1
Q
Most common mutation in melanoma arising in non sun exposed areas
A
Activating mutation in KIT
Silencing of PTEN also occurs in 20% of these melanomas
2
Q
Common mutations in melanoma
A
CDKN2A (codes p16) occurs in 40% of autosomal dominant familial melanoma. Also occurs in sporadic
BRAF 40-50%
RAS 15-20%
TERT 70% sporadic melanoma (telemerase)
Others: PTEN, KIT, NF1
3
Q
Most common mutation in melanoma
A
TERT 70% of sporadic melanomas
4
Q
Classes of melanoma that have radial growth
A
- Lentigo maligna
- Superficial spreading (most common)
- Acral/mucosal lentiginous (unrelated to sun exposure)
Radial growth is horizontal spread in epidermis and superficial dermis without vertical growth. Lacks capacity to metastasize
5
Q
Describe vertical growth of melanoma
A
Nodular growth into deep dermis as an expansile mass, occuring after a period of radial growth. Often has a nodule which is the emergence of a tumour subclone with metastatic potential.
No maturization of the cells in the deep invasive portion.
6
Q
Typical location and patient type for lentigo maligna
A
Face of an older man
Sits indolent for decades in a radial growth pattern
7
Q
Name a condition with increased risk of melanoma
A
Dysplastic nevus syndrome
- Autosomal dominant, variable penetrance
- 50% develop melanoma
8
Q
Pathologic features which predict prognosis for melanoma
A
Unfavourable: Larger breslow thickness, increased mitotic number, tumour regression, ulceration, sentinel lymph node involvement
Favourable: Brisk response of tumour-infiltrating lymphocytes
Prognosis also dependent on location
9
Q
What is the most common adult primary ocular malignancy?
A
Uveal melanoma
10
Q
Describe the important features of uveal melanoma
A
- Presents with painless vision disturbance or asymptomatic
- UV light is not a risk factor
- GNAQ or GNA11 gain of function mutations. NO BRAF MUTATION
- Associated with dysplastic nevus syndrome
- Systemic metastases (liver > lung > bone)
- Prognostic factors: size (lateral extent), cell type (more epithelioid cells is worse), proliferative index
- Location: Choroid > ciliary body > iris
- Iris is more indolent than ciliary body and choroid
11
Q
Most common cancer of sun exposed skin?
A
Basal cell carcinoma
Note: SCC is second
12
Q
Risk factors for cutaneous SCC
A
UV light, immunosuppression (susceptible to transformation by HPV 5 and 8)
Others: industrial carcinogens, chronic ulcers, draining osteomyelitis, old burn scars, ingestion of arsenicals, ionising radiation.
13
Q
Mutations in cutaneous SCC
A
Tp53
Increased signalling in RAS pathway, decreased signalling in Notch pathway
14
Q
What is the precursor for and what are two conditions associated with cutaneous SCC?
A
Actinic keratoses. Others are sporadic.
Xeroderma pigmentosum (more susceptible to SCC). Autosomal recessive epidermodysplasia verruciformis.
15
Q
What are the risk factors for head and neck SCC?
A
HPV infection, smoking, alcohol, betel quid, paan, UV radiation
16
Q
Describe the two types of head and neck SCC?
A
Smoking-associated (HPV negative)
- Keratinising
- Begin as dysplastic lesions
- Favours oral cavity
- Older demographic
- RFs: Tobacco + alcohol
- High risk of second primary (35%) due to field cancerization
- Large primary with variable nodes, distance metastases common, poor outcome
HPV-associated SCC
- Non-keratinising
- Tend to develop without premalignant lesion
- Favours oropharynx
- Younger demographic
- RFs: number of oral sex partners
- Strong p16 protein expression
17
Q
Typical patient, lesion development, location and associated protein elaborated with lung SCC
A
Males, smoking
Squamous metaplasia/dysplasia, to in situ, to invasive cancer
Central
Paraneoplastic syndrome, usually hypercalcaemia from PTH-RP
18
Q
Risk factors for oesophageal SCC
A
Alcohol, tobacco, poverty, caustic oesophageal injury, achalasia, Plummer-Vinson syndrome, diets deficient in fruit and vege, hot beverages, previous mediastinal radiation
19
Q
Typical location and metastatic pathways of oesophageal SCC
A
50% middle third
Rich lymphatics allow circumferential and longitudinal spread
- Upper third to cervical nodes
- Middle third to mediastinal, paratracheal, tracheobronchial
- Lower third to gastric and coeliac
20
Q
Typical age group, most important risk factor and precursor lesion for cervical SCC
A
45-50
HPV 16 + 18
LSIL / HSIL (squamous intraepithelial lesions)
21
Q
Risk factors, precursor lesion and lymphatic drainage of vaginal SCC
A
High-risk HPV, previous cervical or vulvar carcinoma
Premalignant vaginal intraepithelial neoplasia
Upper 1/3 to iliac nodes, lower 2/3 to inguinal nodes
22
Q
Risk factors for bladder SCC
A
Schistosomiasis, chronic bladder irritation and infection
Mixed urothelial carcinoma with SCC is more common than pure SCC.
