Pathology & Tumour Flashcards
Causes of vertebral plana?
EG
Infection - especially TB
Ewing’s sarcoma
Metastatic tumour
What are the three forms of Langerhan’s Cell Histiocytosis?
- EG (localised form) 70%
- Hand-Schuller-Christian disease (chronic recurring form) 20%
- Lettered-Siwe disease (fulminant form) 10%
Differential diagnosis of osteosarcoma?
Osteomyelitis
Ewings
Trauma
Myosotis ossification
Combined vascular malformation sand hypertrophy syndromes
Klippel-Trenaunay - capillary/lymphatic/venous
Parkes-Weber syndrome - AVN malformation
Maffuci- enchondroma todos with vascular malformation
DD of exquisitely tender lesion
Haemangioma Synovial sarcoma Neuroma Abscess Glomus tumour Fibrosarcoma Acute inflammation
Macro and micro Characteristics of Tuberculosis
Centrally necrotic, caseous cavity surrounded by multi-uncleared giant cells (epitheloid) and lymphocytes
Calcified late
Thickened synovium, effusion and pannus
Increased vascularity - osteopaenia
Absence of - sclerosis and periosteal reaction
Two Differential diagnoses of TB
Brucellosis - unpasteurised milk - Mx tetracycline
Rheumatoid
Abx Treatment of TB
RIPE
Rifampicin & Isoniazid for 9 months
Pyramidazole for 2 months
Ethambutol- retrobulbar neuritis
Features of congenital syphilis?
Treponema pallidum crosses placenta in second half pregnancy
Sick and irritable infant
Hepatosplenomegaly
Joint swelling and pseudoparalysis at several weeks old.
Swelling and tenderness at ends of long bones
What is the organism of syphilis? What is pathology
Treponema pallidum - penicillin
Spirochete
Angitis of vasa vasorum or small arterioles. Endarteritis produces vessel wall necrosis and tissue infaction supplied by vessel.
Primary - chancre
Secondary - mucocutaneous lesions and lymphadenopathy
Tertiary - untreated cases. Antibiotics ineffective
Orthopaedic manifestations of syphilis
Tabes dorsalis -
Posterior column degeneration
Lightening pains in lower limbs
Sensory ataxia, joint instability and CHARCOT
Gummata -
Punched out lesions in medulla
Destructive lesions in cortex
Pathological fractures
Sabre tibia
Xray
Periostitis- can be onion peel
Metaphysitis-
Trabecular erosion in juxta-epiphyseal region
Lucent band near physis followed by frank destruction
Similar to leukaemia and neuroblastoma
Dd Scurvy Multifocal OM Battered baby syndrome Caffey's disease - infantile cortical hyperostosis
Define synovial chondromatosis
Monoarticular Benign proliferation disorder of the synovium
Chondroid metaplasia of synovium resulting in production of MULTIPLE INTRA-ARTICULAR LOOSE BODIES
Primary
Secondary - degenerative arthritis with cartilage breaking off and growing in joint
Xray feature of synovial chondromatosis and DD
Stippled calcification of soft tissues around a joint
unless lesions large and ossified
Degenerative changes if SC is secondary
DD
Tumeral calcinosis
Soft tissue chondroma
Hypercalcaemia
Genetic association for enchondroma (MCQ)
IDH1 and IDH2 mutations
Especially Ollier disease and Mafucci syndrome
Define a hamartoma
Name some examples
A hamartoma is a benign, focal malformation that resembles a neoplasm in the tissue of its origin. This is not a malignant tumor, and it grows at the same rate as the surrounding tissues. It is composed of tissue elements normally found at that site, but which are growing in a disorganized mass.
