neoplasia: nomenclature, staging and grading

NEOPLASIA

OLUSIYAN OLUWATOBI

Outline

•Introduction•Definitions•Nomenclature•Characteristics of Benign and malignant tumors•Grading and staging of tumors.•Clinical Effects

INTRODUCTION• Different terms has been used in the past to describe abnormal growth

• Tumors, which in the past has been used as a non-neoplastic term as used by Celsus in describing the cardinal signs of Inflammation to mean swelling but its use now is equated with Neoplasm• Cancer which literally Crab, is a term used mainly for Malignant tumors, Cancer is the leading cause of death in the world, 2nd only to Cardiovascular disease.

Definitions Neoplasia derived from 2 Greek words Neos = New Plasia = Thing FormedHence, Neoplasia in simple terms means the process of forming new things or simply, new growth.A generally acceptable definition from a British Oncologist, Willis“A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change”

Definitions cont’dNeoplasm or tumor is as a result of genetic alterations that are passed down to the progeny of the tumor cells. These genetic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli)NOTE: The entire population of neoplastic cells within an individual tumor arises from a single cell that has incurred genetic change, and hence tumors are said to be clonal. A neoplasm can be benign, potentially malignant (pre-cancer), or malignant (cancer)

NOMENCLATUREAll tumors (both benign and malignant) have two basic components:(a) The Parenchyma: Which is made up of the proliferating

neoplastic cell that divide excessively.(b) The Stroma/Supporting tissue: Which consists of mainly connective tissue, blood vessels and cells of the innate and adaptive immune response. In cases where the parenchymal cells induce/stimulate the formation of abundant collagenous stroma, DESMOPLASIA results. e.g. schirrhous/stony hard breast cancer.

NOMENCLATURE CONT’D• NOTE: Nomenclature of tumors is based primarily on the parenchymal component. The nomenclature is broadly divided into 2, depending on the origin of the tumor either it is of (a) Mesenchymal origin or(b) Epithelial origin

BENIGN TUMORS• A benign tumor is a cohesive expansile mass of tissue with

an innocent gross and microscopic appearance implying that it will remain localized to its site of origin and will be easily amenable to surgical removal.

• The general principle of naming benign tumor is the addition of the suffix “-oma” to the cell of origin.

BENIGN TUMORS OF MESENCHYMAL ORIGINAll cells of mesenchymal origin follows this rule e.g.Fibroblastic cell B.T = FibromaCartilaginous B.T = ChondromaSmooth/skeletal mm B.T =Leiomyoma/rhabdomyoma

• .

Benign Tumours

NOMENCLATURE OF BENIGN TUMORS

BENIGN TUMOURS OF EPITHELIAL ORIGIN Their classification is more complex. They are based on cells of origin, microscopic architecture or other macroscopic patterns.

B.T OF EPITHELIAL ORIGIN CONT’D1. AdenomaGlandular tissues with non-glandular patterns e.g. Thyroid

adenomaNon-glandular tissues with glandular patterns e.g. renal

tubular adenoma

B.T OF EPITHELIAL ORIGIN CONT’D2. PapillomaMicroscopic or macroscopic visible finger-like or warty projections from epithelial surfaces. E.g. Oral papilloma..

.

3.CystadenomaA form of adenoma that form cystic masses .E.g ovarian cystadenoma

MALIGNANT TUMORS• They are collectively referred to as cancers.Malignant

tumors can invade and destroy adjacent structures and also spread to distant sites.

• Malignant tumors arising from mesenchymal tissue = SARCOMA. E.g. Fibrosarcoma, chondrosarcoma,

leiomyosarcoma, rhabdomyosarcoma etc.

