cancer of head & neck - basics
TRANSCRIPT
CANCER OF
HEAD & NECK
Contents
• Introduction• Definition• Nomenclature• Classification • Epidemiology• Etiology• Molecular biology • Tumor metastasis• Clinical features
Introduction
• Cancer is the common term for all malignant tumors.
• Cancer (Latin word) : crab (Ancient Greek word)
• Presumably because, a cancer cell adheres to any part that it seize upon in an obstinate manner like a crab.
• The study of cancer is – “Oncology’’
onco = Greek onkos, meaning bulk, mass, or tumor,
logy = study
Definition
• Common terminologies : cancer or tumor
• Literature terminology : neoplasia or neoplasm
• It is a disorder of cell growth, characterized by uncontrolled, uncoordinated & undesirable cell division.
• There is no exact definition for cancer.
• British oncologist – Dr. Willis tried to define it as –
“A neoplasm is an abnormal mass of tissues,
the growth of which exceeds & is
uncoordinated with that of the normal tissues and
persists in the same excessive manner after
cessation of stimuli, which evoked the response ”
Kumar V. , Abbas A.K. , Fausto N. 2007. Robbins & Corton Pathologic Basis Of Disease.7th ed. Saunders. ISBN 10: 0721601871
Nomenclature
Condition Tissue involved Suffix
Benign Mesenchymal tissue Oma
Benign Epithelial tissue
• adenoma• Papilloma• Cystadenoma• Papillary cystadenoma• polyp
Malignant Mesenchymal tissue Sarcoma
Malignant Epithelial tissue
Carcinoma
Classification
• More than 90% of head and neck malignancies are squamous cell carcinomas.
L. Licitra, E. Felip. Squamous cell carcinoma of the head and neck: ESMO Clinical Recommendations for diagnosis, treatment and follow-up. Ann Oncol . 2009; 20 (4):iv121-iv122. doi: 10.1093/annonc/mdp149.
• According to Stell & Maran’s Textbook Of Head & Neck Surgery & Oncology
CANCERS OF HEAD & NECKSquamous cell carcinoma Non - Squamous cell carcinoma
1. Cancer of oral cavity & oropharynx
2. Cancer of larynx & hypophaynx3. Cancer of nasopharynx4. Cancer of nasal cavity & paranasal
sinuses
1. Cancer of thyroid2. Cancer of salivary glands3. Sarcomas - soft tissue - hard tissue
Epidemiology
• Cancer is a leading cause of death worldwide, accounting for 7.6 million deaths (around 13% of all deaths) in 2008
• Head and Neck Cancer: Worldwide – 640,000 cases /year 356,000 deaths per annum (55% mortality) 5% incidence of all cancers (excl. skin) 5% mortality of all cancers
GLOBOCAN 2008 (IARC) Section of Cancer Information (8/12/2013).
Geographical distribution
- wide variations
France (supraglottic, oral cancers) Hong Kong (nasopharyngeal cancers) India (oral cancers)
Age & gender predilection
Region of cancer
Contribution
Oral cavity 41- 43%
Oropharynx 3rd most common
Larynx 30 %
Hypophaynx 10%
Nasopharynx 1-2%
Nasal cavity Rare
Paranasal sinuses
Rare (60-70% in
maxillary sinus)
Etiology
1. Tobacco
2. Alcohol
3. Dental factors
4. Occupational exposures
5. Infections
6. Nutritional factors
7. Inflammatory cause
8. Genetic factors
9. Immunologic factors
10. Endocrinal disturbances
11. Radiation
Tobacco
Smoking :• 90% cases • Contains 30 known carcinogens : polycyclic aromatic hydrocarbons
: nitrosamines• Alcohol adds up in pathology
Black / darkAir cured
Blend & blondFlute cured
More carcinogenic
The areas of oral cavity which is bathed with saliva, are most common sites to be involved.
Eg. – oropharynx, crypts of tonsil, glossotonsillar sulcus, tongue, soft palate &
posterior pharyngeal wall.
