Diagnostic Cytology Flashcards
What is diagnostic cytology
(4)
The analysis of cytological specimens to aid the diagnosis of disease - not a screening test
Various body sites
Various specimen types
Various preparation techniques
What is another application of diagnostic cytology other than in a hospital setting?
Cell analysis e.g.
Cell culture work
Morphological analysis of cells
Biochemical analysis
Molecular biology based analysis - genomics/proteomics
What are the two diagnostic applications of cytology
Pathology e.g. morphological diagnosis
Differential diagnosis e.g. type/classification of pathology
What are some diagnostic applications of cytology in the lab
Benign vs malignant
Primary vs metastatic
Site of origin
Management strategies
Therapeutics
What body sites are samples for cytology from
(9)
Body cavities
Respiratory tract
Head and neck
Male/female genital tract
Urological
Neurological (CSF)
Soft tissue and bone
GIT
Organs and systems
- thyroid
- lymphoid
- breast
- liver
- kidney
- pancreas
What specimen types would you expect in cytology
Fluids
Washings
Brushings
Fine Needle Aspirates (FNA)
Urine
CSF
What kinds of fluids would you see in cytology
(3)
Often drains
- e.g. liver tumours cause build up of cavity fluid (ascites) -> this can be drained and sent to cytology or it could be aspirates by a needle
- e.g. thyroid cyst fluid etc
Cells in suspension
Give an example of a washing you would see in the lab
(4)
Abdominal washings -> someone under surgery e.g. hysterectomy
Surgeon will do a wash out of the body cavity afterwards
Will test to see if there are any malignant cells in the wash out
If so patient will have to go for chemotherapy
Give an example of a brushing you would see in the lab
Bile duct brushing
-> brush on end of endoscope
Give an example of a fine needle aspirate
Needle is washed out -> cells from FNA put into a fluid and sent to a lab
What is so important about CSF
You might only get a few drops to use
What miscellaneous specimens would you get in cytology
(4)
Imprints
Scrapings e.g. skin
Smears e.g. cervical
Faeces -> looking for fat globules in children failing to thrive
What is the principle behind FNA?
(3)
Cells are aspirated from a solid lesion using a fine needle under negative pressure (vacuum) and processed for microscopic examination
Can always go back and get more
Patients can often tolerate 2 or 3 FNA without anaesthesia
What are the five most common FNAs
Lung (Transbronchial/Percutaneous/ EBUS)
Thyroid (Patient management)
Lymph node (Reactive/primary/metastatic)
Breast (symptomatic/Steriotactic)
Salivary gland (Patient management)
What is an EBUS?
(3)
Endoscopic bronchial ultrasound
Mostly used for mediastinal lymph nodes
Use ultrasound and FNA to access lymph nodes instead of having to go for surgery to open the chest
FNA can be used on what internal organs
Liver
Pancreas
Kidney
Prostate
FNA can be utilised along with what imaging
CT Scan
Ultrasound
EUS
Write about the examination of thyroid tissue
(5)
FNA: patient management
High levels of follicular cells -> patient needs to go on for further investigation -> could be Benign vs malignant tumour
Therapeutic
Consideration:
- blood stained
- colloid (purple material, cracking when dry)
Hertle cells seen in hashimotos
Nuclear vaculation classic for papillary carcinoma of the thyroid
What fluid types can you get in the lab
Body cavity fluids
- Pericardial
- Pleural
- Peritoneal
Ascitic fluid
- Abdomen
Cyst fluid
- Breast, Ovarian, thyroid, others
Joint fluid (synovial)
What is mesothelioma?
(3)
Cancer that begins in the tissue mesothelium that lines the lungs, heart, stomach and other organs
3D balls of cells with inflammatory cells in the background
Often cells high in protein
What do signet cells indicate
Carcinoma
Give three examples of metastatic disease and how you would test for them
Melanoma (Melan A)
Ovarian cancer (Cytokeratin 7)
Ductal carcinoma of breast (Oestrogen receptor)
What respiratory samples could you get
(5)
Sputum (not very often, this usually goes to micro)
Bronchial Wash/aspirate
Broncho-alveolar lavage
Bronchial brush
FNA
- transbronchial
- percutaneous
- Endoscopic bronchial ultrasound (EBUS)
What are the two developments in bronchoscopy
EBUS
ROSE
What is an EBUS
(6)
Endoscopic bronchial ultrasound
Allows us to target lymph nodes
Ultrasound lets us see contrast
Allows for staging and diagnosis on the same sample
Might not even need to do a bronchoscopy -> can go straight to lymph nodes -> late stage
If no indication of lymph node involvement (early stage) then they will go for bronchoscopy only
However lung cancer is often only seen in late stage where the lymph nodes are affected
What is ROSE?