Malignant Tumour

M.T OF EPITHELIAL ORIGIN • M.T of epithelial origin, derived from any of the 3 germ layer (endoderm, ectoderm and mesoderm) are called CARCINOMA.1. AdenocarcinomaM.T with glandular growth pattern microscopically2. Squamous cell carcinomaArising from squamous cell epithelium, specificity of organ of origin is essential3. Polyp / PolypoidThis is a macroscopically, visible projection that arise from the mucosal surface into the lumen, either benign or malignant

• Mixed tumorsThey are tumors which appear to be composed of both epithelial and connective tissues because of divergent differentiation of a single neoplastic clone.It is made up of more than one cell type derived from a single germ layer. Example is Mixed tumor of salivary gland, these neoplasm are called Pleomorphic Adenoma.• TeratomaThey are neoplasms with more than one cell type arising from more thanOne germ layer.Teratomas originate from totipotent germ cells that are normally present in ovaries and testis.They differentiate along different germ lines producing ,fat, muscle, epithelium, any body tissue. E.g. Ovarian Cystic teratoma (dermoid cyst)

Special Nomenclature• Malignant tumors that sound benign

• Lymphoma

• Mesothelioma

• Melanoma

• Seminoma

• Astrocytoma/glioma

• Hepatoma

• Blastoma: are tumors arising from immature tissue or nervous tissue. most of them are malignant e.g. medulloblastoma, retinoblastoma, nephroblastoma

Special Nomenclature Cont’d• Non-tumors that sound like tumors

• Hamartoma –A focal growth that resembles a neoplasm but results from faulty development of the organ.E.g chondroma of the lung,adenoma of the liver

• choristoma – heterotopic rest of cells.A mass of histological normal tissue found in an abnormal location.E.g mass of pancreatic tissue found in submucosal of the stomach,douodemum /S.I;ectopic rest of normal tissue, e.g. a rest of adrenal cells under the kidney capsule, a rest of Brunner’s glands in the jejunum/ileum etc

Nomenclature of tumors Tissue of Origin Benign Malignant

Composed of One parenchymal cell TypeMesenchymal tumors Connective tissue and derivatives

  FibromaLipomaChondromaOsteoma

  FibrosarcomaLiposarcomaChondrosarcomaOsteogenic sarcoma

Endothelial and related tissues Blood vessels Lymph vessels Synovium Mesothelium Brain coverings

 HemangiomaLymphangioma Beningn synovioma  ==Meningioma

AngiosarcomaLymphangiosarcomaSynovial sarcomaMesotheliomaInvasive meningioma

Nomenclature of tumors

Tissue of Origin Benign Malignant

Blood cells and related cells Hematopoietic cells Lymphoid tissueMuscle Smooth Striated

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LeiomyomaRhabdomyoma

LeukemiaLymphoma

Leiomyosarcoma

Rhabdomyosarcoma Epithelial tumors Stratified squamous Basal cells of skin or adnexa Epithelial lining Glands or ducts

  Squamous cell papilloma  ------ AdenomaPapillomaCystadenoma

Squamouscell carcinoma

Nomenclature of tumors

Tissue of Origin Benign Malignant

Epithelial tumors Stratified squamous Basal cells of skin or adnexa Epithelial lining Glands or ducts

 Squamous cell papilloma  AdenomaPapillomaCystadenoma

Squamous cell or epidermoid carcinoma Basal cell carcinoma

AdenocarcinomaPapillary carcinomaCystadenocarcinoma

Nomenclature of tumors

Tissue of Origin Benign Malignant

Respiratory passages

NeuroectodermRenal epitheliumLiver cellsUrinary tract epithelium (transitional)Placental epithelium (trophoblast)Testicular epithelium (germ cells)

. Bronchial adenoma

Nevus Renal tubular adenoma Liver cell adenomaTransitional cell papillomaHydatidiform mole -----

Bronchogenic carcinoma)Malignant melanoma Renal cell carcinomaHepatocellular carcinomaTransitional cell carcinomaChoriocarcinomaSeminoma

Nomenclature of tumors

Tissue of Origin Benign Malignant

More Than One Neoplastic Cell Type- Mixed Tumors, Usually Derived From One Germ Layer

Salivary glands Pleomorphic adenoma (mixed tumor of salivary origin)

