NeoplasiaNeoplasia NeoplasiaNeoplasia

DR EJAZ WARISDR EJAZ WARIS

ASSIS.PROF HISTOPATHOLOGYASSIS.PROF HISTOPATHOLOGY

FMHCFMHC

Objectives of the lecture

• Basics of neoplasia• Classification & nomenclature• Characteristics of tumors• Characteristics of malignant cells

What is a Neoplasm ?

(Literally: New growth) An abnormal tissue mass whose

growth exceeds and is uncoordinated with that of adjacent normal tissue and

persists after cessation of the stimuli that provoked it

Whats the main difference between a neoplastic & a

nonneoplastic growth?

Neoplastic growths are uncontrolled &

irreversible & non-neoplastic growths are controlled & reversible

Components of a tumor

• Parenchyma : composed of tumor cells

• Stroma : supportive tissue

Types of Tumors

– BENIGN NEOPLASM – A neoplasm that grows without invading adjacent

tissue of spreading to distant sites. • Usually well-circumscribed due to the lack of

invasion of surrounding tissues. – MALIGNANT NEOPLASM – A neoplasm that invades the surrounding normal

tissue. – Usually spreads to distant sites given sufficient time. – Usually is not well circumscribed.– Malignant tumor and cancer are synonyms

Benign tumors• Always end with the suffix – oma• e.g• Fibroma• Chondroma• Osteoma• Lipoma• Adenoma• Cystadenoma• Papillary cystadenoma

Malignant tumors• Carcinoma : Malignant tumor of epithelial origin e.g.squamous cell

carcinoma,adenocarcinoma,TCC,RCC

Sarcoma : Malignant tumor of mesenchymal origin e.g. fibrosarcoma,osteosarcoma,liposarcoma

Naming of neoplasms

ORIGIN BENIGN MALIGNANT

I. EPITHELIAL

Stratified squamous

Squamous cell papilloma

Squamous cell carcinoma

Basal cells of skin

Basal cell carcinoma

Epithelial lining from glands or ducts

Adenoma (e.g. of colon)

Adenocarcinoma (e.g. of colon)

Hepatocytes

Hepatocellular adenoma

Hepatocellular carcinoma (also called "hepatoma", a confusing Term that should be avoided)

Melanocytes

Nevus Melanoma (or malignant melanoma)

Renal Renal cell adenoma

Renal cell carcinoma

Transitional

Papilloma TCC

II. MESENCHYMAL

A. Connective Tissue

Bone Osteoma Osteosarcoma

Cartilage Chondroma Chondrosarcoma

Fibroblast Fibroma Fibrosarcoma

B. Hematopoietic

Erythroid Erythroid leukemia

Myeloid Myelogenous leukemia

Lymphoid Lymphocytic leukemiamalignant lymphoma

C. Muscle Smooth muscle

Leiomyoma Leiomyosarcoma

Striated (skeletal) muscle

Rhabdomyoma

Rhabdomyosarcoma

D. Vascular Hemangioma Angiosarcoma

III. GERM CELLS

Teratoma (dermoid)

teratocarcinoma

Other terms

• Choristoma• Hemartoma• Pleomorphic adenoma• teratoma

Characteristics of tumors

1)Differentiation– DIFFERENTIATION – The tissue type represented by the tumor.– Extent to which the tumor cell resemble

its parent cell– Ranges of differentiation :

well,moderately,poorly,undifferentiated – Well differentiated tumors resemble

identifiable tissue types.– Undifferentiated tumors doesnot resemble

Importance of differentiation

– Importance of differentiation • Site of origin in metastatic disease

– example: squamous carcinoma in a lymph node, sites of origin would include lungs, respiratory tract, gyn tract, skin

• Prognosis

– well differentiated often better prognosis than poorly differentiated

• Treatment • treatment varies, example adenocarcinoma vs

squamous

• Anaplasia : lack of differentiation of tumors• Dysplasia :Atypical proliferation of cells characterized

by nuclear enlargement and failure of differentiation which falls short of malignancy

