Neoplasia Lecture 1 Maha Arafa MD KSFP Abdulmalik

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Neoplasia Lecture 1 Maha Arafa, MD, KSFP Abdulmalik Alsheikh, MD, FRCPC

Neoplasia Lecture 1 Maha Arafa, MD, KSFP Abdulmalik Alsheikh, MD, FRCPC

Neoplasia Upon completion of these lectures, the student should: n Define a neoplasm. Contrast

Neoplasia Upon completion of these lectures, the student should: n Define a neoplasm. Contrast neoplastic growth with hyperplasia, metaplasia, and dysplasia. n Know the basic principles of the nomenclature of benign and malignant processes. n Define and use in the proper context: n n n n n Adenoma. Papilloma. Polyp. Cystadenoma. Carcinoma. Adenocarcinoma. Sarcoma. Teratoma. Blastoma. Hamartoma.

Neoplasia Cancer is one of the leading causes of death worldwide. n Emotional and

Neoplasia Cancer is one of the leading causes of death worldwide. n Emotional and physical suffering by the patient. n Different mortality rate …. . n Some are curable n Others are fatal n

Neoplasia = new growth n Neoplasm = tumor n Tumor = swelling n The

Neoplasia = new growth n Neoplasm = tumor n Tumor = swelling n The study of tumors = Oncology n n Oncos = tumor + ology = study of

Neoplasia n Definition: n n n is an abnormal mass of tissue, the growth

Neoplasia n Definition: n n n is an abnormal mass of tissue, the growth of which is uncoordinated with that of normal tissues, and that persists in the same excessive manner after the cessation of the stimulus which evoked the change“ With the loss of responsiveness to normal growth controls Different from dysplasia. hyperplasia, metaplasia and

Neoplasia n Classification Benign n malignant n

Neoplasia n Classification Benign n malignant n

Neoplasia n Benign tumors : Will remain localized n Cannot spread to distant sites

Neoplasia n Benign tumors : Will remain localized n Cannot spread to distant sites n Generally can be locally excised n Patient generally survives n

Neoplasia n Malignant neoplasms: Can invade and destroy adjacent structure n Can spread to

Neoplasia n Malignant neoplasms: Can invade and destroy adjacent structure n Can spread to distant sites n Cause death (if not treated ) n

Neoplasia n All tumors have two basic components: n Parechyma: made up of neoplastic

Neoplasia n All tumors have two basic components: n Parechyma: made up of neoplastic cells n Stroma: made up of non-neoplastic, host-derived connective tissue and vessels Theblood parenchyma: The stroma: Determines the biological behavior of the tumor From which the tumor derives its name Carries the blood supply Provides support for the growth of the parenchyma

Neoplasia n Nomenclature n Benign tumors: n prefix + suffix n Type of cell

Neoplasia n Nomenclature n Benign tumors: n prefix + suffix n Type of cell + (-oma)

Neoplasia n Examples: n Benign tumor arising in fibrous tissue: Fibro + oma =

Neoplasia n Examples: n Benign tumor arising in fibrous tissue: Fibro + oma = Fibroma Benign tumor arising in fatty tissue: Lipo + oma = lipoma

Neoplasia Benign tumor arising in cartilage chondro + oma = chondroma n Benign tumor

Neoplasia Benign tumor arising in cartilage chondro + oma = chondroma n Benign tumor arising in smooth muscle Leiomyo + oma = leiomyoma n Benign tumor arising in skeletal muscle Rhabdomyo + oma = rhabdomyoma n

Neoplasia n epithelial benign tumors are classified on the basis of : The cell

Neoplasia n epithelial benign tumors are classified on the basis of : The cell of origin n Microscopic pattern n Macroscopic pattern n

Neoplasia n Adenoma : benign epithelial neoplasms producing gland pattern…. OR … derived from

Neoplasia n Adenoma : benign epithelial neoplasms producing gland pattern…. OR … derived from glands but not necessarily exhibiting gland pattern n Papilloma : benign epithelial neoplasms growing on any surface that produce microscopic or macroscopic finger-like pattern