Malignant mixed tumor of salivary gland origin

BreastRenal anlage(primordium)

Fibroadenoma Malignant cystosarcoma phyllodes Wilms tumor

Nomenclature of tumors

Tissue of Origin Benign Malignant

More Than One Neoplastic Cell Type Derived From More Than One Germ Layer-

Totipotential cells in gonads or in embryonic rests

Mature teratoma, dermoid cyst

Immature teratoma, teratocarcinoma

Characteristics of B & M Tumor• Differentiation and Anaplasia• Rate of growth• Local invasion• Metastasis

• Differentiation is the extent to which neoplastic parenchymal cells resemble the corresponding normal parenchymal cells, both morphologically and functionally.

• Lack of differentiation is called Anaplasia(‘’to form backward’’).This is the hallmark of malignancy.

• Benign tumors are well-differentiated while malignant tumors usually range moderately differentiated to anaplastic.

1.Differentiation And Anaplasia

Tubular adenoma and adenocarcinoma• tt

The Morphologic changes associated with anaplasia are:-• Pleomorphism• Abnormal nuclear morphology.• Mitosis-Many cells in malignant neoplasm are in mitosis

(proliferative activity of the parenchymal cells)• Loss of polarity(Loss of orientation,organization and

architecture of the cells)• Other changes.N:B-The better the differentiation of a transformed cell,the

more it retains the functional capability of its normal counterpart.

1.Differentiation And Anaplasia

2.Rate of growth• Most benign tumor grow slowly while malignant ones

grow much faster eventually spreading locally and to distant sites and causing death.

3.Local invasion• A benign tumor remains localized at its site of origin, it does

not have the capacity to infiltrate, invade or metastasize to distant site like the malignant tumor does.

• Benign tumor develop a rim of fibrous capsule that separates them from the host tissue(due to their slow growth and expansion) to make the tumor more discrete,easily palpable and excisable by local surgical removal,except the hemamgiomas(neoplasms of tangled blood vessels)

• Some cancers seem to evolve from pre -invasive stage referred to as carcinoma in-situ e.g found in skin,breast,uterus etc which display the cytologic features of malignancy without invasion of the basement membrane.

4.METASTASIS• Metastasis is defined by the spread of a tumor to sites

that are physically discontinuous with the primary tumour.This marks a tumor as malignant because benign tumors do not metastasize.

The invasiveness of cancer permits them to penetrate into blood vessels,lymphatics,and body cavities,providing the oppourtunity for spread.. Exceptions:Gliomas,Basal cell carcinomas of the skin which rarely metastasizes after invasion..

• Metastatic spread strongly reduces the possibility of cure.

Comparisons Between Benign and Malignant Tumors

Characteristics Benign MalignantDifferentiation/anaplasia

Well differentiated; structure may be typical of tissue of origin

Some lack of differentiation with anaplasia; structure is often atypical

Rate of growth Usually progressive and slow; may come to a standstill or regress; mitotic figures are rare and normal

Erratic and may be slow to rapid; mitotic figures may be numerous and abnormal

Local invasion Usually cohesive and expansile well-demarcated masses that do not invade or infiltrate surrounding normal tissues; Encapsulation

Locally invasive, infiltrating the surrounding normal tissues; sometimes may be seemingly cohesive and expansile

Metastasis Absent Frequently present; the larger and more undifferentiated the primary, the more likely are metastases

Comparison

METASTASIS• Metastasis is defined by the spread of a tumor to sites that are physically discontinuous with the primary tumour.This marks a tumor as malignant.

• The likelihood of a primary tumor to metastasize correlates with lack of differentiation,aggressive local invasion,rapid growth and large size.

Spread Of Tumors

• It include;•Direct seeding of body cavities or surfaces/Transcoelomic spread

•Lymphatic spread•Blood(haematogenous spread)

Seeding Of Body Cavities&Surfaces• The malignant neoplasm penetrates into a natural ‘’open field’’ lacking physical barriers.The most often involved is the peritoneal cavity,but any other cavity-pleural,pericardial,subarachnoid, and joint spaces-may be affected.This pathway is particularly characteristics of carcinomas arising from the ovaries.

