Neoplasia
Neoplasia
Neoplasia
Dr Mbayah Etabalé
Anatomical Pathologist and Lecturer of Pathology
Outline
• Definition
• Nomenclature
• Carcinogenesis
• Pre-Malignancy
2
Definition
3
Neoplasm: Definition
• Pre-Molecular Era • A neoplasm consists of 2 basic
An abnormal mass of tissue components:
Its growth exceeds and is Parenchyma
uncoordinated with that of normal Composed of the proliferating tumour
tissue cells
Its growth persists in the same Determines the nature and evolution of
excessive manner after cessation of the disease
stimulus that evoked the change Stroma
Composed of fibrous connective tissue
and blood vessels
• Molecular Era Provides the framework on which the
Disorder of cell growth triggered by a parenchymal tumour cells grow
series of mutations of a single cell
and its progeny
4
Nomenclature
5
Nomenclature
• Neoplasms are named based:
Behavioural patterns
Benign
Malignant
Histological types (histogenesis)
Epithelial
Mesenchymal
6
Benign Epithelial Tumours
• Generally, the suffix –oma is used
• Epithelia can be gland-forming (glandular) or non-
glandular
• Non-glandular, lining, epithelial neoplasms produce
macroscopically or microscopically visible finger-like or
warty projections from surface – papillomas (nipple-
like/finger-like)
Squamous epithelium → squamous cell papilloma
Transitional epithelium → transitional cell papilloma
7
Benign Epithelial Tumours
Squamous Papilloma
8
Benign Epithelial Tumours
• Benign neoplasms of glandular epithelia are termed
adenomas
Colon → colonic adenoma
Thyroid → thyroid adenoma
Kidney → renal adenoma
Liver → liver adenoma
9
Benign Epithelial Tumours
Ovarian Cystadenoma
10
Benign Mesenchymal Tumours
• Generally, the suffix –oma is used
11
Misnomers
Non-Neoplastic Misnomers Neoplastic Misnomers
• Haematoma • Melanoma
• Granuloma • Lymphoma
• Hamartoma • Seminoma
• Glioma
• Hepatoma
12
Malignant Epithelial Tumours
• Generally, the suffix –carcinoma is used for malignant
epithelial tumours
Carcinoma (Greek karkinos – crab)
13
Malignant Mesenchymal Tumours
• The suffix –sarcoma is used for mesenchymal cancers
15
Nomenclature: Teratomas
17
Tumour Nomenclature: Blastoma
• A malignant tumour composed of immature cells
resembling those that form the foetal anlage or primordia
of adult organs (blasts)
• Commonly seen in the paediatric setting
• Examples
Kidney →
Cartilage →
Retina →
Medulla →
Nerves →
Liver →
18
Tumour Nomenclature:
Harmatoma
• A mass of composed of cells and tissues indigenous to the
involved site but which are disorganised
Mole (melanocytic naevus) – skin harmatoma representing an
aggregate of pigment cells that are normally dispersed in the skin
Pulmonary harmatoma – this represents a nodule composed of
cartilage, bronchial epithelium and smooth muscle cells
19
Tumour Nomenclature: Choristoma
• A mass composed of normal cells and tissues found in the
wrong location
• It is also called ectopia or ectopic rest
• Examples:
Ectopic brain tissue in the nasal cavity
Pancreatic choristoma in the stomach or in the liver
20
Tumour Nomenclature: Eponyms
• With some tumours, proper names (usually of their
describers) are used:
Hodgkin lymphoma Thomas Hodgkin (1832)
Ewing sarcoma James Ewing (1866 – 1943)
Wilms tumour Max Wilms (1867 – 1918)
Kaposi sarcoma Moritz Kaposi (1872)
Burkitt lymphoma Denis Burkitt (1958)
21
Benign vs Malignant
Neoplasms
22
Biological Differences
1. Differentiation and Anaplasia
2. Rate of Growth
3. Local Invasion
4. Metastasis
23
Differentiation
• Tumour grade
• Extent to which parenchymal cells resemble comparable
normal cells, morphologically and functionally
• Well-differentiated tumour cells resemble mature normal
cells of tissue of origin
• Poorly-differentiated or undifferentiated tumours have
primitive appearing, unspecialised cells
24
Differentiation: Benign Tumours
