current tumours classification : aims, basis, terminology · current tumours classification : aims,...

Current tumours classification : aims, basis, terminology

Céline Bossard, MD, PhD, JPEMS

09/16/2013

[email protected]

Essential for an appropriate and successful treatment

Based on the morphological examination : Histological type and degree of malignancy

Why ?

Reliable and precise classification of tumour

From the classification to the treatment…

• Benign tumour

> surgical resection only

• Invasive carcinoma

> complete surgical resection

> +/- chemotherapy and or radiotherapy

• Lymphoma

> no surgical resection of tumour in order to measure response to chemotherapy +++

Tumour treatment depends on its origin (histological type) and its aggressiveness (degree of malignancy)

Definitions and basic concepts • Tumour : any swelling or mass

> classically, « tumor » was one of the 4 signs of inflammation (tumor, dolor, color, rubor)

> in contempory usage, the term is used as a synonym for neoplasm or neoplasia

• Neoplasia (neoplasm) : an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists and grows at the expense of the host

> loss of control of cell proliferation : disruption in the normal balance between new cell growth and old cell death (more proliferation than of death)

> tumour arise from one abnormal cell : concept of clonality

Concept of clonality

Most neoplasms are believe to

originate from a single parental

cell that undergoes a

mutational event leading to an

altered pattern of growth

All of the progeny of this cell are

said to be clonal in origin.

> in myeloma : all tumour

cells produce the same

immunoglobulin

Definitions and basic concepts

• Neoplasia : an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists and grows at the expense of the host

> abnormal tissue that resembles to the normal tissue from which it derives, more or less : concept of differentiation

- the larger the resemblance to normal tissue is, the more the tumour is differentiated

- a well-differentiated tumour resembles much and in an homogeneous way the normal tissue

- a mild/poorly differentiated tumour resembles little or in a focal way the normal tissue

- an undifferentiated or anaplastic tumour have lost its differentiation

A well differentiated

cancer of the colon

An undifferentiated

cancer of the colon

Normal glandular epithelium of the colon


• Neoplasia : an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissue and persists and grows at the expense of the host

> tumour persists and grows after the disappearance of the stimuli that gave it birth (growth factor….) : concept of biological autonomy

> this uncontrolled cell proliferation results from the accumulation of genetic abnormalities in cancer-associated genes

- proto-oncogenes (RAS, MYC….)

- tumour suppressor genes (APC….)

- DNA repair genes (MLH1….)


• Malignant : a descriptive term applied to neoplasia having an aggressive behaviour (invasive growth and metastasis)

• Cancer : a common term for all malignant neoplasia

Of what a tumour is made up ?

• Tumour cells (abnormal cells with genetic abnormalities)

• Stroma : the « feeder » tissue does not consist of tumour cells +++

- connective tissue containing extra-cellular matrice, fibroblasts, immune cells…

- vessels

Sheet of tumour cells Stroma

Benign / malignant tumour

• Contrary to benign tumours, malignant tumours end spontaneously in the death of patient

> agressive tumour

• This important behavioural difference is correlated to gross and microscopic criteria

Characteristics of benign and malignant tumours

BENIGN MALIGNANT

Limitation Well Poorly limited

Local growth By Expansion (encapsulated

masses)

By invasion (Infiltrative growth into adjacent tissues,

never encapsulated)

Differentiation Well-differentiated A range of differentiation

Cells Regular, normal Irregular in size and shape

Anaplasia (« without form »)

No Sometimes (poorly differentiated and pleomorphic cells, increased nucleocytoplasmic ratio, nuclear

hyperchomasia, prominent nucleoli)

Rate of growth Slow Rapid

Mitoses Few or none Many, sometimes abnormal

Invasion of adjacent tissue No Yes (Tissue destruction)

Metastasis (or spread of tumour away from the

primary site)

No Yes (lymphatic or hematogeneous spread, in lymph node, lung, liver, bones…)

Well limited

Encapsulated

Expansive growth

pattern

Characteristics of benign tumour


BENIGN MALIGNANT



masses)


never encapsulated)










primary site)