Osteochondroma
Genetics for MHE
EXT1 & EXT2 proteins & genetic loci
Biosynthesis of heparin sulfate
Decreased expression leads to osteochondromas
What are the syndromes associated with non-ossifying fibromas
Familial multi-focal
Neurofibromatosis
Jaffe-Campanacci syndrome
Congenital with cafe-au-lait, mental retardation, non-skeletal abnorms - heart, eyes, gonads
Define fibrous dysplasia
Common developmental abnormality characterised by Hamartomatous proliferation of fibro-osseus tissue within bone
Genetics of fibrous dysplasia
Dominant activating mutations of GS alpha on chromosome 20q13
Produce a sustained adenylate cyclase- cAMP activation
High expressions of FGF-23
Cause of hypophosphataemia in McCune-Albright
Syndromes with fibrous dysplasia
McCune Albright - polyostotic FD, precocious puberty and Coast of Maine spots
Oncogenic osteomalacia- renal phosphate wasting due to FGF 23
Mazabraud syndrome - polyostotic FD, multiple intramuscular myxomas
Genetics of ABCs
Express TRE17/USP6 translocation
Chemotherapy for osteosarcoma
Adriamycin / doxorubicin - Blocks DNa/RNA synthesis via topoisomerase II
Cisplatinum - DNa disruption by covalent bonding
Methotrexate - inhibits dehydrofolate reductase
Ifosfamide - DNA alkylating agent
Genetics of osteopetrosis
Carbonic anhydrase II
TCIRG1 (ATP6i) gene mutation
Chloride channel 7
What are the seronegative arthropathies?
Reiter's Ankylosing spondylitis Psoriatic Enteropathic spondylitis Lupus associated arthritis
HLA-B27
Cellular Characteristics of rheumatoid synovitis
High presence of T-cells in inflamed tissue
Paucity of lymphocytes at invasion front and in synovial fluid
B-cells produce RF - IgM to the Fc of IgG
T-cells regulate inflammatory response
RF complexes activates complement cascade
What are DMARDS?
Synthetics
Methotrexate - give with folic acid
Biological
Infliximab- TNF alpha antagonist. Monoclonal antibody
4 causes of back kneeing
Polio
Lax posterior capsule
PCL deficiency
Fracture Malunion - femur extension, tibia recurvatum
5 causes of hip pain in Pagets
Fracture Osteoarthritis Malignant transformation - 2nd Osteosarc Active disease Spinal stenosis
Causes of Erlenmeyer flask deformity
Gauchers Osteopetrosis Niemann-Pick disorder MHE Lead poisoning Cranio Metaphyseal dysplasia Haemoglobinopathies- sickle / thalassaemia Metaphyseal dysplasia -Pyle disease
Two benign tumours that can metastasise
GCT
Chondroblastoma
Same as only 2 epiphyseal
3 tumours more common in women
Fibrous dysplasia
Parosteal osteosarcoma
GCT
5 mimickers
Big Five Mice
Fibrous dysplasia Metastatic bone disease Infection Cartilage lesions EG
Small round blue cell tumours
Infants
- neuroblastoma
- nephroblastoma - Wilm’s
- retinoblastoma
Kids
- EG / LCH
- Wilm’s
Adults
- Ewings
- MM
- Lymphoma
- Rhabdomyosarcoma
Classification of bone tumours
1) histological
2) grade
3) staging
Lichtenstein - osteogenic, chondrogenic etc
Grade
Low, intermediate, high
Morphological -
Nuclear anaplasia, hyperchromasia, pleomorphism
Enneking - malignant 1 Low grade - 98% 5 yr survival 2High Grade - 80% 5yr survival 3 Metastatic (G1 or G2) 30% A Intra / B Extra - compartmental
Three conditions with Codman’s triangle
Osteosarcoma - high grade
Ewing’s sarcoma - high grade
Infection - osteomyelitis
Why perform biopsy in tumour centre? (Evidence)
Mankin CORR 2006
Complication rates X5 if performed at non-tumour centre
Errors, amputation, survival rate
