NEOPLASIA H.A. MWAKYOMA, MD

DEFINITIONS : TUMOUR: - was originally applied to the swelling caused by inflammation - the term is now equated with neoplasm ONCOLOGY:- (Geek “oncos” = Tumour, is the study of tumours or neoplasm) NEOPLASM:- definition by British oncologist Sir Rupert Willis has come closest

DEFINITION OF NEOPLASM: Is an abnormal mass of tissue The growth of which exceeds and is uncoordinated with that of the normal tissue The growth persists in the same excessive manner after cessation of the stimuli which evoked the change Addition:- the abnormal mass is purposeless, preys on the host (Parasitic)

Additions to the definition of neoplasm cont-- The abnormal mass is virtually autonomous. The neoplasm preys on the host in sofar as the growth of the neoplastic tissue competes with the normal cells and tissues for energy and nutritional substrate

Additions to definition of neoplasm cont-- In as much as these masses my flourish in a patient; The patients wastes away The degree of autonomous of the neoplasm later is not complete All neoplasms ultimately depend on the host for the nutrition and vascular blood supply and endocrine support.

TYPES OF NEOPLASMS There are 2 groups of neoplasms The groups are divided according to their behavioural characteristics namely; BENIGN NEOPLASMS and MALIGNANT NEOPLASMS

BENIGN NEOPLASMS: Are the ones which remain localized Do not invade the tissue in which they grow Do not spread through the host body Do not normally cause serious damage EXCEPT as a result of critical positioning or function

MALIGNANT NEOPLASMS: Invade and destroys the host tissue Spreads throughout the body of the host It is invariably fatal if unchecked by removal or treatment CANCER: Cancer and malignant are commonly used as synonymous of a malignant neoplasm, Ie cancer is a common term for all malignant tumours. (cancer –Latin word for “Crab”)

NOMECLATURE AND CLASSIFICATION OF NEOPLASM It is usual to classify neoplasms according to:- The cell type from which they originate (HISTOGENESIS) Epithelial or Mesenchymal (connective) tissue

CLASSIFICATION OF NEOPLASM cont-- Biological behaviour:- Whether they are benign or malignant Names of individuals:- Hodgkin’s disease – a malignant tumour of lymphnodes = Lymphoma, which has no malignant counterpart).

Names of individuals cont-- Burkitt’s lymphoma - a malignant neoplasm originating from B-cells Grawitz tumour = Renal cell carcinoma (arising from renal tubular cells)

Classification of neoplasm cont-- Organs:- Hepatoma – tumour of the liver parenchymal cells - is a malignant version of Hepatocellular carcinoma Tumours derived from 3 germ layers (Endo-Meso-Ectoderm) Teratoma – derived from totipotential cells in gonadal or embryonal rests (may be benign or malignant)

NOT TRUE TUMOURS: HARMATOMA: Are congenital anomalies due to abberant differentiation of cells that results in a mass of disorganized but mature specialized cells or tissue indigenous to the particular site. Examples; islands of cartilage or bllood vessels within the lung.

Not true tumours cont-- CHORIOSTOMA:- A normal ectopic piece of tissue in an organ that is not normally found at the site Examples; - a piece of adrenal gland under the capsule of the kidney or - a nodule of pancreatic tissue in the submucosal of the small intestine or stomach

COMPONENTS OF TUMOURS: All tumours benign or malignant have 2 basic components; Parenchyma – proliferating neoplastic cells and Supportive stroma – made up of connective tissue, blood and lymphatic vessels

NOMECLATURE OF TUMOURS: Naming of tumours is based on parenchyma component. The SUFFIX“OMA” denotes benign neoplasm Note that there is no rule without exception E.g. Granuloma and Harmatoma are not neoplasms - Heptoma, lymphoma, melanoma are malignant tumors The tissue origin appears as a “PRIFIX”

BENIGN TUMORS: Benign mesenchymal tumours:- Are those arising in muscle, bones, cartilage, fat, blood/lymphatic vessels, fibrous tissue, etc Are classified histogenetically according to cell type

Benign tumours cont--- Benign epithelial tumours:- Are classified on; The basis of cells of origin(histogeneticaly) Microscopic architecture Macroscopic pattern EXAMPLES: ADENOMA: Benign epithelial neoplasm that form glandular pattern or

ADENOMA cont-- Tumours derived from glands but not necessarily reproducing glandular pattern (e.g. renal tubules, adrenal cortex cells)

PAPILLOMA: Benign epithelial neoplasm producing microscopically or macroscopically finger-like or warty projection.

Squamous cell papilloma-skin

POLYP Benign epithelial neoplasm which produces macroscopically visible projections above a mucosa surface and into the lumen. e.g. gastric or colonic

Colon adenomatous polyp

Colon polyp

Familial polyposis

HISTOGENETIC- cell of origin benign tumours Fibrous Fatty Cartilage Smooth muscle Striated muscle Bone Meninges Blood vessels Fibroma Lipoma Chondroma Leiomyoma Rhabdomyoma Osteoma Meningioma Angioma

Tissue of origin benign tumours Stratified squamous epithelium Basal cell Transitional epithelium Sweat gland Liver cell Sebaceous gland Bile duct Placenta epithelium (trophoblasts) Squamous cell papilloma Basal cell papilloma Transitional cell papilloma Sweat gland adenoma Liver cell adenoma Sebaceous gland adenoma Bile duct adenoma Hydatidform mole

Benign tumours -histogenesis There are some tumours which are derived from more than one neoplastic cell type These tumours are of 2 types:- Mixed tumours: Usually are derived from one germ layer e.g. salivary glands (myoepithelial cells) – PLEOMORPHIC ADENOMA- mixed tumour of salivary gland

More than one neoplastic cells cont-- TERATOMA: Are derived from more than one germ layer from totipotent cells in gonads (testes, ovary or embryonic rests)

MALIGNANT NEOPLASMS: Malignant tumour nomeclature are essentially follows the same scheme used for benign neoplasm with certain additions. Cancers arising in MESENCHYMAL tissue are called SARCOMAS (Greek “sark”-fleshy) because they usually have very little connective tissue stroma and so are fleshy. Malignant neoplasms of EPITHELIAL origin, are derived from 3 germ layers and are called CARCINOMAS.

