NEOPLASIA Definitions of terms used in neoplasia Nomenclature of tumors Characteristics of benign & malignant tumors Routes of metastasis Epidemiology of CANCER The molecular basis of neoplasia Carcinogenesis Tumor immunity The clinical effects of tumors Tumor grading and staging The laboratory diagnosis of neoplasia

GENERAL TERMS USED Neoplasm New growth of cells producing a mass Benign neoplasm= Limited new growth without invasion or spread Malignant neoplasm= invasive growth that also spreads Carcinoma : Malignant tumor of epithelial cells Sarcoma : Malignant tumor of connective tissue cells Lymphoma

Cancer is a general term for all malignant growths of whatever type Tumor may be used instead of neoplasm but the term is not accurate Oncology: study of cancer in all its aspects

NEOPLASM Abnormal mass of tissue, the growth of which EXCEEDS and is UNCOORDINATED with that of of the normal tissues, and PERSISTS in the same manner even AFTER CESSATION of the stimulus which produced the change  A neoplasm develops from a single transformed cell !!!

Fundamental to the origin of all neoplasms are heritable (genetic) changes that allow excessive and unregulated proliferation that is independent of physiologic growth-regulatory stimuli.

FEATURESOF TRANSFORMED CELL Persistent & useless Uncontrolled growth* Immortal Transplantable

This may arise from Endoderm Mesoderm Ectoderm Epithelial cells may arise from any of the above Connective tissue is from mesoderm

Classification of tumors Cell of origin Behavior of tumor: Benign or malignant   Appearance of the tumor: Solid/cystic Degree of differentiation

CLASSIFICATION Benign tumors Malignant tumors Mixed tumors Tetatoma of both benign and malignant

Tumors, benign and malignant, have two basic components (1) the parenchyma, made up of transformed or neoplastic cells, and The parenchyma of the neoplasm largely determines its biologic behavior, and the component from which the tumor derives its name

(2) Stroma the supporting, host-derived, non-neoplastic made up of connective tissue, blood vessels, and host-derived inflammatory cells. Stroma, it carries the blood supply and provides support for the growth of parenchymal cells.

Sebaceous cyst

Structure of Neoplasm Parenchymal cell Stromal ( supporting cell ) Degree & type of stromal cells may contribute to the appearance of tumors If there is stromal proliferation hardness of the tumor Scirrhous tumor Desmoplasia e.g.carcinoma of breast, pancreas..etc

If there is lack of many stromal cells, the tumor may be soft or cystic. This feature may be included in the name of the tumor..e.g Cystadenoma of ovary Poorly differentiated cyst adenocarcinoma of ovary Moderately differentiated scirrhous carcinoma of breast   

Serous cyst adenoma of ovary

Scirrhous carcinoma of breast Desmoplasia

Benign tumors Benign tumors are(microscopic and gross characteristics) are Innocent Localized Cannot spread to other sites Easy for surgical resection Survival of the patient is fair. But in certain tumors it can be serious.

Malignant tumors 1.Are cancers, 2 They are not localized 3.They invade, destroy the adjacent structures. 4.Distant metastasis 5. Can cause death

Nomenclature – Benign Tumors -oma = benign neoplasm Microscopic and Macroscopic classification. Mesenchymal tumors Chrondroma: cartilaginous tumor Fibroma: fibrous tumor Osteoma: bone tumor

Epithelial tumor adenoma: tumor forming glands papilloma: tumor with finger like projections papillary cystadenoma: papillary and cystic tumor forming glands polyp: a tumor that projects above a mucosal surface

Benign epithelial tumors Adenoma glandular epithelium tumor often producing a secretion e.g.(mucin) which may be intraepithelial or intraluminal Papilloma epithelial tumor forming finger like projections from epithelia surface with a connective tissue core Polyp a tumor projecting from the mucosal surface of a hollow organ

Adenoma of benign arise in solid organs Liver, Thyroid and kidney typically glandular pattern Since they are benign they remain Discrete pushing compressing the surrounding tissue and remain localized also they show tissue of origin

Malignant tumors Malignant neoplasms arising in mesenchymal tissue or its derivatives are called sarcomas A cancer of fibrous tissue origin is a fibrosarcoma, and a malignant neoplasm composed of chondrocytes is a chondrosarcoma.

Nomenclature – Malignant Tumors Sarcomas: mesenchymal tumor chrondrosarcoma: cartilaginous tumor fibrosarcomama: fibrous tumor osteosarcoma: bone tumor

Carcinomas: epithelial tumors ADENOCARCINOMA: gland forming tumor SQUAMOUS CELL CARCINOMA: squamous differentiation undifferentiated carcinoma: no differentiation note: carcinomas can arise from ectoderm, mesoderm, or endoderm

Malignant neoplasms of epithelial cell origin are called carcinomas Carcinomas that grow in a glandular pattern are called ADENOCARCINOMAS, and those that produce squamous cells are called squamous cell carcinomas.

Squamous cell carcinoma Example-. skin, mouth cervix, bronchus.etc  Adenocarcinoma from glandular origin Example-.G.I.T., endometrium ,breast, kidney, thyroid..etc

SARCOMA : Prefix (origin)+ suffix (sarcoma) e.g.Osteosarcoma,liposarcoma,angiosarcomaleiomyosarcoma,rhabdomyosarcoma

MIXED TUMOR FIBROADENOMA IT HAS DUCTAL ELEMENT ADENOMA ALSO EMBEDED IN LOOSE FIBROUS TISSUE FIBROMA TUMORS OF THE SALIVARY GLAND PLEOMORPHIC ADENOMA

Fibroadenoma Fibroadenoma is the most common benign (noncancerous) growth in the breast. If it is diagnosed on needle biopsy and the mammographic finding is consistent with a fibroadenoma, it is typically simply followed, with no additional excision. In some instances it may be removed for cosmetic reasons. 

