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Laz's Path Questions > Histopathology (Laz's) > Flashcards

Histopathology (Laz's) Flashcards

1
Q

Where do non-traumatic intraparenchymal haemorrhages tend to occur most frequently?

A

Basal ganglia

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2
Q

Define cavernous angioma.

A

Well-defined malformative lesion composed of closely-packed vessels with no parenchyma interposed between vascular spaces
NOTE: it is similar to an arteriovenous malformation but there is no brain substance wrapped up amongst the vessels
NOTE: these tend to bleed at lower pressure causing recurrent small bleeds
NOTE: shows target sign on MRI

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3
Q

What is the biggest cause of death in people < 45 years?

A

Traumatic brain injury

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4
Q

Describe the Braak stages of Alzheimer’s disease.

A

Stage 1: tau pathology in the transentorhinal cortex
Stage 2: posterior hippocampus
Stage 3: immunostaining is visible by eye, affects substantia nigra
Stage 4: superior temporal gyrus
Stage 5: peristriate cortex
Stage 6: striate cortex
NOTE: clinically, symptoms tend to arise in stage 3 or 4

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5
Q

What is the diagnostic gold standard for Parkinson’s disease?

A

Alpha-synuclein immunostaining

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6
Q

What are three important differentials to consider in a patient with Parkinson’s disease?

A

Multiple system atrophy
Corticobasal degeneration
Progressive supranuclear palsy

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7
Q

What is multisystem atrophy?

A

It is an alpha-synucleinopathy like Parkinson’s disease which targets glial cells
It presents similarly to Parkinson’s disease
It mainly affects the cerebellum so the patients are more likely to present with falls

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8
Q

What are the main histological features of Pick’s disease?

A

Marked gliosis and neuronal loss
Balloon neurones
Tau-positive Pick bodies
NOTE: mutations in tau are associated with a fronto-temporal dementia phenotype often associated with Parkinson’s disease
NOTE: there are 17 autosomal dominant syndromes resulting from mutations in tau

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9
Q

Which gene encodes tau?

A

17q21

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10
Q

Describe how the types of tau present in Alzheimer’s disease is different from CBD, PSP and Pick’s disease.

A

Alzheimer’s – when the tau is put through a Western blot, it will form 3 dense bands. If this is dephosphorylated it will show all 6 isoforms of tau
CBD and PSP – produces 2 dense bands which, when dephosphorylated, are shown to be made up of only 4R tau (i.e. it is a 4R tauopathy)
Pick’s disease – it is a 3R tauopathy

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11
Q

What is a characteristic feature of frontotemporal dementia associated with progranulin mutations?

A

Atrophy tends to be unilateral

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12
Q

Which other protein is thought to be implicated in some types of fronto-temporal dementia?

A

TDP-43 (trafficking protein)

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13
Q

On a cellular level, what insult results in ARDS?

A

Acute damage to the endothelium and/or alveolar epithelium

The basic pathology is the same regardless of cause: diffuse alveolar damage

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14
Q

Outline the pathophysiology of ARDS.

A

Exudative phase – the lungs become congested and leaky
Hyaline membranes – form when serum protein that is leaked out of vessels end up lining the alveoli
Organising phase – organisation of the exudates to form granulation tissue sitting within the alveolar spaces

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15
Q

Describe how the pattern of alveolar damage is different with smoking compared to alpha-1 antitrypsin deficiency.

A

Smoking – centrilobular damage

Alpha-1 antitrypsin deficiency – panacinar (throughout the lungs)

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16
Q

Where is the CFTR gene found?

A

7q31.2

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17
Q

What are the histopathological stages of lobar pneumonia?

A

Stage 1: congestion (hyperaemia and intra-alveolar fluid)
Stage 2: red hepatisation (hyperaemia, intra-alveolar neutrophils)
Stage 3: grey hepatisation (intra-alveolar connective tissue)
Stage 4: resolution (restoration of normal tissue architecture)

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18
Q

Describe the histological appearance of atypical pneumonia.

A 
Interstitial inflammation (pneumonitis) without accumulation of intra-alveolar inflammatory cells 
NOTE: causes include Mycoplasma, viruses, Coxiella and Chlamydia
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19
Q

Where do squamous cell carcinomas tend to arise?

A

Centrally – arising from the bronchial epithelium
NOTE: there is an increasing incidence of peripheral squamous cell carcinomas (possibly due to deeper inhalation of modern cigarette smoke)

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20
Q

What is the precursor lesion for adenocarcinoma of the lung?

A

Atypical adenomatous hyperplasia (proliferation of atypical cells lining the alveolar walls)

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21
Q

Which mutations are associated with adenocarcinoma in smokers?

A

Kras
Issues with DNA methylation
P53

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22
Q

Which mutations are associated with adenocarcinoma in non-smokers?

A

EGFR

EML4-ALK

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23
Q

List some common mutations seen in small cell lung cancer.

A

P53

RB1

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24
Q

Which molecular changes are important to test for in adenocarcinoma?

A

EGFR (responder or resistance)
ALK translocation
Ros1 translocation

NOTE: it is important to correctly identify the type of lung cancer because of treatment implications. E.g. bevacizumab can cause fatal pulmonary haemorrhage in squamous cell carcinoma

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25
Q

Which stain is used for melanin?

A

Fontana stain

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26
Q

Which stain is used for amyloid?

A

Congo Red

When viewed under polarised light, it produces apple green birefringence

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27
Q

What is a key immunological lymphoid marker?

A

CD45

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28
Q

List some tumour-like conditions of the bone.

A 
Fibrous dysplasia 
Metaphyseal fibrous cortical defect/non-ossifying fibroma
Reparative giant cell granuloma
Ossifying fibroma
Simple bone cyst
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29
Q

What is fibrous dysplasia?

A

Condition in which fibrous tissue develops in place of normal bone tissue
Can occur in any bone but ribs and proximal femur is most common
Tends to affect patients < 30 years
Causes soap bubble osteolysis on X-ray

NOTE: giant cell tumours can also have a soap bubble appearance on X-ray but tend to affect the bones around the knee

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30
Q

Which eponymous syndrome is characterised by polyostotic fibrous dysplasia?

A

McCune Albright Syndrome – polyostotic fibrous dysplasia + endocrine problems (precocious puberty) + rough border café-au-lait spots

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31
Q

Which mutation causes fibrous dysplasia?

A

GNAS mutation Chr 20 q13 (mutation in a G-protein)

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32
Q

Describe the histological appearance of fibrous dysplasia.

A

The marrow is replaced by fibrous stroma with rounded trabecular bone (‘Chinese letters’)

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33
Q

What is an enchondroma and which bones tend to be affected?

A

A cartilaginous proliferation within the bone
Most tend to be found in the hands and can cause pathological fractures
X-ray may show popcorn calcification
Associated with Ollier’s syndrome and Maffuci syndrome

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34
Q

Which cancers in children tend to spread to the bone?

A 
Neuroblastoma 
Wilm’s tumour 
Osteosarcoma 
Ewing’s sarcoma 
Rhabdomyosarcoma
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35
Q

Describe the X-ray appearance of osteosarcoma.

A

Usually metaphyseal
Lytic
Elevated periosteum (Codman’s triangle)
Sunburst appearance

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36
Q

Describe the X-ray appearance of chondrosarcoma.

A

Lytic with fluffy calcification

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37
Q

List the histological subtypes of chondrosarcoma.

A 
Conventional (myxoid or hyaline) 
Clear cell (low grade) 
Dedifferentiated (high grade) 
Mesenchymal 
NOTE: myxoid = composed of clear, mucoid substance
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38
Q

What is an Ewing’s sarcoma?

A

Highly malignant small round cell tumour
Occurs in people < 20 years old
MIC2 (CD99) antibody

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39
Q

Which genetic abnormality is associated with Ewing’s sarcoma?

A

Chromosomal translocation 11:22 (EWSR1/FLI1) (q24:q12)

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40
Q

List three types of soft tissue tumour.

A

Liposarcoma
Spindle cell sarcoma
Pleomorphic sarcoma

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41
Q

Outline the coding used by cytopathologists when assessing breast aspirates.

A 
C1 = inadequate 
C2 = benign
C3 = atypia, probably benign
C4 = suspicious of malignancy
C5 = malignant
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42
Q

Describe the histology of fibroadenoma.

A

Consists of lots of glandular and stromal cells

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43
Q

What are the two different types of intraductal papilloma

A

Peripheral papilloma – arises in small terminal ductules

Central papilloma – arises in large lactiferous ductules

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44
Q

What is a radial scar?

A

A benign sclerosing lesion characterised by a central zone of scarring surrounded by a radiating zone of proliferating glandular tissue

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45
Q

fDescribe the histological appearance of radial scars.

A

Central stellate area with proliferation of ducts and acini in the periphery

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46
Q

What is flat epithelial atypia/atypical ductal hyperplasia?

A

May be the earliest precursor to low grade DCIS

There are multiple layers of epithelial cells and the lumens become more regular

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47
Q

What is ductal carcinoma in situ?

A

A neoplastic intraductal epithelial proliferation in the breast that has not breached the basement membrane

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48
Q

What is in situ lobular neoplasia?

A

A solid proliferation of cells within the acinus

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49
Q

Describe the histological appearance of low grade DCIS.

A

Lumens are compact and regular (cribriform (punched out) appearance)
Rapid death and proliferation of cells leads to calcification

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50
Q

Describe the two genetic pathways that result in DCIS.

A

Low grade – arise from low grade DCIS or in situ lobular neoplasia and show 16q loss
High grade – arise from high grade DCIS and show complex karyotypes with unbalanced chromosomal aberrations

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51
Q

Describe the histological appearance of:

a. Invasive ductal carcinoma
b. Invasive lobular carcinoma
c. Invasive tubular carcinoma
d. Invasive mucinous carcinoma

A

a. Invasive ductal carcinoma
Cells are pleomorphic and have large nuclei
b. Invasive lobular carcinoma
Cells have a linear arrangement and are monomorphic
NOTE: cords of cells are sometimes referred to as ‘Indian File’ pattern
c. Invasive tubular carcinoma
Elongated tubules of cancer cells invade the stroma
d. Invasive mucinous carcinoma
Lots of ‘empty’ spaces containing mucin

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52
Q

Describe the histological appearance of Basal-like carcinoma.

