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Differential Diagnosis – Role of Laboratory Investigations

Knowledge is the enemy of disease
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Diagnosis is about probability
• No diagnosis is every absolute – so you must continually review it
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• When a patient has a presentation typical of a disease, they usually have a typical history, typical signs
and typical investigation results
...
As the list shortens,
the probability of each diagnosis being right increases
...

• At each stage of the process, the list itself is called the ‘differential diagnosis’
...

• At each stage of the process of narrowing the list down, the diseases at the top of the differential will be
investigated first
...


Principles of Diagnosis
• History
o Of complaint
o Medical history and MH questionnaire
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• Differential diagnosis/diagnosis
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• Differential diagnosis/diagnosis
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• Repeat/review
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• Erythema Multiforme
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Investigations
• Tests of tooth vitality – key investigation
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o CT, MRI
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o Nuclear medicine sounds
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o Immunofluorescence
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• Haemotology/serology assays
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- Example Finals Q: How do you know a vitality test is valid? A: False +ves and False –ves etc
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• The ideal test is specific – it detects only
one condition/disease
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- True +ve indicates the test has worked
correctly
...

o Sensitivity and specificity just reflect how good the test is in the lab
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• Positive Predictive Value rises when a disease is present (and the negative PV falls)
...


Value of the Test depends on how it is used
• A test MUST answer a specific question framed by the clinician in the light of history and examination
...

• Conversely, wrong used tests don’t work – you cannot obtain a diagnosis by throwing every test at a
patient
...

• Screening tests, useful tests are:
o Cheap, rapid, acceptable test that tells whether a person is likely to have a condition or not
...
1st test to decide whether
someone should go on for more deeper investigations
...
g
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• Diagnostic tests, whose usefulness depends on:
o Need for test – why is it done?
o Situation in which used:
! Incidence of disease
...


! Ability to define a “cut off” level
...
5 or even 1
unit
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• Is not a TEST, it is a medical opinion
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- Dysplasia – pre-cancer state
- Lichen plasia – keratosis of buccal mucosa


Biopsy
(Greek: Bios + opsis = life + see, ant
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• The examination and removal of tissue
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• Types of intention:
o Incisional
o Excisional
• Types of procedure:
o Surgical
o Fine needle aspiration

o Trucut and needle biopsy
o Curettage

What can be done with the Tissue?
• Histology
o Routine section stained with Haeatoxylin and Eosin (H+E) and other special stains
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o Frozen section for rapid diagnosis
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• Electron microscopy
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Provided the specimen is taken correctly and presented correctly to the lab
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Would perform an ID block for analgesia and a local infiltration for vasoconstriction
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• Fix the specimen as quickly as possible
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• Fill out the request form with the clinical details
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• Follow up the report… check if it maps the result of what you expect from the pattern of the disease
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• Resorbable sutures for biopsy (10 days – 2 weeks) to prevent patient coming back – patient hates them as
they are very uncomfortable – better to use silk, review after 3 days and then remove (kinder on patient
and they return for a review)
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• For a medical condition of the mucosa – a 10mm biopsy is ideal (6-7mm is acceptable) ! 4-6mm wide
incision clearly down to fat/muscle, biopsy free from underlying tissue
...
Is a dimorphic fungus
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• Best seen on smear – form and site known – scrape cells off
surface epithelium
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• Culture to detect species and resistance to antifungals
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• Electron microscopy, PCR and ELISA for viruses
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• DNA probes
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o RBC and WBC and platelet counts
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• “haematinics” ferritin, folate, B12
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• ESR – Erythrocyte Sedimentation Rate
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• Other coagulation tests
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• Sickle cell test
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• Autoantibodies, gastric parietal cell, thyroid, mitochondrial, ANA, ENA, rheumatoid factor
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• HIV test
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• Angiotensin Converting Enzyme (ACE)
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• Allergy skin tests
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• Liver function tests
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• Cortisol level
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o Familial
• HbA1c glycosylated Hb
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• Clonality Analysis
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SUPPLEMENTARY NOTES

Learning Objectives:
• Understand the importance of different test types in diagnosis
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• Explain how the predictive value of tests varies with how it is used
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Be able to define sensitivity, specificity, Positive Predictive Value and
Negative Predictive Value
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• Understand the roles of clinical and family history, of clinical findings and of special tests in arriving at a
diagnosis
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Recommended Reading
• Chapter 1 Cawson’s Essentials of Oral Pathology and Medicine, 8th edition
...


Differential Diagnosis:
• In a series of steps, each narrowing down the list of possible causes of a complaint
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• This is the process of differential diagnosis
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• It is traditional to put the most probable diagnosis first in the list and to push less likely but more
significant diseases up the list
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• Diagnosis proceeds by collecting
evidence for particular diseases and
also by excluding them
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• Tests of tooth vitality
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o CTI, MRI
o Ultrasound
o Nuclear medicine scans
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o Immunofluorescence
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• Haematology/serology assays
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Key Principles
• A test MUST answer a specific question framed by the clinician in the light of history and examination
...

