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Pathology Flashcards

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1
Q

What’s Codman’s triangle?

A

Dense lesion on XR with indistinct borders and periosteal elevation

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2
Q

What are the radiologic features of osteosarcoma?

A

Can be mixed lytic and sclerotic picture, Codman’s triangle, sunburst periosteal reaction

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3
Q

What’s a hallmark on blood work of osteosarcoma?

A

Raised ALP, particularly in kids

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4
Q

What are prognostic factors in osteosarcoma?

A

Prognostic factors include: size and extent of cortical and soft tissue penetration, weight loss > 10 pounds

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5
Q

What are prognostic factors in osteosarcoma?

A

Prognostic factors include: size and extent of cortical and soft tissue penetration, weight loss > 10 pounds, elevated ALP

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6
Q

What are survival factors in osteosarcoma?

A

Most significant predictors of survival; location, local control of tumour and degree of necrosis after chemotherapy Proximal femoral lesions were more prone to r

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7
Q

What is one of the most frequent genetic changes seen in osteosarcoma?

A

Overexpression of p53

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8
Q

What other conditions can increase the risk for osteosarcoma?

A

Pagets, retinoblastoma, Li-Fraumeni syndromes (germline mutation of p53), balance translocation of chromosomes 5 and 10, Rothmund-Thompson syndrome (women more common), irradiation, bone infarction

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9
Q

What is the definition of osteosarcoma?

A

Highly malignant tumour that produces osteoid or bone Characteristically arise within the metaphysis of the long bones and grows circumferentially thru the cortex into the soft tissue raising the periosteum

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10
Q

Where does osteosarcoma most frequently occur?

A

Rarely invades the joint space, metaphyseal tumour.
56% occur at the knee (64% in distal femur 32% proximal tibia 4% proximal fibula

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11
Q

Who gets osteosarcoma?

A

Predilection for bone areas of rapid growth; peaks in adolescent growth spurt and also found in Pagets Peak age 10-20 yo; 75% occur between 10-30 Male 1.5:1

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12
Q

What’s the common presentation of osteosarcoma?

A

Pain, mass, swelling or can present with fracture (poor prognosis)

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13
Q

How does osteosarcoma metastasise?

A

Haematogenous spread. occurs early and usu to lungs or other bones LNs up to 28%, most frequently in hilar, mediastinal, abdominal Surgical resection of pulmonary lesions improve prognosis Transarticular spread is unusual

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14
Q

What are the histological appearances of osteosarcoma?

A

Predominantly osteoblastic and bone forming, there may be fibrous and cartilaginous foci.
Histologically, presence of sarcomatous osteoblast cells producing a disorganized maze of calcified tissue including osteoid and bone.
May vary from very cellular with little osteoid to one which is sparsely cellular but with abundant calcified matrix Masses of osteoid without accompanying cells are suspicious of sarcoma

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15
Q

What are the risks with limb salvage operations in osteosarcoma?

A

Local recurrences are very high if marginal or intralesional procedures are performed Occurs at 5-10%; 5 year survival at 40-70

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16
Q

What are the contraindications to limb salvage operations in osteosarcoma?

A

Contraindications to limb salvage procedures are mjor involvement to nv bundle, pathological fracture, inappropriate biopsy site, infection, immature skeletal age and extensive ms involvement

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17
Q

Where is the gene for p53 located?

A

Short arm of chromosome 17

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18
Q

Where are the genes for retinoblastoma located?

A

RB1 is on the long arm of chromosome 13

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19
Q

What is RB1?

A

Critical tumour suppressor gene, its protein product pRB plays a vital role in regulating the cell cycle and preventing uncontrolled cell division. Mutations of deletions in both copies of this gene are generally required for retinoblastoma to develop

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20
Q

What is a giant cell tumour?

A

Classically, purely lytic lesion of epiphyseal or metaphyseal-epiphyseal region of bone extending to articular surface characterised by multinucleated giant cells which resemble osteoclasts

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21
Q

What are the histological features of a GCT?