A

Sheets of markedly atypical cells with a prominent lymphocytic infiltrate
Central necrosis is common

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53
Q

Describe the immunohistochemistry findings in Basal-like carcinoma.

A

Positive for basal cytokeratins - CK5/6 and CK14

NOTE: basal-like carcinoma is associated with BRCA mutations

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54
Q

Which histological grading system is used for invasive breast carcinoma?

A

Nottingham modification of the Bloom-Richardson system

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55
Q

Outline the coding of biopsies for suspicious breast lumps.

A 
B1 = normal breast tissue 
B2 = benign abnormality 
B3 = lesion of uncertain malignant potential 
B4 = suspicious of malignancy 
B5 = malignancy (a = DCIS; b = invasive carcinoma)
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56
Q

Describe the histology of gynaecomastia.

A

Epithelial hyperplasia with finger-like projections extending into the duct lumen
Periductal stroma is often cellular and oedematous
Similar to fibroadenoma

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57
Q

List some causes of thyrotoxicosis that are not associated with the thyroid gland.

A

Struma ovarii – ovarian teratoma with ectopic thyroid hormone production
Factitious thyrotoxicosis – exogenous thyroid hormone intake

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58
Q

Describe the histology of Hashimoto’s thyroiditis.

A

There are lots of lymphoid cells with germinal centres

The epithelial cells become large with lots of eosinophilic cytoplasm (Hurthle cells)

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59
Q

List the four types of thyroid cancer in order of decreasing prevalence.

A

Papillary (80%)
Follicular (15%)
Medullary (5%)
Anaplastic

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60
Q

What is the diagnosis of papillary thyroid cancer based on?

A

Nuclear features
• Optically clear nuclei
• Intranuclear inclusions (Orphan Annie eye)
There may also be psammoma bodies (little foci of calcification)
Usually non-functional
On histology, they have a papillary structure (central connective tissue stalk with surrounding epithelium)

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61
Q

Where does follicular thyroid cancer tend to metastasise?

A

Lungs, bone and liver (via the bloodstream)

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62
Q

What are the parathyroid glands derived from?

A

Developing pharyngeal pouches

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63
Q

What are the causes of hyperaldosteronism?

A

35% adenoma (Conn’s syndrome)
60% bilateral adrenal hyperplasia

NOTE: Meeran’s website says Conn’s is more common but this may have changed recently

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64
Q

List three causes of acute primary adrenal failure.

A

Haemorrhage
DIC associated with sepsis (Waterhouse-Friderichson syndrome)
Sudden withdrawal of corticosteroid treatment

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65
Q

Which tumours are associated with the different types of MEN?

A 
MEN1 = pituitary + parathyroid + pancreatic islet cell 
MEN2 = parathyroid + medullary thyroid cancer + phaeochromocytoma 
2B = + marfanoid appearance + mucosal neuromas
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66
Q

List three autoantibodies found in SLE. Which is most specific?

A

Anti-dsDNA
Anti-smith (against ribonucleoproteins) – most specific but low sensitivity
Anti-histone – drug-related (e.g. hydralazine)

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67
Q

How is anti-dsDNA measured?

A

Incubate the patient’s serum with Crithidia Luciliae (protozoan)
It has a big organism with dsDNA (kinetoplast) so if the patient has anti-dsDNA antibodies it will bind to the dsDNA in the kinetoplast
NOTE: it can also be measured with ELISA

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68
Q

Describe the appearance of skin histology in SLE.

A

Lymphocytic infiltration of the dermis
Vacuolisation (dissolution of the cells) of the basal epidermis
Extravasation of blood causes a rash
Immunofluorescence will show immune complex deposition at the epidermis-dermis junction

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69
Q

Describe the appearance of renal histology in SLE.

A

Glomerular capillaries are thickened (wire-loop capillaries) due to immune complex deposition
NOTE: this can be visualised by immunofluorescence

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70
Q

What is the name of non-infective endocarditis associated with SLE?

A

Libman-Sacks endocarditis

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71
Q

What is the localised form of scleroderma called?

A

Morphoea

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72
Q

What pattern of ANA immunofluorescence is seen in scleroderma?

A

Nucleolar

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73
Q

What ANA immunofluorescence pattern is seen in mixed connective tissue disease?

A

Speckled

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74
Q

What criteria is used to classify vasculitides based on the size of the vessel?

A

Chapel Hill Criteria

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75
Q

What is polyarteritis nodosa? What are its main features?

A

A necrotising arteritis which is focal and sharply demarcated
It heals by fibrosis and mainly affects the renal and mesenteric vessels
May present with gut ischaemia or renal impairment
It produces a rosary beads appearance on angiography due to multiple aneurysms
Associated with hepatitis B

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76
Q

Which antibody is associated with granulomatosis with polyangiitis?

A

cANCA – against proteinase 3

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77
Q

Which antibody is associated with Churg-Strauss syndrome?

A

pANCA – against myeloperoxidase

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78
Q

List some gynaecological infections that cause serious complications.

A

Chlamydia (infertility)
Gonorrhoea (infertility)
Mycoplasma (spontaneous abortion and chorioamnionitis)
HPV (cancer)

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79
Q

What feature of high risk HPV viruses are responsible for the carcinogenic effects of HPV?

A

E6 protein – inactivates p53

E7 protein – inactivates retinoblastoma

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80
Q

What are the two types of HPV infection? Describe them.

A

Latent (non-productive)
• HPV DNA continues to reside within basal cells
• Infectious virions are not produced
• Replication of viral DNA is coupled to replication of epithelial cells
• This means that complete viral particles are not produced
• Cellular effects of HPV are not seen
Productive
• Viral DNA replication occur independently of host chromosomal DNA synthesis
• Large amount of viral DNA and infectious virions are produced
• Characteristic cytological and histological features are seen (halo around the nucleus – koilocyte)

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81
Q

Other than CIN, what else is screened for in some centres?

A

High risk HPV using molecular genetic analysis
Hybrid capture II (HC2) HPV DNA Test – smear is mixed with fluid containing RNA probes that match 5 low-risk and 13 high-risk types of HPV

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82
Q

List some causes of endometrial hyperplasia.

A

Persistent anovulation (due to persistently raised oestrogen)
PCOS
Granuloma cell tumour of the ovary
Oestrogen therapy

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83
Q

List some risk factors for endometrial carcinoma.

A

Nulliparity
Obesity
Diabetes mellitus
Excessive oestrogen stimulation

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84
Q

What are the subtypes of type I endometrial carcinoma?

A

Endometrioid adenocarcinoma
Mucinous adenocarcinoma
Secretory adenocarcinoma
NOTE: tends to occur in younger patients, low grade and oestrogen-dependent, arises from atypical endometrial hyperplasia

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85
Q

What are the subtypes of type II endometrial carcinoma?

A

Serous and clear cell tumours

NOTE: occurs in older patients, less oestrogen-dependent and arises in atrophic endometrium

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86
Q

Which genetic mutations are associated with the two types of type II endometrial carcinoma?

A 
Endometrial Serous Carcinoma
•	P53 (90%)
•	P13KCA (15%) Her2 amplification	
Clear Cell Carcinoma
•	PTEN
•	CTNNB1
•	Her2 amplification
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87
Q

What are the chances of moles progressing to malignancy?

A

NO partial moles progress to malignancy
2.5% of complete moles progress to malignancy
10% of complete moles develop into locally destructive invasive moles

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88
Q

Describe how complete and partial moles form.

A

Complete mole
• Occurs when you get fertilisaiton of an EMPTY egg
• Reduplication of the 23X from sperm results in a homozygous diploid 46XX genome
• Can also occur due to fertilisation of an empty egg by 2 sperms with 2 independent sets of 23X or 23Y
Partial mole
• A normal ovum containing 23X gets fertilised by TWO sperm leading to the presence of 3 sets of chromosomes (2 paternal + 1 maternal)
• Dispermia  diandry
• Overdose of male chromosomes drive proliferation
• Can also occur due to fertilisation of a normal egg by a sperm carrying unreduced paternal genome (46XY)

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89
Q

List two types of non-neoplastic functional cysts.

A

Follicular and luteal cysts

Endometriotic cyst

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90
Q

List three types of primary specific ovarian tumour.

A

Surface epithelial tumours
Sex cord stromal tumours
Germ cell tumours

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91
Q

Outline the classification of epithelial ovarian tumours.

A 
Type 1
•	Low grade 
•	Relatively indolent and arise from well characterised precursors (benign tumours) and endometriosis 
•	Mutations: K-Ras, BRAF, P13KCA, Her2, PTEN, beta-catenin
Type 2
•	HIGH GRADE
•	Aggressive 
•	P53 mutation in 75% of cases 
•	NO precursor lesion
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92
Q

Give examples of Type 1 and Type 2 ovarian tumours.

A

Type 1 = low grade serous, endometrioid, mucinous and clear cell
Type 2 = mostly serous

NOTE: endometrioid has a better prognosis than mucinous or serous

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93
Q

List some benign ovarian tumours.

A

Serous cystadenoma
Cystadenofibroma
Mucinous cystadenoma
Brenner tumour

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94
Q

What are the key features of serous tumours?

A

MOST COMMON type of ovarian tumour
Usually cystic
30-50% bilateral
Benign tumours are lined by bland epithelium
Borderline tumours have a more complex, atypical epithelial lining with papillae but no invasion through the basement membrane
Malignant tumours are invasive with a poor prognosis

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95
Q

Which type of ovarian tumour has a strong association with endometriosis?

A

Clear cell tumours

NOTE: endometrioid tumours are associated about 20% of the time

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96
Q

List four types of sex cord stromal tumours and the hormones that they may produce.

A

Fibroma (no hormone production)
Granulosa cell tumour (may produce oestrogen)
Thecoma (may produce oestrogen (rarely androgens))
Sertoli-Leydig cell tumour (may be androgenic)

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97
Q

What are the four main types of germ cell tumour?

A

Dysgerminoma – no differentiation
Teratoma – from embryonic tissues
Endodermal sinus tumour – from extraembryonic tissue (e.g. yolk sac)
Choriocarcinoma – from trophoblastic cells which would form the placenta

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98
Q

What are the key features of an immature teratoma?