4 types of biopsy
FNA
Core
Incisional
Excisional
Tumours with Autumnal hues
PVNS
GCT
Principles of treating a tumour patient
Diagnosis and staging Discussion with patient and family Multidisciplinary approach Determine curative or palliative Multimodality approach Skeletal stability
Multimodal approach
- Pharmacological - analgesia, bisphosph
- Surgery - limb salvage vs amputation
- Chemotherapy
- Radiotherapy
Criteria for limb salvage
Survival rate > amputation
Function > amputation plus prosthesis
Vascular, innervated and stable limb
4 surgical margins
Intralesional- 100% recurrence
Marginal - through reactive zone - 25-50% recurrence
Wide - through normal tissue - <10% recurrence
Radical - entire compartment - ligaments, CT and muscle
Main tumours that chemo used effectively
Osteosarcoma
ewings
De differentiated chondrosarcoma
Malignant fibrous Histiocytoma
Neo-adjuvant 8-12weeks preop
Adjuvant - 6-12 months
Mode of action of radiotherapy
Direct DnA damage
Indirect via Free radical
Keep <50 Gray to avoid tissue healing problems
Tumours that radiotherapy effective
Ewings
Lymphoma
MM/ Plasmacytoma
Soft tissue sarcoma - no difference in survival but debulks for surgery
How to score fracture risk in tumour
Mirel’s - CORR 1989
Pain - mild, mod, funct
Size - 2/3
Site - UL, LL, troch
Type - Blastic, mixed, lyric
Score min 4, max 12 7 - 4% Observe and Rx 8 - 15% +/- FIX 9 - 33% FIX 10 - 100% FIX At 3 months
What is diagnosis in known metastatic lung Ca patient who is now confused, weak, dehydrated and n&v?
Metastatic hypercalcaemia
Diuretics and fluid hydration
How do you determine spine stability in metastatic bone disease?
Kostuik criteria
Divides Denis columns into 6
Instability is 3 or more
Prognosis of MBD
Months
Lung - 6
Kidney - 6
Breast - 24
Thyroid - 40
Prostate - 48
Differential for GCT
Brown tumour
Histological buzzword of chordoma
Physaliferous cells
Histology of adamantioma
Nests of epithelial cells in a fibrous stroma
Which tumours are storiform?
NOF
Malignant fibrous Histiocytoma
Osteosarcoma
Leimyosarcoma
Haemangioperocytoma
Neurogenic sarcoma
Which tumours have coffee bean nuclei?
EG / LCH - plus tennis racquet Birbeck granules
Malignant fibrous Histiocytoma
Chondroblastoma
Which tumour has clock face nuclei?
MM / Plasmacytoma
Which tumours have giant cells
UBC ABC NOF Ostefibrous dysplasia EG / LCH MFH
Chondroblastoma
Chondromyxoidfibroma
Clear-call chondrosarcoma
Which tumour has Chinese letters histology
Fibrous dysplasia
Immature fibrous tissue surrounded by islands of irregularly poorly mineralised woven bone trabeculae
What is a Codman’s tumour?
Chondroblastoma
Benign chondroid tumour characterised by its epiphyseal location.
Similar to GCT but chondroid matrix and occurs in skeletally immature
Mets to lungs - like GCT
Curettage and bone graft as locally aggressive
What is the histological differentiation between enchondroma and chondrosarcoma
Bone encasement pattern vs permeation pattern
What tumour has chicken wire / lace-like calcification
Chondroblastoma
Main Differential of a NOF - non-ossifying fibroma?
Chondro-myxoid fibroma
Rare, benign chondroid tumour Metaphyseal Lytic, eccentric and lobulated Thinking and cortical expansion SHARP, scalloped, sclerotic rim
Surgical curettage and bone graft
DD for CMF is -
ABC
Chondromyxoid sarcoma
Osteomyelitis
What Metaphyseal lesion has a sharp, scalloped sclerotic rim?