SCC is more invasive/fungating
23
Q
Risk factors, protective factor, precursor lesion and subtypes of penile SCC
A
Poor genital hygiene, high risk HPV, smoking, chronic inflammation, balanitis xerotica obliterans
Circumcision provides protective factor.
Penile intraepithelial neoplasia (most are non-HPV related). Usually originates in glans
Verrucous (non HPV related) or Basaloid (HPV related). The latter is more aggressive.
Often early metastasis to inguinal lymph nodes.
24
Q
Name 5 risk factors for Tuberculosis
A
AIDS
poverty
overcrowding
diabetes
chronic renal failure
alcoholism
chronic malnutrition
immunosuppression
chronic lung disease (silicosis)
Hodgkin Lymphioma
25
What is a Ghon focus and a Ghon complex?
Ghon focus is the initial focus of consolidation during primary infection
Ghon complex is the parenchymal lung lesion + affected draining lymph node
Ranke complex is fibrosis and calcification of the Ghon complex
26
Most common presentation of extrapulmonary TB?
Lymphadenitis - cervical is called scrofula
27
Name three manifestations of MEN-1
1. Pituitary adenoma (prolactinoma often, some somatotroph)
2. Pancreatic neuroendocrine tumour (including gastrinoma and insulinoma. Usually aggressive, metastatic disease, common cause mortality)
3. Parathyroid hyperplasia/adenoma (95%, hyperparathyroidism, 40-50)
Remember: 3 Ps
- Gastrinomas more frequently occur in the duodenum.
- Can also get carcinoid, thyroid, adrenocortical adenomas and lipomas.
28
Name the two most common types of cells in pituitary adenomas related to MEN1?
Lactotroph (prolactin)
Somatotroph (growth hormone)
29
Most common tumour of MEN-1?
Parathyroid hyperplasia/adenoma
30
Name four clinical manifestations of MEN1?
1. Intractible peptic ulcers (Zollinger-Ellison syndrome)
2. Renal stones (hyperparathyroidism)
3. Hypoglycaemia (insulinoma)
4. Prolactin excess - irregular periods and lactation in women, erectile dysfunction and decreased libido in men
31
Gene mutation for MEN1 and MEN2?
MEN1 - MEN1 tumour suppressor gene mutation - protein is Menin
MEN2A/2B - activation mutation in RET (in 2B it is a single amino acid missense mutation)
32
Manifestations of MEN2A? (3)
1. Medullary thyroid carcinoma (almost 100%, C-cell hyperplasia, calcitonin, aggressive)
2. Hyperparathyroidism (hyperplasia 10-20%)
3. Phaeochromocytoma (40-50%, bilateral, can be extra-adrenal)
Remember 2Ps 1M
Often have genetic screening to do a prophylactic thyroidectomy
33
Manifestations of MEN2B? (3)
1. Phaeochromocytoma (40%, bilateral, can be extra-adrenal)
2. Medullary thyroid carcinoma (almost 100%, multifocal and more aggressive than MEN2A)
3. Mucosal neuromas (99%, skin, oral mucosa, eyes, respiratory tract, GI tract).
Remember 1P 2Ms
Often have genetic screening to do a prophylactic thyroidectomy
May have marfinoid body habitus.
34
What is MEN 4?
Same phenotype as MEN-1 but with a different gene mutation (CDKN1B)
35
What is the gene involved in cystic fibrosis, and what is the inheritance pattern?