A patient's age determines the preferred imaging method A patient's age determines the preferred imaging method. In general, ultrasonography (US) is preferred if a palpable mass is found, if a patient is younger than 30 years, or if the patient is not pregnant, Mammography and US are both useful if the patient.

Fibroadenoma breast mammogram

TERETOMA Teratomas originate from totipotential stem cells which contains recognizable mature or immature cells or tissues representative of more than one germ-cell layer and sometimes all three.

BENIGN Mature teratoma Dermoid cyst

MALIGNANT Immature teratoma Terato carcinoma

Teratomas originate from totipotential stem cells such as those normally present in the ovary and testis and sometimes abnormally present in sequestered midline embryonic rests

Testicular teratoma Tumor characteristics: Firm, whitish, ovoid mass with discrete yellow and grey areas.

Seminoma testis The firm whitish areas nearby showed extensive intratubular germ cell neoplasia.

Figure 7-4 A, Gross appearance of an opened cystic teratoma of the ovary. Note the presence of hair, sebaceous material, and tooth. You do not need a microscope to appreciate this tumor produces both connective tissue as well as epithelial derived elements. Remember, pure “epithelial” tumors may evoke a fibrous response, such as breast or pancreas or prostate adenocarcinomas, but the connective tissue us regarded as NON-neoplastic. Downloaded from: Robbins & Cotran Pathologic Basis of Disease (on 28 July 2005 03:41 PM) © 2005 Elsevier

Aberrant differentiation (not true neoplasms) Hamartoma: disorganized mass of tissue whose cell types are indiginous to the site of the lesion, e.g., lung Choriostoma: ectopic focus of normal tissue (heterotopia), e.g., pancreas, perhaps endometriosis too Misnomers are often REDUNDANT, to try to correct the misnomer.

BENIGN SOUNDING DESIGNATIONS Misnomers Hepatoma: malignant liver tumor Melanoma: malignant skin tumor Seminoma: malignant testicular tumor Lymphoma: malignant tumor of lymphocytes

Hamartoma Clinical presentation Pulmonary hamartomas are usually asymptomatic and found incidentally when imaging the chest for other reasons. It can occasionally present with haemoptysis, bronchial obstruction and cough (especially endobronchial types) . Pathology Hamartomas may be chondromatous or leiomyomatous (the former being more common) or a mixture. They are unencapsulated, lobulated tumours with connective tissue septa

Dysplasia Literally means abnormal growth Malignant transformation is a multistep process In dysplasia some but not all of the features of malignancy are present, microscopically Dysplasia may develop into malignancy Uterine cervix Colon polyps Graded as low-grade or high-grade, often prompting different clinical decisions Dysplasia may NOT develop into malignancy HIGH grade dysplasia often classified with CIS Do you remember from chapter 1 that DYS- was one of the seven -plasia brothers?

Natural History Of Malignant Tumors Malignant change in the target cell, referred to as transformation Growth of the transformed cells Local invasion Distant metastases. Another linear process, such as the epics of inflammation or healing.

Benign vs Malignant Features Rate of growth slow. Mitoses few and normal Variable. Mitoses more frequent and may be abnormal Differentiation Well differentiated Some degree of anaplasia LOCAL INVASION Cohesive growth. Capsule & BM not breached Poorly cohesive and infiltrative! Metastasis Absent May occur In some tumors, like smooth muscle tumors, counting mitoses may be the main way to differentiate a benign from a malignant process! “If you want to think od “anaplasia” as DE-differentiation, you can, but remember, differentiation NEVER occurs backwards! “LOCAL INVASION” is in HUGE ALL CAPS font because it is the single most important differentiating feature. ALL malignancies can potentially metastasize, but there is at least one common benign condition which is also said to “metastasize”. Can you name it?

Benign vs Malignant Rate of growth Most benign tumors grow slowly while most cancers grow fast Many exceptions Rate of growth for malignant tumors correlates with degree of differentiation Despite rapid growth, cancers usually take years to become clinically apparent Rapid growth may lead to necrosis

Benign vs Malignant Local invasion Benign neoplasms do not have the capacity to invade Invasion is a characteristic of malignancy Benign neoplasms often develop a fibrous capsule

Benign vs Malignant Metastasis Metastases are secondary, remote implants of tumor Metastatic spread is the most important hallmark of malignancy Cancers differ in their ability to metastasize Methods of metastasis: Seeding Lymphatic spread Hematogenous spread

Epidemiology The study of the relationships of various factors determining the frequency and distribution of diseases in the human community Contributes to understanding of risk factors and the origin of cancers Smoking – Lung cancer Fatty diets – Colon cancer

Epidemiology Geographic and environmental factors Breast cancer – Death rates 4-5x higher in US and Europe than in Japan Stomach cancer – Death rates 7x higher in Japan than in the US Hepatocellular carcinoma – Uncommon in US, one of the most common and lethal cancers in some African populations Most geographic patterns related to environmental exposures

Epidemiology Age Heredity Acquired preneoplastic disorders Frequency of cancer increases with age with peak between ages of 55 and 75 Increased accumulation of somatic mutations Heredity 5-10% of cancers Acquired preneoplastic disorders Dysplasia, colonic adenoma