Smokeless :• Most common in Indian suncontinent
Bidi Chutta
khaini paan
Alcohol• Synergistic action with tobacco.• Mostly associated with cancer of - lateral border of tongue
- glossotonsillar sulci
- pharyngoepiglotic fold
7 possible mechanisms –
1. Acts as an solvent
2. Some contents of alcoholic beverages
3. Metabolites like – acetaldehyde
4. Up regulation of enzyme – cyt p450
5. Decreased activity of DNA repair enzymes
6. Impairment of immunity
7. Decrease resistance to cancer
• Different alcoholic beverages have different carcinogenic contentes :
- Beer – Nitrosomethylamine
- Dark liquor – ester,
acetaldehyde
- Wine – tannin
- Light liquor – ester,
acetaldehyde
Dental factors• Sharp tooth
• Oral hygiene
• Patients with ill fitting dentures
• Alcohol containing mouth washes
(to mask the smell of tobacco/alcohol)
Occupational exposuresCancer Associated factors
Cancer of oral cavity & oropharynx
Wood dust, chemicals, coals
Cancer of larynx & hypophaynx
Wood dust, Ni & mustard gas and
asbestos exposure, H2so4 & HCl
exposure in battery plants
Cancer of nasopharynx
Cancer of nasal cavity &
paranasal sinuses
Wood dust, textile & lather dust, flour, formaldehyde, solvents, Ni &
Cr dust, mustard gas, radium, isopropyl alcohol.
Cancer of salivary glands Ni alloy dust & si
Sarcomas Urethane, ethylene derivatives, polycyclic hydrocarbons
Infections
30-100% verrucous carcinoma50% cases of NPC have HPV
5% cases of H&E cancers have HIV inhections (kaposi sarcoma)
Mostly associated with nasopharyngeal cacinoma
42 % oral cancer & all smokers with & without cancer,have higher HSV antibody titre.
Nutritional factors Anti-oxydantsVit A , C, E
Carcinogenic nitrosamine in high salted fish (NPC)
Diet low in iodine : carcinoma of thyroid gland
Inflammatory cause
1. GERD : Risk factor in 36-54 % cases of laryngeal / pharyngeal cancer.
2. PRECANCEROUS CONDITIONS OR LESIONS : leukoplakia, erythroplakia
OSMF – in anterior palatoglossal arch
Genetic factors
• Li- Fraumeni syndrome : autosomal dominant condition
mutation of p53 gene
• Fanconi’s anemia• Bloom syndrome• Ataxia• Telegiactasis
• 4-6% of cancer of larynx & hypophaynx have history of
- plummer vinson syndrome
or
- Patterson Brown – Kelly syndrome
Autosomal recessive disorder with increased chromosomal fragility are associated with
oral cavity & pharyngeal carcinoma.
• Cancer of nasopharynx has strong predilection for interaction between genetic & environmental factors.
• Gardener syndrome• Multiple polyposis• Cowden disease• Multiple endocrine neoplasia (autosomal dominant)
• Li- Fraumeni syndrome• Children with ratinoblastoma• Gardener syndrome• Nevoid basal cell
carcinoma syndrome
Increased incidence of thyroid cancer.25 % cases associated with hereditary form
osteosarcoma
sarcoma
Immunologic factors
• Patient suffering from HIV infection.
• Patient on long term immunosupressive medication for organ transplantations (risk of cancer of skin & oral cavity).
• Compromised general condition
Endocrinal disturbances
• Early menarchy • Nulliparity
• Older age at full term pregnancy• Log term Oral contraceptive
Increased risk for salivary gland carcinomas
Decreased risk for salivary gland carcinomas
Radiation
• NPC : Previous history of radiation therapy for cricoid carcinoma or carcinoma of posterior wall of pharynx.
• Thyroid & salivary gland cancer : history of radiation therapy, exposure to radiation fallot from nuclear power plant or nuclear weapon in childhood .
Biology of tumor growth
• 4 stages of tumor growth
1. Malignant changes in 1 cell (transformation)
2. Growth of transformed cell
3. Local invasion
4. Distant metastasis
Molecular basis of cancerAlteration in 4 normal regulatory genes
I. Growth promoting oncogenes
II. Growth inhibiting tumor suppressor genes
III. Genes that regulate apoptosis
IV. Genes involved in DNA repair
Growth promoting oncogenes
• A proto-oncogene is a normal gene that can become an oncogene due to mutations or increased expression.
• Proto-oncogenes code for proteins that help to regulate cell growth and differentiation.
• An oncogene is a gene that has the potential to cause cancer. In tumor cells, they are often mutated or expressed at high levels
Growth inhibiting tumor suppressor genes
• A tumor suppressor gene, or anti-oncogene, is a gene that protects a cell from the path to cancer.
