1. Nomenclature & Characteristics of Tumours Neoplasia 1
Dr. Faten Ghazal
Professor of Pathology

2. What is neoplasia? Neoplasia is “new growth”.
The new growth produced is called a neoplasm or tumour.
A neoplasm:
is an abnormal growth of mass of tissue
due to excessive cell proliferation that has escaped normal limitations and regulation
and persists in the same excessive manner even after cessation of the stimuli.
Pathology Department

3. Intended Learning Outcomes (ILOs)
By the end of this lecture you will be able to:
Define neoplasia and neoplasm
Identify the basic components of any neoplasm
Classify neoplasms according to clinical behaviour and cell of origin
Define & describe terms of differentiation, anaplasia and cytologic criteria of malignancy
Identify the characteristics of neoplasms
Define & describe terms of epithelial dysplasia & carcinoma in situ
Pathology Department

4. Are all new growths considered neoplasms?
Not all “new growths” are neoplasms since examples of new growth of tissues & cells exist in the process of embryogenesis, regeneration, repair & hyperplasia.
What is the difference between these examples of new growths and neoplasia?
There is loss of control & regulation of replication with formation of an abnormal mass of tissue.
By definition neoplasia is new growth. However not all “New Growth” are neoplasms as growth of tissues and cells occur in embryogenesis, regeneration, and repair, hyperplasia and hormonal stimulation. The proliferation and maturation of cells in normal adults is controlled as a result of which some cells proliferate throughout life (labile cells), some have limited replication as stable cells and others do not replicate (permanent cells). On the other hand neoplastic cells lose control on and regulation of replication and form abnormal mass.
Pathology Department

5. What causes such neoplasms?
They result from mutations of genes that regulate:
Cell growth,
Apoptosis
DNA repair
The stimuli for such uncontrolled proliferation are either acquired spontaneously or induced environmentally or even still unknown

6. What are the basic components of any tumour?
Parenchyma
It is the neoplastic proliferating transformed cells and is responsible for the biologic behaviour of the tumour.
Stroma
It is host derived supporting non-neoplastic fibrous connective tissue that contains blood vessels and inflammatory cells.
Parenchyma is the functional part of the tumour while the Stroma is considered a framework on which the tumour cells can grow.
Pathology Department

7. How can we classify tumours?
Clinical (Biological) Behaviour
a) Benign, b) Malignant & c) Locally (Invasive)
Aggressive Tumours
Cell of Origin (Histogenesis)
a) Epithelial, b) Mesenchymal & c) Mixed Tumours
Pathology Department

8. Classification of Tumours According to
Clinical Behaviour & Cell of Origin
Benign Tumours
Malignant Tumours
Epithelial
Mesenchymal
Epithelial
Mesenchymal
Papilloma
Adenoma
According to origin
Carcinoma
Sarcoma
Mixed
Mixed
Pathology Department

9. What is meant by differentiation?
Differentiation means the extent of which the tumour cells resemble the cell of origin morphologically and functionally
Benign neoplasms are composed of:
well differentiated cells closely resembling their normal cell of origin
Malignant neoplasms are characterized by:
a wide range of parenchymal cell differentiation from well differentiated to poorly differentiated and even completely undifferentiated or anaplastic. Between the 2 extremes lie neoplasms referred as moderately differentiated

10. Cytologic Criteria of Malignancy
1. Hyperchromatism:
Darkly stained nuclei.
2. Pleomorphism:
Variation in size and shape of the tumour cells.
3. Anisonucleosis:
Variation in size and shape of nuclei.
Pathology Department

11. Cytologic Criteria of Malignancy
4. Increased nucleo- cytoplasmic ratio (N/C ratio):
Normal ratio is (1:4) –(1:6) it is increased to (1:1)
5. Nucleolar changes:
Prominent nucleolus or multiple nucleoli.
Pathology Department

12. Criteria of Malignancy6
6. Loss of polarity:
Disrupted orientation of cells (loss of their organised relation to each other & to basement membrane)
7. Mitotic figures:
Numerous normal or abnormal mitotic figures.
8. Tumour giant cells (+/-):
Multinucleated tumour giant cells or giant cells with large bizarre nuclei 7 8
Pathology Department