• Benign neoplasms are well-differentiated
Mimic the structure of the parent tissue microscopically
The neoplastic cells resemble their normal cell counterparts
The neoplastic cells show remarkable uniformity in size, shape and
nuclear configuration
Have relatively infrequent mitotic figures; these are of normal type
25
Differentiation: Benign Tumours
29
30
Anaplastic Large Cell Carcinoma of the Lung
31
Rate of Growth – Benign vs
Malignant Tumours
• In general (but with the caveat that range of tumour
behaviour is wide)
1. Most benign tumours grow slowly whereas most cancers grow
rapidly
2. The growth rate of tumours correlates with their level of
differentiation
3. Rapid growth rate leads to tumour ischemia and necrosis
32
Local Invasion
Benign Tumours Malignant Tumours
• Benign tumours grow as cohesive, • Malignant tumours grow by infiltration
expansile masses that remain localised to and invasion of the surrounding
their site of origin structures
Because they grow slowly, they develop a Poorly demarcated from the surrounding
rim of compressed connective tissue – a tissue
capsule Next to metastasis, invasion is the most
Cause problems by impingement on other reliable feature of malignancy
structures In-situ cancers display the cytologic
features of malignancy without invasion
33
Local Invasion and Benign Tumours
Fibroadenoma
34
Local Invasion and Malignant Tumours
Breast Carcinoma
35
Metastasis
• Spread of tumours to sites that are anatomically separate from their
site of origin
• Hallmark of malignant tumours
• Metastasize in 4 ways:
1. Direct/Local extension
2. Lymphatic spread
3. Haematogenous spread
4. Spread across body cavities and natural passages
i. Transcoelomic spread
ii. Spread along epithelial-lined surfaces
iii. Spread via CSF
36
Metastasis
Liver Metastasis Lymph Node Metastasis
37
Benign Malignant
Histology Resembles cell of origin (well- May show failure of cellular differentiation
differentiated)
Few or no mitoses Many mitoses, some of which are abnormal
forms
Normal or slight increase in NC ratio High NC ratio
Cells are uniform throughout the tumour Cells vary in shape and size (cellular
pleomorphism) and/or nuclei vary in shape and
size (nuclear pleomorphism 38
Carcinogenesis
39
Carcinogenesis
• The process by which normal cells are converted to cancer cells
(oncogenesis)
• Initiated by a non-lethal genetic damage (mutation)
• Mutation may be acquired (chemicals, radiation or viruses) or inherited
in the germline
• Occurs through the sequential accumulation of multiple mutations
• The mutations are non-lethal
• Agents that cause carcinogenesis are called carcinogens
• The acquired mutations give the precursor cells a selective advantage
• Carcinogenic agents classified as follows:
Chemical carcinogens
Physical carcinogens
Biological carcinogens
40
Carcinogenesis
• Stages:
Exposure to carcinogen
Interplay of factors:
Route of exposure of carcinogen
Dose of carcinogen
Duration of exposure to carcinogen
Host susceptibility
Carcinogenic phenotype
• Stages of carcinogenesis
Initiation
Promotion
Progression
41
Chemical Carcinogenesis: Initiation
• A non-lethal genetic change produced by a
carcinogen
• Can take place with:
A single dose of the initiating agent for a short
time (less effective)
A larger dose for longer duration (more
effective)
• During cell division, the mutation may be passed
to the daughter cell; this renders the mutation
irreversible/permanent
• Initiating agents can be classified into 2:
a. Directly-acting carcinogens
b. Indirectly-acting carcinogens
(procarcinogens)
42
Directly-Acting Chemical
Carcinogens
• These are the ultimate carcinogens
• Non-enzymatic reaction
• 2 classes:
Alkylating agents (cyclophosphamide, chlorambucil, busulphan, melphalan,
nitrosourea, β-propiolactone, epoxides, etc.)
