Histopath

Question 1

Define Cavernous Angiomas

Answer 1

Well defined malformative lesions composed of closely packed vessels with no parenchyma interposed between vascular spaces.
Note: it’s similar to an arteriovenous malformation but there’s no brain substance wrapped up amongst the vessels.
Note: these tend to bleed at a lower pressure than intraparenchymal haemorrhages and tend to cause recurrent small bleeds.
Note: shows target sign on MRI

Question 2

Describe the Braak stages of Alzheimer’s disease.

Answer 2

Stage 1: Tau pathology in transentorhinal cortex
Stage 2: posterior hippocampus
Stage 3: immunostaining visible to the eye, affects substantia nigra
Stage 4: superior temporal gyrus
Stage 5: peristriate cortex
Stage 6: striate cortex
Note: Clinically symptoms tend to arise in stages 3 or 4

Question 3

What is Multiple System Atrophy?

Answer 3

It’s an alpha-synucleinopathy similar to Parkinson’s Disease which attacks glial cells.
It presents similarly to Parkinson’s disease.
It mainly affects the cerebellum so the patients are more likely to present with falls.

Question 4

What are the histological features of Pick’s disease?

Answer 4

Marked gliosis and neuronal loss.
Balloon neurones
Tau positive Pick bodies
Note: Mutations in Tau are associated with a Fronto-Temporal Dementia phenotype that is often associated with Parkinson’s disease
Note: There are 17 autosomal dominant syndromes resulting from mutations of Tau

Question 5

Describe how the types of tau present in Alzheimer’s is different from that present in Corticobasal Degeneration (CBD), Progressive Supranuclear Palsy(PSP) and Pick’s Disease.

Answer 5

Alzheimer’s- when the tau is put through Western Blot, it shows up as 3 dense bands. If this is dephosphorylated it shows all 6 isoforms of tau.
CBD, PSP- when the tau is put through Western Blot it shows up as 2 dense bands, if these are dephosphorylated it shows up as only 4R tau isoform- so CBD and PSP are ‘4R tauopathies’
Pick’s disease- 3R tauopathy

Question 6

Outline the pathophysiology of ARDS.

Answer 6

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

Question 7

What are the histopathological stages of Lobar Pneumonia

Answer 7

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

Question 8

Which molecular changes are important to test for in adenocarcinoma?

Answer 8

EGFR (responder or resistance)
ALK (translocation)
Ros1 (translocation)

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

Question 9

List some tumour like conditions of the bone

Answer 9

Fibrous dysplasia
Metaphyseal fibrous cortical defect/non-ossifying fibroma
Reparative Giant cell granuloma
Ossifying fibroma
Simple bone cyst

Question 10

What is Fibrous Dysplasia

Answer 10

Condition where fibrous tissue develops in place of normal bone tissue
Can happen in any bones but most often in ribs and proximal femur
Most common in people less than 30 yrs
Causes soap bubble osteolysis appearance on X-ray

Note: giant cell tumours also cause soap bubble osteolysis on X-ray, but this most tends to happen in the bones around the knees

Question 11

What is an enchondroma and in which bones does it occur?

Answer 11

A Cartilaginous proliferation within the bone.
Most tend to happen in the hands
Can cause pathological fractures
May show popcorn calcifications on X-Ray
Associated with Ollier's and Mafucci Syndromes

Question 12

Which cancers in children tend to spread to bones?

Answer 12

Neuroblastoma
Wilm's Tumour
Osteosarcoma
Ewing's sarcoma
Rhabdomyosarcoma

Question 13

List the Histological subtypes of chondrosarcoma...

Answer 13

Conventional (Myxoid or Hyaline)
Clear Cell (Low Grade)
Dedifferentiated (High Grade)
Mesenchymal
Note: Myxoid= composed of clear mucoid substance

Question 14

Describe the histological appearance of the following breast cancers:
A) Invasive Ductal Carcinoma
B) Invasive Lobular Carcinoma
C) Invasive Tubular Carcinoma
D) Invasive Mucinous Carcinoma

Answer 14

A) Invasive Ductal Carcinoma
Cells are pleomorphic with abnormally large nuclei
B) Invasive Lobular Carcinoma
Cells in linear arrangement with monomorphic nuclei
Note: cords of cancer cells in linear arrangement are referred to as being an ‘Indian File Pattern’
C) Invasive Tubular Carcinoma
Elongated tubules of cancer cells invading the stroma
D) Invasive Mucinous Carcinoma
Lots of ‘empty’ spaces, filled with mucin.

Question 14

Outline the coding for biopsies of suspicious breast lumps

Answer 14

B1) Normal Breast tissue
B2) Abnormal benign tissue
B3) Abnormal tissue of uncertain malignant potential
B4) Tissue suspicious of malignancy
B5) Malignant tissue (a= DCIS; b= invasive carcinoma)

Question 14

What’s the basis for papillary thyroid cancer diagnosis

Answer 14

Nuclear Features:
1) Optically clear nuclei
2) Intranuclear inclusions- “Orphan Annie eyes”
May have Psammoma bodies- little foci of calcification
Usually non-functional
On histology have papillary structure- central connective tissue stalk surrounded by epithelium

Question 15

How can you measure anti-dsDNA

Answer 15

1) You can use ELISA
2) You can culture a sample with Crithidia Luciliae (prototozoan kinetoplast)
It has a large mitochondrion with a large kinetoplast (network of anti-dsDNA)
If anti-dsDNA is present in the sample they will bind to the protozoan dsDNA

Question 16

Describe skin histology appearance in SLE

Answer 16

1) Lymphocytic infiltration of the Dermis
2) Vacuolisation (dissolution of cells) of the Basal Epidermis
3) Extravasation of blood causes a rash
4) Immunofluorescence shows immune complex deposition at the Dermis-Epidermis junction.

