Neoplasia

new growth

=> tumor

transforemd

-> dont respond to inhibitory growth signals

-> a degree of autonomy

-> need host for nutrition and blood supply

its microscopic and gross characteristics are considered to be relatively innocent, implying that it will remain localized and is amenable to local surgical remova

implies that the lesion can invade and destroy adjacent structures and spread to distant sites (metastasize) to cause death

1. parenchyme -> part of tumor that grows (dtermines benign/malignant) neoplstic

2. stroma -> supply tuor with blood non neopalstic

• Attach the suffix – oma to cell type from which the tumor arise: easy for mesenchimal tumors

• Epithelial or mesenchymal cells

• Fibrous tissue – fibroma

• Cartilage – chondroma chondrocytes

• Bone – osteoima

• More complex nomenclature is applied to benign epithelial tumor

carcinoma

sarcoma

epithelial malignant tumor

Adenocarcinoma

• Carcinomas that grow in glandular pattern, or arise from glandular epithelial cells

Squamous cell carcinoma

• Carcinomas which arise from squamous cells

Tumours which originate from totipotential germ cell in ovary, testis and sometimes in midline embryonic rest

Germ cells have capacity to differentiate into any ofthe cell types found inthe adult body

Mixed tumors – tumors with divergent

differentiation

Progenitor cell in this tumors has the capacity to differentiate down more than one lineage

Mass of disorganised tissue which contain the same tissue as the organ in which it is found

Congenital anomaly consisting of a heterotopic nest of the cell

Lymphoma

Sacroma

Melanoma

Seminoma

• Extent to which neoplasms resemble their cells of origin, both morphologically and functionally

• Anaplasia is lack of differentiation – loss of the structural and functional differentiation of normal cells

• Benign neoplasms are well differentiated, never anaplastic

• Malignant neoplasms range from well differentiated to poorly differentiated and anaplastic

• ANAPLASIA= MALIGNANT!!!

• Pleomorphism = Variation in size and shape

• Nuclear abnormalities= Hypechromatism, variation in size

and shape, prominent single or multiple nucleoli

• Increased nuclear cytoplasmatic ratio

• Tumor giant cells

• Atypical mytosis= Tripolar or quadripolar mitotic figures Loss of polarity

growth slowly and develop a rim of compressed fibrous tissue

progressive infiltration , invasion, and destruction of surrounding tissue

liver & lung

bening dont metastasize

Environmental exposures appear to be the dominant risk factors for many common cancers, suggesting that a high fraction of cancers arepotentially preventable. The role of genetic factors!

-> arsen

-> asbest

-> benzene (myeloid)

chronic inflammation -> carcinoas

immunodeficiency -> lymphomas

is an alteration that gives a cancer cell a fundamental growth advantage for its neoplastic transformation. Most of them are acquired, but can be inherited

Passenger mutations do not directly drive cancer initiation and progression, but contribute to carcinogen-associated cancer and tumor drug resistance to therapy. Always acquired

Protoongogenes to oncogenes = gain of function (RAS)

tumor supressor genes = loss of function (TP53)

can also cause tumors

1. NMYC gene -> neuroblastoma

2. HER2 -> breast cancer

• Self-suffciency in growth signals

• Insensitivity to growth-inhibitory signals

• Altered cellular metabolism

• Evasion of apoptosis

• Immortality

• Sustained angiogenesis

• Invasion and metastasis

• Evasion of immune survelliance

• Cyclin D-CDK4, cyclin D-CDK6, and cyclin E-CDK2 regulate the G1-to-S transition by phosphorylating the Rb protein (pRb).

• Cyclin A-CDK2 and cyclin A-CDK1 are active in the S phase. Cyclin B-CDK1 is essential for the G2-to-M transition.

• Two families of CDK inhibitors can block activity of CDKs and progression through the cell cycle.

• The so-called “INK4 inhibitors,” composed of p16, p15, p18, and p19, act on cyclin D-CDK4 and cyclin D-CDK6.

• The other family of 3 inhibitors p21,p27 and p57 can inhibit all CDKs

• Hypophosphorylated RB + E2F= transcriptional block

• Hyperphosphorylated RB = free E2F= transcriptional activation

• One of the four key regulators of the cell cycle (p16, cyclinD, CDK4, RB) is mutated in most human cancers!!!

• TP53= central monitor of sress in the cell

• DNA damage leads to p53 activation by phosphorylation inducing CDKNIA (p21) which prevents RB phosphorylation and leads to G1-S block in the cell cycle

most commonly muted supressor gene

blocks angiogenesis -> slows cancer growth

1. Loosening of the intracellular junctions between tumor cells by loosing E-cadherin function

2. Degradation of basment membrane and interstitial connective tissue by

   MMPs,cathesin D,...

3. Loos of adhesion to ECM proteins

4. Locomotion leading tumor cells through basment membrane and ECM

• Neoantigenes:newly formed antigenes due to genetc mutations • Preexisting proteins expressed by tumor cells:

- Tyrosinase ; expressed only in normal melanocytes and melanomas

- Cancer-testis-antigenes; expressed only in the germ cells in the testis

• Viral proteins as antigenes

• Progressive loss of body fat and lean body mass

• Anemia

• Weakness

• Anorexia

=> weight loss

occures in patients with cancer but cant be explained with it

• hypercalemia

• chushing syndrome

• nonbacterial thrombotic endocarditis

RAS

BRAF (in melanomas)

eip. tumors arrising di glands or forming glandular patterns

adenomaaas producing larde cystic masses common in ovary

epithelial tumors forming gross or microscopic fingerlike projections

tumor projecting macroscopically above the mucosa (colon polyp)