Adenoma

Adenoma

Papilloma

Papilloma

Neoplasia n Polyp : a mass that projects above a mucosal surface to form

Neoplasia n Polyp : a mass that projects above a mucosal surface to form a macroscopically visible structure. e. g. - colonic polyp - nasal polyp

Polyp

Polyp

Neoplasia n Examples : Respiratory airways: Bronchial adenoma n Renal epithelium: Renal tubular adenoma

Neoplasia n Examples : Respiratory airways: Bronchial adenoma n Renal epithelium: Renal tubular adenoma n Liver cell : Liver cell adenoma n Squamous epithelium: squamous papilloma n

Neoplasia n Malignant tumors: n Malignant tumor arising in mesenchymal tissue : SARCOMA n

Neoplasia n Malignant tumors: n Malignant tumor arising in mesenchymal tissue : SARCOMA n From fibrous tissue: Fibrosarcoma n From bone : Osteosarcoma n From cartilage : chondrosarcoma

Osteosarcoma

Osteosarcoma

Neoplasia n Malignant tumors arising from epithelial origin : CARCINOMA Squamous cell carcinoma n

Neoplasia n Malignant tumors arising from epithelial origin : CARCINOMA Squamous cell carcinoma n Renal cell adenocarcinoma n cholangiocarcinoma n

Carcinomas arising from any epithelium of the body that exhibit squamous differentiation are termed

Carcinomas arising from any epithelium of the body that exhibit squamous differentiation are termed squamous cell carcinoma.

Nomenclature other descriptive terms may be added such as: Papillary Cystadenocarcinoma of the Ovary

Nomenclature other descriptive terms may be added such as: Papillary Cystadenocarcinoma of the Ovary

Neoplasia Exceptions Melanoma ( skin ) n Mesothelioma (mesothelium ) n Seminoma ( testis

Neoplasia Exceptions Melanoma ( skin ) n Mesothelioma (mesothelium ) n Seminoma ( testis ) n Lymphoma ( lymphoid tissue ) n See table 6 – 1 page 168 ( Robbin’s )

Neoplasia n Based on the biological behavior : n n Benign and malignant Based

Neoplasia n Based on the biological behavior : n n Benign and malignant Based on the cell of origin : One neoplastic cell type : lipoma, adenocarcinoma n More than one neoplastic cell type : fibroadenoma n More than one neoplastic cell type derived from more than one germ-cell layer: teratoma n Derived from embryonic tissue: blastoma n (could be benign e. g. osteoblastoma, or malignant e. g.

Lipoma

Lipoma

Fibroadenoma

Fibroadenoma

Teratoma

Teratoma

Neoplasia n Teratoma: Teratoma contains recognizable mature or immature cells or tissues representative of

Neoplasia n Teratoma: Teratoma contains recognizable mature or immature cells or tissues representative of more than one germ-cell layer and some times all three. n Teratomas originate from totipotential cells such as those normally present in the ovary and testis. n

Neoplasia n Such cells have the capacity to differentiate into any of the cell

Neoplasia n Such cells have the capacity to differentiate into any of the cell types found in the adult body. So they may give rise to neoplasms that mimic bone, epithelium, muscle, fat, nerve and other tissues. n Most common sites are: ovary & testis

Neoplasia n n If all the components parts are well differentiated, it is a

Neoplasia n n If all the components parts are well differentiated, it is a benign (mature) teratoma. If less well differentiated, it is an immature (malignant) teratoma.