• Tumor-suppressor genes, or more precisely, the proteins for which they code, either have a dampening or repressive effect on the regulation of the cell cycle or promote apoptosis, and sometimes do both.
Genes that regulate apoptosis
• The tumor-suppressor protein p53 accumulates when DNA is damaged due to a chain of biochemical factors.
• Part of this pathway includes alpha-interferon and beta-interferon, which induce transcription of the p53 gene - p53 protein level and enhancement of cancer cell-apoptosis.
• P53 - stopping the cell cycle at G1/interphase, to give the cell time to repair, however it will induce apoptosis if damage is extensive and repair efforts fail.
• Any disruption to the regulation of the p53 or interferon genes will result in impaired apoptosis and the possible formation of tumors.
Essential alterations for malignant transformation
• Self sufficiency in growth signals
• Insensitivity to growth inhibiting signals
• Evasion of apoptosis
• Defects in DNA repair
• Limitless replicative potential
• Sustained angiogenesis
• Ability to invade & metastasize
Acquired / environmental• DNA damaging agents• chemicals• radiations• virus Inherited mutations in
• gene affecting DNA repairning• cell growth & apoptosis
Normal cells
DNA damage
Successful DNA repair
Failure of DNA repair
Mutation in the genome of somatic cells
Activation of growth promoting oncogenes
Alteration in genes regulating the apoptosis
Inactivation of tumor supressor genes
Unregulated cell proliferation
Decreased apoptosisClonal expansion
Malignant neoplasm
Tumor progression
Angiogenesis & Escape from immunity Additional mutations
Tumor metastasis• Pathway of metastasis
1. Haematogenous spread
2. Lymphatic spread
3. Other routes
- Trancelomic spread
- Spread through the epithelial surface
- Spread through CSF
- Implantation
Mechanism & molecular basis for metastasis
CLINICAL FEATURES
• Unfortunately patients are most often identified only after development of symptoms at advanced stages of disease.
• Discomfort is the most common symptom that leads a patient to seek care & may be present at the time of diagnosis in up to 85 % of cases.
• As the high risk sites of oral carcinoma are lower lip, anterior floor of mouth & the lateral border of tongue, the examination of oral cavity should not be neglected.
• Careful assessment of cervical & submandibular lymph nodes should be done & followed by examination of oral cavity.
General features
Common signs and symptoms of head and neck cancers include:
• A chronic sore throat • Hoarseness of voice • Difficulty in swallowing • Earache • Headaches • Unusual bleeding in the mouth • A discolouration on the gums, tongue, or lining of the mouth • Nasal obstruction • Numbness of the face • Trouble when breathing or speaking • Undefined weight loss
Local features
1. Red , white or red & white lesions (flat / elevated)
2. Change in surface texture (smooth, granular, rough, crusted)
3. Chronic ulcer , not responding to conservative management
4. Ulcer with irregular edge & induration of underlying soft tissues.
5. Varying degree of pain
6. Occasional episodes of bleeding
7. Exophytic growth may present as a cauliflower like irregular growth / flat
8. Submucosal growth with surrounding indurations (pain in advanced
stages )
9. Bleeding & fixity to surrounding structures
Local features
10. Buccal mucosa cancers involving the infratemporal fossa may lead to
trismus (D/D OSMF)
11. Hypoglossal palsy & restriction of tongue mobility, progressive difficulty
in mastication & speech, pooling of saliva, friability & surface bleeding.
12. Trismus affects the nutritional status, functional impairment (obstruction
from large mass) – decrease tolerance to CT, RT & surgery.
13. Unexplained loosening of the involved tooth/teeth.
14. Tumor closer to midline & posterior in position in oral cavity/ orophaynx
may involve bilateral lymph nodes.
15. Involved lymph nodes are –
Initially – soft, mobile, non-tender, enlarged
firm to hard in texture, usually non tender,
tender (due to inflammatory response )
Advanced stage (aggressive disease) – fixation of nodes to adjacent tissue
due to invasion of cells through the capsule
16. Fixation of primary tumor to adjacent tissue overlying bone suggests
involvement of periosteum & possible spread to bone.