A

Microscopically, solid sheet of proliferating mesenchymal cells and multinucleated giant cells scattered evenly Cellularity and shape of cells vary as do mitotic figures Minimal mitotic activity generally have a benign course

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22
Q

What’s the natural history of a GCT?

A

Natural history is one of progression and local aggressiveness with extension beyond the cortex into soft tissue; recurrence depends on adequacy of excision and grade of tumours Recurrent tumour carry higher risk of malignancy and recurrence is higher in hands and distal radius Recurrence may occur after many years Pulmonary metastasis in <10%; metastasis is unpredictable

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23
Q

What’s the chance of mets to lymph nodes in osteosarcoma?

A

28%

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24
Q

Who gets GCT?

A

Women more common, very rare prior to skeletal maturation

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25
Where are GCTs found?
Most often seen in distal femur (25%) and proximal tibia (23%), distal radius (10%)
26
What are the radiologic features of GCT?
May cause mild bone expansion. Differentiating between benign and malignant forms is difficult. On CT, density of tumour is similar to surrounding ms On MRI, T2 shows high signal intensity
27
What does GCT look like macroscopically?
Tumour is solid but often soft and friable It replaces bone marrow and has a brown reddish appearance There may be focal cystic areas Focal yellow areas represent lipid laden macrophages and may be focal areas of haemorrhage Production of bone is rare
28
What is a medication that can be used for GCT?
Denosumab- can be used to shrink tumours prior to surgery, manage lung mets or for unresectable/ recurrent tumours
29
What is an aneurysmal bone cyst?
Distinct benign pseudotumourous lesion of unknown aetiology but may be secondary to intraosseous vascular disturbance Classically, lytic eccentric expansive trabeculated lesion
30
Where are ABC’s found?
May occur in any bone; most commonly in metaphyseal region of long bones or spine Usu metaphyseal but involve epiphysis or diaphysis
31
Who gets ABC?
Peak age between 10-20; 75% <20
32
What are the imaging appearances of ABC?
Xr ballooning or expansile cystic change May be focal sclerosis at the margin or periosteal new bone There is no calcification or mineralization within cyst Fallen fragment sign is not seen Periosteum usu elevated and intact; enveloping a thin rim of reactive bone
33
What does an ABC look like macroscopically?
May appear bluish and cavity has appearance of sponge filled with blood and other fluid Not pulsatile but it is a vascular lesion Bone tissue walls are thin, often with fibrous septa Multiloculated with bloody cellular cavities- Although blood filled, these are not lined by vascular endothelium
34
What are the histological features of an ABC?
Fibrous septa contain numerous giant cells, spindle cells and immature bone Histologically, there may be focal or diffuse collection of haemosiderin or reactive foam cells or histiocytes and chronic inflammatory cells may be seen in septal zones
35
What is the natural history of ABC?
Clinical course is variable but usu show progression Growth may be aggressive and mimic sarcoma Spontaneous remission may occur Recurrences are common in 20%
36
What is the treatment for an ABC?
Treatment may involve excision or curettage and BG Adjunctive cryosurgery (liquid nitrogen) or phenol also used
37
What is an osteoid osteoma?
Small solitary benign bone forming lesion, juxtaposition-articular Occurs as a well defined nidus of remodelling spicules of cancellous type bone within cortex; may be seen in medullary cavity
38
Who gets osteoid osteoma?
Peak age 11-20 (90% between 5-30) Male 2:1
39
What’s the typical presentation with an osteoid osteoma?
Pain often severe at night, relieved by aspirin
40
What is the theory with osteoid osteoma and pain relieved by aspirin?
Pain: unmyelinated nerve fibres have been demonstrated; prostaglandins linked to tissue and hence relief with aspirin
