengs
e)
- “Onion-skin” periosteal reaction - Due to uneven tumour
- “Sunburst” or “hair-on-end” perosteal reaction - beacuse in steady tumour growth Sharpe’s fibres (the tiny fibres that connect the periosteum to the bone) becomes streched out perpendicular to the bone and ossify
f)
- 1st line treatment usually: Neoadjuvant chemotherapy and surgery
- Radiotherapy for inaccessible sites - less effective
Here are two x-rays. What are the names for these two specific radiological features? What tumour is being show?
Ewing sarcoma
List the 3 main pathways of tumour spread to bone
- Haematogenous or lymphatic spread (most common)
- Direct extension
- Intraspinal seeding (via the Batson plexus of veins)
List the 5 carcinoma primary sites which most commonly metastasise to bone.
- Breast
- Lung
- Thyroid
- Kidneys
- Prostate
(BLT with ketchup and pickles)
Which 3 tumours commonly metastasise to bone in children?
- Neuroblastoma (a primitive tumour derived from the neural crest).
- Wilms tumour (a malignant kidney tumour).
- Rhabdomyosarcoma (a malignant tumour of skeletal muscle).
List 3 treatment options for metastatic carcinoma
- Chemo/radiotherapy
- Bisphosphonates
- Surgery (to stabilise pathological fractures)
A pathologist issues the following report on a pedunculated bone tumour taken from the lower femoral metaphysis of a 20-year-old male patient. The tumour was pointing away from the knee joint. “There is a cap of hyaline cartilage which is undergoing endochondral ossification and which merges with the underlying trabecular bone. There are no atypical features”. What tumour is being described here?
An osteochondroma (exostosis).
A 25-year-old male presents with severe pain at night in his upper right thigh, which is relieved by aspirin. An x-ray shows a 1.1 cm lucency in the cortex of his right femur with a surrounding rim of reactive bone formation. Under the microscope, this shows a central nidus consisting of osteoid trabeculae separated by a vascular fibrous stroma. The nidus has a sharp margin which interfaces with a surrounding rim of mature bone. Which tumour is being described here?
This is an osteoid osteoma.
(Osteoblastoma is like an osteoid osteoma but is larger than 2 cm and involves the posterior components of the vertebrae and the pain does not respond to aspirin. In addition these tumours do not induce a marked bony reaction)
Which bone tumour has a soap bubble appearance on x-ray and involves the epiphysis of long bones in young adults?
Giant cell tumour of bone.
List 3 risk factors for osteosarcoma? Explain them
- Familial retinoblastoma
- Paget’s disease
- Previous history/chemotherapy
How does the pathologist make the diagnosis of osteosarcoma?
Under the microscope, osteosarcomas show a proliferation of malignant osteoblasts producing osteoid.
List 3 tumour suppressor genes that are involved in the pathogenesis of osteosarcoma.
- Retinoblastoma (Rb)
- p53.
- CDKN2A. This gene encodes 2 tumour suppressors (p16 and p14)
List 2 oncogenes which are over-expressed in low-grade osteosarcomas.
- MDM2, which inhibits p53.
- CDK4, which inhibits Rb.
What causes the sunburst pattern seen with osteosarcoma on imaging?
This occurs when the tumour grows quickly and the periosteum does not have enough time to lay down a new layer and instead the Sharpey’s fibres stretch out perpendicular to the bone.
Which tumour shows a progressively enlarging, destructive mass involving the axial skeleton with a characteristic rings and arcs pattern of calcification?
Chondrosarcoma
What does a pathologist see under the microscope to make a diagnosis of chondrosarcoma?
A mass formed of malignant chondrocytes with enlarged, dark, irregular nuclei, and binucleate forms.
If a pathologist sees metastatic adenocarcinoma in a bone biopsy, what technique can he/she use to help determine the likely origin of the tumour? Provide 2 examples
Immunohistochemistry - Tumours have particular antigen expression profiles which can be detected by using labelled antibodies
eg. metastatic prostatic adenocarcinoma will express prostate specific antigen and metastatic breast carcinoma will express oestrogen receptors.