CLINICAL FEATURESof
SPECIFIC LESIONS
• Clinical Examination:
– Tumours, when first seen, are almost always confined to the head and neck with no distant metastasis
– Head and neck tumours are rarely irremovable, all structures can be removed with the tumour in continuity and repaired later • The majority of cases are potentially treatable
• Whether to treat or not depend on:
– the age– the health status of the patient – advance stage– local disease
• Full assessment will lead to one of the following conclusions:– Patient is potentially curable– Primary tumour is curable but patient develop another
illness– Patient is incurable but should be treated– Patient is incurable and should not be treated
• History:– Age:
• Patient are generally over 45 years.
• Tumours affecting younger age group are usually
sinister, defective immunological make-up
• Most tumours are of epithelial origin and they require
years of abuse by smoking and tobacco
• Tumours in younger patients, who do not smoke, is
usually very sinister
• Tumours developing in an immuno-compromised
patients do not respond to any treatment modality
• Complaint:
– Vary widely and is often unreliable
– Painless lump which persisted for a varying period of time
– Persistent ulceration
– Difficulty of wearing denture
– Later Symptoms:
• Pain locally or referred to the jaw or ear
• Difficulty with chewing food and swallowing
• Altered speech and respiratory difficulty
– Asymptomatic and noticed during routine dental examination
• Examination:
– Think in term of T Staging, delineate its border by
inspection and palpation
– Record and draw the lesion from different angles using
normal anatomical landmarks
– The status of teeth should be assessed as causative and if
radiotherapy is to considered
CARCINOMA OF ORAL CAVITY
CARCINOMA OF LIP
• Age and sex:– The sixth decade and Male : female ratio is 80:1
• 93% affect the lower lip with squamous cell carcinoma, exophytic type
• 5% in the upper lip and commonly basal cell carcinoma, commoner in females– Solar exposure, more radiation on the lower lip– Commoner in fair complexion– Smoker - cigarette, cigar, pipe stem – In the upper lip, SCC metastasizes earlier than lower lip
– Covered with non-keratinized stratified squamous epithelium which is
transparent, appear red, and contain no hair, sebaceous gland or pigments
– Crusted oozing, non-tender, indurated ulceration of <1 cm
– On the vermilion border it closely cover the orbicularis oris muscle but on
the lingual side mucous gland is present within the muscle and mucosa
– Perineural invasion through mental nerve
– Lymphatic drainage:• Mucosal and cutaneous systems.• Lower lip:
– One medial trunk which drain the inner third of the lip into the submental group
– Two lateral trunk which drain the outer two-third into the submandibular lymph nodes
– Anastomosis account for bilateral metastases• Upper lip:
– Drain into the periauricular, parotid, submandibular and submental lymph nodes
CARCINOMA OF LABIAL MUCOSA
• Lower labial mucosa > upper
• Tobacco pouching
• Exophytic growth , swelling, ulceration
• Unilateral or bilateral lymph nodes may be involved
CARCINOMA OF BUCCAL MUCOSA
Site : along or inferior to a line opposite to occlusion line
(distal to third molars)
Sign : painful lesion
Appearance
Metastasis : The submandibular lymph nodes to the lower deep
cervical chain
CARCINOMA OF TONGUE
• A disease of the middle age and elderly with equal
sex incidence, youngers
• 85% occurs in the lateral border of the anterior 2/3
while tip, dorsum and ventral surface are rarely
involved
• Appearance : painless indurated mass or ulcer
• The lesion may be infiltrative (small on the outside
but palpation shows deep invasion) or exophytic
and usually of the well-differentiated type
– Specialized keratinized epithelium with collection of
minor salivary gland and muscle fibres
– The interlacing muscle fibres form an easy pathway for
cancer spread and the constant movement of the tongue
disseminates the disease widely
• Excision should be wide with 2 cm
safe margin
• Lymph drainage:
– Tip of the tongue:• To the submental lymph nodes – to the lower
deep cervical chains
– The anterior 2/3:• the lower deep cervical chains – jugulo-
omohyoid nodes
– The posterior 1/3:• drain to the upper deep cervical chains
The tip and middle part of the tongue have rich bilateral capillary network
but less in the lateral margins
– Anterior medial part:
• Commoner than the lateral part
• Felame > male
• Spread medially into the ventral
surface of the tongue and laterally
• Deep spread to the base of the
tongue and the hyoglossus and
genioglossus muscles
• Shows bilateral lymphatic spread to
the submandibular and the
submental nodes
CARCINOMA OF FLOOR OF THE MOUTH
– Lateral part:
• Spread medially to the side of the tongue
• May involve sublingual &/or submandibular
glands
• Lateral spread to the alveolar ridge where
presence or absence of the teeth govern the
outcome:
– Teeth act as a barrier against buccal
spread
– In edentulous patient, the alveolar
process has resorbed and cortex is
incomplete, tumour reaches the
cancellous spaces and the canal and
spread through the nerve.