CFTR gene on chromosome 7q31.2
Autosomal recessive
36
What is the pathophysiology of cystic fibrosis?
CFTR mutation, which affects chloride and bicarbonate transport across cell membranes.
Almost everywhere = Increased ENaC activity, resulting in increased sodium in the cell, pulling water into the cell and causing thick secretions
Sweat glands = Decreased ENaC activity, resulting in poor transport of sodium
Increased bicarbonate into cells, causing secreted fluids to be acidic, resulting in increased mucin production and plugging of ducts (cause of pancreatic insufficiency)
37
List the 6 mutation classes of cystic fibrosis
Class 1: defective protein synthesis (no CFTR at surface)
Class 2: most common - abnormal amino acid position 508 (70%) – abnormal protein folding, processing and trafficking (no CFTR at surface)
Class 3: defective regulation (normal amount of CFTR at surface but non functional)
Class 4: decreased conduction
Class 5: reduced abundance
Class 6: decreased membrane CFTR stability
Class 1-3 are severe. Class 4-6 are mild.
38
What proteins are affected in primary ciliary dyskinesia, and what is the inheritance pattern?
Defects in ciliary motor proteins (dynein)
Autosomal recessive
39
What is associated with primary ciliary dyskinesia?
1. Kartagener syndrome (situs inversus, bronchiectasis and sinusitis)
Cilia are required for proper organ rotation during embryogenesis.
50% of primary ciliary dyskinesia have this.
2. Male infertility due to defective sperm motility
40
Describe the differences between schwannoma and neurofibroma
Schwannoma :
- Schwann cell differentiation (PNS myelinating cell)
- Sporadic or familial loss of NF2 on chromosome 22 (merlin)
- Malignant transformation rare
Neurofibroma:
- Schwann cells admixed with perineural-like cells, fibroblasts, mast cells, spindle cells
- Sporadic or familial loss of NF1 (neurofibromin)
- Can transform into malignant peripheral nerve sheath tumours
41
Describe the 3 types of neurofibroma
1. Superficial cutaneous
- Pedunculated nodules
- Can be sporadic or NF1 related
2. Diffuse
- Large plaque like skin elevation
- Usually NF1 related
- Some malignant transformation
3. Plexiform
- Can be deep or superficial
- Typically NF1 related
- Malignant transformation
42
What is a precursor lesion for and what grade are malignant peripheral nerve sheath tumours?
50% from plexiform neurofibromas
Mostly high grade (85%)
Usually involve large peripheral nerves. Can differentiate in some ares to glandular/cartilage/osseous lesions.
43
Typical location within the spinal layers and within the vertebral canal of spinal schwannomas
Intradural extramedullary. Note 15% extradural.
Usually cervical and lumbar spine.
44
Typical location of limb schwannomas
Eccentrically on peroneal and ulnar nerves
45
Typical age and location of liposarcomas. What are 3 different subtypes?
60-70s
Deep soft tissue of proximal extremities and retroperitoneum
- Well differentiated
- Myxoid
- Pleomorphic (most aggessive, metastasizes)
46
What is the most common adult;
- soft tissue tumour?
- sarcoma?
Lipoma
Liposarcoma
47
What is the gene mutation in Li-Fraumeni?
TP53 (autosomal dominant)
25x greater chance of developing a malignant tumour by age 50. Often have multiple primary tumours.
Common tumours;
- Sarcoma (osteo, rhabdomyo)
- Leukaemia
- Adrenocortical carcinoma
- Brain tumour (astrocytoma, choroid plexus carcinoma, medulloblastoma)
- Breast cancer
48
What are the common gene mutations for hereditary non-polyposis related colorectal cancer (HNPCC)?
MSH2 or MLH1
- Mismatch repair gene mutation
- Inherit one abnormal copy (MMR gene), issue with somatic mutation of the other
- Causes microsatellite instability
- Most common cancer is colon (right side often)
- Other cancers; endometrial (2nd), ovarian, prostate, urothelial tract, small bowel, gastric, HPB and CNS (glioblastoma)
49
What are the common cancers related to BRCA mutations? Which are more associated with BRCA 1 or 2?
Breast, ovarian, pancreatic and prostate.
BRCA1 has a stronger association with breast and ovarian. Often poorly differentiated and triple negative breast cancer. Less commonly fallopian tube, uterine, peritoneal.