Describe the molecualar sequence of carcinogensis
- A molecular change happens in a gene which normally controls cell growth, cell survival or cell sensescene
- These genetic changes overcome normal repair mechanisms and are transmitted to daughter cells
- Natural selection favours survivial of the most aggressive clones
- Mutations and epigenetic alteration give cancer cells a set of properties called cancer hallmarks
List the 8 cancer hallmarks
- Sustaining proliferative signalling
- Evading growth supressors
- Activating invasion and metastasis
- Enabling replicated immortality
- Inducing angiogensis
- Avoiding immune destruction / Resisting cell death
- Tumour promoting inflammation (enabling charcteristics)
- Genome instability and mutation (enabling charcteristics)
List the 6 main players of cancer
- Regulators of apoptosis
- Tumour supressor genes
- Angiogenic factors
- Immune system avoidiance
- Telomerase
- Oncogenes
Carcinogens cause DNA damage increasing risk of cancer. This includes chemicals and infective agents. List a known bacterial carcinogen and list 2 tumours associated with this infection.
Helicobacter.pylori infection of the stomach is associated with gastric adenocarcinoma and lymphoma
List 3 skin tumours which are associated with non-ionising radiation (UVB from sunlight).
- Squamous cell carcinoma.
- Basal cell carcinoma.
- Malignant melanoma.
What is an oncogene?
Proto-oncognes are genes that are essental for normal cell growth and differentiation. Mutations of proto-oncogenes form oncogenes that lead to unregulated cell growth.
List 5 types of oncogenes
- Growth factors
- Growth factor receptors e.g., HER 2 is commonly expressed cancers
- Signal transducer
- Nuclear regulators
- Cell cycle regulators e.g., cyclins and cyclin-dependant kinases
What is Knudsons two-hit hypothesis?
Knudsons two hit hypothesis applies to tumour suppressor genes and states that both copies of the gene must be affected to cause disease.
Describe the MAP-kinase pathway
- A growth factor binds to a receptor tyrosinase knase (RTK), located on the membrane of the cell
- This activates a protein located in the inner membrane called Raz
- Raz activates a cytoplasmic protein called Raf whicg activates another cytoplasmic protien call MEK
- MEK phosphorylates ERK
- ERK travels to the nucleus where it can activate several transcription factors which can switch on several genes which are involved in the cell cycle, cell growth or cell metabolisms
- The proteins of the cylce are then switched off
- In cancers these protein can be mutated leading to permantely switched on causing uncontrolled transcription
Two important tumour suppressor genes are p53 and Retinoblastoma. Describe the normal function of p53.
- If DNA is damaged in the G1 phase thistriggers the expression of the p53 gene which stops the cell from eneterig the S phase of the cycle to allow DNA repair to take place
- p53 stops the cycle by causing transcription of cyclin-dependant kinase inhibitors called p21
- p21 blocks the CDK4/Cyclin D complex
- If the DNA damage is so severe that it cannot be repaired p53 can stop the cycle or can cause senescene and if it’s too severe it can trigger apoptosis
Two important tumour suppressor genes are p53 and Retinoblastoma.What is the function of the retinoblastoma (Rb) gene in the cell cycle?
- Retinoblastoma regulates the progression from G1 to the S phase of the cell cycle
- The E2F transcription factor is released when retinoblastoma is phospharylated by the CDK4/cyclin D comples
- Retinoblastoma mutation results constituctively free E2F allowing progression from the cell cycle and uncontrolled growth of cells
BCL2 is a regulator of apoptosis. How do apoptosis regulators work?
- Apoptosis regulator stop normal cells from dying but promote apoptosis if DNA damage cannot be repaired
- BCL2 prevent apoptosis by stabilising the mitochodnrial membrane and blocking the release of cytochromeC
- If BCL2 is disrupted cytochrome C is released triggering apoptosis
- BCL2 is overexpressed in a form of lymphoma called follicular lymphoma
What is the role of tolermase in carcinogensis
- Telomeres are sections of DNA that normally shorten during serial cell divisions eventually causing cell senescene
- Cancers often show upregulation of the enzyme telomerase which elongates telomeres
How do cancers create a new blood supply to support their growth?
Cancers commonly produce fibroblast growth factors and vascular endothelial growth factor which are both angiogenic factors responsile for blood vessel creation
Describe 4 difference bet
What does neoplasm/neoplasia mean?
Neoplasm means ‘new growth’/tumour. This is growth that is unregulated, clonal and irreversible. Neoplastic tumours can be benign or malignant.
Desrcibe the differences between benign and malignant tumours
Describe what dysplasia?