Sign & symptoms :• Painful / painless lesion • Restricted tongue movement• Slurring of speech• Excessive salivation• loosening / exfoliation of teeth• Root resorption
Deeper spread, mylohyoid muscle act as a barrier anteriorly, posteriorly
the floor is close to the skin, appear as a palpable lump in the
submandibular area.
Lymphatic drainage – through submandibular lymph nodes to the upper
deep cervical chains
CARCINOMA OF GINGIVA & ALVEOLOUS
Least associated with tobacco chewing
The lesion is usually painless
Looks like inflammatory or reactive lesion
(eg. Pyogenic granuloma)
Warts around the denture flanges
– Carcinoma of the lower alveolus affects the antero-lateral part and spread to the floor of the mouth
– Tongue and floor of the mouth tumours reach the lower alveolus by marginal spread in the mucosa and submucosa overlying the sublingual, submandibular glands and the mylohyoid muscle. They act as barrier against deep infiltration.
• Edentulous jaws, mylohyoid line is on the occlusal ridge and the loss of the cortical bone barrier will allow tumour to spread downward into the medullary cavity
– The inferior alveolar nerve provide a pathway for perineural spread in
a predominately proximal direction with little involvement of the bone
• Nerve looks clinical normal till late
• Spread is not continuous, multiple pathological samples is required
– Lymphatic spread to the submandibular lymph nodes
CARCINOMA OF PALATE
• Disease of the elderly (60 – 70 years)• Associated with reverse smoking• Common location for carcinoma of the minor salivary
gland • Presented as smooth, rounded, bulging masses• Squamous cell carcinomas present as ulcerative or
exophytic lesion
• Invade the bone at an early stage
• Involve the tonsillar pillars, soft palate, nasal
cavity, nasopharynx and the antrum
• Metastases to submandibular and upper deep
cervical chains
CARCINOMA OF OROPHARYNX
• Site : soft palate & oropharyngeal mucosa• Appearance : like other lesions• Size : greater than that of other sites• Symptoms : dysphagia (most common)
: pain (dull, sharp, radiating to ear)
• Derived from lining epithelium
of lymphoid tissue.
• Older age & male predilection
• Initial lesion is small & difficult
to detect.
CARCINOMA OF NASOPHARYNX
SIGN :• First sign is firm to hard
(enlarged) cervical lymph nodes
• Neurological symptoms
SYMPTOMS :
• Serious otitis media
• Otalgia
• Obstruction of eustachian tube
• Hearing loss
• Nasal obstruction
• Pharyngeal pain
CARCINOMA OF MAXILLARY SINUS
• The sinus is related to the orbit, nose, alveolar process, infratemporal fossa
and nasopharynx.
• It has an outlet to the nose, ethmoid sinuses and the root of the teeth
• Old age & male predilection
SIGN :• Ulceration or mass on the hard palateSYMPTOMS :
• Pain• swelling• Nasal obstruction• Unilateral nasal stiffness• Pain / paresthesia of midface
(involvement of maxillary nerve)
• The inferior orbital fissure provide a route for entry of tumours into the orbit, the periostium offer an excellent resistant barrier to spread into the orbit.
• The roots of the upper premolars and molars and the alveolus are in intimate contact to the floor.
• The infratemporal fossa is the space behind the maxillary antrum and it connects to the para-pharyngyeal space, and the sphenoid bone superiorly with foramen spinosium and ovale with their emerging nerves.
Lymphatic drainage:• Drain posteriorly to the retropharyngeal nodes • Directly to the jugulo-digastric nodes• If it cross to the nose or the cheek it will drain to submandibular lymph
nodes
Premalignant lesions & conditions
Precancerous lesion (precancer/ premalignancy)
A benign, morphologically altered tissue that has a greater than normal risk of malignant transformation .