Neoplasia nomenclature - historic eponyms – “first described by…” Hodgkin’s disease Malignant lymphoma (HL)

Neoplasia nomenclature - historic eponyms – “first described by…” Hodgkin’s disease Malignant lymphoma (HL) of B Ly cell origin Burkitt tumor NHL – B Ly cell in children (jaw and GIT) Ewing tumor Bone tumor (PNET) Grawitz tumor Kidney tumor - clear cell adenocarcinoma Kaposi sarcoma Malignant tumor derived from vascular epithelium (AIDS) Brenner tumor Ovarian tumor derived from Brenner cells Askin tumor Malignant chest wall tumor of PNET Merkel tumor Skin tumor derived from Merkel cell

WHAT ARE HAMARTOMAS AND CHORISTOMA? Hamartoma: a mass composed of cells native to the

WHAT ARE HAMARTOMAS AND CHORISTOMA? Hamartoma: a mass composed of cells native to the organ e. g. pulmonary hamartoma. Choristoma: a mass composed of normal cells in a wrong location e. g. pancreatic choristoma in liver or stomach. n Malformation and not neoplasm.

Pulmonary Hamartoma

Pulmonary Hamartoma

Pancreatic choristoma in gall bladder

Pancreatic choristoma in gall bladder

Neoplasia Hamartoma and Choristoma n They are distinguished from neoplasms by the fact that

Neoplasia Hamartoma and Choristoma n They are distinguished from neoplasms by the fact that they do not exhibit continued growth. they are group of tumor-like tissue masses which may be confused with neoplasms

Neoplasia Lecture 2 Maha Arafa, MD, KSFP Abdulmalik Alsheikh, MD, FRCPC

Neoplasia Lecture 2 Maha Arafa, MD, KSFP Abdulmalik Alsheikh, MD, FRCPC

Objectives n Compare and contrast benign and malignant tumors with respect to: n n

Objectives n Compare and contrast benign and malignant tumors with respect to: n n n n n demarcation from surrounding tissue (capsule, local invasiveness. rate of growth degree of differentiation (Explain the meaning of differentiation). distant spread (metastases). Describe the morphologic changes associated with poorly differentiated tumors; define and understand the usage of the terms anaplasia, pleomorphism, nuclear atypia, abnormal mitoses and tumor giant cells. Understand the clinical significance of invasiveness and metastasis. Describe the anatomic pathways utilized by tumors in metastatic spread. Know which pathways are commonly used by carcinomas versus sarcomas. List some common sites of distant metastases. Recognize the epidemiologic data of cancer distribution in regard to age, race, geographic factors, and genetic backgrounds. List some inherited syndromes with a genetic predisposition to

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of growth n Local invasion n metastasis

Neoplasia 1. Differentiation and anaplasia: n Differentiation means : the extent to which the

Neoplasia 1. Differentiation and anaplasia: n Differentiation means : the extent to which the parenchymal cells of the tumor resemble their normal counterparts morphologically and functionally

Neoplasia well differentiated = closely resemble their normal counterparts n Moderately differentiated n Poorly

Neoplasia well differentiated = closely resemble their normal counterparts n Moderately differentiated n Poorly differentiated n Undifferentiated ( Anaplasia ) n

Neoplasia Benign tumors = well differentiated n Malignant tumors = well differentiated -----> anaplastic

Neoplasia Benign tumors = well differentiated n Malignant tumors = well differentiated -----> anaplastic n

Neoplasia n In the histological examination of a tumor you should look for :

Neoplasia n In the histological examination of a tumor you should look for : Pleomorphism : variation in size n High nuclear/ cytoplasm ratio ( N/C ratio) n Hyperchrmasia ( dark cell ) n Mitosis …. ? abnormal one n

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of growth n Local invasion n metastasis

Neoplasia n Rate of growth: n Benign tumors: n grows slowly n are affected

Neoplasia n Rate of growth: n Benign tumors: n grows slowly n are affected by blood supply, hormonal effects , location n Malignant tumors : n grows faster n Correlate with the level of differentiation

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of growth n Local invasion n metastasis

Neoplasia n Local invasion : n Benign tumors : n Remain localized n Cannot

Neoplasia n Local invasion : n Benign tumors : n Remain localized n Cannot invade n Usually capsulated n Malignant tumors : n Progressive invasion n Destruction n Usually not capsulated

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of

Neoplasia Characteristics of benign and malignant neoplasms n Differentiation and anaplasia n Rate of growth n Local invasion n Metastasis

Neoplasia n Metastasis : n Definition : the development of secondary implants discontinuous with

