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BASICS OF CYTOLOGY
What is cytology ?
Cytology is the study of free cells to diagnose disease.
What are the advantages of cytology ?
Quick diagnosis
Same day diagnosis possible for benign lesions
Cheap compared to histology
Less invasive for patientS
Faster recover time
What are the disadvantages of cytology ?
require high expertise for interpretation
May be sensitive and specific than histology
Ancillary tests are sometimes not possible
Why are the advantages of histology compared to cytology ?
Gold standard for diagnosis
Easier to perform ancillary tests
Allows grading of tumours
Determines receptor status of malignant lesions
Allows special stains, immunocytochemistry and molecular panels
What are the disadvantages of histology?
Same day results are difficult
More expensive
More invasive for patients
Cytology Sample Collection
How can cytology diagnostic samples be obtained?
Scraping a tissue surface
Cells from urine or sputum
Brushing or washing cells during surgical procedures
Aspiration with a needle from lumps or lesions
What sites can cytology samples be taken from?
Bladder
Pancreas
Bile duct
Pleural fluid
Pericardial fluid
Peritoneal fluid
Synovial fluid
Breast
Thyroid
Salivary and parotid glands
Hydrocoele fluid
Lymph nodes
Processing Cytology Samples
What happens when fluid samples are centrifuged?
Centrifugation separates components:
Plasma → rises to the top
Buffy coat → middle layer containing white blood cells and tumour cells
Red blood cells → bottom layer (small and dense)
Cells from the buffy coat are pipetted and spread on a glass slide as a monolayer for staining.
What fluids are commonly analysed in cytology?
Urine
CSF
Serous effusions
Lung
Abdomen
Cysts
What is a cytocentrifuge (cytospin)?
A technique used when fluids contain very few cells, concentrating them onto a slide for microscopy.
Cytology Stains
What is the Romanowsky stain used for?
Used on air-dried specimens
Provides good cytoplasmic detail
Consists of:
May-Grünwald
Giemsa
What is the Papanicolaou stain used for?
Used on wet-fixed specimens
Provides good nuclear detail
Consists of:
Haematoxylin
EA50
OG6
Cerebrospinal Fluid Cytology
What is cerebrospinal fluid (CSF)?
A clear watery fluid surrounding the brain and spinal cord.
Where is CSF located?
Subarachnoid space
Central canal of the spinal cord
What is the origin of CSF?
It is an ultrafiltrate of blood plasma.
Why is cancer spread to the CNS serious?
It causes:
Neurological symptoms
Rapid mortality
Urine Cytology
What conditions can urine cytology detect?
Infection
Inflammatory disease of the urinary tract
Cancer
Precancerous conditions
Why is urine cytology commonly performed in haematuria clinics?
Patients with blood in urine (haematuria) are investigated because 10–25% may have cancer, usually bladder cancer.
What additional tests are usually performed alongside urine cytology?
Ultrasound
Cystoscopy
Which occupations increase bladder cancer risk?
Workers in the dye industry, especially exposure to aniline dye intermediates such as benzidine.
What is the average latency period for occupational bladder cancer exposure?
23.3 years from exposure to diagnosis.
What lifestyle factor increases bladder cancer risk?
Smoking, due to exposure of bladder cells to chemicals in cigarette smoke.
Types of Bladder Cancer
What is the most common bladder cancer type?
Urothelial (transitional cell) carcinoma – about 90% of cases in the UK.
What are urothelial cells?
Cells lining the bladder that:
Bunch together when bladder empty
Stretch into a single layer when bladder fills
What percentage of bladder cancers are squamous cell carcinoma?
About 5%.
What infection increases risk of squamous bladder cancer?
Bilharzia (schistosomiasis) caused by a freshwater parasitic worm.
Where is squamous bladder cancer more common geographically?
Africa
Asia
How common is bladder adenocarcinoma?
Very rare – 1–2% of cases.
What cancers can originate in bladder muscle or structural tissue?
Sarcomas
What is small cell carcinoma of the bladder?
An aggressive poorly differentiated neuroendocrine tumour.
Bronchoscopy & Lung Cytology
What is a bronchoscope/endoscope?
A tube with fibreoptics or a camera used to examine airways and obtain samples.
What features does a bronchoscope include?
Viewing lens
Instrumentation channel
Can deliver:
Water
Anaesthetic
Biopsy tools
What cytology sampling methods are used during bronchoscopy?
