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Molecular Pathology > Malignant disease of the Bone > Flashcards

Malignant disease of the Bone Flashcards

1
Q

Is Primary malignancy of the bone common?

A

relatively rare in the UK.

~550 cases per year.

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2
Q

what is the 10 year survival rate for primary bone malignancy?

A

~55%.

Most patients who die from bone sarcoma are >70 years old.

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3
Q

What can Bone sarcoma be divided into?

A

Osteosarcoma
Ewing’s Sarcoma
Chondrosarcoma

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4
Q

what are primary malignancy of the bone are referred to as?

A

sarcoma

Reflect the connective tissue origin.

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5
Q

what is the tissue origin of an Adenoma?

A

glandular (usually epithelial)

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6
Q

what is the tissue origin of an Neuroblastoma?

A

neural

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7
Q

what is the tissue origin of an Germinoma?

A

germ cells

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8
Q

~30% of bone sarcoma are associated with what kind of sarcoma?

A

osteosarcoma.

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9
Q

what age is associated with osteosarcoma?

A

This form of sarcoma is mostly associated with young age of onset
Teenagers.
Due to rapid growth during teenage years. Loads of growth signals. If something goes wrong growth can go out of control and become cancer

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10
Q

where do the tumour tends to develop?

A

in the knee regions (usually around the metaphysis of long bones)
~60%
Knee has most impact, wear and tear from walk and add growth hormones of teenage years

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11
Q

What causes Osteosarcoma?

A

Aetiology of osteosarcoma is unclear but several factors have been identified:
Cancer pre-disposing syndromes.
Bone dysplastic conditions (Pagets)
Familial osteosarcoma.
Radioactive isotopes (particularly strontium-90)

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12
Q

what is Paget’s Disease?

A

Condition characterised by excessive breakdown and reformation of bone.
Bone remodelling is disorganised.

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13
Q

common complication of paget’s disease?

A

Weakens the affected bone.

Fractures are common.

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14
Q

what viral infections are associated to cause Paget’s?

A

Measles.

Respiratory syncytial virus.

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15
Q

which genetic mutations are causes of Paget’s?

A

.P62 mutations.

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16
Q

What is P62 (or sequestome 1)?

A

is a protein which targets other proteins for destruction.

Binds to other proteins and causes them to be ubiquinylated.

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17
Q

How can it be mutated in Paget’s?

A

Can be mutated in Paget’s causing proteins to not be destroyed.
Osteoclasts become inappropriately activated.

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18
Q

Treatment of Paget’s should be limited to specific individuals.
What clinical aspects are considered?

A

Danger of nerve involvement.
Involvement of weight-bearing joint.
Significantly symptomatic.

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19
Q

which treatments can be used?

A

Bisphosphonates are useful.
risedronate – a tablet taken once a day for 2 months (30mg)
zoledronate – a one-off injection (5mg)

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20
Q

Familial osteosarcoma is associated with which particular cytogenetic abnormality?

A

Del(13q14)

21
Q

what is the importance of the gene 13q14?

A

13q14 contains pRB gene.

Retinoblastoma associated protein.

22
Q

significance of Retinoblastoma associated protein?

A

pRB is important in ensuring quiescence in cells (G0).

Loss of pRB is associated with ~50% of sporadic OS

23
Q

What kind of imaging is required in diagnosis?

A

X-rays become attenuated by dense tissues.
Low density tissues project more X-rays causing the tissue to appear dark.
High energy X-rays required for bony tissue.

24
Q

What are the radiological signs of osteosarcoma? x4

A

Medullary and cortical bone destruction
Moth-eaten appearance
Aggressive periosteal reaction
Soft-tissue mass

25
Q

What is seen in the histology of osteosarcoma at Low magnification?

A

H&E

Completely taken over by cells; all purple stain meaning more protein than should be
All tumour where should be spongy bone

26
Q

At a high mag?

A

Not much pink

Should be terminally differienated cells; but evidence of lots of mitosis; poor prognosis

27
Q

Surgical treatment of osteosarcoma?

A

Surgery is key step to remove tumour burden.
Amputation historically but increasingly limb salvage is preferred.
Complications of surgery can be significant.

28
Q

Chemotherapy treatment

A

Neo-adjuvant chemotherapy is used to offer a prognosis.

Mifamurtide has important role in preventing relapse.

29
Q

what is Ewing’s Sarcoma?

A

Form of sarcoma which was discovered in 1920 by James Ewing.

There are a family of Ewing tumours.

30
Q

most commonly in which group of people?

A

Most commonly associated with young adults, adolescents and children.
10-20 years of age.
Males more commonly impacted (1.6:1)

31
Q

Histopathology

High magnification PAS.

A

High magnification H&E

32
Q

what is EWS1-FLI1?

A

fusion protein

a master regulator of carcinogenesis in Ewing’s.

33
Q

What is EWS1?

A

a RNA-binding protein.

34
Q

What is FLI1?

A

an ETS transcription factor.

35
Q

t(11;22)(q24;q12) is found in ..

A)99.5% of Ewing’s patients.
B)90% of Ewing’s patients.
C)10% of Ewing’s patients.

A

B

36
Q

which IHC marker is used for Ewing’s?

A

CD99

37
Q

What is Chrondrosarcoma?

A

Malignant disease of chondrocytes.

No osteoid!

Approximately a third of bone sarcoma fall into this category.

38
Q

What group of people are mainly affected?

A

Can impact patients of any age.
In contrast to most other osteosarcoma.
75% of cases in males.

39
Q

Treatment options?

A

Chrondrosarcoma are very resistant to treatment.

Surgery and proton beam therapy only realistic option.

40
Q

Histology of Chondrosarcoma

A
41
Q

what is third most common site of metastasis?

A

Bone metastases

More common than primary bone cancer.

42
Q

prognosis?

A

are associated with poor prognosis in cancer (6 months in metastatic melanoma).

43
Q

Which cancers are responsible for 70% of bone mets?

A

Breast and prostate cancer

44
Q

What are the types of Bone metastases?

A

Osteolytic.

Osteoblastic.

Mixed.

45
Q

what is the Osteolytic type?

A

Result in destruction of normal bone.

46
Q

when is the osteolytic type commonly seen?

A

Commonly seen in breast ca bone mets, multiple myeloma and non-Hodgkin lymphoma.

47
Q

the cancer cells express which peptide?

A

parathyroid hormone related peptide (PTHrP).

48
Q

what is the Osteoblastic type?

A

Results in deposition of new bone.

49
Q

when is it Commonly seen?

A

in prostate ca, small cell lung cancer and Hodgkin lymphoma.

Molecular Pathology (10 decks)

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