Acylating agents (acetylimidazole, dimethylcarbamyl chloride)
43
Indirectly-Acting Chemical
Carcinogens
• Constitute the majority of chemical carcinogens
• Categories
1. Polycyclic aromatic hydrocarbons
Largest group
2. Aromatic amines and azo-dyes
3. Naturally occurring products
4. Miscellaneous agents
44
Indirectly-Acting Carcinogens
46
Initiators and Promotors
48
Physical Carcinogens
• Radiation carcinogens
Non-ionizing radiation – ultraviolet rays
Ionising radiation – X-rays, α-rays, β -rays, γ-rays, radioactive
isotopes
• Non-Radiation carcinogens
Gall bladder stones – gall bladder adenocarcinoma
Urinary stones – urinary bladder squamous cell carcinoma
Old scars (burns, chronic wounds) – squamous cell carcinoma
49
Carcinogenic Agents - Radiation
Source of Radiation Tumours Type of Radiation
50
Biological Carcinogens
• Parasites
S. haematobium – squamous cell carcinoma of the urinary bladder
C. sinensis – cholangiocarcinoma
• Fungi
Aspergillus flavus > aflatoxin > HCC
• Bacteria
H. pylori – gastric carcinoma / gastric lymphoma
• Viruses
51
Carcinogenic Agents – Oncogenic
Viruses
• Addition of new DNA to the nucleus of the host cells
resulting in mutants
• 2 types of oncoviruses
DNA virus
Invades the cell > direct incorporation of viral DNA in host DNA >
mutation > neoplasia
RNA virus
Invades the cell > production of reverse transcriptase > formation of
DNA > incorporation of viral DNA in host DNA > mutation > neoplasia
52
Carcinogenic Agents – Oncogenic
Viruses
Virus Type Mechanism Tumour Type
53
54
Genetic Lesions in
Cancer
55
Outline
1. Point Mutations
2. Gene Rearrangements
3. Chromosomal Deletions
4. Gene Amplifications
5. Aneuploidy
6. Epigenetic Changes
56
1. Point Mutations
• A point mutation is an alteration in a single base
• The alteration can be in the form of:
Single base substitution
Single base deletion
Single base insertion
57
2. Gene Rearrangements
• Due to chromosomal translocations and inversions
58
2. Gene Rearrangements
Placement of a Proto-Oncogene Next to an Enhancer / Promoter
• Follicular Lymphoma
Chromosomal abnormality: t(14;18)(q32;q21), IGH::BCL2
Ch 14 – promoter site for immunoglobulin expression
Ch 18 – BCL2 gene (anti-apoptotic gene)
• Burkitt Lymphoma
Chromosomal abnormality: t(8;14)(q24;q32), IG::MYC
Ch 8 – MYC gene (proto-oncogene)
Ch 14 – promoter site for immunoglobulin expression
59
2. Gene Rearrangements
Creation of a Novel Fusion Hyperactive Oncogene
60
3. Chromosomal Deletions
• Loss of a portion of a chromosome
• Examples
del 13q14, site for RB gene associated with Retinoblastoma
del 17p, site for TP53 gene associated with many cancers
61
4. Gene Amplification
• Increase in the number of copies of a gene sequence
• Examples in neoplasia:
1. HER-2 (ERBB2) positive breast carcinomas
~20% of breast carcinomas
Worse prognosis
Targeted therapy using trastuzumab (Herceptin)
2. NMYC amplified Neuroblastoma
25 – 30% of neuroblastomas
Poor prognosis
62
4. Gene Amplification
64
5. Epigenetic Changes
• DNA methylation
• Histone modification
• miRNAs
Quora
65
5. Epigenetic Changes: Histone
Modification
• These modifications provide either an ON or
OFF signature which result in the tight
regulation of gene expression (histone code)
https://doi.org/10.1093/femsml/uqad032
66
5. Epigenetic Changes: DNA Methylation
• Involves covalent modification of cytosine nucleotides at the C5
position in specific areas of CpG dinucleotides
Researchgate
67
5. Epigenetic Changes: MicroRNAs
• Non-coding, single-stranded RNAs
68
5. Epigenetic Changes
69
