Neoplasia: Nomenclature, Staging and Grading

1. NEOPLASIA
OLUSIYAN OLUWATOBI

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

3. 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.

4. Definitions
Neoplasia derived from 2 Greek words
Neos = New
Plasia = Thing Formed
Hence, 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”

5. Definitions cont’d
Neoplasm 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)

6. NOMENCLATURE
All 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.

7. 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

8. 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
ORIGIN
All cells of mesenchymal origin follows this rule e.g.
Fibroblastic cell B.T = Fibroma
Cartilaginous B.T = Chondroma
Smooth/skeletal mm B.T =Leiomyoma/rhabdomyoma

9. • .

10. Benign Tumours

11. 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.

12. B.T OF EPITHELIAL ORIGIN CONT’D
1. Adenoma
Glandular tissues with non-glandular patterns e.g. Thyroid
adenoma
Non-glandular tissues with glandular patterns e.g. renal
tubular adenoma

13. B.T OF EPITHELIAL ORIGIN CONT’D
2. Papilloma
Microscopic or macroscopic visible finger-like or warty projections
from epithelial surfaces. E.g. Oral papilloma
..
.
3.Cystadenoma
A form of adenoma that form cystic masses .E.g
ovarian cystadenoma

14. 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.

15. Malignant Tumour

16. 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. Adenocarcinoma
M.T with glandular growth pattern microscopically
2. Squamous cell carcinoma
Arising from squamous cell epithelium, specificity of organ of
origin is essential
3. Polyp / Polypoid
This is a macroscopically, visible projection that arise from the
mucosal surface into the lumen, either benign or malignant

18. • Mixed tumors
They 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 der
from a single germ layer. Example is Mixed tumor of salivary gland,
these neoplasm are called Pleomorphic Adenoma.
• Teratoma
They are neoplasms with more than one cell type arising from more
One germ layer.Teratomas originate from totipotent germ cells that a
normally present in ovaries and testis.They differentiate along differ
germ lines producing ,fat, muscle, epithelium, any body tissue. E.g.
Ovarian Cystic teratoma (dermoid cyst)

19. 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

20. 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

21. Nomenclature of tumors
Tissue of Origin Benign Malignant
Composed of One parenchymal cell
Type
Mesenchymal tumors
Connective tissue and derivatives
Fibroma
Lipoma
Chondroma
Osteoma
Fibrosarcoma
Liposarcoma
Chondrosarcoma
Osteogenic sarcoma
Endothelial and related tissues
Blood vessels
Lymph vessels
Synovium
Mesothelium
Brain coverings
Hemangioma
Lymphangioma
Beningn synovioma
==
Meningioma
Angiosarcoma
Lymphangiosarcoma
Synovial sarcoma
Mesothelioma
Invasive meningioma

22. Nomenclature of tumors
Tissue of Origin Benign Malignant
Blood cells and related cells
Hematopoietic cells
Lymphoid tissue
Muscle
Smooth
Striated
---
----
Leiomyoma
Rhabdomyoma
Leukemia
Lymphoma
Leiomyosarcoma
Rhabdomyosarcoma
Epithelial tumors
Stratified squamous
Basal cells of skin or adnexa
Epithelial lining
Glands or ducts
Squamous cell papilloma
------
Adenoma
Papilloma
Cystadenoma
Squamouscell carcinoma

23. 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
Adenoma
Papilloma
Cystadenoma
Squamous cell or epidermoid
carcinoma Basal cell carcinoma
Adenocarcinoma
Papillary carcinoma
Cystadenocarcinoma

24. Nomenclature of tumors
Tissue of Origin Benign Malignant
Respiratory passages
Neuroectoderm
Renal epithelium
Liver cells
Urinary tract epithelium (transitional)
Placental epithelium (trophoblast)
Testicular epithelium (germ cells)
. Bronchial adenoma
Nevus
Renal tubular adenoma
Liver cell adenoma
Transitional cell papilloma
Hydatidiform mole
-----
Bronchogenic carcinoma
)
Malignant melanoma
Renal cell carcinoma
Hepatocellular carcinoma
Transitional cell carcinoma
Choriocarcinoma
Seminoma

25. 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
Breast
Renal anlage(primordium)
Fibroadenoma Malignant cystosarcoma phyllodes
Wilms tumor

26. 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

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

28. • 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

29. Tubular adenoma and adenocarcinoma
• tt

30. 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

31. 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.

32. 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.

33. 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.

34. Comparisons Between Benign and Malignant Tumors
Characteristics Benign Malignant
Differentiation/ana
plasia
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

35. Comparison

36. 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.

37. Spread Of Tumors
•It include;
•Direct seeding of body cavities or
surfaces/Transcoelomic spread
•Lymphatic spread
•Blood(haematogenous spread)

38. 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.

39. 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.

40. 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

41. 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.

42. • 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..

43. Pathways of spread: Hematogenous
• More common in the venous circulation
-drain to the liver and lungs
-near vertebral columnparavertebral plexus e.g
carcinomas of thyroid and prostate.
• Less common: thick walled arteries.

44. 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

45. INVASION OF THE ECM
The 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.

46. 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

47. VASCULAR DISSEMINATION &
HOMING OF TUMOUR CELLS
Intravasation 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.

48. 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.

49. • 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.

50. 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.

51. ORGAN TROPISM
Organ 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.

52. COLONIZATION
Establishment of a new colony; cell proliferation and
development depends on supply of blood flow i.e seed
and soil(tumor and recipient tissue).

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

54. 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.

55. 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)----------,,

56. 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

57. 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.

58. 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??

59. 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

60. 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.

61. •THANK YOU.