Neoplasia n Metastasis : n Definition : the development of secondary implants discontinuous with the primary tumor, possibly in remote tissues

Neoplasia n Metastasis : Cancers have different ability to metastasize n Approximately 30% patients

Neoplasia n Metastasis : Cancers have different ability to metastasize n Approximately 30% patients present with clinically evident metastases. n Generally, the more anaplastic and the larger the primary tumor, the more likely is metastasis n

Neoplasia n Metastasis : three pathways Lymphatic spread : n Hematogenous spread : n

Neoplasia n Metastasis : three pathways Lymphatic spread : n Hematogenous spread : n Seeding of the body cavities: pleural, peritoneal cavities and cerebral ventricles n

Neoplasia n Lymphatic spread : favored by carcinomas n Breast carcinoma axillary lymph nodes

Neoplasia n Lymphatic spread : favored by carcinomas n Breast carcinoma axillary lymph nodes n Lung carcinomas bronchial lymph nodes n

Neoplasia Hematogenous spread : n favored by sarcomas n Also used by carcinomas n

Neoplasia Hematogenous spread : n favored by sarcomas n Also used by carcinomas n Veins are more commonly invaded n The liver and lungs are the most frequently involved secondary sites n

Neoplasia n In the histological examination of a tumor you should look for :

Neoplasia n In the histological examination of a tumor you should look for : Pleomorphism : variation in size n High nuclear/ cytoplasm ratio ( N/C ratio) n Hyperchrmasia ( dark cell ) n Mitosis …. ? abnormal one n

Neoplasia n Dysplasia : Definiton: a loss in the uniformity of the individual cells

Neoplasia n Dysplasia : Definiton: a loss in the uniformity of the individual cells and a loss in their architectural orientation. n Non-neoplastic n Occurs mainly in the epithelia n Dysplastic cells shows a degree of : pleomorphism, hyperchrmasia, increased mitosis and loss of polarity. n

Neoplasia Dysplasia does not mean cancer n Dyplasia does not necessarily progress to cancer

Neoplasia Dysplasia does not mean cancer n Dyplasia does not necessarily progress to cancer n Dysplasia may be reversible n If dysplastic changes involve the entire thickness of the epithelium it is called : CARCINOMA IN-SITU n

Neoplasia n Carcinoma in-situ n Definition: an intraepithelial malignancy in which malignant cells involve

Neoplasia n Carcinoma in-situ n Definition: an intraepithelial malignancy in which malignant cells involve the entire thickness of the epithelium without penetration of the basement membrane. n Applicable only to epithelial neoplasms.

Dysplasia Features: n n Increased rate of multiplication. Disordered maturation. • Nuclear abnormality –

Dysplasia Features: n n Increased rate of multiplication. Disordered maturation. • Nuclear abnormality – Increased N/C ratio – Irregular nuclear membrane – Increased chromatin content • Cytoplasmic abnormalities due to failure of normal maturation

Dysplasia Uterine cervix Sever Dysplasia Mild Dysplasia

Dysplasia Uterine cervix Sever Dysplasia Mild Dysplasia

Dysplasia (cervical pap smear)

Dysplasia (cervical pap smear)

Dysplasia n Clinical significance: It is a premalignant condition. n The risk of invasive

Dysplasia n Clinical significance: It is a premalignant condition. n The risk of invasive cancer varies with: n ü ü ü grade of dysplasia (mild, moderate, sever) duration of dysplasia site of dysplasia

Dysplasia n Differences between dysplasia and cancer. lack of invasiveness. Reversibility

Dysplasia n Differences between dysplasia and cancer. lack of invasiveness. Reversibility

Carcinoma in situ A true neoplasm with all of the features of malignant neoplasm

Carcinoma in situ A true neoplasm with all of the features of malignant neoplasm except invasiveness n Displays the cytological features of malignancy without invasion of the basement membrane. n

Squamous cell Carcinoma Uterine Cervix Dysplasi a

Squamous cell Carcinoma Uterine Cervix Dysplasi a

Neoplasia n Epidemiology Will help to discover aetiology n Planning of preventive measures n

