Questions
There are 3 mandatory case studies. You must answer all three
Submit your answers in a single Word document, clearly indicating your name,
student number, and each Case Study number and sub-section
CASE STUDY ONE
A 32-year-old man presents to his GP with symptoms of productive cough and fever.
He is a non-smoker and does not have any past medical history. He works as a civil
engineer and he does not drink any alcohol. There is no history of any recent travel.
The patient looks unwell, his temperature is 37.9°C and stethoscope testing of his
chest indicates pneumonia. Routine blood tests confirm infection. He is prescribed
antibiotics.
The patient returns several weeks later with no significant improvement. The GP
sends for some further blood tests. Liver function tests are still abnormal indicating
an underlying liver pathology. The results are below:
Test
Bilirubin
Aspartate aminotransferase
Alkaline phosphatase
Ferritin
HIV
CMB
EBV
Hep A, B and C
Serum iron
Transferrin saturation
Total iron binding capacity
Result
18
114
196
1100
Negative
Negative
Negative
Negative
30
70%
40
The results indicate high levels of ferritin, indicative of haemochromatosis.
a) What type of tissue sample, would be taken to confirm this diagnosis? (2
marks)
b) List the special stains comprising a liver panel/set (6 marks) and explain how
you would expect this panel to stain on a tissue sample from this patient and
facilitate confirmation of the diagnosis of haemochromatosis (6 marks) NB 12
marks in total for part b)
c) There are two forms of haemochromatosis (primary and secondary). Explain
the differences between these two types of haemochromatosis (5 marks)
d) Discuss the use of Cellular Pathology and Molecular techniques in the
confirmation of primary haemochromatosis (6 marks)
e) What types of quality control measures would be applied in the Cellular
Pathology laboratory in order to assure the quality of staining on the liver
tissue sample? (5 marks)
CASE STUDY TWO
A 54-year-old male who is a long-term smoker presents with a history of worsening
cough with haemoptysis. He confesses to a poor appetite and weight loss of over 5kg
over the past 3 months. He works as a builder and is unable to say whether he may
have been exposed to asbestos.
The patient appears emaciated. There is conjunctival pallor (indicative of anaemia)
and digital (finger) clubbing. Examination of the chest reveals reduced breath sounds.
Palpation of the abdomen and lymph nodes is unremarkable.
a) What is the most likely suspected pathological diagnosis in this case? (2
marks)
b) In terms of cellular pathology tests/techniques, how might this suspected
diagnosis be confirmed? Your answer should include description of all steps
from sample receipt to microscopy (16 marks)
Assuming that a malignant diagnosis is confirmed, below is a table of available
antibodies:
CA125
CD10
CDX2
Chromogranin A
CK5/6
CK7
CK14
CK20
ER
GCDFP
Hep B
HER2
NSE
P63
PR
Synaptophysin
TTF1
Vimentin
c) Select those antibodies which could be used to distinguish between a final
diagnosis of non-small cell adenocarcinoma and squamous cell carcinoma and
explain your reasons for selection of each (14 marks)
d) If a diagnosis of NSCLC were confirmed, explain which additional Cell Path and
/or molecular tests might be performed in terms of assessing patient
prognosis/treatment options. Your answer should make reference to the 4
main altered genes which have been shown to be associated with the
development of lung cancer (8 marks)
CASE STUDY THREE
A 55-year-old woman presents to the Emergency Department after slipping on an icy
road and falling on her outstretched right hand. She complains of pain in her right
wrist which has not responded to simple analgesia and has been unable to use her
right hand since falling. She has a history of polymyalgia rheumatica though has not
had a flare up for a couple of years. She is a non-smoker.