Lymphatic spread It is the principal mode by which carcinoma spread but sarcomas may also use this route. Wall of lymphatic's are thin and are readily penetrated by tumor cell tissue which is carried alongto the sentinel node in the lymphatic node chain.

• Carcinomas may reach the thoracic duct and enter the superior vena cava from which further spread through the blood stream may occur.

Pathways of spread: Lymphatic• Tumors spread is by the nearby lymphatic vessels.• Follows natural routes of drainage e.g carcinomas of d

breast frm outer upper quadrant will first drain into the axillary lymph nodes.

• Sentinel lymph node: first node to receive flow from the primary tumor-Virchow’s node: left supraclavicular LN which receives lymph from visceral cancer(stomach,S.I,breast and lung cancer)-radiolabeled tracer&colored dyes for S.L.N mapping.

• LN enlargement may be caused by:---growth of cancer cells-reactive hyperplasia; may limit the cancer growth

Haematogenous spread• Haematogenous spread is typical of sarcomas but is

also seen with carcinomas.• Thick walled arteries are resistant to invasion but the

veins are readily penetrated.• With venous invasion,the bloodborne tumour cells follow

the venous flow draining the site of neoplasm,and the tumour cells often rest in the 1st capillary bed they encounter.

• The LIVER and the LUNGS are most frequently involved in hematogenous dissemination because ALL PORTAL AREA DRAINAGE FLOWS TO THE LIVER and ALL CAVAL BLOOD FLOWS TO THE LUNGS.

• N.B :Not all systemic distributions of metastases follows the natural pathway of venous drainage .For example:-

• Breast and prostate carcinoma preferentially spreads to the bone.

• Bronchogenic carcinomas tend to involve the adrenals and the brain.

• Neuroblastomas spread to the Liver and bones.• Conversly,although well vascularized,the skeletal muscle and spleen are rarely sites of metastasis..

Pathways of spread: Hematogenous• More common in the venous circulation

-drain to the liver and lungs-near vertebral columnparavertebral plexus e.g carcinomas of thyroid and prostate.

• Less common: thick walled arteries.

Mechanism of spread of tumor• The metastatic cascade is divided into 2 phases:

• (a)Invasion of the Extracellular matrix• (b)Vascular dissemination,homing of tumor cells,and colonization

INVASION OF THE ECMThe ECM is composed of the:--Basement membrane(B.M)--Interstitial connective tissue(ICT)Each component is made up of collagens,glycoproteins,and proteoglycans.

N:B--A carcinoma must first breach the underlying B.M,then traverse the interstitial connective tissue,and ultimately gain access to circulation by penetrating the vascular B.M.This process is repeated in reverse when tumor cell emboli extravasate at a distant site.

INVASION OF THE ECM (CONT’D)• Invasion of the ECM initiates the metastatic cascade and it involves the following steps:

--Detachment of tumor cells from each other --Degradation of ECM(B.M+ICT)--Changes in attachment of tumor cells to ECM proteins.

-- Migration and invasion of tumor cells

VASCULAR DISSEMINATION & HOMING OF TUMOUR CELLSIntravasation of tumor cells involves;--Adhesion molecules--Proteolysis of B.M of blood vessels.Once in circulation,tumor cells are vulnerable to destruction by a variety of mechanisms:

(a)Mechanism of shear stress(b)Anoikis-Apoptosis of cells in circulation due to loss of adhesion.

(c)Innate and adaptive immune defences.

Within circulation,tumor cells tend to aggregate in clumps to enhance their survival & implantability.This is favoured by:

--Homotypic adhesion among tumor cells--Heterotypic adhesion btw tumor cells and blood cells,particularly platelets.

--Tumor cells may also bind & activate coagulation factors,resulting in the formation of tumor-emboli.