Pre-Malignancy
70
Pre-Malignancy
• Conditions associated with the development of a
malignancy
1. Benign tumours undergoing malignant transformation
2. Chronic inflammatory disease states
3. Hyperplasia
4. Intra-epithelial Neoplasia (Dysplasia)
71
Malignant Transformation of Benign
Tumours
• Patients with multiple colonic adenomas have a high incidence of developing
colonic carcinoma
72
Chronic Inflammation
1. Hashimoto Thyroiditis Diffuse
complicating to Thyroid Large B
Cell
H. Pylori
infection
Lymphoma Lymphoma
2. H. pylori Gastritis
complicating to:
Reactive
1. Gastric MALToma Distant polyclonal
spread immune
2. Gastric Carcinoma stimulation
3. Ulcerative Colitis
complicating with Colorectal
Carcinoma Monoclonal
MALToma B-Cell
neoplasm
73
Hyperplasia
• Endometrial hyperplasia is associated with an increased risk of
progression to endometrial carcinoma
Nonatypical endometrial hyperplasia confers a 2 – 4-fold increased risk
compared to the general population
Atypical endometrial hyperplasia confers a 45-fold increased risk
compared to the general population
74
Intraepithelial Neoplasia
• Commonly called DYSPLASIA
75
Squamous
Intraepithelial Intraepithelial Lesion
Lesion (LSIL) (HSIL)
Cervical Intraepithelial Neoplasia
76
Hallmarks of Cancer
77
Hallmarks of Cancer
• Fundamental changes in cell
physiology found in all cancer cells
1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitory
signals
3. Evasion of apoptosis
4. Altered cellular metabolism
5. Limitless replicative potential
(immortality)
6. Sustained angiogenesis
7. Invasion and metastasis
8. Evasion of immune surveillance
80
Proto-Oncogenes and Oncogenes
1. Increased growth factor synthesis
Glioblastomas secreting PDGF for their PDGFR
Sarcomas secreting TGF-α for their TGF-αR
81
Proto-Oncogenes and Oncogenes
83
Tumour Suppressor Genes
84
Harsh Mohan Textbook of Pathology, 7e
2. Retinoblastoma Gene and Protein
• Locus: 13q
• RB, a key negative regulator of the cell cycle, is directly or indirectly inactivated
in most human cancers
Binds to and sequester E2F transcription factor thereby preventing DNA replication (S
Phase)
• Clinical examples
Retinoblastoma
Inherited germline LOF mutation in one allele, 13q, followed by a “second hit” in the remaining
allele
First hit may be an inherited germline mutation (hereditary retinoblastoma) or acquired (sporadic
retinoblastoma)
HPV-induced squamous cell carcinoma
High-risk HPV-associated protein E7 displaces E2F from the RB protein binding site; E2F is
therefore free to mediate DNA replication
Osteosarcoma
Sarcomas
Small cell lung carcinoma
85
2. p53 Gene and Protein
• Locus: 17p
• > 70% of human cancers have defect in the p53 gene; the remaining 30% have defects in
the genes upstream or downstream p53
• p53 protein regulates the cell cycle by:
Triggering temporary cell cycle arrest (quiescence) to allow for DNA repair
p53 also upregulated the expression of DNA repair genes to allow for DNA repair
Triggering permanent cell cycle arrest (replicative senescence) of cells with irreparable DNA
damage
Triggering apoptosis of cells with irreparable DNA damage
• Examples:
Acquired bi-allelic p53 mutations present in many carcinomas: breast, lung, colon, etc.
In some sarcomas, p53 gene is normal but MDM gene is overexpressed (MDM protein inhibits
p53)
Germline p53 mutation (Li-Fraumeni syndrome) is associated with a 25-fold increased risk
relative to the general population of development of a variety of cancers by age 50: sarcomas,
breast cancer, leukaemia, brain tumours, etc.