X-rays confirm she has a transverse fracture of the distal radius with minimal dorsal
displacement of the wrist; there is also a fracture to the ulnar.
a) What type of sample could be taken for histopathological diagnosis? (2 marks)
b) There are three main reasons to obtain a bone biopsy. List the 3 reasons
including an example of each. Interpret which would be pertinent to this case
(4 marks)
c) Explain the difference between a genetic bone disorder (GBD) and a metabolic
bone disease (MBD) (2 marks)
d) Describe how handling of this type of sample would be different from that
described in Case Study 2 part b) (4 marks)
The following is a list of commonly used special stains for bone:
Alizarin Red
H&E
Reticulin
Aniline blue
Masson Trichrome
Schmorl’s
Van Gieson
Von Kossa
Goldner’s trichrome
PAS
Toluidine blue
e) Explain which of these you would choose to facilitate confirmation of a
diagnosis of osteoporosis in a non-mineralised sample of bone (8 marks)
f) If two bone samples were received by the Cellular Pathology laboratory, and
the request cards indicated that one was suspected as having osteoporosis and
the other was suspected of bone cancer; what would be the implications of
mixing these two samples up? Your answer should include impact on the
patient and their diagnosis, as well as the measures in place in the laboratory
which aim to prevent this happening (10 marks)
BIOL40442
Cellular Pathology 2020/21
Seminar 6
• 20/01/21 – Intro to module and assessment; Intro to Critical Appraisal
• 03/02/21 – Questions: Cellular Pathology Overview; Histopathology &
Cancer
Critical Appraisal practice (GI/colorectal, Liver papers)
• 10/02/21 – Questions: GI/colorectal Cancer; Liver Pathology
Seminars summary
Critical Appraisal practice (Breast & Lung papers)
• 17/02/21 – Questions: Breast & Lung Cancer
Critical Appraisal practice (Bone and Skin papers)
• 03/03/21 – Questions: Bone & Skin Pathology
Critical Appraisal practice (Neuropathology paper)
• 10/03/21 – Revision and Practice test questions
End of Module Phase Test
Thursday 25th March 9am- 1pm UK GMT
Worth 50% of final grade
This is a 2-hour test (you are being given 4 hours to complete/upload it)
1pm is a DEADLINE – not a target! DO NOT SUBMIT LATE!
You should be aiming to upload after approx. 2-3 hours
End of Module Phase Test
Three Case Studies to answer
Each broken down into sub-sections
Marks allocated to each sub-section
Examples
CASE STUDY 1:
A patient is suspected of having Helicobacter pylori infection of
the stomach. A gastric biopsy is performed and the sample sent
to the histopathology laboratory.
a) Explain the sequential steps in handling the sample from specimen reception to sectioning
(10 marks)
b) Discuss the Cellular Pathology stains or techniques which might be used to confirm the
diagnosis, including advantages and disadvantages of each (8 marks)
c) What are the potential implications for this patient with regards to progressions of
pathological diseases? (2 marks)
• 20 marks in total
a) Explain the sequential steps in handling the sample from specimen
reception to sectioning (10 marks)
• What would you write?
• 10 marks available!
• 10 steps, or 5 steps with description/explanation?
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a) Explain the sequential steps in handling the sample from specimen
reception to sectioning (10 marks)
• One mark for each of:
• Specimen reception/fixation
• Dissection
• Processing
• Embedding
• Sectioning
• One extra mark for each if these are described
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b) Discuss the Cellular Pathology stains or techniques which might be used
to confirm the diagnosis, including advantages and disadvantages of each
(8 marks)
• What would you write?
• 8 marks (include advantages/disadvantages)
b) Discuss the Cellular Pathology stains or techniques which might be used
to confirm the diagnosis, including advantages and disadvantages of each
(8 marks)
• One mark for each of H&E, Giemsa and IHC. Other stains such as gram/grocott might be used
for exclusion of other infective agents. Final 4 marks available for discussion of the use of
each (advantages and disadvantages, which is best and why etc) rather than simple
description
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c) What are the potential implications for this patient with regards to
progressions of pathological diseases? (2 marks)
• What would you write?