Chondromyxoidfibroma
DD - NOF, myxoid chondrosarcoma
Myxoid chondrosarcoma -
Clear permeations of surrounding bone and HYPERCELLULARITY THROUGHOUT
What are he types of chondrosarcoma
Intramedullary Clear cell Mesenchymal Dedifferentiated Secondary - Osteochondromas - MHE - enchondromatosis
What is a clear -cell chondrosarcoma
The malignant form of a chondroblastoma
How are chondrosarcomas graded
Differentiated (survival %) Well (90) Intermediate (60) Poor (30) Dedifferentiated (10)
Differentials for a chondrosarcoma
Secondary Osteosarcoma
Osteomyelitis
MBD
Malignant fibrous Histiocytoma
Differential diagnosis for chordoma
Fibrosarcoma
MBD
Chondrosarcoma
What is the spectrum of diseases known as histiocytosis x
Cell of origin is Langerhan’s cell. Dendritic APC found everywhere especially skin and bones
Eosinophilic granuloma
Hand-Schuller-Christian disease - exophthalmos, diabetes insipidus, bone destruction
Letterer-Siwe hepatosplenomegaly, lymphadenopathy, anaemia, acute infections. Fatal
Classic cause of vertebral plana
EG
What so the pattern of tumours in Olliers / Maffuci disease
Multiple enchondromas
Unilateral in long bones, bilateral in hands
Prognosticators for Ewings
90% tumour necrosis with Neo-adj chemo Metastatic disease - lung bad, bone terrible Wide excision Pelvic - bad Increased LDH or ALP bad
What is the other name for Trevor’s disease?
Dysplasia Epiphysealis Hemimelica
Medial physis overgrowth.
Knee or ankle most common. Valgus
What’s the chromosomal translocation of synovial cell sarcoma?
X;18
What distinguishes PVNS from Synovial cell sarcoma on xray ?
SCC is calcified in 50%
How are simple UBCs classified?
Neer classification
2cm from growth plate - INACTIVE
Stanley’s trilogy for transmural bone lesion with large soft tissue component
Ewings
Lymphoma
Infection
Also - all small round blue cell
What are the different types of osteosarcoma and what are their grades
Intramedullary - HIGH
Parosteal - LOW
Periosteal - INTERMEDIATE
Tangiectatic
Secondary - HIgH
- Pagets
- Radiation
Genetic associations of osteosarcoma
RB-1 retinoblastoma gene - 13q/recessive - TSG
P53 gene - 17p/dominant TSG
Retinoblastoma patients have increased risk of OS x1000
Also - Pagets, radiation, Rothmund-Thompson syndrome
Describe radiological appearance of osteoid osteoma
Well circumscribed intra-cortical lesion with a radiolucent nidus
Indications for surgery in spinal metastatic bone disease.
Persistent severe pain
Instability
Progressive neurology
Tissue biopsy
Radiological findings of Hyperparathyroidism
Osteoporosis
Subperisoteal resorption in Middle phalanges of fingers, particularly MF and IF
Erosions at symphysis pubis, distal clavicles, vertebral end plates
Brown tumours
Chondrocalcinosis
What are the 6 principles of chronic osteomyelitis management?
Surgical debridement of all devitalised tissues
Dead space management
Skeletal stabilisation
Soft tissue coverage
Appropriate antibiotics - local or systemic
Optimise host factors
Sclerotic lesions of bone - VINDICATE
VINDICATE Vascular - hamangioma Infection Neoplasm- OO, osteosarc Drugs - Fluoride, Vit D IDiopathic Congenital - bone islands, poikiloisis, petrosis Autoimmune Trauma Endocrine - HPTH, Pagets
Sclerotic lesions of bone - VINDICATE
VINDICATE Vascular - haemangioma Infection Neoplasm- OO, osteosarc Drugs - Fluoride, Vit D Idiopathic Congenital - bone islands, poikiloisis, petrosis Autoimmune Trauma Endocrine - HPTH, Pagets
Risk factors for OA
Systemic - age, ethnic origin, sex, bone density, hormones, nutrition, genetics, obesity
LOCAL - Trauma, instability, malalignment, laxity, weakness
Factors for 2nd OA Acromegaly, Hyper PTH, Pagets Gout, Pseudo, chondrocalcinosis Trauma, AVN, EDS, Septis, Charcot, DDH Wilsons, Amyloid, haemoglobinopathies