BRCA 2 has a stronger association with male breast and prostate. Breast cancers are often poorly differentiated but ER positive. Less commonly bile ducts, stomach, melanocytes and B lymphocytes.
BRCA regulate DNA-damage response and repair. Autosomal dominant inheritance.
50
What is the most frequently diagnosed infant malignancy?
Neuroblastoma
- Also the most common extracranial solid tumour of childhood
- Tumours of primordial neural crest cells, 40% adrenal medulla, remainder sympathetic chain (25% paravertebral abdomen, 15% posterior mediastinum)
51
What is the gene associated with neuroblastoma? Also what is the main histological finding and the different subtypes?
ALK mutation
Small round blue cell tumour
Ganglioneuroma (benign)
Ganglioneuroblastoma
Neuroblastoma
- Usually sporadic. 1-2% familial
- Tiny masses may regress spontaneously
- Schwann cells is a favourable finding
52
What is the typical age group for neuroblastoma and what is a characteristic symptom/sign?
18 months (40% in infancy, generally younger than in Wilms tumour)
Opsomyoclonus from paraneoplastic syndrome (dancing eyes and feet). Older children may only present with symptoms from bone/resp/GI mets.
53
What are favourable features of neuroblastoma?
Age <18 months
Histological grade
Stage 1, 2A or 2B
Stage 4S
No MYCN gene amplification
Thoracic primary
54
What are the criteria for stage 4S for neuroblastoma?
Localised primary tumour (stage 1 - 2B) with dissemination limited to skin, liver and/or bone MARROW
Note: Only <10% nucleated cells to be malignant and <10% bone marrow involvement, otherwise stage 4 (not 4S)
Most children present stage 3 or 4 (60-80%).
The staging is the International Neuroblastoma Staging System and can only be scored post-operatively
55
A 16 month old presents with metastatic disease, classical blueberry muffin appearance, with elevated catecholamines in their blood test. What is the primary malignancy?
Neuroblastoma
- Often has local nodes and metastases early. Goes to liver, lungs, bone, bone marrow, periorbital region and cutaneous (blueberry muffin)
- 90% produce catecholamines (HTN less common compared to phaeochromocytoma)
- Can develop FNH after chemotherapy treatment
56
What is a dermoid cyst, and how does it differ from an epidermoid?
Congenital ectodermal inclusion cyst which occurs during closing of the neural tube in the 5th-6th week.
It is lined by squamous epithelium and contains skin appendages. Epidermoid cysts do not contain skin appendages.
57
What are the two common locations of an orbital dermoid?
Extraconal upper outer quadrant at the frontozygomatic suture
Superonasal at the frontolacrimal suture.
Most common orbital mass in children.
58
Common location for a spinal dermoid?
Lumbosacral region 60%, then cauda equina 20%.
Can be congenital or acquired (post neonatal LP or spinal surgery)
59
What is the most common paraganglioma and where do most of the extra-adrenal paragangliomas occur?
Adrenal medullary phaeochromocytoma
Head and neck
Paraganglioma arise from parasympathetic and sympathetic neuroendocrine cells.
Tumours around the head and neck are often parasympathetic. Tumours below the neck are often sympathetic.
60
What is the typical age, gene mutation and familial syndromes associated with paraganglioma?
50-60s
Succinate dehydrogenase complex
MEN 2A, MEN 2B, hereditary paraganglioma syndrome
Paragangliomas often stain positive for chomogranin and synaptophysin.
61
Typical demographics, locations and complications of germinomas
10-12 year old, males
Midline: Pineal gland (50% of all pineal tumours), floor of 3rd ventricle, suprasellar
Hydrocephalus, parinaud syndrome (vertical gaze palsy), diabetes insipidus, hypopituitarism, optic chiasm compression
These resemble seminomas and ovarian dysgerminomas.
62
What are some important features of an ovarian dysgerminoma?
Mostly 20s-30s
Most unilateral (90%)
Malignant, 1/3 aggressive
Good prognosis
Some produce hCG, most produce LDH
May be associated with a dermoid cyst.
63
What are some important features of a testicular seminoma?
40s
hCG can be raised if syncytiotrophoblasts (15%)
Must be pure seminoma on histology, without elevated AFP.