A

Indicates presence of embryonic elements (most commonly neural tissue)
Malignant tumour that grows rapidly, penetrates the capsule and forms adhesions
Spreads within peritoneal cavity and metastasises to the lymph nodes, lungs, liver and other organs

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99
Q

Name two secondary ovarian tumours.

A

Krukenberg Tumour – bilateral metastases composed of mucin-producing signet ring cells (usually from breast or gastric cancer)
Metastatic colorectal cancer

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100
Q

List three familial syndromes associated with ovarian cancer.

A

Familial breast-ovarian cancer syndrome
Site-specific ovarian cancer
Cancer family syndrome (Lynch type II)

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101
Q

List some specific genetic associations for serous, mucinous and endometrioid carcinoma.

A

Serous – BRCA

Mucinous and endometrioid - HNPCC

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102
Q

Name a benign tumour of the vulva.

A

Papillary hidradenoma

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103
Q

Which arteries tend to be involved in myocardial infarction (in order of most to least frequent)?

A

LAD – 50%
RCA – 40%
LCx – 10%

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104
Q

Describe the microscopic changes that take place in myocardial infarction.

A

Under 6 hours – normal histology
6-24 hours – loss of nuclei, homogenous cytoplasm, necrotic cell death
1-4 days – infiltration of polymorphs then macrophages
5-10 days – removal of debris
1-2 weeks – granulation tissue, new blood vessels, myofibroblasts, collagen synthesis
Weeks to months – strengthening and decellularising the scar

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105
Q

What is reperfusion injury?

A

Consequence of letting blood go back into the area of myocardial necrosis
Oxidative stress, calcium overload and inflammation cause further injury
Arrhythmias are common
It can cause stunned myocardium – reversible cardiac failure lasting several days

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106
Q

What is hibernating myocardium?

A

Chronic sublethal ischaemia leads to lower metabolism in myocytes which can be reversed with vascularisation

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107
Q

Outline the histology of heart failure.

A

Dilated heart
Scarring and thinning of the walls
Fibrosis and replacement of ventricular myocardium

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108
Q

What is dilated cardiomyopathy?

A

Caused by progressive loss of myocytes leading to a dilated heart

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109
Q

What is hypertrophic cardiomyopathy?

A

Thickening of the heart muscle
Family history in 50% of cases
Some are associated with a specific abnormality in the beta-myosin heavy chain

NOTE: other mutations include myosin binding protein-C and troponin T

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110
Q

Which valve is most commonly affected in rheumatic valvular disease?

A

Left-sided valves (almost always mitral)

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111
Q

How is the arrangement of endothelial cells in the liver different from other parts of the body?

A

The endothelial cells do not sit on a basement membrane and the endothelium is discontinuous (there are no tight junctions)

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112
Q

What is the role of stellate cells and what could happen to them when activated?

A

Storage of vitamin A

When activated, they become myofibroblasts that lay down collagen (this is responsible for scarring in liver disease)

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113
Q

Outline the arrangement of structures within a normal liver.

A

There will be portal tracts consisting of a branch of the hepatic artery, a branch of the portal vein and a bile duct
Blood will flow from the portal tract to the central vein
There is a ring of collagen around the portal tract called the limiting plate
There are three zones of hepatocytes in between the portal tract and the central vein
Zone 3 is closest to the central vein and contains the most metabolically active enzymes

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114
Q

Describe the arrangement of hepatocytes, endothelial cells, stellate cells and Kupffer cells in a normal liver.

A

There are spaces in between endothelial cells and there is a gap in between the endothelial cells and the hepatocytes (space of Disse)
Stellate cells sit within the space of Disse
Kupffer cells are found within the sinusoids
Blood can easily get through the spaces in the endothelial cells into the space of Disse where they are exposed to hepatocytes

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115
Q

Describe how the arrangement of cells changes in liver disease.

A

Kupffer cells become activated (inflammatory response)
Endothelial cells stick together so blood finds it more difficult to get into the space of Disse
Stellate cells become activated and secrete basement membrane-type collagens into the space of Disse
Hepatocytes lose their microvilli
All these changes make it difficult for blood to be exposed to hepatocytes

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116
Q

What is a common histological feature of all acute hepatitis?

A

Spotty necrosis

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117
Q

What is interface hepatitis?

A

Aka piecemeal hepatitis
Inflammation crosses the limiting plate making it difficult to distinguish where the portal tract ends and the hepatocytes begin
Characteristically seen in chronic viral hepatitis and autoimmune hepatitis

Portal inflammation = inflammation confined within limiting place
Lobular inflammation = inflammation across entire lobule

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118
Q

List some histological features of alcohol hepatitis.

A

Ballooning – cell swelling
Mallory Denk bodies/Mallory hyaline - pink intracellular material
Apoptosis
Pericellular fibrosis

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119
Q

In which part of the liver do the histological features of alcoholic hepatitis tend to be seen and why?

A

Zone 3
Alcohol is not toxic, but acetaldehyde is toxic
Zone 3 cells contain the most alcohol dehydrogenase thereby producing the most acetaldehyde
Furthermore, by the time blood reaches zone 3 (after passing zones 1 and 2) it is relatively hypoxic making the cells in zone 3 even more vulnerable to damage

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120
Q

What is primary biliary cholangitis?

A

Autoimmune conditions characterised by bile duct loss associated with chronic inflammation (with granulomas)

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121
Q

What is the diagnostic test for PBC?

A

Anti-mitochondrial antibodies (AMA)

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122
Q

What is the histological appearance of PBC?

A

Bile ducts surrounded by epithelioid macrophages, suggestive of chronic granulomatous destruction of bile ducts

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123
Q

What is primary sclerosing cholangitis?

A

Autoimmune condition characterised by periductal bile duct fibrosis leading to loss of bile ducts
NOTE: in PBC, bile duct loss is caused by inflammation, whereas in PSC it is caused by fibrosis
NOTE: PSC is associated with ulcerative colitis and is associated with an increased risk of cholangiocarcinoma

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124
Q

What is the diagnostic test for PSC?

A

Bile duct imaging

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125
Q

What causes haemochromatosis and which gene is implicated?

A

Caused by increased gut iron absorption
HFe gene on chromosome 6
NOTE: women tend to present later because they have naturally lower iron levels

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126
Q

What is haemosiderosis?

A

Type of iron overload characterised by the accumulation of iron in macrophages
Usually occurs as a result of receiving blood transfusions

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127
Q

What is Wilson’s disease?

A

Characterised by an accumulation of copper due to the failure of excretion of copper by hepatocytes into the bile
Low serum copper, low caeruloplasmin, high urine copper
Rhodanine stain
NOTE: treated with penicillamine (copper chelator)

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128
Q

How is autoimmune hepatitis diagnosed?

A

Type 1: Anti-smooth muscle antibodies (ASMA), anti-soluble liver antigen, ANA
Type 2: anti-LKM, associated with IgA deficiency

NOTE: type 2 tends to present at a younger age (paediatrics) and has a poor response to steroids

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129
Q

Which precursor lesion has the highest risk of developing into breast cancer?

A

In situ lobular neoplasia

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130
Q

Which gene is mutated in Wilson disease?

A

ATP7B on chromosome 13

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131
Q

What are the stages of lupus nephritis?

A

Class I: minimal mesangial lupus nephritis with immune complexes but no structural alteration
Class II: mesangial proliferative lupus nephritis with immune complexes and mild/mod increase in mesangial matrix and cellularity
Class III: focal lupus nephritis with active swelling and proliferation in less than half the glomeruli
Class IV: diffuse lupus nephritis with involvement of more than half the glomeruli
Class V: membranous lupus nephritis with subepithelial immune complex deposition
Class VI: advanced scleroising with complete sclerosis of >90% of the glomeruli.

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132
Q

What are some common associations of polycystic kidney disease?

A 
Hepatic cysts (and cirrhosis with PKD1) 
Berry aneurysms)
Mitral valve prolapse
Aortic root dilatation 
Abdominal wall hernias
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133
Q

Which antibody is associated with drug-induced lupus?

A

Anti-histone

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134
Q

What is the most common type of lung cancer?

A

Adenocarcinoma

NOTE: this is the most common cause of lung cancer in both smokers and non-smokers

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135
Q

Describe how alcohol can cause acute pancreatitis.

A

It leads to spasm/oedema of the sphincter of Oddi and the formation of protein-rich pancreatic fluid which is thick and causes an obstruction
NOTE: most other causes of acute pancreatitis will do so via direct acinar injury

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136
Q

Describe the three main patterns of injury in acute pancreatitis and describe what they result from.

A

Periductal – necrosis of acinar cells near ducts (usually secondary to obstruction)
Perilobular – necrosis at the edges of the lobules (usually due to poor blood supply)
Panlobular – results from worsening periductal or perilobular inflammation

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137
Q

List some complications of acute pancreatitis.

A

Pseudocyst formation, abscesses
Shock
Hypoglycaemia
Hypocalcaemia

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138
Q

List some complications of chronic pancreatitis.

A

Malabsorption
Diabetes mellitus
Pseudocysts
Pancreatic carcinoma

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139
Q

What is the characteristic feature of autoimmune pancreatitis?

A

Large numbers of IgG4 positive plasma cells typically found around the ducts

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140
Q

What are the two types of pancreatic cancer and which is more common?

A

Ductal (85%)
Acinar (15%)
NOTE: many ductal carcinomas may actually arise from acini after a process called acini-ductal metaplasia (these ductal carcinomas have a different natural history to truly ductal carciomas)

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141
Q

Name two types of cystic neoplasm of the pancreas.

A

Serous cystadenoma

Mucinous cystadenoma

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142
Q

Name two types of dysplastic precursor lesion that ductal carcinoma can arise from.

A

Pancreatic intraductal neoplasia (PanIN)

Intraductal mucinous papillary neoplasm

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143
Q

Which mutation is very common in pancreatic cancer?

A

K-ras (95%)

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144
Q

Describe the microscopic appearance of ductal carcinoma.

A

Adenocarcinomas (secrete mucin and form glands)

Mucin-secreting glands are set in desmoplastic stroma

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145
Q

By what mechanism does pancreatic cancer cause migratory thrombophlebitis?

A

Circulating pancreatic cancer cells release mucous which activates the clotting cascade

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146
Q

What can be measured as a screening test for neuroendocrine tumours?