• Only 2 marks available
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c) What are the potential implications for this patient with regards to
progressions of pathological diseases? (2 marks)
• The infection may be treated with antacids and acid suppression therapy and be
eliminated/controlled
• Chronic cases may develop into gastric cancer
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CASE STUDY 2:
A 55 year old female patient attends her routine mammography screening
and an area of microcalcification is detected in her left breast.
A needle core tissue biopsy is taken and sent to the Histopathology
laboratory. Initial H&E assessment diagnoses the patient to have a high grade
ductal breast adenocarcinoma.
Immunohistochemistry (IHC) testing of the sample indicates it is Oestrogen
Receptor (ER) negative and Progesterone Receptor (PR) negative.
a) What are the benefits of taking a needle-core biopsy over a fine needle aspiration (FNA)? (4 marks)
b) What is the grading method commonly used for Breast Cancers and what are the 3 main components of
this grading system? (5 marks)
c) What are the treatment options for this patient? (5 marks)
d) What other cellular pathology tests could be performed to investigate alternative treatments? (6 marks)
• 20 marks in total
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a) What are the benefits of taking a needle-core biopsy over a fine needle
aspiration (FNA)? (4 marks)
• What would you write?
• 4 marks (4 benefits?)
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a) What are the benefits of taking a needle-core biopsy over a fine needle
aspiration (FNA)? (4 marks)
• It is not possible to distinguish in-situ from invasive cancers using an FNA; this is possible
using a needle-core biopsy
• Very little prognostic information can be ascertained due to the nature of a cytological
sample; histological samples can provide this.
• Sometimes only a broad indication of the malignancy can be given and no specific sub types
can be identified when using an FNA; this is not a limiting factor when using tissue biopsies
• It is very difficult to ascertain any kind of functional assessment e.g. ER/PR/HER2 status from
an FNA; this is not a limiting factor when using tissue biopsies
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b) What is the grading method commonly used for Breast Cancers and what
are the 3 main components of this grading system? (5 marks)
• What would you write?
• 5 marks available – a question, 3 main components, plus 1 mark…

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b) What is the grading method commonly used for Breast Cancers and what
are the 3 main components of this grading system? (5 marks)
• Nottingham Method of Grading is used for Breast cancers.
• 3 Main components are Tubule formation, Nuclear Pleomorphism, and Mitotic counts
• 5th mark available if these are described (Tubule formation = degree of differentiation,
score 1-3; Nuclear Pleomorphism = variation in size and shape of tumour cells, score 1-3;
Mitotic counts = proportion of cells with mitotic figures, score 1-3). Add scores for all
three individual components together, Score 3-5 = Grade 1; Score 6-7 = Grade 2; Score
8-9 = Grade 3.
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c) What are the treatment options for this patient? (5 marks)
• What would you write?
• 5 marks available (?5 options)
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c) What are the treatment options for this patient? (5 marks)
• As the needle-core biopsy assessment has indicated the lesion to be cancerous, a lumpectomy
or mastectomy would be offered to the patient.
• It may also be mentioned that an axillary lymph node clearance may be appropriate (extra
marks if sentinel lymph node biopsy is mentioned).
• Radiotherapy and/or chemotherapy
• ER/PR positive tumours respond to Tamoxifen, so drug therapy would not be appropriate for
this patient.
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d) What other cellular pathology tests could be performed to investigate
alternative treatments? (6 marks)
• What would you write?
• 6 marks available
20
d) What other cellular pathology tests could be performed to investigate
alternative treatments? (6 marks)
• As the tumour is ER/PR negative (and therefore unresponsive to tamoxifen), HER2 IHC could be
performed (if HER2 positive, the patient would respond to Herceptin drug therapy). Since the majority
(86%) of HER2 positive cancers are Grade 3, it is probable that this patient would be HER2 positive.
• Description of the IHC HER2 scoring methodology would be appropriate (i.e. 0/1+, 2+, 3+) and
how these relate to likelihood of response to Herceptin (i.e. 0/1+ negative and therefore non-responsive;
3+ positive and therefore responsive; 2+ equivocal and should be sent for HER2 FISH to ascertain the
HER2 gene amplification status
• Description of the HER2 FISH methodology including the fact that only patients with amplified genes
would respond to Herceptin).