Nodal disease to retroperitoneum before haematogenously to lung, liver, brain and bone. Usually slower to metastasize than NSGCT
64
What are the non-germinomatous (/seminomatous) germ cell tumours and a few important features of each? (males)
1. Embryonal carcinoma
- 20-30s, locally aggressive
2. Yolk sac tumour
- Common in infants with good prognosis
- Post-pubertal type is rarely pure, often mixed with other GCTs
- AFP positive
3. Choriocarcinoma
- Highly malignant, widespread haemorrhagic metastases
- Pure form is rare
- Elevated hCG
4. Teratoma
- More than 1 germ cell layer
- Pure in prepubertal, mixed in adults.
- Malignant transformation into somatic malignancies (SCC, sarcoma)
65
Most common mixed germ cell tumour in females
Dysgerminoma and yolk sac tumour
66
What tumour contains Schiller-Duval bodies?
Yolk sac tumour
67
What is the gene, its protein and its inheritance pattern for neurofibromatosis 1?
NF1 on chromosome 17.
Neurofibromin.
Autosomal dominant.
68
What does CAFE SPOT stand for? (NF1)
C - >6 cafe au lait spots
A - axillary or inguinal freckling
F - fibroma
E - eye/iris hamartoma
S - skeletal (sphenoid wing dysplasia, thinning of long bone cortex +/- pseudoarthrosis)
P - primary relative with NF1
OT - optic nerve glioma (pilocytic astrocytoma)
69
Apart from CAFE SPOT, what other diseases are associated with NF1?
50% learning difficulties
Epilepsy
Malignant PNST
Glial tumours (brainstem glioma, spinal astrocytoma)
Phaeochromocytoma
Leukaemia
GIST
70
What is the gene, its protein and its inheritance pattern for neurofibromatosis 2?
NF2 on chromosome 22.
Merlin.
Autosomal dominant
71
What does MISME stand for? (NF2)
Multiple inherited schwannomas, meningiomas and ependymomas (latter of spinal cord)
72
What is characteristic of Sturg Weber syndrome, and what are other presenting symptoms and associations?
Facial port wine stains and pial angiomas
Seizures, developmental delay, paralysis/sensory deficit of one hemisphere, choroidal/scleral angiomatous involvement causing retinal detachment or glaucoma
Coarctation of the aorta. Paragangliomas.
Note this is a sporadic condition.
73
What is the Vogt triad?
Present in 30% of patients with tuberous sclerosis
Seizures, intellectual disability, facial angiofibroma (latter most common).
74
What are the genes involved in tuberous sclerosis, what do they code, and what do they usually regulate?
TSC1 - hamartin
TSC 2 - tuberin (more common)
Usually inhibit mTOR which controls cell size
75
What does HAMARTOMAS stand for? (TSC)
H - hamartomas of skin, retina, CNS
A - AML
M - mitral regurgitation
A - Ash leaf spots
R - rhabdomyoma (cardiac)
T - tubers (cortical, subcortical, SEGA)
O - autOsomal dominant
M - mental retardation
A - angiofibroma (facial)
S - seizures
76
Other findings in tuberous sclerosis apart from HAMARTOMAS
Subependymal nodules
Subependymal giant cell astrocytomas (from hamartomatous nodules)
Pulmonary LAM
Liver, kidney and pancreatic cysts
Shagreen patches
Subungal fibromas
77
What is the gene involved in Von-Hippel Lindau, the inheritance pattern, and what does usually regulate?
VHL gene on chromosome 3 (tumour suppressor)
Autosomal dominant
Mutations results in VEGFR overexpression
78
What does HIPPEL stand for? (VHL)
H - haemangioblastoma (posterior fossa, spinal cord, retina)
I - increased risk of RCC (clear cell)
P - pancreatic lesions (cyst, cystadenoma, cystadenocarcinoma, NET)
P - phaeochromocytoma
E - endolymphatic sac tumours
L - liver and renal cysts
79
Other diseases found in VHL apart from HIPPEL?
Polycythaemia from EPO overexpression
Epididymal cysts
Papillary cystadenoma of epididymis
Choroid plexus papilloma
80
What is the gene associated with familial adenomatous polyposis syndrome and its inheritance pattern ?
75% FAP is inherited
APC gene
Autosomal dominant
81
Typical age and number of polyps in familial adenomatous polyposis syndrome?