A

Chromogranin

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147
Q

What are the two types of gallstone and what are their distinguishing features?

A 
Cholesterol
•	May be single 
•	Mostly radiolucent (NOT seen on AXR)
Pigment 
•	Often multiple 
•	Contain calcium salts of unconjugated bilirubin 
•	Mostly radio-opaque
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148
Q

What is the term used to describe diverticula of the gallbladder? How do they form?

A

Rokitansky-Aschoff sinuses – form as a result of the gallbladder contracting against an obstruction

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149
Q

Describe the role of the following parts of the nephron:

a. Proximal convoluted tubule
b. Loop of Henle
c. Distal convoluted tubule
d. Collecting duct

A

a. Proximal convoluted tubule
Actively absorbs sodium
Carriers out hydrogen exchange to allow carbonate resorption
Co-transport of amino acids, phosphate and glucose
Reabsorption of potassium
b. Loop of Henle
Descending limb and thin ascending limb: permeable to water, impermeable to ions and urea
Ascending limb: actively resorbs sodium and chloride
This creates a counter-current multiplier that is aligned with the vasa recta
c. Distal convoluted tubule
Impermeable to water
Regulates pH by active transport of protons and bicarbonate
Regulates sodium and potassium by active transport (aldosterone)
Regulates calcium (PTH, 1,25-dihydroxy vitamin D)
d. Collecting duct
Reabsorb water (principal cells, ADH)
Regulates pH (intercalated cells, proton excretion)

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150
Q

What is the inheritance pattern of polycystic kidney disease and which genes are implicated?

A

Autosomal dominant (most of the time)
Genes: PKD1 (Chr16) and PKD2 (Chr4)
NOTE: PKD is associated with an increased risk of berry aneurysms (and subarachnoid haemorrhage)

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151
Q

How does acute tubular injury lead to reduced GFR?

A

Blockage of tubules by casts
Leakage from tubules into interstitial space
Secondary haemodynamic changes

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152
Q

Describe the histological appearance of acute tubulo-interstitial nephritis.

A

Heavy interstitial infiltration with eosinophils and granulomas

Clinical features include oliguria, fever and a rash

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153
Q

What causes crescents to appear in acute glomerulonephritis?

A

Occurs in severe glomerulonephritis due to proliferation of cells within Bowman’s capsule

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154
Q

List some causes of acute crescentic glomerulonephritis.

A

Immune complex deposition
Anti-GBM disease (Goodpasture’s)
Pauci-immune (ANCA)
NOTE: these can rapidly lead to irreversible renal failure

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155
Q

List some causes of immune complex-associated crescentic glomerulonephritis.

A

SLE
IgA nephropathy
Post-infectious glomerulonephritis

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156
Q

What are the antibodies directed against in anti-GBM disease?

A

Against the alpha 3 subunit of type IV collagen

NOTE: these antibodies can cross-react with the alveolar basement membrane leading to pulmonary haemorrhage and haemoptysis

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157
Q

What are the main features of pauci-immune crescentic glomerulonephritis?

A

Scanty glomerular immunoglobulin deposits
Usually associated with ANCA
Triggers neutrophil activation and glomerular necrosis

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158
Q

What is thrombotic microangiopathy?

A

Damage to the endothelium in glomeruli, arterioles and arteries resulting in thrombosis
Red cells can be damaged by fibrin causing MAHA or HUS

Causes include E. coli, ADAMTS13 deficiency, drugs, scleroderma, antiphospholipid syndrome

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159
Q

List some causes of nephrotic syndrome.

A 
Primary glomerular disease (non-immune complex mediated)
•	Minimal change disease 
•	Focal segmental glomerulosclerosis 
Primary renal disease (immune complex mediated)
•	Membranous glomerulonephritis 
Systemic disease 
•	SLE 
•	Amyloidosis 
•	Diabetes mellitus
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160
Q

Describe the histological appearance of focal segmental glomerulosclerois.

A

Some glomeruli are partially scarred
This responds less well to immunosuppression
Associated with sickle cell disease, HIV and heroin use
Most common cause of nephrotic syndrome in Afro-Caribbeans

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161
Q

What is membranous glomerulonephritis?

A

Common cause of nephrotic syndrome in adults
Characterised by immune deposits outside the glomerular basement membrane (subepithelial)
Primary disease is autoimmune
It can occur secondary to epithelial malignancy, SLE, drugs and infections
Thickening of basement membrane shows ‘spike and dome’ pattern

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162
Q

Which antibodies are often found in primary membranous glomerulonephritis?

A

Antibodies against phospholipase A2 type M receptor (PLA2R)

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163
Q

List and describe the stages of diabetic nephropathy.

A

Stage 1: thickening of the basement membrane on electron microscopy
Stage 2: increase in mesangial matrix, without nodules
Stage 3: nodular lesions/Kimmelstein-Wilson nodules
Stage 4: advanced glomerulosclerosis

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164
Q

What is amyloidosis?

A

Deposition of extracellular proteinaceous material exhibiting beta-pleated sheet structure

165
Q

Name two causes of isolated microscopy haematuria.

A

Thin basement membrane

IgA nephropathy

166
Q

What is thin basement membrane disease and what causes it?

A

Basement membrane < 250 nm thickness
Caused by a hereditary defect in type IV collagen synthesis
Microscopic haematuria is the only consequence in most cases

167
Q

What is Alport syndrome?

A

X-linked disease caused by a mutation in the alpha-5 subunit of type IV collagen (some forms affect alpha-3 and alpha-4)
Leads to progressive damage resulting in renal failure in middle-age
Often accompanied by deafness and ocular disease

168
Q

What is IgA nephropathy?

A

Most common cause of glomerulonephritis
Caused by mesangial IgA immune complex deposition
NOTE: Henoch-Schonlein purpura is a type of IgA nephropathy
30% will progress to end-stage renal failure

169
Q

What are some diseases associated with chronic kidney disease?

A

Ischaemic heart disease

Calcium and phosphate derangement (due to resulting hyperparathyroidism, osteomalacia and osteoporosis)

170
Q

What are consequences of hypertensive nephropathy?

A

Shrunken kidneys with granular cortices
Nephrosclerosis on histology (arterial hyalinosis, arterial intimal thickening, ischaemic glomerular changes, segmental and global glomerulosclerosis)

171
Q

What system is used to classify lupus nephritis?

A

ISI/RPS classification

172
Q

What is a key histological feature of the oesophageal mucosa?

A

Presence of submucosal glands

173
Q

What does the body and fundus of the stomach have in abundance?

A

Specialised glands responsible for producing acid and enzymes
E.g. chief cells (pepsinogen) and parietal cells (acid)

174
Q

What are the three layers of the gastric mucosa?

A

Columnar epithelium
Lamina propria
Muscularis mucosa

175
Q

What does the presence of goblet cells in the stomach signify?

A

Intestinal metaplasia

NOTE: goblet cells are not normally seen in the stomach

176
Q

Define dysplasia.

A

Changes showing some of the cytological and histological features of malignancy but with no invasion through the basement membrane

177
Q

What are the main histological features of squamous cell carcinoma of the oesophagus?

A

Cells produce keratin (normal oesophageal squamous epithelium is non-keratinised)
Intercellular bridges

178
Q

What is mucosa-associated lymphoid tissue and what is their presence indicative of?

A

Chronic gastritis caused by H. pylori infection induces lymphoid tissue in the stomach
The presence of lymphoid follicles in a stomach biopsy, is highly suggestive of H. pylori infection
This is important because it is associated with an increased risk of lymphoma

179
Q

Name a key virulence factor that enables H. pylori to cause chronic infection.

A

Cag-A positive H. pylori has a needle-like appendage that injects toxins into intercellular junctions allowing bacteria to attach more easily
Hydrogenase - produces energy by oxidising molecular H2

180
Q

Define gastric ulcer.

A

The depth of the loss of tissue goes beyond the muscularis mucosa (into the submucosa)

181
Q

What are the two main morphological subtypes of gastric adenocarcinoma? What are their key features?

A

Intestinal: well-differentiated, presence of big gland containing mucin
Diffuse: poorly differentiated, composed of single cells with no attempt at gland formation

182
Q

Name two types of diffuse adenocarcinoma of the stomach.

A

Linitis plastica

Signet ring cell carcinoma

183
Q

List some other pathogens that affect the duodenum.

A

CMV
Cryptosporidium
Giardiasis
Whipple’s disease (Tropheryma whippelii)

184
Q

What is lymphocytic duodenitis?

A

When you get the inflammatory changes (increased intraepithelial lymphocytes) without architectural changes
Many people with this condition either have coeliac disease or will go on to develop coeliac disease

185
Q

What is a classic histological feature of HSV infection?

A

Cells with multiple nuclei

186
Q

What are giant cell tumours? Where do they tend to be found and what is their histological appearance?

A

Benign tumour of the bone characterised by the presence of lots of osteoclasts (giant cells)
They tend to be found at the ends of long bones
It has a lytic appearance on X-ray
Histology shows many osteoclasts on a background of spindle/ovoid cells

187
Q

Describe the X-ray appearance of Ewing’s sarcoma.

A

Onion skinning of the periosteum

Lytic with or without sclerosis

188
Q

Describe the histology of intraductal papillomas.

A

Histology will show a large dilated duct with a polypoid mass in the middle
The mass tends to have a fibrovascular core

189
Q

Describe the appearance of usual epithelial hyperplasia.

A

Irregular lumens

190
Q

Describe the histological appearance of high grade DCIS.

A

Cells are large and few lumens left

Cells are pleomorphic and occlude the duct

191
Q

What is histological grading of breast cancer dependent on?

A

Tubule formation
Nuclear pleomorphism
Mitotic activity

Each factor gets a score out of 3

192
Q

What is the most important prognostic factor in invasive breast cancer?

A

Status of axillary lymph nodes

193
Q

What is the most common cause of non-toxic goitre?

A

Iodine deficiency
NOTE: brassicas (e.g. cabbages) interfere with thyroid hormone synthesis
It may also be caused by a hereditary enzyme deficiency

194
Q

What is the most common cause of secondary hyperparathyroidism?

A

Renal failure

195
Q

Describe the vascular histology in scleroderma.