Question 17

What is Polyarteritis Nodosa?
What are its main features?

Answer 17

1) A Necrotising arteriosclerosis which is focal and sharply demarcated
2) It heals by Fibrosis and mainly affects the Renal and Mesenteric vessels
3) May present with Gut Ischaemia or Renal Impairment
4) It produces a Rosary Beads appearance on Angiography due to multiple Aneurysms
5) Associated with Hepatitis B

Question 18

What are the 2 types of HPV infection? Describe their features.

Answer 18

[1] Latent (non-productive)
1) HPV DNA continues to reside within Basal cells
2) Infectious virions are not produced
3) Replication of viral DNA is coupled to replication of epithelial cells
4) This means that complete viral particles are not produced
5) Cellular effects of HPV are not seen
[2] Productive
1) Viral DNA replication occurs independently of host cell DNA synthesis
2) Large amounts of Viral DNA and infectious virions are produced
3 Characteristic cytological and histological features are seen- halo around the nucleus (Koilocytes)

Question 19

Which Genetic Mutations are associated with the two types of Type 2 Endometrial Carcinoma?

Answer 19

[1] Endometrial Serous Carcinoma
1) P53 (90%)
2) PK13CA (15%) Her2 amplification

[2] Clear Cell Carcinoma
1) PTEN
2) CTNNB1
3) Her2 amplification

Question 20

Describe how complete and partial moles form

Answer 20

[1] Complete Moles
1) Occurs when you get an empty egg fertilised by a sperm
2) Reduplication of 23X from sperm results in a Homozygous Diploid 46XX genome
3) Can also occur due to fertilisation of an empty egg by 2 sperm with 2 independent sets of 23X or 23Y

[2] Partial Moles
1) A normal ovum containing 23X gets fertilised by 2 sperm leading to the presence of 3 sets of chromosomes (2 paternal and 1 maternal)
2) Dispermia/diandry
3 Overdose of male chromosomes drives proliferation
4) Can also occur due to fertilisation of a normal egg by a sperm with unreduced paternal chromosomes (46XY)

Question 21

Outline the classification of Epithelial Ovarian Tumours

Answer 21

[1] Type 1
1) Low Grade
2) Relatively Indolent and arise from well characterised precursors (benign tumours) and endometriosis
3) Mutations: K-ras, BRAF, P13KCA, Her2, PTEN, beta-catenin

[2] Type 2
1) High Grade
2) Aggressive
3) P53 mutation in 75% of cases
4) NO precursor lesions

Question 22

What are the Key features of Serous Tumours?

Answer 22

1) Most common type of Ovarian tumour
2) Usually Cystic
3) 30-50% are bilateral
3) Benign Tumours are line by Bland Epithelium
4) Borderline Tumours have a more complex atypical lining with papillae but no invasion through the Basement Membrane
5) Malignant Tumours are invasive with a poor prognosis

Question 23

List 4 types of Sex Cord Stromal Tumours and the hormones they may produce

Answer 23

1) Firbromas (No Hormones produced)
2) Granulosa Cell Tumours (May produce Oestrogen)
3) Thecomas (May produce Oestrogen, Rarely Androgens)
4) Sertoli-Leydig cell Tumours (May be Androgenic)

Question 24

What are the 4 types of Germ Cell Tumours?

Answer 24

1) Dysgerminoma- No Differentiation
2) Teratoma- From embryonic tissue
3) Endodermal Sinus Tumour- From Extraembryonic tissues (eg Yolk Sac)
4) Choriocarcinoma- From Trophoblastic Cells which would form the Placenta

Question 25

What are the key features of an Immature Teratoma?

Answer 25

1) Indicates Presence of Embryonic elements (most commonly Neural tissue)
2) Malignant tumour that grows aggressively, penetrates the Capsule and forms Adhesions
3) Spreads within peritoneal cavity metastasising to the lymph nodes, lungs, liver and other organs

Question 26

Describe the microscopic changes that take place in Myocardial Infarction

Answer 26

Under 6 hours- Normal histology
6-24 hrs- 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-Months- Strengthening and Decellularisation of scar

Question 27

What is Reperfusion Injury?

Answer 27

1) Consequence of when blood is returned to an area of myocardial necrosis
2) a.Oxidative stress, b.calcium overload and c.inflammation lead to further injury
3) Arrhythmias are common
4) Can cause a stunned myocardium- reversible cardiac failure lasting several days

Question 28

Outline the structures within a normal liver

Answer 28

1) Portal tracts consisting of a.Hepatic artery branch b.Portal vein branch and c.Bile duct

2) Blood flows from Portal tracts towards and into the Central vein

3) A ring of collagen lines the bile tracts called the limiting plate

4) From the Portal tracts to the central vein exist three zones of hepatocytes. The zone closest to the central vein is zone 3 and contain the most metabolically active enzymes.