- Dysplasia is disordered growth which can progress to carcinoma if the stressor is not removed
- It can arise from longstanding hyperplasia (endometrium) or metaplasia (oesophagus and bronchus)
What is the difference between carcinoma in situ and invasive carcinoma?
The term carcinoma in-situ refers to an epithelial neoplasm showing all of the cellular features associated with malignancy but which has not yet invaded through the epithelial basement membrane, separating it from potential routes of metastasis (blood vessels and lymphatics).
There are cytological differences between benign and malignant cells. How do you distinguish a benign cell from a malignant cell?
What is the term used to describe a malignant tumour of epithelial origin?
Carcinoma
What is the term used to describe a malignant tumour of glandular epithelium or a tumour showing glandular differentiation?
Adenocarcinoma
What is the term used to describe a keratin-producing malignant tumour of squamous epithelium?
Squamous cell carcinoma
What is the term used to describe a malignant tumour of soft tissue?
Sarcoma
What is the term used to describe a malignant tumour of lymphocytes?
Lymphoma. If malignant lymphocytes or malignant myeloid cells involve the bone marrow and appear in the peripheral blood, this is leukaemia.
What is the term used to describe a malignant melanocytic tumour?
Malignant melanoma
What is the term used to describe a benign tumour of blood vessels?
Haemangioma
What is the term used to describe a malignant tumour of blood vessels?
Angiosarcoma
What is the term used to describe a benign tumour of fat?
Lipoma
What is the term used to describe a malignant tumour of fat?
Liposarcoma
What is a benign skeletal muscle tumour called?
Rhabdomyoma
What is a malignant skeletal muscle tumour called?
Rhabdomyosarcoma
What is a benign tumour of smooth muscle called?
Leiomyoma
What is a malignant smooth muscle tumour called?
Leiomyosarcoma
What is a benign peripheral nerve sheath tumour called?
Schwannoma
What is a malignant peripheral nerve sheath tumour called?
A malignant peripheral nerve sheath tumour!
What is a benign tumour of fibroblasts called?
Fibroma
What is a malignant tumour of fibroblasts called?
Fibrosarcoma
Fill in the missing boxes
Fill in the missing boxes
What is a tumour grade?
The grade of a tumour is defined as the extent to which the tumour histologically resembles the cell or tissue of origin.
Describe the relationship between the tumour grade and agressiveness and differentiation of the tumour
- The higher the tumour grades, the more aggressive the tumour is likely to be
- A well differentiated or grade 1 tumour will closely resemble the parent tissue
- A poorly differentiated or grade 3 tumour may not be very similar to the parent tissue (and may only be identified by investigation of antigens which are present in the tumour)
Which tumour has the grade and why? Suggest what grades the two tumours are
Tumour 2 has the higher gade beacuse it is poorly differentianted and resembles the parent tissue the least
List 3 factors which allow tumours to invade
- Decreased cell adhesion - reduced expression of e-cadherin and expression of integrin receptors.
- Secretion of proteolytic enzymes – collagenases, gelatinases and stromeolysins.
- Increased cell motility - loss of contact inhibition
Describe the 7 steps which are involved in tumour metastasis.
- Detachment of tumour cells.
- Invasion of connective tissue to reach lymphatics and blood vessels.
- Intravasation into the lumen of the vessels.
- Evasion of host defence by natural killer cells and T-cells.
- Adherence to endothelium at the remote location eg. liver, lung, bone.
- Extravasation of cells from the vessel into the tissue at the new location.
- Survival and growth at the new location.
Which virus causes patients who are immunosuppressed to develop multiple squamous cell carcinomas of the skin?
Human papilloma virus.
List four mechanisms by which tumour cells can evade immune surveillance.
- Selection of antigen-negative clones.
- Loss of MHC molecules.
- Expression of transforming growth factor beta.
- Expression of PD1 ligand which can switch of T-cells.
What is the tumour stage and what system is currently used for staging tumours?
- The stage of a tumour refers to how large it is and extent of tumour spread
- We currently use the TNM system for staging cancers.
- T = tumour size or extent of local invasion
- N = lymph node metastases
- M = distant metastases.
What is the Warburg effect?
Most cancers produce energy by a high rate of glycolysis with formation of lactic acid whereas normal cells have a low rate of glycolysis with oxidation of pyruvate in mitochondria. This effect is called the Warburg effect