No Yes

Characteristics of benign tumour

Well limited

Encapsulated

Expansive growth

pattern

Well differentiated

proliferation,

resembles to thyroid

gland

Regular cells in

size and shape

No mitoses


BENIGN MALIGNANT



masses)


never encapsulated)










primary site)

No Yes

Diagnosis of malignant tumour

Poorly limited

Infiltrative growth pattern

No capsule


BENIGN MALIGNANT



masses)


never encapsulated)








Invasion of adjacent tissue

No Yes (Tissue destruction)


primary site)

No Yes

Diagnosis of malignant tumour

Increased abnormal

mitoses

Poorly differentiated

Increased variation in

cell size

Invasion into adjacent tissue

Cellular atypia :

nuclear

hyperchromasia and

pleomorphism

Poorly limited

Infiltrative growth pattern

No capsule

Borderline tumours

• A borderline epithelial tumour lacks obvious invasive growth pattern but has mitotic activity and nuclear abnormalities intermediate between clearly benign and unquestionably malignant tumours of a similar cell, but its future behavior is uncertain

> ex : borderline tumours of the ovary

Continuum between some benign tumours and malignant tumours

• Also called « tumour progression »

> Progressive acquisition and accumulation of genetic abnormalities that leads to a malignant phenotype

The « polyp to cancer » sequence in large bowel

• Most polyps are small (<0.5 cm) and entirely benign. • The majority of colon cancers arise from pre-existing adenomatous polyps. • The risk of progression from benign polyp to cancer varies, but approximately 10%

of adenomatous polyps >1.5 cm contain an invasive carcinoma. • The risk of developing cancer from sporadic 1 cm polyps was 8% at 10 years and

24% at 20 years.

The rational for the CRC screening program : detect polyps to prevent CRC

A tumour classification : why ?

• To reach a consensus on the nomenclature

Uniform, reproductible nomenclature

to speak « the same langage » for everybody

• To allow accurate exchange of informations between pathologists, oncologists and geneticists.

• To define clinical sub-groups

who have different biological and clinical features

who will benefit from appropriate treatment

who have different outcomes (prognosis)

• To facilitate epidemiological studies

WHO classification of tumours : the « Blue Books »

• The outcome of a collaborative effort by a multidisciplinary and international working group of experts of the World Health Organization

• Available and specific for each organ - tumours of the digestive system - tumours of haematopoietic and lymphoid tissues - tumours of the breast and female genital organs - tumours of the urinary system and male genital organs - etc… • Provides standardized guidelines on clinical, histological and genetic

typing of human tumours. • Provides an international standard for pathologists, oncologists and

geneticists.

• These classifications change with time since our knowledges improve

Classification of tumours : basis • Two main components of the classification of tumours:

Histogenesis Anticipated Biological Behaviour

based upon the presumed cell of

origin

eg. epithelium

based upon the probable

behaviour of a tumour

eg. benign or malignant

• Other components of classification to predict prognosis

> assessment of differentiation : termed GRADE

> assessment of the spread of the tumour : termed STAGE.

Classification of tumours

• Histogenesis refers to the presumed cell/tissue of origin of a tumour.

• Tumours from a specific histological tissue often have microscopic features similar to that tissue.

> tumours arising from

squamous epithelium have a

squamous pattern

> tumours arising from glandular

epithelium have features

resembling this epithelium.

Nomenclature : prefix and suffix

• Prefix and Suffix are central to the histogenetic classification of neoplasia

> prefix defines tissue or cell of origin : tumour cells closely resemble their normal counterpart

Prefix Cell or Tissue of origin

Squamous Squamous epithelium

Adeno Glandular epithelium

Lipo Adipose tissue

Osteo Bone

Chondro Cartilage

Rhabdo Skeletal muscle

Leiomyo Smooth muscle

Angio Blood vessel

Adeno : tumour with glandular differentiation

Rhabdo : tumour with skeletal muscle differentiation

Leiomyo : tumour with smooth muscle differentiation

Angio : tumour with vascular differentiation

Squamous : tumour derived from squamous epithelium

Nomenclature

Sufix -oma

Papilloma

Adenoma

Lipoma

Osteoma

Chondroma

Rhabdomyoma

Leiomyoma

Hemangioma

• Suffix « -oma » defines benign tumours

Squamous

papilloma

Adenoma

Some exceptions…

• Lymphoma : malignant tumour derived from lymphocytes

• Melanoma : malignant tumour derived from melanocytes

• Seminoma : malignant tumour originates from male reproductive cells in testis

Nomenclature

Suffix –carcinoma,

-sarcoma

Squamous cell carcinoma

Adenocarcinoma

Liposarcoma

Osteosarcoma

Chondrosarcoma

Rhabdomyosarcoma

Leiomyosarcoma

Hemangiosarcoma

• Suffix « -carcinoma », « -sarcoma » defines malignant tumours > carcinoma or malignant epithelial neoplasms are classified based on their

