Cancer = Latin for crab

NOMENCLATURE :
Neoplasia - New Growth Neoplasm Benign, Malignant Oncology ( Greek oncos = tumor ) In short Growth dysregulation.

Neoplasia Outline
Tumor nomenclature Definitions Benign tumors Malignant tumors Mixed tumors Confusing terms

Definition:
A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of normal tissues and persist in the same manner after cessation of the stimuli which evoked the change.

Persistence genetic alteration passed on , parent - progeny.

 Tumors are clonal entire population of neoplastic cells in an individual tumor arises from a single cell. Benign Tumors Malignant Tumors

Small Slow-growing Non-invasive Well-differentiated Stay localized

large fast growing invasive poorly differentiated metastasize

 Two basic components of all tumours :

(1) Clonal neoplastic cells ( Parenchyma ) (2) Reactive stroma connective tissue, blood vessels, macrophages and lymphocytes. Interaction between the two critical for tumor cell survival. Stromal support scant tumor is soft Stromal support abundant desmoplasia

Classification :
Neoplasm

Benign

Malignant

Carcinoma

Sarcoma

Benign vs. Malignant

Benign Tumors
Usually designated by adding -oma to cell type adenoma benign tumor arising from glandular cells but may or may not form glandular structures. leiomyoma benign tumor arising from smooth muscle cells chondroma benign tumor arising from chondrocytes Other benign tumor names papilloma has finger-like projections cystadenoma has hollow spaces (cysts) inside polyp projects upward, forming a lump can be benign or malignant.

Thyroid adenoma

Thyroid adenoma

Leiomyoma

Chondroma

Oral papilloma

Oral papilloma

Ovarian cystadenoma

Ovarian cystadenoma

Ovarian cystadenoma

Malignant Tumors
Carcinomas arise in epithelial tissue ( 3 germ cell layers) adenocarcinoma tumor cells grow in glandular pattern. squamous cell carcinoma tumor cells resemble stratified squamous epithelium. Sarcomas arise in mesenchymal tissue chondrosarcoma malignant tumor of chondrocytes angiosarcoma malignant tumor of blood vessels rhabdomyosarcoma malignant tumor of skeletal muscle cells

Adenocarcinoma

Squamous cell carcinoma

Rhabdmyosarcoma

Mixed Tumors
Mixed tumors divergent differentiation along two lineages. Examples
pleomorphic adenoma glands + fibromyxoid
stroma fibroadenoma glands + fibrous tissue

Not to be confused with teratomas

arises from all three layers.

Pleomorphic adenoma

 Hamartomas : disorganized but benign appearing masses composed of cells indigenous to a particular site. eg:- pulmonary chondroid hamartoma Choristoma: heterotopic rests of well developed and normally organised tissue. eg:- normal pancreatic tissue in stomach, duodenum.

Definitions
Differentiation-extent to which neoplastic cells resemble normal cells both morphologically and functionally Anaplasia lack of differentiation wherein reversal of differentiation to a more primitive level.

Pleomorphism variation in size &shape Abnormal nuclear morphology hyperchromatic Mitoses especially bizzare atypical mitoses Loss of polarity Metaplasia replacement of one type of cell with another type due to damage, repair or regeneration. eg: GERD Dysplasia literally means disordered growth.
Characterized by a constellation of changes that include a loss in the uniformity of the individual cells as well as a loss in their architectural orientation.

 Cell nuclei become hyperchromatic Nuclear membranes become irregular Nuclear to cytoplasmic ratio increased.