(3)
Rapid on-site evaluation of fine needle aspirates (FNA)
Specimen management
Adequate samples for diagnosis and ancillary testing
Have we enough cells for downstream analysis and have the cells been preserves correctly -> are there sufficient abnormal cells
What should you consider for biopsies
Small fragments
Assessment of invasion
What should you consider for cytology samples
(4)
Mucus
Blood
Biological hazard
Representative specimen
What should you consider for larger resections
Fixation
Perfusion of fixative
What should you consider for biological hazards
Fresh or unfixed tissue
How would you investigate lung cells
(6)
Benign vs Malignant
Primary -> squamous, adeno or small cell carcinoma
Secondary -> metastatic from where
Ancillary studies
- differential diagnosis
- Therapy related
What are the two main types of lung cancer?
(2)
Small cell versus non-small cell carcinoma
NSC = squamous cell carcinoma vs adenocarcinoma
How is typing a lung tumour important for therapeutics
Tyrosine kinase inhibitors (EGFR and ALK)
Immunotherapy such as PD-L1
What are two names of EGFR inhibitors
Erlotnib
Gefitinib
What is a name of an ALK inhibitor
Crizotinib
Comment on the stats for lung cancer in Ireland
Over 2500 cases per year
Single most common cancer death
Approx 1800 deaths a year
Incidence in you women higher than EU average but decreasing in men
Reduction in squamous carcinoma but increase in adenocarcinoma
Only 55% live over 1 year after diagnosis
15% survive overall
Difficult to diagnose and treat
What increases risk of lung cancer
(6)
Smoking (up to 90% of cases)
Environmental
Radon
Asbestos
Environmental carcinogens
Chronic lung disease
How does smoking cause lung cancer
(5)
Cytochrome p450 activation
GST inactivation
DNA repair genes
Apoptosis bcl-bax pathway
p53, kras, Rb, E-cadherin-beta catenin complexes
Comment on p53 and lung cancer
p53 protein and antibodies can be measured in blood as a prognostic inficator
What is chromogranin used for?
detection of small cell carcinoma
What percentage of lung cancer are small cell carcinomas
15%
What percentage of lung cancer are non small cell lung cancer
65%
What are the three types of NSCLC
Squamous cell carcinoma
Adenocarcinoma
Large cell carcinoma
What percentage of NOS/other?
20%
Write about the laboratory diagnosis is lung cancer
(6)
Need to use IHC/Molecular methods to sub-class lung tumour
Keratins -> CK5/6, CK7/CK20
p63
TTF-1
Napsin A
Chromogranin
What therapeutics is there for lung cancer
EGFR
ALK
What markers are used for NSCLC classification
p63
TTF-1
Napsin A
What is considered a promising marker for squamous cell carcinoma?
PD-L1
What are the treatment options for squamous cell carcinoma
Surgery
Chemotherapy
Radiotherapy
What growth patterns are seen in adenocarcinoma
Glandular, papillary, mucins producing and lepidic growth patterns
What are the oncogenic drivers of adenocarcinoma?
(5)
EGFR
KRAS
ALK
MET
BRAF
What percentage of adenocarcinomas are caused by EGFR
10-40%
Why would an EGFR mutation be considered a good thing in adenocarcinoma
These respond to tyrosine kinase inhibitors
What happens to ALK in adenocarcinoma
ALK rearrangement in 5% of adenocarcinoma
Responds to Crizontinib
What happens in most of the lung cancer treatments?
Between 6 months to 2 years, patients will develop resistance
Research into strategies/treamtents to overcome resistance
Write about small cell lung cancer
(7)
High grade tumours
- present with early metastases
- fatal in 2-4 months if untreated
- less than 7% survive more than 5 years
Cisplatin and Etoposide used for treatment
Prophylactic cranial irradiation can be used if patient responds to chemotherapy at primary site
Rapid development of resistance -> relapse in 6-12 months with resistance
What ancillary studies are there for Lung cancer
(4)
Histochemistry but limited applications
Tumour classification -> site of origin and primary or secondary, adeno, squamous, small cell, melanoma etc
Flow cytometry -> non-Hodgkins Lymphoma
Prognostic and therapy markers
Write about immunocytochemistry
Important in diagnostic cytology and research
Fixation
- alcohol fixation, air dried or special fixation protocols
Cell blocks
Application:
- identify or confirm cell type
- identify cell constituents
Identify primary origin of metastatic tumours
- especially in fluids and FNAs
Prognostic and therapy markers
Write about quality control
(6)
Documentation of any discrepancy
Remedial action
Quality of the slide preparation
Quality of the stains
Quality of coverslipping
Re-process sample
- Limitation if low cell yield
What is UKNEQAS?
(5)
New EQA scheme for diagnostic cytology
Staining quality
- PAP and MGG
Interpretive scheme
- Digital format
Write about screening
(5)
Primary screening of slides
- SHO/Registrars/Medical scientists
Mark cells of interest
Suggest diagnosis
Reporting session with Consultant
Developments in UK for BMS reporting (specialist diploma)
Write about Reporting
(6)
Consultant reports the case
Additional tests may be requested at this stage -> often pre-requested at FNA procedure
Allocate SNOMED/SNOP codes
Computer generated report
Authorised and edited if necessary
Validated and released