MALIGNANT NEOPLASMS cont-- TISSUE OF ORIGIN Fibrous Fatty Cartilage Bone Smooth muscle Streated muscle Synovium Blood vessels TYPE OF TUMOUR Fibrosarcoma Liposarcoma Chondrosarcoma Osteosarcoma Leiomyosarcoma Rhabdomyosarcoma Synoviosarcoma Angiosarcoma

MALIGNANT NEOPLASMS cont- TISSUE OF ORIGIN Stratified squamous epithelium Basal cell Transitional epithelium Glandular epithelium Melanocyte Placental epithelium Liver cells (hepatocytes) TYPE OF TUMOUR Squamous cell carcinoma Basal cell carcinoma Transitional cell carcinoma Adenocarcinoma Melanoma Choriocarcinoma Hepatocellular carcinoma

BENIGN VS MALIGNANT TUMOURS Differences between benign and malignant tumours:- BASIC DIFFERENCES. Degree of differentiation Resemblance to normal “parent” tissue Well differentiation Moderately differentiated Poorly differenciated or anaplastic (primitive cell types)

BASIC DIFFERENCES cont-- Note that tumours may be undergoing uncontrolled proliferention, but may still be able to differentiate into cell types that closely resemble their normal counterparts Benign tumours are usually well differentiated Malignant tumours may vary from well to poorly differentiated

BASIC DIFFERENCES cont-- Poorly differentiated tumours are usually “aggressive” (carry a poorer prognosis due to rapid growth, early metastasis and/or poor response to therapy) Rate of tumour growth: Most benign tumours grow slowly over a period of years Most malignant tumours tend to grow rapidly over a period of months (from discovery) but also tend to grow erratically.

Rate of growth cont-- The rate of growth may depend on tissue type:- e.g. SARCOMA tend to grow rapidly than carcinomas The rate of growth generally correlates degree of differentiation, with undifferentiated tumours tending to grow faster

Rate of growth cont-- Rarely both benign and malignant tumours may actually stop growing and reduce in size or disappear (the so-called “miracle” cure), e.g. very rarely malignant melanoma may regress and disappear Hormones may influence the rate of growth of tumour e.g. leiomyoma of uterus (fibroid), may grow rapidly in pregnancy and disappear after menopause (oestrogen dependent)

BASIC DIFFERENCES cont-- Local invasion: Generally benign tumours grow slowly by expansion and develop a fibrous capsule Fibrous capsule usually allow easy surgical enucleation Some benign tumours are not well encapsulated.

LOCAL INVASION: Malignant tumours are locally invasive, They infiltrate the surrounding tissue and Usually give irregular margins that are not encapsulated Surgical removal requires a wide excision margin of “normal tissue to be resected (say, 2-3 cm) to ensure that all malignant cells are removed.

Local invasion cont-- Malignant tumours may “erode” into normal blood vessels, increasing the likehood of metastasis ((see later)

METASTASIS: By definition, malignant tumours can metastasise, although their ability to do so varies greatly Note that a tumour does not have to have metastasized before it is labled malignant

ABBERANT OR ABNORMAL FUNCTION Is more likely to occur in malignant tumours e.g. the secretion of abnormal or excess quantities of hormones

MICROSCOPIC DIFFERENCES: Organization of tumour cells: polarity:- tumour cells are organized into structures resembling their tissue of origin; e.g. glandular tumors often form glandular structures The more regular and ordered these structures are, the less likely they are malignant

POLARITY cont-- Glands that are haphazard in size and organization suggest malignancy Therefore there is LOSS OF POLARITY in malignant tumours unlike in benign ones. (lack of oriatation – disordered arrangement)

MICROSCOPIC DIFFERENCES cont-- Nuclear- cytoplasmic ratio (N:C ratio): Unlike in benign tumours, the nuclei in malignant tumours are disproportionately larger for the cell. The N:C ratio approach 1:1, instead the normal 1:4 or 1:6

Microscopic differences cont-- Variation in size and shape (Pleomorphism): In malignant tumours, both cells and nuclei are variable in size and shape (Pleomorphic) and hapharzadly arranged, unlike in benign tumours.

Microscopic differences cont-- Staining of nuclei: Characteristically, the nuclei contain abundance of DNA and extremely dark staining (Hyperchromatism) in malignant tumours rather than benign ones.

Microscopic diffrences cont-- Mitoses: There is a large number of mitoses, often used as a parameter of the aggressiveness of cancer. The presence of mitoses does not necessarily indicate that the tumour is malignant – MORE important are Atypical bizarre (ABNORMAL) mitotic figures.

MITOSES cont-- Benign tumours grow slowly with low mitotic rate. Malignant tumours grow rapidly with high mitotic rate and abnormal mitoses