10-15 years old
100 polyps need to be present, can be in the thousands
Note: Often colorectal adenocarcinoma by age 30, almost always by 50. Standard of care is prophylactic colectomy.
82
Where are the extra-colonic polyps located in familial adenomatous polyposis syndrome? And what are other associated conditions to FAP?
Stomach and ampulla of Vater.
Hepatoblastoma, Desmoid tumour, nasopharyngeal angiofibroma, congenital retinal pigment epithelium hypertrophy
83
How is Gardner syndrome different to FAP?
Differences: Multiple osteomas, desmoid tumours, epidermal cysts, thyroid cancer, supernumeray teeth, dentigerous cysts
Similarities: Variant of FAP, APC gene, colorectal adenomas and cancer risk
84
What are important features of juvenile polyposis syndrome
- Autosomal dominant.
- <5 years old
- Hamartomas, mostly in large bowel
- Can cause obstruction or intussusception
- 50% develop colonic adenocarcinoma by age 45 due to dysplasia within hamartoma
- Increased risk of gastric, small bowel and pancreatic cancer
- Pulmonary AV malformation
85
How is Turcot syndrome different from FAP?
Difference: medulloblastoma, glioblastoma
Similarities: Variant of FAP, APC mutation, same colorectal adenomatous polyps and cancer risk
86
What is the most common mutation and its inheritance pattern for Peutz-Jeghers syndrome?
STK11
Autosomal dominant
87
What is characteristic of Peutz-Jeghers? What is the age of presentation? What are the risks associated?
Multiple hamartomatous polyps (usually small bowel, then large bowel then stomach) + mucocutaneous pigmentation.
10-15 years old
Lifetime risk of cancer of 40%.
- Screen from birth for testicular sex-cord stromal tumours
- Late childhood for gastric and small intestine
- 20-30s for colon, pancreatic, breast, ovarian (sex-cord), uterine
88
What is the gene mutation in Marfans syndrome and its inheritance pattern?
70-85% familial
FBN1 gene (extracellular glycoprotein fibrillin-1)
Autosomal dominant
89
Describe the mechanisms that cause Marfans syndrome due to loss of fibrillin
- Loss of support in extracellular matrix (aorta, ligaments and ciliary zonules that support lens)
- Activation of TGF-beta (inflammation, metalloproteases, bony overgrowth, myxoid changes of mitral valve)
90
What is Felty syndrome?
Rheumatoid arthritis, splenomegaly and neutropenia
It is frequently associated with large granular lymphocytic leukaemia
91
A 30 year old presents with sore joints and is positive for anti-citrullinated peptide antibody and rheumatoid factor. What is the diagnosis?
Rheumatoid arthritis
- Females, 20-40
- CD4 helper T cells, TNF most implicated
- Anti-TNF biologics (increased TB risk)
- Synovitis > inflammatory pannus > fibrous ankylosis > bony ankylosis
- 50% genetic. HLA-DR4 related.
- Anti-citrullinated peptide antibody (ACPA/anti-CCP) or RF positive
92
What are some extra-articular manifestations of rheumatoid arthritis?
- Pleural or pericardial effusion, pleural thickening
- Interstitial lung disease (up to 25%, UIP/NSIP/OP)
- Rheumatoid nodules
- Bronchiectasis
- Bronchiolitis obliterans
- Caplan syndrome: association of rheumatoid arthritis with pneumoconiosis
- Pulmonary hypertension
- Episcleritis
- Rheumatoid vasculitis (leukocytoclastic)
- Anaemia from chronic inflammation
- Peripheral neuropathy
93
What antibodies are specific for SLE? What are some other antibodies which can be seen in SLE?
Anti-dsDNA and Anti-Smith
ANA
Antiphospholipid antibodies
Lupus anticoagulant
94
What does SOAP BRAIN MD stand for? (SLE)
S - Serositis (pleuritis, pericarditis, effusions)
O -Oral/nasal ulcer
A - Arthritis (non-erosive synovitis with little deformity, of 2 + joints)
P - Photosensitivity
B - Blood disorders (vasculitis [fibrinoid necrosis], leukopenia, thrombocytopenia, ITP, haemolytic anaemia, antiphospholipid antibody syndrome [clots])
R - Renal disease (glomerulonephritis or tubulointerstitial nephritis, most common cause of death, red cell casts)
A - Antinuclear antibody
I - Immunologic phenomenon
N - Neurological disorders (seizure, myelitis, neuropathy, psychotic event)
M - Malar rash
D - Discoid rash / diffuse alveolar haemorrhage
Can also have non-specific symptoms like fatigue, fever, alopecia
95
What causes a bilateral symmetric sacroilitis?