A

Intimal proliferation gives an onion skin appearance

196
Q

Which type of lung cancer is most likely to:
A) Spread to the bone
B) Arise in the periphery

A

A) squamous cell carcinoma

B) adenocarcinoma

197
Q

What is a nutmeg liver suggestive of?

A

Congestive hepatopathy - liver failure due to venous congestion (usually resulting from heart failure)

198
Q

Outline the pathophysiology of bullous pemphigoid.

A

Autoimmune disorder driven by IgG and C3 which attack the basement membrane (hemidesmosomes)

They recruit eosinophils which release elastase which further damages anchoring proteins (anchoring lower keratinocytes to the basement membrane)

Linear deposition of IgG can be seen along BM

199
Q

What is acantholysis?

A

Loss of intercellular connections leading to loss of cohesion between keratinocytes
NOTE: this can occur due to a lot of dermatological conditions so immunofluorescence is needed to identify where the immune-mediated attack is taking place

200
Q

What can neutrophil recruitment to the epidermis in plaque psoriasis cause?

A

Formation of Munro’s microabscesses

201
Q

What is lichen planus and what are its main features?

A

Lichenoid reaction pattern
Pruritic, purple, papules and plaques
Presents with papules and plaques that are slightly purplish in colour on the wrists and arms
In the mouth it presents as white lines (Wickham striae)

202
Q

Which histological feature is classic of seborrhoeic keratosis?

A

Horn cysts – entrapped keratin surrounded by proliferating epidermis
NOTE: the epidermis is proliferating in an orderly manner

203
Q

List some different types of inflammatory reactions patterns in the skin.

A 
Vesiculobullous – forms bullae 
Spongiotic – becomes oedematous 
Psoriasiform – becomes thickened
Lichenoid – forms a sheeny plaque 
Vasculitic – associated with vasculitis 
Granulomatous – associated with granulomas
204
Q

Outline the pathophysiology of pemphigus vulgaris.

A

IgG-mediated disease where the damage is occurring within the keratinocyte layers (intraepidermal bullae)

IgG antibodies target desmosomal proteins
Shows netlike pattern of intercellular IgG deposits

205
Q

Outline the pathophysiology of pemphigus foliaceus.

A

IgG-mediated attack on the outer layer of keratinocytes (where the stratum corneum is found)

206
Q

What is hyperparakeratosis?

A

Thickening of the skin on the surface where the patient has been scratching
The epidermis gets thicker

207
Q

Which layer of the epidermis disappears in plaque psoriasis and why?

A

Stratum granulosum – there is not enough time to form it

NOTE: psoriasis skin turnover time is around 7 days (as opposed to 50 days in normal skin)

208
Q

Describe the histological appearance of lichen planus.

A

Distinction between dermis and epidermis is difficult to see due to lymphocyte-mediated destruction of the bottom layer of keratinocytes
Saw-tooth rete ridges
Hyperparakeratosis
There is band-like lymphocytic infiltration just under the epidermis
NOTE: this is also seen in mycosis fungoides

209
Q

Describe the histological appearance of malignant melanoma.

A

Melanocytes start migrating upwards through the epidermis (pagetoid spread)
They become active and lose the ability to differentiate
Melanoma thickness > 4 mm has a > 50% mortality

210
Q

List some underlying conditions that can lead to the formation of calcium oxalate stones.

A

Absorptive hypercalciuria – excessive calcium absorption from the gut
Renal hypercalciuria – impaired absorption of calcium in the proximal renal tubule
Hypercalcaemia (e.g. hyperparathyroidism)

211
Q

Define papillary adenoma.

A

Benign epithelial kidney tumour composed of papillae and/or tubules
They must be < 15 mm in size
They tend to be well circumscribed

212
Q

What are the genetic associations of papillary adenomas?

A

Trisomy 7 and 17

Loss of Y chromosome

213
Q

What is a renal oncocytoma?

A

Benign epithelial kidney tumour composed of oncocytic cells
They are usually well-circumscribed and usually sporadic
Often an incidental finding

NOTE: an oncocyte is an epithelial cell that has a lot of mitochondria giving it acidophilic, granular cytoplasm

214
Q

Describe the histological appearance of oncocytes.

A

Large cells with pink granular cytoplasm and a prominent nucleolus

215
Q

What is an angiomyolipoma?

A

Benign mesenchymal kidney tumour composed of thick-walled blood vessels, smooth muscle and fat
Derived from perivascular epithelioid cells
NOTE: often an incidental finding but may cause flank pain, haemorrhage and shock (if > 4 cm)

216
Q

Name the subtypes of renal cell carcinoma in order of prevalence.

A

Clear cell renal carcinoma (70%)
Papillary renal cell carcinoma (15%)
Chromophobe renal cell carcinoma (5%)

NOTE: papillary renal cell carcinoma is associated with dialysis

217
Q

What is a common genetic finding in clear cell renal carcinoma?

A

Loss of chromosome 3p

218
Q

Describe the histological appearance of the two types of papillary renal cell carcinoma.

A

Type 1: composed of a single layer of small and flat cells. You see a lot of islands of cells.
Type 2: there is stratification (multi-layering) of the cells
NOTE: type 2 tends to have a worse prognosis than type 1

219
Q

Define chromophobe renal cell carcinoma.

A

Epithelial kidney tumour composed of sheets of large cells that display distinct cell borders, reticular cytoplasm and a thick-walled vascular network
The cells are pale and eosinophilic
NOTE: grossly appears as a well-circumscribed solid brown tumour

220
Q

What grading system is used for clear cell and papillary renal cell carcinoma?

A

ISUP Nuclear Grade

221
Q

What risk progression index is used for clear cell carcinoma?

A

Leibovich risk model

222
Q

What is Nephroblastoma (Wilm’s tumour)?

A

Malignant triphasic kidney tumour of childhood:
• Blastema (small round blue cells)
• Epithelial
• Stromal
Typically present with an abdominal mass in children aged 2-5 years
NOTE: 95% have an excellent prognosis

223
Q

What are the three main subtypes of urothelial carcinoma?

A

Non-invasive papillary urothelial carcinoma
Invasive urothelial carcinoma
Flat urothelial carcinoma in situ

224
Q

Describe the macroscopic appearance of non-invasive papillary urothelial carcinoma.

A

Appears as frond-like growths
Can be divided into low or high grade dependent on nuclear atypia
NOTE: high grade tumours have many genetic aberrations (e.g. RB, TB53)

225
Q

What is a possible mechanism for the onset of BPH?

A

Increased oestrogen with ageing induces androgen receptors and stimulates hyperplasia

226
Q

List some mutations that are implicated in prostate cancer.

A

PTEN
AMACR
P27
GST-pi

227
Q

Which genetic factor is associated with testicular germ cell tumours?

A

Amplification of i12p

228
Q

List the five histological subtypes of testicular germ cell tumours.

A 
Seminoma
Embryonal carcinoma 
Post-pubertal teratoma 
Yolk sac tumour 
Choriocarcinoma
229
Q

Describe the histological appearance of

a. Seminoma
b. Embryonal carcinoma
c. Post-pubertal teratoma
d. Yolk sac tumour
e. Choriocarcinoma

A

a. Seminoma
Mostly made up of clear cells with a prominent lymphocytic infiltrate
b. Embryonal carcinoma
High-grade appearance with prominent nucleoli
c. Post-pubertal teratoma
The tumour is trying to produce a variety of tissues (e.g. keratin, cartilage, glands)
This is malignant – any component of the tumour can become malignant
d. Yolk sac tumour
Smaller cells
Lace-like pattern
Some pink inclusions
e. Choriocarcinoma
Made up of two cell types: cytotrophoblasts (clear looking cells) and syncytiotrophoblasts (multinucleated cell)
NOTE: both components are needed to define choriocarcinoma

230
Q

What is an adenomatoid tumour?

A

Benign tumour consisting of small tubules lined by mesothelial cells

231
Q

List some describe a few types of benign penile diseases.

A

Lichen sclerosus/balanitis xerotica obliterans – inflammatory condition that causes phimosis
Zoon’s balanitis – inflammatory condition that causes red areas
Condylomas – HPV 6 and 11
Peyronie’ disease – scarring, inflammation and thickening of the corpus cavernosa

232
Q

List and describe some benign diseases of the urethra.

A

Urethritis
Prostatic urethral polyp – papillary lesion in the prostatic urethra
Urethral caruncle – common lesion at the urethral meatus in women
NOTE: malignant diseases include urethral carcinoma (squamous cell carcinoma) and malignant melanoma

233
Q

List and describe some diseases of the scrotum.

A

Epidermoid cyst (common)
Scrotal calcinosis
Angiokeratomas (benign vascular lesions)
Fournier’s gangrene – necrotising fasciitis of the scrotum and perineum
Scrotal squamous cell carcinoma

234
Q

List three types of benign renal neoplasm.

A

Papillary adenoma
Renal oncocytoma
Angiomyolipoma

235
Q

Name a syndrome that is associated with renal oncocytoma.

A

Birt-Hogg-Dubé syndrome

236
Q

Which hereditary condition is associated with angiomyolipoma?

A

Tuberous sclerosis

237
Q

Define clear cell renal carcinoma.

A

Epithelial kidney tumour composed of nests of clear cells set in a delicate capillary vascular network
Grossly appears golden-yellow with haemorrhagic areas

238
Q

Define papillary renal cell carcinoma.

A

Epithelial kidney tumour composed of papillae and/or tubules
By definition > 15 mm in size
NOTE: this is the malignant counter part of papillary adenoma. They appear grossly as a fragile, friable brown tumour

239
Q

Describe the histological appearance of chromophobe renal cell carcinoma.

A

Sharply defined cell borders and a thick vascular network

240
Q

What scoring system is used for prostate cancer? Explain how it is calculated.

A

Gleason score
Expressed as x + y = z
Calculated by adding the top two most common patterns/grades seen on histological grading
Higher scores are associated with a poorer prognosis

241
Q

Name three types of testicular non-germ cell tumours.

A

Lymphoma – more in older men, poor prognosis
Leydig cell tumour – may cause precocious puberty (if pre-pubertal)
Sertoli cell tumour – 90% benign

242
Q

Describe the microanatomy of bone.

