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

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

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

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

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

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

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

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

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

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

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

Criteria of Malignancy 6 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

Extended Modular Program Abnormal Mitosis Extended Modular Program

Abnormal Mitosis

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

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

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

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

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

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

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.

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

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

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??

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

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

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

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

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

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

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

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

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.

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.

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

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

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

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

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

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

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

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

Pre-invasive carcinoma = Carcinoma in situ

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

Squamous Intraepithelial Lesion Epithelial Dysplasia SIL= Squamous Intraepithelial Lesion