– Dysplasia is recognized by alterations in the appearance of cells

– cell nuclei become hyperchromatic – nuclear membranes become irregular

• nuclear to cytoplasmic ratio increases • Dysplasia may regress, persist or progress

Carcinoma in situ• Full-thickness dysplasia extending from

the basement membrane to the surface of the epithelium. Applicable only to epithelial neoplasms. If the entire lesion is no more advanced than CIS, then the risk of metastasis is zero. This is because there are no blood vessels or lymphatics within the epithelium above the basement membrane

desmoplasia• The change that occurs in the stroma as

tumor invades is called desmoplasia. Desmoplasia refers to the stroma composed of connective tissue and blood vessels that surrounds the infiltrating tumor. The spindle shaped cells that make up the desmoplasia are not themselves neoplastic. Desmoplasia is a response to invasion of tissue by malignant tumor cells

2)Rate of growth

• Benign tumors are slow growing and show capsule formation

• Malignant tumors are rapid and fast growing,sometimes at an erratic pace to be diagnosed at a time when tumor has spread at distant sites

Local Invasion

• Growth into the surrounding tissue by direct extension/expansion

• Benign tumors never locally invade• Malignant tumors always invade

the souurounding tissues

Metastasis• Tumor implants discontinuous from

the primary tumor is metastasis

• Spread of tumor to distant sites by 1)lymphatic,

• 2)hematogenous routes, or• 3) seeding of body cavities.

Routes of spread• Seeding of body cavities and surfaces:

This occurs when a malignant neoplasm penetrates into a natural "open field" such as peritoneal cavity, pleural space, pericardial cavity, etc. Most common examples, ovarian carcinoma and mucin secreting ovarian and appendiceal carcinomas (pseudomyxoma peritonei).

Routes of spread• Lymphatic spread: This is the most common

pathway for dissemination of carcinomas (although sarcomas can also use this route). The pattern of lymph node involvement follows the natural routes of drainage.

• Hematogenous spread: This pathway is typical of sarcomas. Arteries are more difficult for tumor to penetrate than veins. With venous invasion, the blood-borne cells follow the venous flow draining the site of the tumor. Liver and lungs are frequently involved

Malignant cell

Charateristics • Disturbed polarity and loss of

cohesiveness: nuclei oriented in different directions and are irregularly spaced. Cells become detached from one another.

• Pleomorphism: abnormal variation in size, shape

• Nuclear to cytoplasmic ratio increased. It increases from 1:4 to 1:1

Characteristics• Nuclear Chromatin shows irregular

clumping and hyperchromasia. • Prominent nucleoli• Irregular Nuclear membrane • Scanty more eosinophilic cytoplasm• Abnormal mitoses: may be present• Giant cells in anaplastic tumors

GRADING AND STAGING OF TUMORS

Grading of tumorsGrading of tumors Grade: The grade of a tumor is based on Grade: The grade of a tumor is based on

the degree of differentiation of the tumor the degree of differentiation of the tumor cells, the degree of cytologic atypia and cells, the degree of cytologic atypia and the number of mitoses within the tumor.the number of mitoses within the tumor.

In general, low grade tumors are well In general, low grade tumors are well differentiated, have minimal cytologic differentiated, have minimal cytologic atypia and low mitotic rates. High grade atypia and low mitotic rates. High grade tumors are poorly differentiated, have tumors are poorly differentiated, have marked cytologic atypia and high mitotic marked cytologic atypia and high mitotic rates.rates.

Staging of tumorsStaging of tumors

Stage: The stage of a tumor is Stage: The stage of a tumor is based on the size of the primary based on the size of the primary tumor, the extent of invasion into tumor, the extent of invasion into surrounding tissue, the spread to surrounding tissue, the spread to regional lymph nodes and the regional lymph nodes and the presence or absence of blood-presence or absence of blood-borne metastases. borne metastases.