A

Made up of several micro-columns
Haversian canals are found at the middle of the micro-columns
Volkmann canals are canals that connect the Haversian canals
Around the Haversian canals are concentric lamellae and in between these units will be interstitial lamellae
Around the entire bone you will find circumferential lamellae
In the middle the bone will be trabecular lamellae

243
Q

Which static parameters are measured in the histological analysis of bone in metabolic bone disease?

A

Cortical thickness
Trabecular bone volume
Thickness, number and separation of trabeculae

244
Q

Which technique is used to measure histodynamic parameters when investigating metabolic bone disease?

A

Tetracycline labelling

245
Q

What are the effects of long-term steroid use on bone?

A

Affects all three bone cell types
Leads to decrease in bone quality
Ultimately results in osteonecrosis and fracture

246
Q

Define renal osteodystrophy.

A

Term used to describe all the skeletal changes of chronic renal disease:
• Increased bone resorption (osteitis fibrosa cystica)
• Osteomalacia
• Osteosclerosis
• Osteoporosis
• Growth retardation

247
Q

Describe the histological appearance of Paget’s disease.

A

Lines will be seen between areas of new bone formation so it looks like a mosaic/jigsaw puzzle

248
Q

Which virus is associated with Paget’s disease?

A

Parvomyxovirus

249
Q

What are the four stages of fracture repair?

A

Organisation of a haematoma at the site of the fracture (pro-callus)
Formation of a fibrocartilaginous callus
Mineralisation of the fibrocartilaginous callus
Remodelling of the bone along weight-bearing lines

250
Q

Which sites are most commonly affected by osteomyelitis?

A

Vertebra
Jaw (secondary to dental caries)
Toe
Long bones (usually metaphysis)

251
Q

Describe the X-ray changes seen in osteomyelitis.

A

Usually appear about 10 days after onset
Mottled rarefaction and lifting of periosteum
First week changes – irregular sub-periosteal new bone formation (involucrum – layer of new bone that forms around dead bone)
Later changes – irregular lytic destruction
Some areas of the necrotic cortex may become detached (sequestra). This takes 3-6 weeks

252
Q

What congenital skeletal lesions are associated with syphilis?

A

Osteochondritis
Osteoperiostitis
Diaphyseal osteomyelitis

253
Q

List some acquired skeletal lesions that are associated with syphilis.

A

Non-gummatous periostitis
Gummatous inflammation of joints and bones
Neuropathic joints (tabes dorsalis)
Neuropathic shaft fractures

254
Q

What are the HLA associations of rheumatoid arthritis?

A

HLA DR4 and HLA DR1 (Chr6p21)

Other alleles: TFNA1P3, STAT4

255
Q

Which type of multinucleate giant cell may be seen in rheumatoid arthritis?

A

Grimley-Sokoloff cell (like a Langerhans cell but does not have horshoe nuclei)

256
Q

What are the key clinical and radiological features of osteosarcoma?

A

Peak in adolescence
60% around the knee
X-ray: usually metaphysial, lytic, permeative, elevated periosteum (Codman’s triangle)

257
Q

What are the main clinical, radiological and histological features of chondrosarcoma?

A

Malignant cartilage producing tumour
Affects axial skeleton, proximal femur and proximal tibia
X-ray: lytic with fluffy calcification
Histology: malignant chondrocytes with or without chondroid matrix

258
Q

What histological feature is typically seen in hyperparathyroidism?

A

Brown cell tumour – several multinucleated giant cells on a background of fibrous stroma with haemorrhage

259
Q

List some genetic associations of Hirschsprung disease.

A

Down syndrome

RET proto-oncogene Cr10

260
Q

List three types of non-neoplastic polyp.

A

Hyperplastic
Inflammatory (pseudopolyp)
Haemartomatous (juvenile polyposis syndrome, Peutz-Jeghers (LKB1))

261
Q

Which gene is mutated in FAP?

A

APC gene – chromosome 5q21

NOTE: almost 100% will develop cancer in 10-15 years

262
Q

What is Gardner’s syndrome?

A

Same features of FAP but with extra-intestinal manifestations: multiple osteomas of the skull and mandible, epidermoid cysts, desmoid tumours and supernumerary teeth

263
Q

Which gene mutation is associated with HNPCC?

A

1 of 4 DNA mismatch repair genes is mutated

264
Q

List some features of an adenoma of the colon that are associated with increased risk of becoming a carcinoma.

A

Size of polyp (> 4 cm = 45%)
Proportion of villous component
Degree of dysplastic change within a polyp

265
Q

Which stains are used during colposcopy?

A 
Lugol's iodine (looks at glycogen content within cells - cancerous cells don't have much glycogen)
Acetic acid (acetowhite appearance is associated with HPV)
266
Q

Where are the genes that cause neurofibromatosis located?

A

NF1 – 17q11

NF2 – 22q12

267
Q

Which genetic mutations are associated with gliomas in adults and in children?

A 
Diffuse infiltration (adults) – IDH1/2 
Circumscribed gliomas (children) – MAPK (BRAF)
268
Q

List some examples of circumscribed gliomas.

A

Pilocytic astrocytoma (MOST COMMON)
Pleiomorphic xanthoastrocytoma
Subependymal giant cell astrocytoma

269
Q

What is the hallmark histological feature of pilocytic astrocytoma?

A

Piloid (hairy) cell
Often see Rosenthal fibres and granular bodies
Slow-growing with low mitotic activity

270
Q

List some key features of astrocytoma.

A

Usually Grade II-IV
Cerebral hemispheres are the most common site in adults
Can progress to become a higher grade (malignant progression)
IDH2 mutation in 80% of cases
Mitotic activity and vascular proliferation is absent

271
Q

List some key features of glioblastoma multiforme.

A

Grade IV
Most patients > 50 years
High cellularity and high mitotic activity
Microvascular proliferation and necrosis
90% occur de novo with wildtype IDH
10% occur secondary to astrocytoma and have IDH mutation

272
Q

List some key features of oligodendrogliomas.

A

Grade II-III
Tends to present with a long history of neurological signs (usually seizures)
Slow-growing
Better prognosis than astrocytoma (better response to chemotherapy and radiotherapy)

273
Q

Which gene mutations are associated with oligodendroglioma?

A

IDH1/2

Co-deletion of 1p/19q

274
Q

What is a medulloblastoma?

A

Embryonal tumour originating from neuroepithelial precursors of the cerebellum and dorsal brainstem
They are always found in the cerebellum

275
Q

Describe the histological appearance of medulloblastoma.

A

Small blue round cell tumour with expression of neuronal markers (very little differentiation)
NOTE: synaptophysin is an example of a neuronal marker

276
Q

What histological feature is suggestive of partial neuronal differentiation?

A

Homer-Wright rosettes

277
Q

Outline the molecular classification of medulloblastoma.

A

WNT-associated
SHH-associated
Non-WNT/non-SHH

278
Q

List some key features of pilocytic astrocytoma.

A 
Usually grade I
Mainly occurs in children
Associated with NF1
Often cerebellar 
BRAF mutation in 70% of cases
279
Q

What is a characteristic histological feature of oligodendroglioma?

A

Round cells with clear cytoplasm (fried egg)

280
Q

Which histological feature of a meningioma is important in determining grade?

A

Mitotic activity (number of mitoses per 10 high power fields)
Grade 1 < 4
Grade 2: 4-20
Grade 3 > 20
NOTE: brain invasion is also an important thing to assess (presence of brain invasion makes it grade II)

Grade 2 and 3 will require radiotherapy as well as surgery

281
Q

Which tumours most commonly metastasise to the brain?

A

Lung
Breast
Melanoma

282
Q

What are the two types of cerebral oedema?

A

Vasogenic – due to disruption of blood-brain barrier
Cytotoxic – secondary to cellular injury (e.g. hypoxia, ischaemia). This is usually due to damage to astrocyte end feet

NOTE: AQP4 is the water transporter in the brain

283
Q

Where is CSF produced and where does it drain to?

A

Produced: choroid plexus
Drained: via arachnoid granulations into the superior sagittal sinus

284
Q

ƒWhat is the normal range for ICP?

A

7-15 mm Hg

285
Q

Which diseases are excluded by this definition of ‘stroke’?

A

Subdural and epidural haemorrhage

Infarction due to infection or tumour

286
Q

Which part of the cerebral vascular tends to be affected by infarcts resulting from emboli?

A

Middle cerebral artery branches

287
Q

List and describe the main neuropathological features of Alzheimer’s disease.

A

Extracellular plaques – extracellular accumulations of amyloid beta
Neurofibrilliary tangles – intra-neuronal pathology caused by disruption of the cytoskeleton of neurones
Cerebral amyloid angiopathy – deposits of protein in blood vessel walls which impairs normal vascular function

288
Q

Outline the main histological features of Parkinson’s disease.

A

Characterised by the presence of Lewy bodies which are intracellular accumulations of alpha-synuclein
Parkinson’s disease is caused by abhorrent metabolism of alpha-synuclein
NOTE: this was discovered because mutations in the alpha-synuclein gene are associated with rare familial forms of Parkinson’s disease

289
Q

Describe the main histological features of asthma.

A

Lots of eosinophils and mast cells
Goblet cell hyperplasia
Mucus plugs within airways
Thickening of bronchial smooth muscle and dilatation of blood vessels
Whorls of shed epithelium (Curschman spirals)
Charcot-Leyden crystals

290
Q

List some histological features of chronic bronchitis.

A

Dilated airways
Mucus gland hyperplasia
Goblet cell hyperplasia
Mild inflammation

291
Q

What is bronchopneumonia?

A

Infection is centred around the airways
Tends to be associated with compromised host defence (mainly the elderly) and is caused by low virulence organisms (e.g. Staphylococcus, Haemophilus, Pneumococcus)
It will show patchy bronchial and peribronchial distribution often involving the lower lobes

292
Q

What is lobar pneumonia?

A

Infection is focused in a lobe of the lung
90-95% caused by S. pneumoniae
Widespread fibrinosuppurative consolidation

293
Q

What is large cell carcinoma of the lung?

A

Poorly differentiated tumour composed of large cells
There is no evidence of squamous or glandular differentiation
It has a poor prognosis

294
Q

Outline the changes that give rise to atherosclerosis.