origin and histologic pattern > sarcoma or malignant mesenchymal neoplasms are designated by their cell of

origin

Squamous cell carcinoma

Adenocarcinoma

Skin,

oesophagus,

anal canal,

uterin cervix…

Stomach,

colon, lung,

pancreas, bile

ducts, breast,

ovary,

prostate…

Some eponym tumours….

• Ewing’s sarcoma > first described by James Ewing in 1920 > unknown histogenesis for a long time > derived finally from neuroectodermal tissue • Hodgkin’s disease or Hodgkin’s lymphoma > first described by Thomas Hodgkin in 1832 > a subgroup of lymphoma, a tumour derived

from lymphocytes ● Burkitt’s lymphoma > described by Denis Parsons Burkitt in 1956

while in worked in Equatorial Africa Etc….

http://www.hodgkinshistory.com/info/whatishodgkins.html

Tumour phenotyping by immunohistochemistry

• When morphological criteria are insufficient to provide a precise tumour classification :

- undifferentiated tumour

- lymphoma

- the tumour of origin of a metastasis

• Immunophenotyping allows to determine the precise histogenesis of a tumour

• Based on the detection of antigen expressed by tumour cells by immunohistochemistry

• By exploiting the principle of antibodies binding specifically to antigens in biological tissues

CD20+ B-cell lymphoma

Lymph node

metastasis of a

breast

adenocarcinoma :

tumour cells

express

cytokeratin

Tumour grade • Cancer grade is based on histological criteria : - degree of differentiation - mitosis - nuclear pleomorphism - necrosis • Specific from each cancer

• Describes the aggressiveness of a tumour and its property to

grow and spread

• Is correlated to the prognosis : > a low grade tumour has a less aggressive course than a

high grade tumour.

Scarff-Bloom-Richardson (SBR) Grade for breast adenocarcinoma

Tubule

Formation (degree

of differentiation)

Nuclear

Pleomorphism

Mitotic

Count

Grade 1 Grade 2 Grade 3

Lymphoma

– Aggressive lymphomas (high-grade lymphomas)

> large cells

> high mitotic count

> necrosis

– Indolent Lymphomas (low-grade lymphomas)

> small to medium cells

> low mitotic count

> no necrosis

Tumour stage • Staging describes the extent of an individual's cancer based

on the extent of the original (primary) tumour and the extent of spread in the body (metastasis).

• Knowing the stage helps to plan a appropriated treatment and determine a prognosis.

> stage I colorectal cancer are treated by surgical resection only

> stage II by surgical resection +/- chemotherapy (if risk factors)

> stage III by surgical resection + chemotherapy

> stage IV colorectal cancer are treated by chemotherapy only, if nonresectable

What are the criteria of the staging System?

• For most cancers, the stage is based on 3 main factors determined by clinical examination (physical and imaging) and pathological examination (pTNM) of the removed tumour:

- Tumour size (pT)

- Lymph node involvement (pN)

- Presence or absence of metastasis (M)

pTNM staging system

TNM staging system

• Each cancer type has its own staging system, so letters and numbers do not always mean the same thing for every kind of cancer.

• Once the T, N, and M are determined, they are combined, and an overall "Stage" of I, II, III, IV is assigned.

• Stage I cancers are the least advanced and often have a better prognosis. Higher stage cancers are often more advanced, but in many cases can still be treated successfully.

Pathological examination :

gross and microscopic

Histological type Benign/malignant

Grade Stage

Appropriate treatment

DIAGNOSIS

PROGNOSIS

Phenotype

current tumours classification : aims, basis, terminology · current tumours classification : aims,...

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