Neoplasia n Epidemiology Will help to discover aetiology n Planning of preventive measures n To know what is common and what is rare. n Development of screening methods for early diagnosis n

Neoplasia n Factors affecting incidence of cancer n n Geographic and Environmental Age Heredity

Neoplasia n Factors affecting incidence of cancer n n Geographic and Environmental Age Heredity Aquired preneoplastic disorders

Neoplasia n Factors affecting incidence of cancer n n Geographic and Environmental Age Heredity

Neoplasia n Factors affecting incidence of cancer n n Geographic and Environmental Age Heredity Aquired preneoplastic disorders

Neoplasia n Geographic and Environmental factors: Rate of stomach carcinoma in Japan is seven

Neoplasia n Geographic and Environmental factors: Rate of stomach carcinoma in Japan is seven times the rate in North America and Europe. n Breast carcinoma is five times higher in North America comparing to Japan n Liver cell carcinoma is more common in African populations n

Neoplasia n Geographic and Environmental factors: Asbestos : mesothelioma n Smoking : lung cancer

Neoplasia n Geographic and Environmental factors: Asbestos : mesothelioma n Smoking : lung cancer n Multiple sexual partners: cervical cancer n Fatty diets : colonic cancer n Please see table 6 -3 for occupational cancers

Neoplasia n Factors affecting incidence of cancer n Geographic and Environmental n Age Heredity

Neoplasia n Factors affecting incidence of cancer n Geographic and Environmental n Age Heredity n Aquired preneoplastic disorders n

Neoplasia n Age: Generally, the frequency of cancer increases with age. n Most cancer

Neoplasia n Age: Generally, the frequency of cancer increases with age. n Most cancer mortality occurs between 55 and 75. n Cancer mortality is also increased during childhood n Most common tumors of children: Leukemia, tumors of CNS, Lymphomas, soft tissue and bone sarcomas. n

Neoplasia n Factors affecting incidence of cancer Geographic and Environmental n Age n n

Neoplasia n Factors affecting incidence of cancer Geographic and Environmental n Age n n Heredity n Aquired preneoplastic disorders

Neoplasia n Heredity Inherited Cancer Syndromes n Familial Cancers n Autosomal Recessive Syndromes of

Neoplasia n Heredity Inherited Cancer Syndromes n Familial Cancers n Autosomal Recessive Syndromes of Defective DNA repair n

Heredity n Inherited Cancer Syndromes: Inheritance of a single mutant gene greatly increases the

Heredity n Inherited Cancer Syndromes: Inheritance of a single mutant gene greatly increases the risk of developing neoplasm n E. g. Retinoblastoma in children : n n 40% of Retinoblastomas are familial n carriers of the gene have 10000 fold increase in the risk of developing Retinoblastoma n E. g. multiple endocrine neoplasia

Heredity n Familial Cancers: All common types of cancers occur in familial form n

Heredity n Familial Cancers: All common types of cancers occur in familial form n E. g. breast, colon, ovary, brain n Familial cancers usually have unique features: n n Start at early age n Multiple or bilateral n Two or more relatives

Heredity n Autosomal Recessive Syndromes of Defective DNA repair : n Small group of

Heredity n Autosomal Recessive Syndromes of Defective DNA repair : n Small group of autosomal recessive disorders n Characterized by DNA instability Please see table 6 -4 for more examples

Neoplasia n Factors affecting incidence of cancer Geographic and Environmental n Age n n

Neoplasia n Factors affecting incidence of cancer Geographic and Environmental n Age n n Heredity n Aquired preneoplastic disorders

Neoplasia n Aquired preneoplastic disorders: Some Clinical conditions that predispose to cancer n Dysplastic

Neoplasia n Aquired preneoplastic disorders: Some Clinical conditions that predispose to cancer n Dysplastic bronchial mucosa in smokers lung carcinoma n Liver cirrhosis liver cell carcinoma n Margins of chronic skin fistula squamous cell carcinoma