41
What are the imaging appearances of an osteoid osteoma
Usually <1cm Hot, well circumscribed lesion on bone scan Xrs shows poorly circumscribed cortical bone sclerosis with centralized radiolucent nidus CT may be able to detect the nidus There is hypervascularity and abundant mineralization and hence the hot bone scan
42
Where do osteoid osteomas occur?
Occurs as a well defined nidus of remodelling spicules of cancellous type bone within cortex; may be seen in medullary cavity Predilection for lower limbs with femur (25%) and tibia (20%)
43
What is the macroscopic appearance of an osteoid osteoma?
Large lesions are reddish in colour
44
What are the microscopic features of an osteoid osteoma?
Usu intracortical where a well circumscribed round nidus consists of interlacing spicules of cellular remodelling cancellous bone; numerous osteoblasts and clasts Osteoid is abundant Cartilage and bone marrow not present Richly vascularised tissue
45
What are microscopic features of the nidus of an osteoid osteoma?
Nidus is characterized by more abundant mineralization centrally and separated from host bone peripherally
46
What is an osteochondroma?
Common type of exotosis (surface bone growth) characterized by the following - Exophytic (pedunculated or flat) growth on the surface of bone - Cartilaginous cap covered with fibrous band (fibrous layer of periosteum) - Contiguity with underlying cortical and trabecular bone and marrow - Cartilage in cap undergoing endochondral ossification
47
What causes a solitary osteochondroma?
Arise in peripheral zone of the growth plate when epiphyseal cartilage abnormally separates from growth plate, ie ectopic focus of endochondral ossification May be due to trauma or deficiency of perichondral ring
48
Who gets solitary osteochondromas?
Male adolescents; 2/3 diagnosed prior to age 20
49
Where in the body do you generally find solitary osteochondromas?
Usu arise in metaphysis of long bones; slow growing 24% distal femur (31% overall), 13% proximal tibia (16%) and 17% proximal humerus.
50
What are the imaging findings of an osteochondroma?
Appear radiodense on xrs; pedunculated or sessile Extend into soft tissue and away from nearest joint (reflects epiphyseal growth) Surface may be radiolucent or bulbous with extensive calcification Variable size CT used to establish continuity cortical and medullary continuity with tumour MRI delineates cartilage cap (high T2 signal) Bone scans are hot in active osteochondromas
51
What is the macroscopic appearance of an osteochondroma?
Grossly, it has a bosselated or smooth bluish gray cap covered by thin fibrous band Cap 2-3mm in thickness and has smooth surface and ossifies after maturation Cortical shell blend into host cortex; usu not cortical at base.
52
What is the microscopic appearance of an osteochondroma?
thin periosteal fibrous connective tissue covers a smooth cartilaginous zone ‘Columns of cartilage cells undergoing endochondral ossification Below the zone of ossification, contains marrow and mature trabecular bone
53
What is the risk of malignant transformation with an osteochondroma?
<1%- usually chondrosarcoma but can also be osteosarcoma Cartilage cap thicker than 3mm more risk
54
What is multiple hereditary exostosis?
AKA osteochondromatosis/ diaphyseal aclasis Autosomal dominant condition characterised by multiple osteochondromas
55
What is the rate of MHE in the population
1 in 50,000; 10% will have family history; 50% passed down to descendants Most diagnosed before age 2
56
Where are the common sites for MHE?
Bilateral symm involvement frequent Ilium is frequently involved in multiple hereditary exotosis
57
What is the risk of malignant transformation with MHE?
Malignant transformation in 5-25%; preferentially affecting flat bones Chondrosarcoma most common
58
What is the aetiology of MHE?
Theories regarding aetiology include fragmentation of cartilage cells during growth or aberrant placement during embryogenesis
59
What is dysplasia epiphysealis hemimelia?