Ankylosing spondylitis, psoriatic, reactive and enteric-associated arthritis
96
What seronegative spondyloarthritis does enteritis-associated arthritis present similarly to?
Ankylosing spondylitis
97
Typical demographics and three features of scleroderma
50-60 year old, females
Idiopathic condition characterised by; - autoimmune chronic inflammation
- widespread vascular damage
- skin/organ interstitial and perivascular fibrosis
98
What are the two types of scleroderma and blood tests that can be positive?
Diffuse: widespread skin involvement at onset, rapid progression, early visceral involvement.
Limited: skin involvement confined to fingers, forearms, face, with visceral involvement late. May develop CREST syndrome (calcinosis, raynauds, oesophageal dysmotility, sclerodactyly and telangiectasia)
ANA in almost 100% (not specific)
Anti-Scl if pulmonary fibrosis and peripheral vascular disease
Anti-centromere antibody (usually CREST)
99
Typical demographics and positive blood markers in Sjogren syndrome
Women, 50-60
Anti-Ro, Anti-La
ANA
RF
100
Briefly describe primary and secondary Sjogren syndrome
Primary:
- Limited to lacrimal and salivary glands
- Lymphocytic infiltration and fibrosis
- Increased risk of B-cell lymphomas (marginal zone i.e. MALToma)
Secondary (60%):
- Association with other autoimmune diseases
- Rheumatoid arthritis (most common), SLE, polymyositis, scleroderma, vasculitis, mixed connective tissue disease, thyroiditis, primary biliary cirrhosis
- ⅓ extraglandular manifestation: synovitis, pulmonary fibrosis, peripheral neuropathy
101
What are the causes of extramedullary haematopoiesis?
- Congenital haemoglobinopathies (thalassaemia, sickle cell, spherocytosis)
- Myelofibrosis or myelodysplastic syndromes
- Leukaemia
102
What are the causes of haemochromatosis?
Hereditary: HFE mutation, less hepcidin synthesis thus increasing GIT absorption of iron
Secondary: Blood transfusions, iron supplements, increased oral iron intake, chronic liver disease, ineffective erythropoeisis (suppress hepcidin, more GIT absorption)
103
List in order of decreasing severity, the organs where haemosiderin is deposited in iron overload
Hepatocytes of liver (micronodular cirrhosis), pancreas (fibrosis), myocardium, pituitary, adrenal, joints, skin
104
Typical demographics of iron overload and what does it increase the risk of developing significantly?
40-50s, males
200x increased risk of HCC
105
Typical demographics of IgG4 related disease?
Middle aged to older males
106
List some IgG4 related diseases
- Hypertrophic pachymeningitis
- Hypophysitis
- Chronic sclerosing sialadenitis
- Riedel thyroiditis
- Orbital disease (pseudotumour)
- Interstitial pneumonia
- Fibrosing mediastinitis
- Coronary disease
- Autoimmune pancreatitis
- Sclerosing cholangitis
- Sclerosing mesenteritis
- Cholecystitis
- Retroperitoneal fibrosis
- Inflammatory aortic aneurysm
- Prostatitis
107
What are the important features of haemophilia A?
- Factor VIII deficiency (essential co-factor for factor IX)
- X-linked recessive (males + homozygous females)
- 30% sporadic
- Prolonged APTT and normal PT
- Infusions of recombinant factor VIII, antibodies that bind factor IXa to X, bypassing need for factor VIII.
108
What are the important features of haemophilia B?
- Factor IX deficiency
- X-linked recessive
- Prolonged APTT and normal PT
- Recombinant factor IX.
109
What can cause aplastic crisis in sickle cell disease?
Infection by parvovirus B19 causing sudden decrease in red cell population
110
Osteomyelitis due to which pathogen is at increased risk in patients with sickle cell disease?
Salmonella
111
What are the causes of immune thrombocytopenia?
Primary / idiopathic
Secondary (SLE, HIV, B-cell neoplasms)
Drug induced
Usually have megathrombocytes.