13. Extended Modular Program
Abnormal Mitosis
Extended Modular Program

14. Abnormal Mitosis

15. Squamous Cell Carcinoma Hepatocellular carcinoma
Functional changes:
The better the differentiation of the tumour cell, the more it retains the functional capabilities found in its normal counterpart e.g. keratin formation in………….,
bile secretion in…………
Keratin pearls
A hallmark of well differentiated squamous cell carcinoma is that the nests of invading cells still attempt to make keratin which then gets deposited in the center of the nests, resulting in a keratin "pearl". A “pearl” in a squamous cell carcinoma qualifies it to be “well” differentiated.
From the Iowa Collection
Squamous Cell Carcinoma
Hepatocellular carcinoma

16. 10. Chromosomal Abnormalities
All tumour cells have abnormal genetic composition
Most malignant tumours show DNA aneuploidy often in the form of increase in number of chromosomes reflected morphologically by increase in nuclear size

17. What is meant by Anaplasia?
Anaplasia means backward differentiation (dedifferentiation): i.e. loss of structural & functional differentiation
Some tumours arise from stem cells where there is failure of differentiation rather than dedifferentiation.
Anaplastic cells have:
pleomorphic, hyperchromatic nuclei, increased nucleocytoplasmic (N/C) ratio, large nucleoli, increased number of mitoses with atypical forms

18. Can you tell the cell of origin?
A highly anaplastic tumour so that the cell of origin can not be identified

19. What are the Characteristics of Tumours?
Rate of Growth: slow or rapid
Gross Features:
Capsulation: (+/-)
Borders: well circumscribed or invasive
Effects on surrounding tissue: compression or infiltration
Secondary effects: -/+ haemorrhage & necrosis
Microscopic Features:
Phenotype: epithelial, mesenchymal or mixed
Degree of differentiation: well, moderately, poorly or anaplastic)
Criteria of malignancy: -/+
Distant spread or metastases:
Does not occur or can occur

20. I. Rate of Growth a-Benign Tumours: Grow slowly (months to years).
Exceptions:
Leiomyoma of uterus (benign tumour of smooth muscle cell) : its rate of growth is influenced by estrogens e.g.:??
size during pregnancy and after menopause.
Pituitary gland adenoma: shrinks as progressive enlargement compresses their blood supply resulting in necrosis

21. I. Rate of Growth
b- Malignant Tumours: Enlarge progressively and rapidly.
Poorly differentiated tumours grow rapidly than the well differentiated tumours.
May show central areas of ischaemic necrosis called umbilication.

22. What are the Characteristics of Tumours?
Rate of Growth: slow or rapid
Gross Features:
Capsulation: (+/-)
Borders: well circumscribed or invasive
Effects on surrounding tissue: compression or infiltration
Secondary effects: -/+ haemorrhage & necrosis
Microscopic Features:
Phenotype: epithelial, mesenchymal or mixed
Degree of differentiation: well, moderately or poorly or anaplastic)
Criteria of malignancy: -/+
Distant spread or metastases:
Does not occur or can occur

23. According to Clinical Behaviour:
II. Gross Features & Local Invasiveness
According to Clinical Behaviour:
Benign Tumours
Encapsulated or non-capsulated well circumscribed
Grow by expansion
Some benign tumours have tongues beyond the capsule and thus are liable to recur e.g..?? Search for the next lecture
No secondary changes (??)
Pleomorphic Adenoma of the salivary gland
= Areas of haemorrhage & necrosis
Pathology Department

24. According to Clinical Behaviour:
II. Gross Features & Local Invasiveness
According to Clinical Behaviour:
Malignant Tumours
Grow rapidly by progressive infiltration, invasion, destruction & penetration of the surrounding tissue.
Show more frequent secondary changes as areas of haemorrhage & necrosis
Don’t develop well defined capsule but some tumours may appear capsulated due to compressed surrounding tissue.
The infiltrative mode of growth makes it necessary to remove the tumour with WIDE surgical margin
What is the importance??