A

1 - endothelial injury
2 - LDL enters the intima and becomes oxidised
3- macrophages take up oxidised LDL via scavanger receptors and become foam cells
4 - apoptosis of foam cells causes inflammation and cholesterol core of plaque
5 - increase in adhesion molecules on endothelium leads to more macrophages and T cells entering the plaque
6 - vascular smooth muscle cells form the fibrous cap

295
Q

How long does it take for ischaemia to lead to irreversible injury to the myocardium and myocyte death?

A

20-40 mins if severe

296
Q

What signs might be picked up on examination of a patient with papillary muscle rupture as a result of an MI?

A

Mitral regurgitation

297
Q

What is arrhythmogenic right ventricular cardiomyopathy?

A

Myocyte loss with fibrofatty replacement typically affecting the right ventricle

298
Q

What are the diagnostic criteria for rheumatic heart disease?

A

Develops 2-4 weeks after a group A strep infection + 2 major criteria OR 1 major + 2 minor

299
Q

What are the major criteria for rheumatic heart disease?

A 
Carditis 
Arthritis 
Sydenham's chorea 
Erythema marginatum 
Subcutaneous nodules

NOTE: minor criteria include fever, raised ESR/CRP, migratory arthralgia, previous rheumatic fever, malaise

300
Q

Describe some histological features that may be seen in acute acute rheumatic fever.

A

Verrucae - beady fibrous vegetations
Aschoff bodies - small giant-cell granulomas
Anitschkov myocytes - regenerating myocytes

301
Q

What is non-bacterial thrombotic endocarditis?

A

Aka marantic endocarditis
Formed by thrombi in hypercoagulable states or DIC
Small, bland vegetations formed of thrombi occur at the lines of closure

302
Q

How is acute rheumatic fever treated?

A

Benzylpenicillin

Alternative: erythromycin

303
Q

Which organisms cause acute bacterial endocarditis?

A

Staphylococcus aureus

Streptococcus pyogenes

304
Q

Which organisms subacute bacterial endocarditis?

A 
Streptococcus viridans 
Staphylococcus epidermidis 
Coxiella
Mycoplasma
Candida 
Haemophilus
305
Q

Which murmurs are usually heard in infective endocardtiis?

A

Mitral regurgitation or aortic regurgitation

306
Q

Describe the presentation of mitral valve prolapse.

A

Shortness of breath
Chest pain
Mid-systolic click and late systolic murmur (Barlow murmur)

307
Q

List some types of pericarditis.

A 
Fibrinous (MI, uraemia)
Purulent (staphylococcus)
Granulomatous (TB)
Haemorrhagic (tumour, TB, uraemia)
Fibrous (constrictive)
308
Q

Describe the CT appearance of interstitial lung disease.

A

Honeycomb lung

NOTE: a key clinical sign of interstitial lung disease is end-inspiratory crackles

309
Q

List the types of interstitial lung disease.

A

Fibrosing
Granulomatous
Eosinophilic
Smoking related

310
Q

List some causes of fibrosing interstitial lung disease.

A 
Cryptogenic fibrosing alveolitis (idiopathic pulmonary fibrosis)
Pneumoconiosis
Cryptogenic organising pneumonia
Connective tissuedisease 
Drug-induced 
Radiation pneumonitis
311
Q

List some causes of granulomatous interstitial lung disease.

A

Sarcoid
Extrinsic allergic alveolitis
Vasculitides

312
Q

Describe the key pathological features and progression of idiopathic pulmonary fibrosis.

A

Histological pattern of fibrosis = usual interstitial pneumonia
Progressive patchy interstitial fibrosis with honeycomb change, beginning at the periphery of the lobule
Hyperplasia of type II pneumocytes causing cyst formation (honeycomb fibrosis)
Treated with steroids and immunosuppressants

313
Q

What is pneumoconiosis and which part of the lungs are affected?

A

Occupational lung disease due to inhalation of mineral dusts and inorganic particles
Most affect the upper lobes
NOTE: asbestosis is similar but caused by asbestos exposure and tends to affect the lower lobes

314
Q

What is extrinsic allergic alveolitis?

A

Group of immune-mediated lung disorders caused by intense or prolonged exposure to inhaled organic antigens –> widespread ALVEOLAR inflammation

315
Q

Outline the histological features of extrinsic allergic alveolitis.

A

Presence of polypoid plugs of loose connective tissue within alveoli/bronchioles - granuloma formation and organising pneumonia

316
Q

Which type of cell does small cell lung carcinoma arise from?

A

Neuroendocrine cell

317
Q

Which gene mutation in non-small cell lung cancer is associated with a poor response to cisplatin?

A

ERCC1

318
Q

What pulmonary artery pressure would be considered pulmonary hypertension?

A

> 25 mm Hg

319
Q

List the classes of pulmonary hypertension.

A 
Class 1: idiopathic 
Class 2: associated with left heart disease 
Class 3: due to lung disease 
Class 4: due to chronic VTE 
Class 5: mulifactorial
320
Q

Which cells do carcinoid tumours arise from?

A

Enterochromaffin cells

They produce 5HT

321
Q

Describe the symptoms of carcinoid syndrome.

A

Bronchoconstriction
Flushing
Diarrhoea

322
Q

List some features of a carcinoid crisis.

A 
Life-threatening vasodilation 
Hypotension 
Tachycardia 
Bronchoconstriction 
Hyperglycaemia
323
Q

Which test is used for carcinoid syndrome?

A

Urine 5-HIAA

NOTE: treated with ocreotide (somatostatin analogue)

324
Q

What metabolic complication is associated with villous adenomas?

A

Hypoproteinamic hypokalaemia (due to leakage of large amounts of protein and potassium)

325
Q

What are the roles of secretin and CCK?

A

Secretin: made by S-cells in the duodenum, controls gastric acid secretion and buffering with HCO3-
CCK: made by I-cells in the duodenum. Causes release of digestive enzymes

326
Q

What do the alpha, beta and delta cells in the pancreas secrete?

A

Alpha - glucagon
Beta - insulin
Delta - somatostatin

Others: D1 is a peptide that stimulates the secretion in water, pancreatic polypeptide (PP) self-regulates secretory activities

327
Q

What are the consequences of a gastrinoma?

A

Aka Zollinger-Ellison syndrome
Recurrent ulceration

NOTE: VIPoma will cause diarrhoea/metabolic acidosis/hypokalaemia, glucagonoma causes necrolytic migrating erythema

328
Q

Which scoring system is used to indicate the prognosis of liver cirrhosis?

A

Modified Child-Pugh score
Based on ascites, encephalopathy, bilirubin, albumin and PT
NOTE: < 7 = A, 7-9 = B, 10+ = C

329
Q

Which type of bladder cancer is associated with schistosomiasis?

A

Squamous cell carcinoma

NOTE: most bladder cancer will be transitional cell (urothelial) carcinoma

330
Q

Describe the presentation of Whipple’s disease.

A 
Steatorrhoea 
Abdominal pain
Weight loss 
Arthritis 
Periodic acid-Schiff positive macrophages on jejunal biopsy
331
Q

What are the two main types of vulval intraepithelial neoplasia?

A

Usual Type: younger women, warty/basaloid SCC

Differentiated Type: older women, keratinising SCC, higher risk of malignant transformation

332
Q

What type of cancer are most vulval carcinomas?

A

Squamous cell carcinoma

333
Q

What is a distinguishing histological feature of serous cystadenoma of the ovary?

A

Psammoma bodies

From columnar epithelium

334
Q

List some risk factors for cervical cancer.

A 
Early age at first intercourse 
Multiple partners 
Multiparity 
Smoking 
HIV 
Immunosuppression
NOTE: it is a squamous cell carcinoma (less commonly it can be adenocarcinoma)
335
Q

Which cancers does BRCA increase the risk of?

A

Breast
Ovarian
Prostate
Pancreatic

336
Q

Why is lobular carcinoma in situ (LCIS) always an incidental finding?

A

No microcalcifications or stromal reactions so can’t be seen on mammography
Cells do NOT have the adhesion protein E-cadherin

337
Q

Describe the consequences of a stroke in the territory of ACA.

A

Contralateral leg paralysis
Sensory loss
Cognitive defects (apathy, confusion, poor judgment)

338
Q

Describe the consequences of a stroke in the territory of MCA.

A

Contralateral weakness and sensory loss of face and arm
Cortical sensory loss
May have contralateral homonymous hemianopia
Aphasia if dominant hemisphere
Neglect if non-dominant hemisphere

339
Q

Describe the consequences of a stroke in the territory of PCA.

A

Contralateral hemianopia
Midbrain: CN 3 and 4 palsy
Thalamic: sensory loss, amnesia, decreased consciousness
Bilateral: cortical blindness

340
Q

Describe the consequences of a stroke in the territory of the basilar artery.

A

Proximal: impaired eye movement, nystagmus, dysarthria
Distal: somnolence, memory and behavioural

341
Q

Describe the consequences of a stroke in the territory of PICA.

A 
Ataxia (ipsilateral)
Horner's (ipsilateral)
Facial sensory loss (ipsilateral)
Contralateral limb impairment of pain and temperature 
Nystagmus
342
Q

Describe the consequences of a stroke in the territory of lacunar infarcts.

A

Pure motor hemiparesis
Pure sensory loss
Ataxic hemiparesis

Depends on the part of hte brain affected)

343
Q

Which artery is most commonly affected in extradural haemorrhage?

A

Middle meningeal artery

NOTE: subdural haemorrhages are caused by venous bleeding from damaged bridging veins

344
Q

Which types of brain tumour are associated with NF1 and NF2?

A

NF1: optic glioma, neurofibroma
NF2: vestibular schwannoma, meningioma, ependyoma, astrocytoma

345
Q

Name a familial syndrome that is associated with glioblastoma multiforme and medulloblastoma.

A

Turcot syndrome

346
Q

What is Li Fraumeni syndrome associated with?

A

Astrocytoma
PNET
Non-brain tumours such as sarcomas, breast cancer and leukaemia

347
Q

What are the two main forms of multiple sclerosis?

A

Primary progressive

Relapsing remitting

348
Q

What are some X-ray features of osteoarthritis?

A

Loss of joint space
Osteophytes
Subchondral sclerosis
Subchondral cysts

349
Q

Describe the typical presentation of osteoid osteoma.