• Extra marks available if answer addresses triple negative/basal like breast tumours (negative for ER, PR
and HER2, therefore unresponsive to either Tamoxifen or Herceptin and currently an area of research;
e.g. PARP inhibitors, Immuno-checkpoint inhibitors and EGFR and PTEN inhibitors).
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CASE STUDY 3:
A patient presents with a blistering skin disease.
A skin biopsy sample is taken and sent to the histopathology
laboratory for diagnosis
a) Explain the classification of blistering skin diseases and the mechanisms underlying blister
production (4 marks)
b) Discuss the sample handling and processing requirements needed to make a diagnosis of
blistering skin disease; compare this to routine histology samples (4 marks)
c) Describe the potential types of blistering skin disease and discuss the Cellular Pathology
techniques which would be applied to a skin sample in order to facilitate diagnosis of the
blistering skin disease (12 marks)
• 20 marks in total
22
a) Explain the classification of blistering skin diseases and the mechanisms
underlying blister production (4 marks)
• What would you write?
• 4 marks available
23
a) Explain the classification of blistering skin diseases and the mechanisms
underlying blister production (4 marks)
• Blisters can be intraepidermal (grouped according to the process causing the blister
formation) or subepidermal/basal (grouped on the nature of inflammatory cell infiltrate
within the blister.
• Blisters may be caused by friction due to shearing forces or as a result of reaction to
drugs, toxins, viruses and other irritants.
• Blistering may occur as a consequence of existing pathological conditions such as eczema
or impetigo, or it can be due to a primary blistering disorder, in which bullae (blisters greater
than 5mm diameter) are the only clinical feature.
• Primary blistering disorders are of an autoimmune nature, causes by direct antibody,
immune complex or complement deposition.
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b) Discuss the sample handling and processing requirements needed to
make a diagnosis of blistering skin disease; compare this to routine
histology samples (4 marks)
What would you write?
4 marks available (compare)
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b) Discuss the sample handling and processing requirements needed to
make a diagnosis of blistering skin disease; compare this to routine
histology samples (4 marks)
Frozen (unfixed) tissues are generally required as IMF techniques employed to
diagnose; compared to formalin fixation of routine histology samples
Exception is EB where EM is employed; EM requires specific fixation
(glutaraldehyde). Routine histology requires formalin fixation of tissues.
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c) Describe the potential types of blistering skin disease and discuss the
Cellular Pathology techniques which would be applied to a skin sample in
order to facilitate diagnosis of the blistering skin disease (12 marks)
• What would you write?
• 12 marks available! Types, discuss, techniques for diagnosis
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c) Describe the potential types of blistering skin disease and discuss the
Cellular Pathology techniques which would be applied to a skin sample in
order to facilitate diagnosis of the blistering skin disease (12 marks)
• Pemphigus – H&E and IMF on frozen sections (demonstrate IgM, IgG and C3 in intracellular
spaces between keratinocytes, in all levels of the epidermis)
• Bullous pemphigoid – H&E and IMF on frozen sections (demonstrates linear deposits of IgG
along the BM)
• Dermatitis hepetiformis – H&E and IMF on frozen sections (IgA deposit is granular, not
linear)
• Epidermolysis Bullosa (EB) – includes EB simplex, Junctional EB and Dystrophic EB (require
EM)
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CASE STUDY 4:
An elderly patient is suspected to have died with
Neurodegenerative disease. At post-mortem, the brain is sent to
the histopathology laboratory for confirmatory diagnosis
a) Discuss the sample handling techniques of brain samples in the Histopathology laboratory
and how this differs from routine samples (8 marks)
b) With reference to the hallmarks of Alzheimer’s disease, discuss the Cellular Pathology
staining techniques which could be employed to distinguish between Alzheimer’s disease and
Parkinson’s Disease (12 marks)
• 20 marks in total
29
a) Discuss the sample handling techniques of brain samples in the
Histopathology laboratory and how this differs from routine samples (8
marks)
• What would you write?