25. What are the Characteristics of Tumours?
Rate of Growth: slow or rapid
Gross Features:
Capsulation: (+/-)
Borders: well circumscribed or invasive
Effects on surrounding tissue: compression or infiltration
Secondary effects: -/+ haemorrhage & necrosis
Microscopic Features:
Phenotype: epithelial, mesenchymal or mixed
Degree of differentiation: well, moderately, poorly or anaplastic)
Criteria of malignancy: -/+
Distant spread or metastases:
Does not occur or can occur

26. Classification of Tumours According to
Clinical Behaviour & Cell of Origin
III. Microscopic Features
Benign Tumours
Malignant Tumours
Epithelial
Mesenchymal
Epithelial
Mesenchymal
Papilloma
Adenoma
According to origin
Carcinoma
Sarcoma
Mixed
Mixed
Pathology Department

27. Nomenclature – Benign Tumors
III. Microscopic Features
Nomenclature – Benign Tumors
Epithelial Tumours (Epithelial Cell Origin)
Adenoma:
Is a tumor formed of glands (microscopic description)(mostly)
Papilloma:
Is a tumor with finger like projections arising from surface epithelium formed of connective tissue core and covered by epithelium. It will be named according to type of covering epithelium (gross & microscopic descriptions)
Named according to cell of origin:
prefix (cell of origin) + adenoma or papilloma
e.g. liver cell adenoma, squamous cell papilloma,…..
Adenoma is a term generally applied to tumours forming glands but not necessarily exhibiting glandular pattern, e.g. adrenocortical adenoma. Other special types of benign tumours arising from different cells or in specific organs will be studied later in systems. But remember melanocytes can produce benign tumour called nevus
Pathology Department

28. Nomenclature – Benign Tumors
III. Microscopic Features
Nomenclature – Benign Tumors
Mesenchymal Tumours & other related tissues
Named according to cell of origin (prefix) + oma or ioma
Fibrous tissue: (Fibr)oma
Smooth muscle cell: (leiomy)oma
Bone tissue, osteocyte: (Oste)oma
Adipose tissue, lipocyte (fat): (Lip)oma
Cartilaginous tissue, chondrocyte: (Chondr)oma
Blood vessels (haem ang): (haemang)ioma
Lymphatic vessels (lymph ang): (lymphang)ioma
Meninges: (mening)ioma

29. Nomenclature – Benign Tumours
Epithelial
Mesenchymal
Mixed
Mixed tumour of salivary gland (pleomorphic adenoma)
Fibroadenoma of the breast
Benign Cystic Teratoma is a special type of mixed tumour that arise from a totipotent cell
Pathology Department

30. Nomenclature – Malignant Tumors
III. Microscopic Features
Nomenclature – Malignant Tumors
Carcinomas: Epithelial Tumours
Named according to cell of origin (Prefix) + carcinoma
Stratified squamous epithelium: Squamous Cell Carcinoma
Basal cell: Basal Cell Carcinoma
Transitional epithelium: Transitional (Urothelial) Carcinoma
Glands: Adenocarcinoma e.g. colonic adenocarcinoma
Kidney: Renal Cell Carcinoma
Liver cell: Hepatocellular Carcinoma
Melanocytes: Malignant Melanoma
Placenta: Choriocarcinoma
Pathology Department

31. Nomenclature – Malignant Tumors
III. Microscopic Features
Nomenclature – Malignant Tumors
Mesenchymal Tumours & other related tissues
Named according to cell of origin (prefix) + sarcoma
Fibrous tissue: (Fibro)sarcoma
Smooth muscle cell: (Leiomyo)sarcoma
Bone tissue: (Osteo)sarcoma
Adipose tissue (fat): (Lipo)sarcoma
Cartilaginous tissue : (Chondro)sarcoma
Blood vessels (angio): (angio)sarcoma
Lymphatic vessels (lymph): (lymphangio)sarcoma
Meninges: Invasive Meningioma
Adenoma is a term generally applied to tumours forming glands but not necessarily exhibiting glandular pattern, e.g. adrenocortical adenoma
Pathology Department

32. Nomenclature – Malignant Tumors
Epithelial
Mesenchymal
Mixed
Malignant Mixed tumour of salivary gland
Cystosarcoma phylloides of breast
Malignant (Immature teratoma) is a special type of mixed tumour that arise from a totipotent cell
Malignant Mesothelioma (M. tumour of pleura, peritoneum)
Synovial Sarcoma
Pathology Department