• Arrest and Extravasation of tumor emboli at distant sites involves:

Adhesion to vascular endothelium via adhesion molecules e.g Integrins,Laminin receptors and (CD44 adhesion molecules-which is used by normally T-cells to migrate to selective sites in the lymphoid tissue).

Migration through the B.M is by proteolytic enzymes.

HOMING OF TUMOR CELLS• The site at which circulatating tumor cells leave the capillaries to form secondary deposits is related to the :-

• --(a)Anatomic location and vascular drainage of the primary tumor-Most metastases occurs in the 1st capillary bed available to the tumor..but there r exceptions…

• --(b)The tropism of particular tumors for specific tissues.

ORGAN TROPISMOrgan tropism may be related to the following mechanisms:-

Affinity of organ for neoplastic cells by their endothelial cells expressing ligands for tumor cell receptors.

Some target organs may liberate chemoattractants that invite tumor cells at that site.E.g-some breast cancer express d chemokine receptors-CXCR4 and CCR7.

Some target tissues may be unpermissive,i.e’’unfavourable soil’’, for the growth of tumor cells ‘’seedlings’’.E.g skeletal muscles and spleen.

COLONIZATIONEstablishment of a new colony; cell proliferation and

development depends on supply of blood flow i.e seed and soil(tumor and recipient tissue).

Tumor grading and staging• These are terms used to quantify the clinical aggressiveness of a given neoplasm.

GRADING OF TUMOR• This is the description of the tumor based on the degree of differentiation of the tumor cells.i.e based on the extent to which tumor cells resemble their normal counterpart when a biopsy of tissue is viewed under a microscope.

• It is an indication of how quickly a tumor is likely to grow and spread.

• Well differentiated tumor tends to grow and spreads slowly than poorly &undifferentiated ones.

CLASSIFICATION OF TUMOUR GRADE

• The grading system differs depending on the type of cancer.

• The generalized one used is:• Gx :-Grade cannot be assessed(undetermined grade)• G1:-Well differentiated(Low grade)—Grows slowly• G2:-Moderately differentiated(Intermediate grade)• G3:-Poorly differentiated(High grade)—Grows rapidly• G4:-Undifferentiated(High grade)----------,,

Grading cont.• Some cancers are graded differently.• Breast cancer:By the Nottingham grading system(score

ranging from 3-9)• Prostate cancer:By Donald Floyd Gleason scoring system

(score ranging from 2 -10)• Renal cell carcinoma :-By Fuhrman system

STAGING OF TUMOR• Staging is a way of describing the size of cancer and its extent of spread into surrounding tissues or to other parts of the body.

• The major staging system currently in use is the American Joint Committee On Cancer Staging.

THE TNM STAGING SYSTEM• TNM stands for:T=primary Tumor,N=regional lymph Node and M=Metastases.

• This system uses number to describe the cancer.• T-is characterised as T1-T4 based on the increasing size of the tumor with 1 being small and 4 being large.

• N-refers to whether it has spread to the lymph nodes.N0 means no nodal involvement,N1-N3 would denote involvement of an increasing number and range of nodes.

• M-M0 signifies no distant metastasis whereas M1 or M2 indicates the presence of metastases.

• *T2 N1 MO vs T4 N3 M1??

STAGING CONTD(gastric carcinoma)

• T1…………..Mucosa/sub mucosa• T 2………….tumor penetrate muscularis propia• T 3………….tumor erode serosa• T 4………….adjacent organ• N 0………….no nodal involvement• N 1………….metastasis in 1-6 regional lymph node• N 2…………..metastasis in 7-15 regional lymph node• N 3……….. Metastasis more than 15 lymph node• M 0………..no distant metastasis• M 1………….distant metastasis.• So what is T3 N2 M1

Importance of staging• Staging is important to help us know the type of treatment to give.

• If cancer is in just one place,a local treatment such as surgery or radiotherapy could get rid of it completely.

• But if it has spread,systemic treatment such as chemotherapy,hormone therapy & biological therapy that circulates throughout the body will be needed.

• N.B-Staging is of a greater clinical value.

•THANK YOU.