Eg : leukoplakia
erythroplakia
mucosal changes associated with smoking habits
carcinoma insitu
Bowen disease
Actinic keratosis, cheilitis & elastosis
Leukoplakia
Mild / thin leukoplakia
Homogenous / thick leukoplakia
Ulcerated leukoplakia
Nodular/ speckled leukoplakia
Verrucous leukoplakia
Erythroleukoplakia
Malignant potential : 0.3 – 10 %
Erythroplakia
Homogenous & smooth Erythroplakia Granular Erythroplakia
Erythroleokoplakia
Mucosal changes associated with smoking habits
Stomatitis nicotina Snuff dipper's lesion
Cigarette smoker’s lip lesion
Carcinoma insitu
-Mostly involve skin- but sometime also may involve mucosa- SCC in situ is termed as – Bowen Disease
Actinic keratosis
• A cutaneous premalignant lesion
• Gives – SAND PAPER APPEARANCE
• KERATIN HORN may present
Cheilitis
Precancerous condition
It is a disease or patient’s habit that doesn’t necessarily alter the clinical appearance of the local tissue but it is associated with a greater than normal risk of precancerous lesion / cancer development in the tissue.
Eg : OSMF
syphilis
sideropenic dysphagia
OLP
Diskeratosis congenita
Lupus Erythmatosis
OSMF oral submucous fibrosis
Malignant potential : 0.2 – 0.5 % in INDIA
OLP (Oral lichen planus)
Wickham’s striae are diagnostic
Malignant potential : 0.4 – 12.3 %
OLP
Erosive lichen planus
It presents a chronic multiple oral mucosal ulcers, which occurs when there is extreme degeneration of basal cell layer of epithelium.
Malignant potential : 1 – 15 %
Diskeratosis congenita(zinssner- engman-cole syndrome)
Lupus Erythmatosis
Staging of cancer
Staging is the process subdivision of cases of cancer into same groups in which behavior will be similar.
• Over the last decade the 2 principle staging classification system of head & neck cancer, those of AJCC & UICC have undergone a convergent evolution & are now to all interest & purposes identical.
• Classification by anatomical extent of disease is determined clinically & histopathologicalyl is the one that the TNM system primarily uses:
T : enlargement of & invasion by primary tumor
N : spread to regional lymph nodes
M : spread to different metastatic sites
4 classifications –1. Clinical classification / pretreatment Clinical classification (cTNM)
2. Pathological classification / postsurgical H/P classification (pTNM)
3. Retreatment classification (rTNM)
4. Autopsy classification (aTNM)
Other descriptors
i. “m” suffix (> 1 primary at single site)
ii. “y” prefix : ycTNM, ypTNM
Gx : Grade Of Differentiation Can Not Be Assessed
G1 : Well Differentiated
G2 : Moderately Differentiated
G3 : Poorly Differentiated
G4 : Undifferentiated
Rx : Grade Of Differentiation Can Not Be Assessed
R0 : No residual tumor is present
R1 : microscopic residual tumor
R2 : macroscopic residual tumor
T. Primary Tumor
TX. Primary tumor cannot be assessed
T0. No evidence of primary tumor
Tis. Carcinoma in situ
T1, T2, T3, T4. Increasing size and/or local extent of the primary tumor
N. Regional Lymph Nodes
NX. Regional lymph nodes cannot be assessed
N0. No regional lymph node metastasis
N1, N2, N3. Increasing involvement of regional lymph nodes
Mx : Metastasis cannot be assessed
M0 : No evidence of metastasis
M1 : Presence of metastasis
1. Barnes L, Eveson JW, Reichart PA, Sidransky D. World Health Organization classification of tumours. Pathology and genetics. Head and neck tumours. World Health Organization; 2005.
2. Isaäc van der Waal. Potentially malignant disorders of the oral and oropharyngeal mucosa; terminology, classification and present concepts of management. 2009; 45(4-5):317–323
Classification schemes that histologically categorize precursor and related lesions
Definition WHO 2005
Squamousintraepithelial
neoplasia(SIN)
Ljubljana classification
system
An increase in the number of cells, but with no cellular atypia
Squamous cell
hyperplasia
Squamous cell (simple)
hyperplasia
Changes are confined to the lower third of epithelium
Mild dysplasia
SIN 1 Basal/parabasal cell hyperplasia
Changes extend to the middle third of the epithelium. Cytological changes can
be more marked
Moderatedysplasia
SIN 2 Atypical hyperplasia
Changes involve at least 2/3rd of the epithelium & atypia is more marked.
SevereDysplasia
SIN 3 Atypical hyperplasia
Changes involve the full thickness of epithelium, but no invasion of basement
membrane
Carcinomain situ
SIN 4 Carcinoma in situ