33. III. Microscopic Features
Tumour angiogenesis:
Formation of new blood vessels which are formed from pre-existing ones to provide nourishment to tumor.
Tumour stroma:
is formed of fibrous tissue is stimulated by basic fibroblast growth factor (b-FGF) formed by tumor cells:
Scanty stroma results in
soft and fleshy tumours (e.g. sarcoma, lymphoma)
Excessive stroma results in
hard and gritty tumours (e.g. infiltrating duct carcinoma of the breast). It is referred to as desmoplasia.

34. III. Microscopic Features
Inflammatory Reaction:
Prominent inflammatory reaction present in tumors could be due to either:
Ulceration with secondary infection.
Cell-mediated immune response by the host in an attempt to destroy the tumour resulting in chronic inflammatory reaction or granulomatous reaction, e.g. seminoma of testis.

35. What are the Characteristics of Tumours?
Rate of Growth: slow or rapid
Gross Features:
Capsulation: (+/-)
Borders: well circumscribed or invasive
Effects on surrounding tissue: compression or infiltration
Secondary effects: -/+ haemorrhage & necrosis
Microscopic Features:
Phenotype: epithelial, mesenchymal or mixed
Degree of differentiation: well, moderately or poorly or anaplastic)
Criteria of malignancy: -/+
Distant spread or metastases:
Does not occur or can occur

36. Metastasis (meta=transformation, stasis=residence)
IV. Distant Spread or Metastasis
Metastasis (meta=transformation, stasis=residence)
Definition:
Metastasis is
the transfer of malignant cells from the site of origin (primary site) to another remote site (secondary site)
Metastases are
secondary implants of the tumour that are discontinuous with the primary tumour.
Benign tumors do not metastasize while malignant tumors can metastasize.
This attribute is the most important one that assign a tumour as malignant

37. Basal Cell Carcinoma and Giant Cell Tumour of Bone
IV. Distant Spread or Metastasis
Metastasis and invasiveness are the 2 most important features that distinguish benign from malignant tumours.
Not all cancer have the same equivalent ability of metastasis
Locally aggressive (malignant) tumours rarely metastasize, example:
Basal Cell Carcinoma and Giant Cell Tumour of Bone

38. Epithelial Dysplasia
Epithelial dysplasia is disorderly proliferation of epithelial cells with loss of uniformity of individual cells & their architectural orientation to each other and to basement membrane (loss of polarity)
Characteristics of Dysplastic epithelium
Have pleomorphic & hyperchromatic nuclei
Loss of polarity & maturation
Abundant mitoses & in abnormal location (not confined to basal layer)
e.g. disordered class of students in age and uniform

39. Epithelial Dysplasia
If in stratified squamous epithelium it is classified into:
Mild: the dysplasia affects the lower 1/3,
Moderate: dysplasia affects the lower 2/3
Severe: dysplasia affects more than lower 2/3
If dysplasia is present in whole epithelial thickness it is called:
Carcinoma In situ
Epithelial dysplasia can occur in glandular epithelium

40. The markedly dysplastic epithelium on the …………..side??
left
Extended Modular Program
Pathology Department

41. Dysplastic Epithelium
Left
Right
Hyperchromatic, pleomorphic nuclei, loss of polarity (orientation), increased mitoses, increased N/C ratio
Normal Epithelium
Dysplastic Epithelium
Pathology Department

42. Pre-invasive carcinoma =
Dysplastic changes involving the entire epithelial thickness without invasion of basement membrane
Pre-invasive carcinoma =
Carcinoma in situ
Pathology Department

43. Pre-invasive carcinoma =
Carcinoma in situ

44. Is Dysplasia synonymous to Cancer?
Dysplasia is NOT synonymous to cancer.
2. Can Dysplasia regress??
Mild to moderate dysplasia (not involving the entire epithelial thickness) can regress completely when the stimuli are removed
Pathology Department

45. Squamous Intraepithelial Lesion
Epithelial Dysplasia
SIL=
Squamous Intraepithelial Lesion