AKA osteochondroma of the epiphysis/ Trevor’s disease/ tarsoepiphyseal aclasis Benign, asymmetric lesion resembling osteochondroma pathologically that originates from epiphysis rather than metaphysis. Can cause limb deformation
60
What is the prevalence of dysplasia epiphysealis hemimelia/ Trevor’s disease?
1 in a million 3:1 Males: Females Usually diagnosed in childhood prior to age 8
61
What are the most common sites for dysplasia epiphysealis hemimelia/ Trevor’s disease?
Lower limbs, particularly around the ankle
62
Is fibrous dysplasia considered a hamartoma?
Yes! a hamartoma is a benign lesion that resembles a neoplasm but is comprised of an abnormal moisture of cells and tissues native to the organ in which is arises, growing in a disorganized manner. Hamartoma grow at the same rate as the surrounding normal tissue and do not metastasize. They represent an error in tissue development
63
What is fibromatosis?
Benign proliferation of fibrous tissue e.g. Dupuytren’s, plantar fibromatosis
64
What is a Desmoid fibromatosis?
Deep seated benign lesion. Usually limited growth potential and may regress Frequently occur locally after surgical excision and may invade bone (periosteal reaction), muscle, tendons and other tissue
65
What is the peak incidence of desmoid fibromatosis?
Women in 2nd and 4th decades but can appear at anytime in both sexes Present as firm, diffuse swellings with ill-defined margins
66
What is the histological appearance of of desmoid fibromatosis?
Barely perceptible proliferation of spindle shaped, thin fibroblasts (same as fibrosarcoma), lacks pleomorphism and rare mitoses
67
Where do you find desmoid fibromatosis?
Limb and limb girdle preferentially
68
Does desmoid fibromatosis recur after surgery?
Yes in up to 65%
69
What is desmoid fibromatosis associated with?
Gardner’s syndrome (polyposis colonic cancer, epidermis and sebaceous cysts and osteomas) Intra-abdominal desmoid can cause obstruction of the bowel and ureters and may bleed spontaneously
70
What is a fibrous metaphyseal defect (non-ossifying fibroma)?
Most common benign lesion of the skeleton, fibrous cortical defect is a smaller counterpart. Benign, self-limiting fibroblastic cortical defect commonly found in the metaphysis of long bones in children and adolescents
71
What is the natural history of non-ossifying fibroma?
Typically resolve spontaneously with skeletal maturation and move into the diaphysis regressing and becoming sclerotic with time. Large lesions can cause pathologic fracture especially if lesion occupies >50% cross sectional area
72
What are the imaging appearances of non-ossifying fibroma?
On XR eccentrically located with thinning of cortex, inner boundaries demarcated with sclerosis Often ovoid and multi-loculated. Usually solitary- multiple lesions can be associated with neurofibromatosis or polyostotic fibrous dysplasia
73
What is the macroscopic appearance of a non-ossifying fibroma?
Well circumbscibed, white/ yellow due to fibrous tissue and lipid accumulation
74
What is the histological appearance of a non-ossifying fibroma?
Proliferative spindle cells in a matted or whorled pattern with foam cells and benign multinucleated giant cells. Collagen is rare Spindle cells can take on cellular and even pleomorphic patterns which can lead to misdiagnosis
75
What is a spindle cell?
Mesenchymal origin E.g. fibroblasts, smooth muscle cells, myofibroblasts Can be also pathological and is generally more of a morphological term and if seen by pathologists will sometimes need further testing such as immunohistochemistry to differentiate
76
What is fibrous dysplasia?
Developmental abnormality of skeleton (hamartoma) Hallmark: replacement of bone and marrow by tissue composed of fibrous tissue and irregular, minute spicules of woven bone (normal osteoclasts)
77
Where do you find fibrous dysplasia?
Any bone Most common: femur 35%, tibia 18%, ribs 11%, humerus 7%, mandible 6%
78
What is the prevalence of fibrous dysplasia
Most common type is monostotic, affects females more and presentation is generally in the first few decades of life.
79
What are the characteristics of the the polyostotic form of fibrous dysplasia?