A

Small benign bone forming lesion typically at the tibial diaphysis/proximal femur
Causes night pain relieved by aspirin
X-ray shows radiolucent nidus with surrounding sclerotic bone (Bull’s eye)

350
Q

What is the most common type of benign bone tumour?

A

Osteochondroma (aka exostosis)

It appears as a cartilage capped bony spur (mushroom) on X-ray
Tends to occur at the site of a previous fracture (several years before)

351
Q

What is the difference between hyperkeratosis and acanthosis?

A

Hyperkeratosis: increase in stratum corneum
Acathosis: increase in stratum spinosum

WARNING: dont get confused with acantholysis

352
Q

Which clinical signs can be elicited in psoriasis?

A

Auspitz - rubbing the lesions causes pin-point bleeding

Koebner phenomenon - lesions form at sites of trauma

353
Q

List some causes of erythema multiforme.

A

Infections: HSV, mycoplasma
Drugs: sulphonamides, NSAIDs, penicillin, phenytoin, allopurinol

354
Q

What is the main histological feature of dermatitis herpetiformis?

A

Subepidermal bullae

Caused by IgA antibodies bind to basement membrane

355
Q

List some subtypes of malignant melanoma.

A

Lentigo maligna - occurs on sun exposed areas of elderly Caucasians, flat, slow growing
Superficial spreading - irregular borders with variation in colour
Nodular - younger age group, more aggressive
Acral lentiginous - occurs on palms, soles and subungual areas

356
Q

What is Nikolsky sign?

A

Rubbing the skin leads to exfoliation of the outermost layer of skin

This is seen in TEN and SJS

357
Q

Describe the clinical presentation of pityriasis rosea.

A

Salmon pink rash appears first (herald patch) followed by oval macules in a christmas tree distribution
Usually appears after viral illness and remits spontaneously

358
Q

Which HLA alleles are associated with scleroderma?

A

HLA DR5 and DR8

359
Q

What is Buerger’s disease?

A

Inflammation and thrombosis of arteries in the extremities (usually legs) occurring in young, heavy smokers
Corkscrew appearance on angiogram

360
Q

List the key features of microscopic polyangiitis.

A

Pulmonary haemorrhage
Glomerulonephritis
pANCA (anti-myeloperoxidase)

361
Q

Which proteins are implicated in haemodialysis-associated amyloidosis?

A

Deposition of beta-2 microglobulin

362
Q

Outline the clinical features of amyloidosis.

A 
Kidney: nephrotic syndrome (MOST COMMON)
Heart: conduction defect, heart failure
Hepatosplenomegaly 
Macroglossia
Neuropathies (e.g. carpel tunnel)
363
Q

What is the pathognomonic histological feature of sarcoidosis?

A

Non-caseating granulomas

Also get Schaumann bodies and asteroid bodies (inclusions of protein and clacium)

364
Q

List the circumstances in which a death needs to be reported to the coroner.

A

Cause of death is unknown
Death was violent or unnatural
Death was sudden and unexplained
Person who died was not visited by a medical practitioner during their final illness
Medical certificate is not available
Person who died was not seen by the doctor who signed the medical certificate within 14 days before death or after they died
Death occurred during an operation or before the person came out of anaesthetic
Medical certificate suggests the death may have been caused by an industrial disease or industrial poisoning
Death in custody

365
Q

How can the histology in chronic hepatitis be used to grade and stage the disease?

A

Severity of inflammation = grade (how bad does it look)

Severity of fibrosis = stage (how far has it spread)

366
Q

Which type of bone is considered immature and is usually pathological?

A

Woven bone

367
Q

How does primary hyperparathyroidism affect urine calcium levels?

A

Increases urine calcium

NOTE: it causes increased reabsorption of calcium in the kidneys, but the hypercalcaemia means that more calcium is filtered in the first place

368
Q

Which type of ovarian neoplasm typically causes the largest tumours?

A

Mucinous tumour

369
Q

What is a key distinguishing feature between mucinous and serous ovarian neoplasms?

A

Mucinous - tends to be unilateral and can be very large

Serous - often bilateral

370
Q

Describe the histological differences between fibromas and thecomas.

A

Fibroma - intersecting bundles of spindle cells

Thecoma - fibrous tissue containing spindle cells and lipids

371
Q

What are some key features of embryonal carcinoma?

A

Very aggressive tumour
Produces hCG and AFP
Neoplastic cells are anaplastic

372
Q

What is a key difference between seminomatous and non-seminomatous germ cell tumours?

A

Seminomatous - radiosensitive, present in the 30s, 15% produce hCG, do not produce AFP
Non-seminomatous - radioresistant, presents in the 20s, may secrete AFP or hCG

373
Q

Describe the smear findings of a syphilitic ulcer.

A

Necrotic centre
Periarteritis and endarteritis obliterans
Pericellular infiltrate of mononuclear cells and giant cells

374
Q

What metaplasia occurs at the transformation zone of the cervix?

A

Columnar to squamous

375
Q

What is the best investigation to confirm the benign status of ovarian cyst?

A

Fine needle aspiration

376
Q

What is a key difference between the presentation of subdural haemorrhage and extradural haemorrhage?

A

Subdural: venous blood loss, takes longer, may take days or weeks to cause neurological changes (e.g. headache, confusion)
Extradural: arterial blood loss, initial lucid interval is followed by rapid development of neurological signs

377
Q

Which parts of the brain tend to be affected by lacunar infarcts?

A

Basal ganglia
Internal capsule
Thalamus
Pons

378
Q

What is the most common cause of nephrotic syndrome in adults?

A

Focal segmental glomerulosclerosis

379
Q

Define microalbuminuria.

A

Excretion of 30-300 mg of protein in the urine per day

380
Q

Which test is done to determine whether a breast cancer is lobular or ductal?

A 
Ductal = E-cadherin positive 
Lobular = E-cadherin negative
381
Q

Which stain is used to detect alpha-1 antitrypsin?

A

Periodic acid-Schiff stain

382
Q

ST depression in a patient presenting with chest pain at rest is suggestive of damage to which part of the heart?

A

Subendocardial necrosis due to ischaemia of the inner 1/3 of the heart muscle

ST elevation is seen in transmural infarction

383
Q

What percentage stenosis of a coronary artery is required to cause chest pain at rest?

A

> 90%

384
Q

Define ‘erosion’.

A

Loss of surface epithelium with or without lamina propria (muscularis mucosa is intact)

385
Q

What is a key difference between the histological appearance of chronic ulcers compared to acute ulcers?

A

Chronic ulcers have an element of fibrosis

386
Q

What is the point at which the oesophageal mucosa transitions from squamous to columnar epithelium called?

A

Z-line

387
Q

What is a key difference between the potential complications of anterior and posterior duodenal ulcers?

A

Anterior –> perforation –> peritonitis

Posterior –> gastroduodenal ulcer –> haemorrhage

388
Q

List some causes of chronic pancreatitis.

A 
Alcohol (80%)
Gallstones 
Haemochromatosis 
Idiopathic
Autoimmune (IgG4)
389
Q

What are the stages of sarcoidosis?

A

Stage 1: BHL only
Stage 2: BHL with pulmonary infiltrates
Stage 3: pulmonary infiltrates without BHL
Stage 4: pulmonary fibrosis

390
Q

What are that main features of lateral medullary syndrome?

A

Characterised by sensory deficits that affect the trunk and extremities contralaterally (opposite to the lesion), and sensory deficits of the face and cranial nerves ipsilaterally (same side as the lesion)

391
Q

Name and describe a few different types of fracture.

A

Transverse: fracture is at right angles to the bone’s long axis
Comminuted: bone is splintered into a number of small pieces
Greenstick: occurs in children, the fracture is transverse but only partial, the bone bends away from the long axis but remains attached
Compound: when the fracture penetrates the skin surface (aka open fracture)
Oblique: fracture axis is oblique to the long axis of the bone
Spiral: tends to be due to rotational injury, leaves sharp points, similar appearance to oblique

392
Q

Name two causes of gastritis in immunocompromised patients.

A

CMV

Strongyloides

393
Q

Which type of breast cancer is sometimes referred to as ‘no special type’?

A

Invasive ductal carcinoma

394
Q

Which type of bladder cancer is associated with schistosomiasis?

A

Squamous cell carcinoma

395
Q

Which oncogene is associated with medullary thyroid cancer?

A

RET proto-oncogene

396
Q

Which antigens are targeted in:
Pemphigus foliaceus
Pemphigus vulgaris
Bullous pemphigoid

A

Pemphigus foliaceus - desmoglein 1
Pemphigus vulgaris - desmosomes (desmoglein 1 and 3)
Bullous pemphigoid - hemidesmosomes

397
Q

Which type of cancer classically has ‘oat cells’?

A

Small cell lung cancer

398
Q

Where are osteoclasts found within the bone?

A

Within Howship’s lacunae

399
Q

Which type of mastitis affects young women who smoke?

A

Periductal mastitis

400
Q

What is the most common type of endometrial cancer?

A

Endometrioid (80%)

401
Q

Which type of glomerulonephritis is associated with hepatitis B and C viruses?

A

Membranous glomerulonephritis AND membranoproliferative glomerulonephritis

402
Q

What is a key difference between the pattern of immune complex deposition in membranous and membranoproliferative glomerulonephritis?

A

Membranous - subepithelial (spike and dome)

Membranoproliferative - subendothelial (tram track)

403
Q

What is Young syndrome?

A

Congenital cause of bronchiectasis characterised by rhinosinusitis, azoospermia and bronchiectasis

404
Q

Which cells might be found in the lungs of a patient with pulmonary oedema due to heart failure?

A

Haemosiderin-containing macrophages

NOTE: aka heart failure cells

405
Q

What might be the first presentation of Crohn’s disease?

A

Aphthous ulcers

Also characterised by cobblestone mucosa and skip lesions

406
Q

Describe the histological appearance of acinar cell carcinoma of the pancreas.

A

Neoplastic epithelial cells with eosinophilic granular cytoplasm
Positive for lipase, trypsin and chymotrypsin

407
Q

Which commonly used medication is associated with hepatic adenoma?

A

OCP

May present with abdominal pain and intraperitoneal bleeding (may shrink if the OCP is stopped)

408
Q

Which inborn errors of metabolism can cause cirrhosis?

A

Galactosaemia

Glycogen storage disease

Laz's Path Questions (9 decks)

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