• 8 marks available.
• Discuss, differs
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a) Discuss the sample handling techniques of brain samples in the
Histopathology laboratory and how this differs from routine samples (8
marks)
Fixation of entire brains takes several weeks;
Suspension of entire brain in bucket of formalin
Sample will often be PM material (entire brains) but brain biopsies are also received in
histology
Whole brains need slicing into coronal sections;
Megablocks of coronal slices frequently used
Sectioning needs to be thicker;
H&E staining protocol often different from standard to stain the necessary components.
Brief description of standard processing/handling techniques to provide comparison (different
dissection categories – A to E for samples from biopsies to resection needing complex
dissection etc; formalin fixation ~6-24 hours; processing to paraffin wax, embedding,
sectioning at 3-5µm).
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b) With reference to the hallmarks of Alzheimer’s disease, discuss the Cellular
Pathology staining techniques which could be employed to distinguish between
Alzheimer’s disease and Parkinson’s Disease (12 marks)
• What would you write?
• 12 marks available!
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b) With reference to the hallmarks of Alzheimer’s disease, discuss the Cellular
Pathology staining techniques which could be employed to distinguish between
Alzheimer’s disease and Parkinson’s Disease (12 marks)
• Hallmarks of AD include:
1) Loss of neurons (atrophy)
2) Senile plaques containing Beta amyloid
3) Neurofibrillary tangles composed of phosphorylated microtubule associated TAU protein
4) Neuropil threads – TAU protein in nerve cell processes
5) Cerebral amyloidosis – amyloid deposits
Cont’d
33
b) With reference to the hallmarks of Alzheimer’s disease, discuss the Cellular
Pathology staining techniques which could be employed to distinguish between
Alzheimer’s disease and Parkinson’s Disease (12 marks)
• Cell path staining techniques:
1) Atrophy demonstrated by measurement, weight of entire brain at dissections;
• 2) BRAAK & BRAAK staging
• 3) Beta amyloid – IHC (?A4 antibody)
• 4) TAU protein – IHC
• 5) Amyloid – Congo red (special stain; red under light microscopy; birefringence green under
polarised light)
• Extra marks if amyloid hypothesis mentioned/discussed.
• Parkinson’s – diagnosed more via symptoms and PET scans to assess dopaminergic activity;
Lewy body disease – demonstrated via IHC (antibodies NFP, Ubiquitin, ??crystallin and ?A4)
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Revision Tips…
•Read the content in the Learning Room!
•Don’t rely on the extra time to look everything up!
•Make sure you have a thorough knowledge of the basis of Cell Path
(from specimen receipt to staining/microscopical diagnosis)
•Quality process underpins everything we do in the lab
•Cancer topics x7 (you will be asked about 3 of these, so read about
them all!)
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Revision Tips…
•Use the Table you generated as Activities throughout the Content
(Weeks 28 -32) for revision – this was designed to help you with the
case studies:
–Epidemiology (patients affected e.g. population, young/old;
male/female etc; symptoms etc)
–Cell Path diagnosis (sample types, techniques used in Cell Path H&E, Special stains, IHC, EM, molecular etc; main grading/staging
system used for each – spot for anomalies/differences)
–Prognosis/treatment (drug treatment options based on Cell Path;
personalised medicine; new treatments, research etc)
•Remember – this module is looking at APPLICATION of Cell Path in
diagnosis & prognosis
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Research Questionnaire
• If you are happy to consent to participating in my short module research questionnaire,
please complete this now and email the consent form back to me
• I will then provide a link to the questionnaire
37
The end!
Thank you!
I won’t see you next week ?
Best of luck in the Phase Test!
I hope you have enjoyed this Module?
Don’t forget to feedback via MySay 15th March – 1st April!
Video re How to understand assessment questions – approx. 10 mins
39

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