Monomelic or hemisomic in distribution Most common: femur 35%, tibia 18%, humerus 7% Hands and foot more common in this form
80
What are the imaging findings with fibrous dysplasia?
Fine, granular, homogenous appearance (ground-glass) I.e. fibro-osseous appearance MRI shows diminished signal; increased on T2 if cartilage is present.
81
What is the macroscopic appearance of fibrous dysplasia?
Marrow and bone replaced with a fine, gritty, tan tissue. Remodelling of bone can lead to bulging osseous masses or cysts
82
What are the histological appearances of fibrous dysplasia?
Bland fibrous tissue producing an abundant collagen matrix that is sparsely cellular admired with irregular spicules of woven bone (Chinese alphabet) Cartilage present in 10% with calcification
83
What’s the natural history of fibrous dysplasia?
Variable- can progress to marked deformities and fractures Coxa vara in the femur is a common complication (shepherd’s crook deformity) In more local involvement progresses slowly, favourable prognosis
84
What’s the treatment for fibrous dysplasia?
Conservative For lower limb lesions in those <18, internal fixation is recommended
85
What is McCune-Albright syndrome?
Genetic, non-inheritable disease characterised by a triad of hyperpigmentation of skin (cafe au lait spots), polyostotic fibrous dysplasia and hyperfunctional endocrinopathies e.g. precocious puberty Almost exclusively occurs in females
86
What is the genetic issue that leads to McCune-Albright syndrome?
Somatic mutations in the gene and coding of the G protein family leads to activation of adenylate cyclase (excess cAMP) and proliferation an autonomous hyperfunction of hormonally responsive cells.
87
What is the relation of sarcoma and fibrous dysplasia?
Rare but well known complication 0.5% risk, more common if polyostotic disease, most common in skull facial bone and femur Poor prognosis Most frequent osteogenic sarcoma, but can also have fibrosarcoma, chondrosarcoma and malignant fibrous histiocytoma
88
What is Fibrosarcoma
Rare- 4% of malignant bone tumours Primary malignant spindle cell sarcoma of bone composed of cells with a fibroblastic nature 1/3 are complications of other conditions e.g. Paget’s, bone infarction or irradiated bone Very rare in <15 year old
89
What are the histological appearances of fibrosarcoma?
Proliferation of malignant cells with enlarged, hypochromatic, plump nuclei, often proliferating in an interdigitating fashion resembling a HERRINGBONE pattern
90
What are the imaging findings with fibrosarcoma?
XR: purely lytic changes, often large and poorly marginated, usually metaphyseal or diaphyseal in location. May be destructive changes, periosteal reaction uncommon
91
What are the most common locations of fibrosarcoma?
Most common in pelvis, proximal humerus, proximal tibia and femur.
92
What is the macroscopic appearance of fibrosarcoma?
Flesh-like or silky appearance
93
What is the treatment of fibrosarcoma
Surgical, requires adequate excision Prognosis is poor
94
What is malignant fibrous histiocytoma? AKA pleomorphic sarcoma
Malignant tumour likely of facultative histiocytes Associated with Pagets, bone infarction or radiation; also enchondromatosis, low grade osteosarcomas, fibrous dysplasia and metallic implants
95
What are the common locations of malignant fibrous histiocytoma (pleomorphic sarcoma)?
Knee, distal femur (26%) + prox tibia (9%), ilium 8%, humerus 7% and skull 7%
96
What are the histological characteristics of malignant fibrous histiocytoma?
Composed of a mixture of cells, fibroblasts, myofibroblasts, histiocytes, giant cells arranged in a swirling cartwheel or storiform pattern with associated inflammation, collagen matrix, foam cells and macrophages
97
What are the XR appearances of malignant fibrous histiocytoma?
Predominant lytic appearance, usually metaphyseal or diaphyseal associated with sclerotic focal area Rarely calcification or periosteal reaction
98
What is an enchondroma?
Most common cartilaginous lesion, benign, usually found in the medullary canal Most often diagnosed from 10-40 years old

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