86
3. Evasion of Apoptosis
• Pro-apoptotic genes e.g. Bax, Bad, Bid, p53
Mutations express in a recessive fashion
LOF mutations in genes encoding pro-apoptotic proteins leads to
evasion of apoptosis thereby giving the tumour cells a survival
advantage
Fas (CD 95) mutation in HCC
87
3. Evasion of Apoptosis
• Due to acquired abnormalities that interfere with the
intrinsic (mitochondrial) pathway of apoptosis
1. Loss of TP53 function: every tumour
TP53 activates PUMA which opposes BCL2 (anti-apoptotic protein) >
tilts towards BAX/BAD A0 > mitochondrial permeability > escape of
cytochrome c into cytoplasm > caspase A0
2. Overexpression of anti-apoptotic genes: BCL2
In follicular lymphoma, BCL2, an anti-apoptotic gene is overexpressed
leaving to increased B-cell survival
In chronic lymphocytic leukaemia, loss of expression miRNA that target
BCL2 leading to increased anti-apoptotic activity
88
4. Altered Cellular Metabolism - Warburg
Effect
• With adequate O2 levels, normal cells metabolise each molecule
of glucose aerobically to generate 36 ATP molecules (aerobic
respiration)
90
5. Limitless Replicative Potential
(Immortality)
92
7. Invasion and Metastasis
• Invasion and metastasis are defining features of
malignancies
• 3 steps:
1.Invasion of extracellular matrix (ECM)
Invasion of basement membrane
Invasion through interstitial matrix
Intravasation into blood vessels and lymphatics
2.Vascular dissemination
3.Homing of tumour cells
Extravasation from blood vessels
Formation of micrometastases
Growth into macrometastases
95
8. Evasion of Immune
Surveillance – Anti-Tumour
Mechanisms
• Host dendritic cells ingest dying tumour cells
4. Secretion of immunosuppressive substances e.g., TGF-β, IL-10, PGE2, VEGF, etc. but
tumour cells and stromal cells
5. Induction of regulatory T cells (T regs)
97
Hallmarks of Cancer
• Fundamental changes in cell physiology found in all
cancer cells
1. Self-sufficiency in growth signals
2. Insensitivity to growth-inhibitory signals
3. Evasion of apoptosis
4. Altered cellular metabolism
5. Limitless replicative potential (immortality)
6. Sustained angiogenesis
7. Invasion and metastasis
8. Evasion of immune surveillance
3. Infiltrating macrophages help detached cells (due to proteases breaking down cell-cell and cell-
matrix interaction) evade cell death (hallmark) by providing alternative adhesion molecules:
integrins
99
Genomic Instability
• Despite frequent mutagenic exposure, cancer occurs infrequently due to a system of DNA damage
sensing and repair
• Individuals with defects in DNA damage repair system are prone to development of accumulating
numerous mutations over time (genomic instability)
100
MMR Syndromes
1. Xeroderma Pigmentosum
Inherited germline mutation of genes coding for nucleotide excision repair enzymes
NER enzymes critical in repairing damage caused by UV radiation (CT crosslinking)
Consequent decreased ability to repair UV-associated DNA damage
High risk of skin cancers: squamous cell carcinoma, basal cell carcinoma
103
Effects of the Tumour on the Host
• Local Effects
• Systemic Effects
104
Local Effects of the Tumour
• Mass effect e.g. palpable breast mass deforming the breast
• Compression of normal tissue with loss of function e.g. pituitary atrophy and
hypopituitarism due to pituitary adenoma
• Pain due to compression of nerves
• Destruction of normal tissue
Punched-out bone lesions in multiple myeloma
Perforation of a hollow organ
• Obstruction of a hollow organ
• Irritation and inflammation e.g. bronchial cancer causing coughing
• Bleeding due to erosion of blood vessels e.g. vaginal bleeding
• Necrosis e.g. ischaemic necrosis due to obstruction of a nutrient vessel