Bronchial biopsy
Brush cytology
Saline washings
What is bronchoalveolar lavage (BAL)?
A procedure where sterile saline washes distal airways and alveoli to collect cells.
When is BAL used?
Deep lung tumours
Opportunistic infections (e.g., Pneumocystis carinii in HIV)
Haemoptysis
Persistent cough or wheeze
Lung Cancer Types
What are normal bronchial cytology cells?
Ciliated cells
Macrophages
Neutrophils
Mucus
RBCs
What is squamous cell lung carcinoma?
Second most common lung cancer
Originates in central bronchi
Often linked to smoking
Tumours often show central necrosis
Develops via squamous metaplasia
What is lung adenocarcinoma?
Most common lung cancer
Originates from alveolar epithelium
Often has many DNA mutations
Often advanced at diagnosis
What is small cell (oat cell) lung carcinoma?
Highly malignant
Early metastasis
Responds well to chemotherapy and radiotherapy
Neuroendocrine tumour producing ectopic hormones
Thyroid Cytology
What is the thyroid gland?
A butterfly-shaped gland at the base of the neck.
What hormones does the thyroid produce?
Thyroxine (T4)
Triiodothyronine (T3)
What functions do thyroid hormones regulate?
Heart rate
Blood pressure
Body temperature
Energy metabolism
What are thyroid nodules?
Lumps arising within a normal thyroid gland.
How common are thyroid nodules?
About 1 in 10 people develop one by age 50.
What percentage of suspicious thyroid nodules are malignant?
Less than 10%
What technique is used to sample thyroid nodules?
Fine Needle Aspiration (FNA).
Thyroid Pathology
What are follicular cells?
Main thyroid cells that produce T3 and T4 and form cuboidal epithelium around follicles.
What is thyroid colloid?
Material within thyroid follicles
Appears blue/mauve with MGG stain
Seen as background wash
What can excess colloid indicate?
Benign goitre.
What causes most goitres?
Iodine deficiency (≈90%), causing thyroid hyperplasia.
What is Hashimoto’s thyroiditis?
An autoimmune disease causing progressive destruction of the thyroid gland.
Thyroid Cancer
What is the most common thyroid cancer?
Papillary thyroid carcinoma (~85%).
Key features of papillary thyroid carcinoma?
More common in women
Age 20–55
Slow growing
Forms papillae
Has nuclear grooves
Treated mainly with surgery
What is medullary thyroid carcinoma?
Cancer arising from parafollicular (C) cells.
Key features of medullary thyroid carcinoma?
25% hereditary
Causes diarrhoea
Amyloid stroma
Parafollicular cell hyperplasia
Psammoma bodies
Treatment for medullary thyroid carcinoma?
Total thyroidectomy with bilateral neck dissection.
Breast Cytology
How common is breast cancer?
It accounts for 25% of cancers in women.
What is the peak incidence of breast cancer?
Age 55–69
When does breast screening begin?
age 50.
What is the 5-year survival rate for breast cancer
80–90%
What structures make up the breast?
Fat
Stroma
Glandular tissue
Ductal system
6–10 main ducts opening at nipple
Signs of breast cancer?
Breast lump
Change in breast shape
Skin dimpling
Nipple discharge
Inverted nipple
Red or scaly skin patch
What percentage of breast cancers are genetic?
About 5–10%.
Which gene mutation is linked to hereditary breast cancer?
BRCA mutation
What is the most common breast cancer type?
Ductal carcinoma (~80%)
What is DCIS?
Ductal carcinoma in situ – non-invasive cancer confined to ducts
Cytological features of ductal carcinoma?
Cellular smear
Less cohesive cells
No myoepithelial cells
Crowded epithelial sheets
Necrosis may be present
What is lobular carcinoma?
Cancer arising from breast lobules, accounting for 10–15% of cases.
Why is lobular carcinoma hard to detect?
Often does not form a lump
Low cellularity
Minimal atypia
Cells arranged in linear cords
What is fibroadenoma?
common benign breast lesion in young women.
Cytology of fibroadenoma?
Cellular aspirates
Large branching sheets of ductal cells
Myoepithelial cells (“sesame seeds”)
What does HER2 indicate in breast cancer?
A receptor controlling cell growth, division and repair.
What happens in HER2-positive cancers?
Tumour grows faster
Spreads more quickly
But responds well to targeted drugs