Occurs in women <40
Improve post splenectomy, steroids, IVIG, rituximab
Acute occurs quicker and in children, usually postviral. Steroids only if severe.
112
What is the most common mutation in langerhans cell histiocytosis? What are other mutations? What is LCH?
LCH is clonal proliferations of immature dendritic cell called the Langerhan cell, fitting under myeloid neoplasm. It has a proclivity for spontaneous remission
Activating valine-to-glutamate at residue 600 in BRAF (55-60%)
Less common mutations involving Tp53, RAS, MET
113
What is a characteristic histological finding in LCH?
Birbeck granules in cytoplasm is characteristic.
The neoplasms express HLA-DR, S100 and CD1a
114
What are the 3 types of LCH?
- Multifocal multisystem LCH
- Unifocal / multifocal unisystem LCH
- Pulmonary LCH
115
What are the 5 classifications of lymphomas? And list a few examples in each
1. Precursor B cell neoplasms (immature B cells)
- B-ALL (leukaemia/lympoma)
2. Peripheral B cell neoplasms (mature B cells)
- CLL / SLL
- Follicular
- DLBCL
- Burkitt
- Mantle cell
- Marginal
3. Precursor T cell neoplasms (immature T cells)
- T-ALL (leukaemia/lympoma)
4. Peripheral T cell and NK-cell neoplasms (mature)
- Peripheral T cell lymphoma not specified
- Anaplastic large cell lymphoma
- Adult T-cell lymphoma/leukaemia
- Extranodal NK/T cell lymphoma
5. Hodgkin lymphomas (neoplasms of Reed-Sternberg cells)
- Classic Hodgkins lymphoma (nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte-deplete)
- Non-classic Hodgkins lymphoma
116
General differences between non-hodgkins and hodgkins lymphoma
NHL: Involves multiple peripheral nodes, non-contiguous spread, often extranodal presentation
HL: Often localised to single axial group of nodes (cervical, mediastinal, para-aortic) with contiguous spread, not usually extranodal presentation
117
What is the pathogenesis of myeloma?
B-cell proliferation of neoplastic plasma cells which synthesise monoclonal Ig (M complement) and free light chains (Bence Jones proteins)
Factors produced by the neoplastic plasma cells mediate bone destruction by augmenting osteoclasts (also causes hypercalcaemia)
Renal dysfunction thought to be due to toxic effects of Bence Jones proteins
118
What is the CRAB criteria and what is it used for?
Diagnosis of multiple myeloma
C: hyperCalcaemia
R: Renal dysfunction
A: Anaemia
B: Bone lesions
Other ways to help diagnose MM:
- Bone marrow biopsy showing plasma cells
- Electrophoresis and immunofixation
- Serum Ig, urine bence-jones
119
Typical demographics and most common causes of death in multiple myeloma
65-70 year old, males
1. Infection
2. Renal dysfunction
120
Poor prognostic factors for multiple myeloma
TP53
MYC (aggressive)
High IL6
121
Common histological findings in multiple myeloma
Eccentric nucleus, plasmablasts or bizarre multinucleated cells, flame cells, Mott cells (grapelike cytoplasmic droplets), Russell bodies (cytoplasmic globular inclusions), Dutcher bodies (nuclear inclusions), Rouleaux formation (high levels of M protein causing linear arrays of red cells)
122
What are the typical demographics and common presentations of sarcoidosis?
Adults <40, female
Bilateral hilar lymphadenopathy or parenchymal lung involvement (90% of cases), then eyes 25% (iritis) and skin (erythema nodosum).
123
What are the typical demographics, commonly positive blood marker and pathophysiology of GPA?
40s, males
PR3-ANCA positive
T cell mediated hypersensitivity response
Pathology Quiz
flashcards
Decks in class (15)
# Cards
-
O&G131
-
Multi-system/genetics123
-
Cardiothoracic - Heart/Vascular/Mediastinum97
-
Head and Neck163
-
MSK115
-
RBC and WBC13
-
Spine85
-
Abdomen - Gastrointestinal tract111
-
Abdomen - HPB + pancreas104
-
Abdomen - GU tract incl male genitalia136
-
Abdomen - Adrenal, spleen, peritoneum48
-
Breast65
-
CNS - excluding neoplastic103
-
CNS - neoplastic89
-
Cardiothoracic - Chest168