105
Systemic Effects of the Tumour
• Cancer cachexia
• Fever
• Paraneoplastic syndromes
• Tumour lysis syndrome
106
Cachexia
• Clinical constellation: ii. IL-1
Progressive fat and muscle loss iii. IFN-α
107
Paraneoplastic Syndromes
• Signs and symptoms produced by tumours at sites not
anatomically related to the tumour or produced by hormones
that are not indigenous to the normal counterparts of the
tumours
• 10% of cancer cases
• Classification
1. Endocrine
2. Neuromuscular
3. Haematologic
4. Dermatologic
5. Renal
6. Idiopathic
108
Endocrine Paraneoplastic Syndromes
• Small cell carcinoma of the lung → Cushing syndrome
Secrete ACTH and pro-opiomelanocortin
109
Haematologic Paraneoplastic
Syndromes
• Pancreatic carcinoma → migratory thrombophlebitis
(Trousseau syndrome)
Secrete thromboplastin
• Lymphoma → anaemia
Cryoglobulin (“cold antibodies”) production
110
Neuromuscular Paraneoplastic
Syndromes
• Thymoma → myasthenia gravis
Antibodies to ACh receptors
111
Dermatologic Paraneoplastic
Syndromes
• Gastric carcinoma → acanthosis
nigricans (hyperpigmentation on
the neck and intertriginous areas)
112
Renal Paraneoplastic Syndromes
• Nephrotic syndrome caused by the deposition of tumour
antigen-antibody immune complex in the glomerular
basement membranes
113
Osseous Syndromes
• Hypertrophic osteoarthropathy
Largely lung cancer
1. Periosteal new bone formation at the
ends of long bones, metatarsals,
metacarpals, proximal phalanges
2. Arthritis of adjacent joints
3. Digital clubbing
114
Laboratory Diagnosis
of Tumours
115
Laboratory Diagnosis
• Tumour markers
• Cytological evaluation
Exfoliative
Abrasive
Aspiration
• Flow cytometry
• Liquid Biopsy
• Molecular techniques
Cytogenetics
Fluorescent in-situ hybridisation (FISH)
PCR-technology
Microarrays
116
Tumour Markers
• These are substances found
at higher-than-normal levels
in biological fluids or tissues
in individuals with certain
cancers
• Tumour cells produce
substances, many of which
are proteins, which enter the
bloodstream (and/or urine)
where it can be measured
117
Histological Assessment of
Neoplasms
1. Guide to tumour behaviour: benign vs malignant
2. Guides treatment
3. Can inform on response to treatment
118
Histological Assessment of
Neoplasms
1. Benign
2. Malignant
a) Tumour Type
b) Degree of Differentiation (Grading)
i. Architectural and cytological similarity to normal counterpart
ii. Cellular and nuclear pleomorphism
iii. Mitotic activity of tumour
c) Completeness of Resection
d) Extent of Tumour Spread (Staging)
119
Immunohistochemistry (IHC)
• An immunological method of recognising a cell by one or more of its specific components (antigens)
• Monoclonal antibodies specific to the antigen of interest are introduced into the paraffin–embedded tissue
• If the antigen is present, the antibody binds to it; the chromogen becomes visible
• Principles:
Antibody-antigen reaction
Nucleic acid amplification studies
• Can detect changes in tumour burden months or years before conventional imaging
modalities
• Role
Disease diagnosis by detecting tumour cells
Quantification of metastatic burden
Monitoring response to therapy
121
Flow Cytometry
• Computerised technique by which
individual cell characteristics are
recognized and quantified:
Cytoplasmic antigen
Cell membrane antigen
Nuclear antigens
122
In-Situ Hybridisation
• Hybridisation refers to the process of binding two
complementary strands of DNA
• In-situ refers to the hybridisation taking place in
the actual tissue (vs in extracted DNA)
• A probe (short commercially prepared
complementary DNA strand) specific to a DNA
sequence of interest is used