• Conversely, wrongly used tests don’t work – you cannot obtain a diagnosis by throwing every test at a
patient
...


• Diagnostic tests, whose usefulness depends on:
o Need for test – why is it done?
o Situation in which used?
o Incidence of disease
...


SUPPLEMENTARY NOTES ON BIOPSY-TAKING

Differential Diagnosis and Investigations for Oral and Head & Neck Disease
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• Understand diagnostic theory
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Be aware of the implications of false
positive and false negative results
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• Appreciate the fundamental importance of accurate diagnosis as the basis of rational prevention and
treatment and be aware of the dangers of empirical therapies
...
This information is not covered in the lecture but has been partly covered in
microbiology, immunology and pathology courses and will be covered in future lectures
...


Notes on Biopsy

INDICATION
• To make or confirm clinical diagnosis of swellings, ulcers, erosions, colour changes, texture changes
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PRECAUTIONS AND PROCEDURES
• Usual medical problems (E
...
bleeding tendency, infection risk, steroid etc as for any minor surgical
procedure)
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• Oral incisional biopsy should carry minimal risks
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FIXATION AND SUBMISSION TO THE LAB
• Specimens are routinely placed IMMEDIATELY in 10% buffered formal saline – you must have 10x the
volume of the sample and the container must be large enough not to squash the specimen
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The main
indications for this are to perform immunofluorescence and diagnosis of possible malignancy
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• Pots must be labeled
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• Those sent by post must meet Post Office Regulations
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• Allows specialist to see undisturbed clinical lesion
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• May induce less or more anxiety
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• Costs, patient and hospital time and resource
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• Potential seriousness
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• Access to hospital
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When to Biopsy
The value of biopsy in diagnosis varies with the type of lesion
...
Biopsy should never be an automatic step in diagnosis
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Deciding to perform a Biopsy
• Define a differential diagnosis
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• Types of biopsy (incisional and excisional)
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What to Biopsy
In general practice, most pathologists would expect dentists to submit for examination any tissue removed
from the patient
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In a practice
setting, most biopsy will be for confirmation of a relatively secure clinical diagnosis, e
...
lichen planus, fibrous
epulis, denture-induced granuloma, low-risk white patches
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If it is worth excising, it is worth examining
histologically
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1
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It is preferable to have the biopsy performed by the person or
team which will manage the patient’s care
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Refer the patient to a hospital for
urgent opinion and biopsy
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Haemangiomas and other vascular lesions which may bleed excessively
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3
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Infection could be disastrous
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Any patient who obviously needs hospital care or treatment once the diagnosis is made
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Lesions on the soft palate where tearing of the tissue and retching make biopsy difficult
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Any lesion where your experience might prevent you from obtaining an ideal specimen
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7
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Types of Biopsy
The type of biopsy most commonly performed in practice is a surgical biopsy
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There are 2 types of Surgical Biopsy
1
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Useful for large lesions
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EXCISIONAL: The whole lesion is removed
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g
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Occasionally used in practice (e
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large
denture-induced granulomas)
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Decide whether to perform an incisional or excisional biopsy:
• This will depend on the clinical diagnosis, size of the lesion, anatomical site and accessibility
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Select area to be removed:
• The area selected will depend on the likely diagnosis
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•
•
•
•

Always include some adjacent normal tissue
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If the lesion is thought to be premalignant, always include red areas
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3
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• Consider general anaesthesia for oropharyngeal specimens, when gagging is a problem or for
problematic patients
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• However, avoid injecting directly into the biopsy site as this will distort the tissues
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Pass a Suture through the area to be removed:
• A suture is a good way to hold and control the tissue during removal, to prevent it being swallowed
or aspirated by the suction
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• Avoid using forceps as they crush the tissue and can make microscopic interpretation impossible
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Incise around the area to be removed:
• Try to keep the incision at right angles to the surface so that the edges of the specimen are not
beveled
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6cm wherever possible and elliptical to aid closure
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Separate the specimen from the underlying tissue:
• Use the suture to raise the specimen and undermine it keeping the thickness about 2mm minimum
wherever possible
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• When lesions lie beneath the mucosa, ensure adequate depth to obtain a representative sample of
the deep tissue
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Place the specimen in Fixative immediately unless some is required for culture or specific tests:
• Specimens are routinely fixed in 10% formal saline
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Do not allow the specimen to dry out
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8
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9
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• The purpose is to ensure as accurate as a diagnosis as possible and not to see if the pathologist can
guess the diagnosis without the relevant information
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• Enclose radiographs and clinical photos if appropriate and available
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