DYSPLASIA -65yr old tobacco chewer -oral mucosa shows leukoplakia (white plaque) -full thickness severe dysplasia on mucosal biopsy

GROWTH
Concept: Benign tumours grow slowly Cancers grow rapidly

RATE OF GROWTH
Rate of Growth is determined by three main factors : (1) The doubling time of tumour cells. (2) Fraction of tumour cells in replicative pool. (3) Rate at which cells are shed or die. Growth Fraction : Proportion of cells with in the tumour population that are in the proliferative pool (Cancer chemotheraphy). Aggressive tumours Lymphoma, leukemias melt with CT Cancer of colon and breast Debulk cell cycle Drug therapy

BENIGN VERSUS MALIGNANT TUMOURS

Invasion
Distinguish malignant tumours Metastases

INVASION
Definition : Growth into the surrounding tissue by direct extension / expansion. Benign tumours Expansile probing margins Localized growth Do not have the capacity to infiltrate May have a capsule or clear line of separation If resected to not recur If incompletely removed local recurrence only

Malignant tumours :
Progressive growth Infiltration ~ poor line of demarcation Invasion Destruction of adjacent tissue Metastatic spread Death if not treated

METASTASIS
Spread of tumour to distant sites by lymphatic, hematogenous routes or seeding of body cavities.

About 30% of tumours present with metastases Poorly differentiated tumours more likely to spread

1. Detachment of tumour cells

Down regulation of E- cadherin expression Eg : Adeno Ca of colon Ca of breast Reduced expression of protein catenins that links E cadherin to cells cytoskeleton.

2. Attachment to basement membrane :

- Tumour cells also over express integrin which act as receptor for different components of extra cellular matrix such as laminin, fibronectin, collagen and vitronectin. - The metastatic potential is directly proportional to the density of integrin

(b) Down regulation of anti - proteases

Break down of collagen and proteoglycans have the following effects:

4. Invasion of the circulation :

Matrix metalloproteinase. Down regulating antiproteases.

5. Homing of tumour cells

Adhesion of tumour cells to endothelium Degradation of vessel wall Organ tropism.
- Tumour cells express adhesion molecules whose ligands are expressed on vascular endothelial cells of target organ. - Preference for metastasis to specific organ are explained by chemokines. ( LN, Lung express CXCR4 and CCR7 ) - Eg : Prostatic Ca Vertebral bone
Neuroblastomas Liver, Bone.

Metastatic cascade

PATHWAYS OF SPREAD
Seeding of body cavities and surfaces Lymphatic spread Hematogenous spread

Types : 1. Direct Spread :

Direct infiltration of malignant cells into adjacent tissue, lymphatic or blood vessels. (1) Local spread (2) Lymphatic invasion (3) Perineural invasion (4) Venous invasion (5) Arterial invasion.

Osteogenic sarcoma

Pagetoid spread Tumour infiltrating into the adjacent duct and spread between the epithelial lining and the myoepithelial cell lining the BM of duct Eg : Breast Ca
Perineural Invasion Adenoid cystic carcinoma

Lymphatic spread
Sentinel lymphnode : The first lymphnode in a regional lymphatic drainage that gets involved by tumour metastasis. Eg : Sentinel lymphnode mapping is important in - breast carcinoma - Melanoma - Colonic Ca

Breast Ca spread through lymphatic and large in sub capsular sinus

Retrograde embolism :
Embolisation of tumour in the reverse direction to unusual sites when the flow of lymph is blocked by tumorous permeation. E.g. : Gastric cancer cells blocks the lymphatic drainage thoracic duct into the left subclavian left cervical nodes. ( Virchow ) Enlarges ( Troisiers sign )

Blood Vascular spread

Transcoelomic spread
Malignant cells detached and fall through the natural spaces and spread.
(1) Spread through peritoneal cavity. Krukenberg tumour : (Ovarian metastasis) - Ca of stomach, colon, breast infiltrate the peritoneal layer and then fall through the abdominal space due to gravity and settle on the ovaries - Ovaries are enlarged capsule is smooth and intact. - Cut section shows diffuse replacement of the ovary by mucin secreting Ca. Pseudomyxoma peritonei : - Mucin secreting adeno Ca of appendix or ovary rupture, discharge the mucin and tumour cells into the peritoneal cavity. - The tumour cells grow and secrete large amount of mucinous material filling the abdominal cavity.

METASTASES

LIVER METASTASES FROM A PRIMARY BREAST CARCINOMA normal liver function tests!

CANCER
one out of every five people who die this year will die of tumors