• Once a probe has been deployed and has
hybridized to its target, it has to be visualised
123
FISH
• Fluorescent In-Situ Hybridisation
• The probe has a specialised dye
molecule that will fluoresce when
exposed to ultraviolet light
• Requires a specialized FISH
microscope
124
CISH
• Chromogenic In-Situ Hybridisation
• The probe is visualized following an
enzymatic reaction which produces
a coloured substance
• Can be interpreted using
conventional light microscopy
125
Chromosomal Microarray (CMA)
• CMA looks for extra (duplicated) or missing (deleted) chromosomal segments
126
Chromosomal Microarray (CMA)
1. A platform (microchip) with spots is used same gene at a given locus, both will bind
evenly (1:1 ratio) with the probes and a new
2. Each spot contains probes (nucleotide colour e.g., yellow, will form from the
sequences) complementary to known DNA combination of test and control colours
sequence in each chromosome
7. If test sample has a deletion at a given
3. Patient’s DNA sample labelled with a locus, the reference sample will be in excess
fluorescent dye e.g., green (negative variance), and the spot will be red
4. A reference DNA sample (normal, control) 8. If the patient sample has a duplication at a
labelled with a different fluorescent dye given locus, it will be in excess (positive
e.g., red variance) and the spot will light green
5. Both DNA samples are mixed and then 9. A computer programme analyses the data:
placed on the microchip platform; nature of variance (+ve or –ve), location of
hybridisation follows; laser scanning is the variance, magnitude of the variance,
used visualize the fluorescent pattern etc.
6. If both test and control sample contain
127
Chromosomal Microarray (CMA)
Researchgate
129
Tumour Grading
• This is an assessment of the cytological differentiation of a neoplasm i.e. how well it
resembles the normal tissue counterpart
• Parameters used in tumour grading:
Formation of specialised structures associated with the normal tissue counterpart e.g.
formation of glands / tubules in colonic adenocarcinoma
Degree of nuclear pleomorphism
Rate of mitotic activity
Presence or absence of necrosis (sarcomas)
131
TNM Staging System
• Three parameters used in staging:
Tumour Size (T)
Regional Nodal Metastasis (N)
Distant Metastasis (M)
132
Example of Tumour Staging – Colorectal
Carcinoma
T N M
TX Cannot be assessed NX Cannot be assessed MX Cannot be assessed
T0 No evidence of primary tumour N0 No regional lymph node metastasis M0 No distant metastasis
Tis Intraepithelial or intramucosal tumour N1 Metastasis to 1 – 3 regional nodes M1 Distant metastasis
T1 Tumour invades the submucosa N2 Metastasis to ≥ 4 regional nodes
T2 Tumour invades the muscularis propria
T3 Tumour invades the serosa
T4 Tumour invades beyond the serosa
AJCC Stage pT pN pM
Stage 0 Tis N0 M0
Stage I T1 to T2 N0 M0
Stage II T3 to T4 N0 M0
Stage III T1 to T4 N1 to N2 M0
133
Example of Tumour Staging – Carcinoma
of the Kidney
T N M
T0 No evidence of primary N0 No regional lymph M0 No distant
tumour node metastasis metastasis
T1 Tumour ≤ 7 cm ø and N1 Spread to 1 node M1 Distant
confined to the kidney metastasis
T2 Tumour ≥ 7 cm ø and N2 Spread to ≥ 2 nodes
confined to the kidney
T3 Spread to local tissue
T4 Spread beyond local AJCC T N M
tissue Stage
I T1 N0 M0
II T2 N0 M0
III T1/T2 N1 M0
T3 N0/N1 M0
IV T4 Any N M0
Any T Any N M1 134
References
• Robbins Basic Pathology 10th Edition
• Pathology Illustrated 7th Edition
• Harsh Mohan Textbook of Pathology 7th Edition
• Rubin’s Pathology – Clinicopathologic Foundations of
Medicine, 7e
• www.pathologyoutlines.com
• ilovepathology YouTube Channel
135