Staging systemsStaging systems The staging system used here is the The staging system used here is the

American Joint Committee (AJC) on American Joint Committee (AJC) on Cancer Staging. The staging scheme Cancer Staging. The staging scheme varies by tumor site, but all tumors varies by tumor site, but all tumors are assigned a "T" stage referring to are assigned a "T" stage referring to tumor size, degree of penetration of tumor size, degree of penetration of surrounding tissue; a "N" indicative surrounding tissue; a "N" indicative of presence of lymph node of presence of lymph node involvement and a "M" which involvement and a "M" which indicates the existence of indicates the existence of metastasesmetastases

TNM STAGING SYSTEMTNM STAGING SYSTEM T" for tumor: T" for tumor: T1 might mean primary tumor is smaller than 1 cm T1 might mean primary tumor is smaller than 1 cm

in diameter in diameter T2 might mean primary tumor is larger than 1 cm T2 might mean primary tumor is larger than 1 cm

in diameter in diameter T3 might mean primary tumor is invading T3 might mean primary tumor is invading

something non-resectable something non-resectable "N" for regional lymph nodes: "N" for regional lymph nodes: N0 would mean no tumor in regional lymph nodes N0 would mean no tumor in regional lymph nodes N1 might mean tumor in a few nearby lymph nodes N1 might mean tumor in a few nearby lymph nodes N2 might mean many nodes, or some nodes farther N2 might mean many nodes, or some nodes farther

downstream, are involved downstream, are involved "M" for metastases: "M" for metastases: M0 would mean no distant metastases M0 would mean no distant metastases M1 would imply distant metastases, etcM1 would imply distant metastases, etc

Self Assessment Self Assessment Questions:Questions:

What is a neoplasm? Write two special What is a neoplasm? Write two special characters? characters?

What is a papilloma, adenomaWhat is a papilloma, adenoma What is dysplasia, Metaplasia, Anaplasia What is dysplasia, Metaplasia, Anaplasia

Hyperplasia? Mention examples?Hyperplasia? Mention examples? Mention major classes of neoplasms with Mention major classes of neoplasms with

five differentiating features? five differentiating features? Mention three features of malignant Mention three features of malignant

tumor?tumor?

Self Assessment Self Assessment Questions:Questions:

What is carcinoma-in-situ? What is carcinoma-in-situ? What is grading? And staging?What is grading? And staging? How are neoplasms named?How are neoplasms named? What is CIN? ClassifyWhat is CIN? Classify What are the common routes of What are the common routes of

cancer spread?cancer spread? How do we diagnose cancer?How do we diagnose cancer? Brief note of tumor markers?Brief note of tumor markers?

Benign Benign Malignant:Malignant:

Slow growing,Slow growing, capsulated, capsulated, Non-invasive Non-invasive do not do not

metastasize, metastasize, well well

differentiated, differentiated, suffix “oma” eg. suffix “oma” eg.

Fibroma.Fibroma.

Fast growing, Fast growing, non capsulated, non capsulated, Invasive & Invasive &

Infiltrate Infiltrate Metastasize. Metastasize. poorly poorly

differentiated, differentiated, Suffix Suffix

“Carcinoma” or “Carcinoma” or “Sarcoma”“Sarcoma”

Tumor Diagnosis:Tumor Diagnosis:

HistoryHistory and Clinical examinationand Clinical examination ImagingImaging - X-Ray, US, CT, MRI - X-Ray, US, CT, MRI Tumor markers Tumor markers Laboratory Laboratory

analysis analysis CytologyCytology –Pap –Pap smear, FNABsmear, FNAB BiopsyBiopsy - Histopathology, markers. - Histopathology, markers. MolecularMolecular TechTech – Gene detection. – Gene detection.

Bilateral Cystadenoma Bilateral Cystadenoma Ovary:Ovary:

Lipoma Intestine:Lipoma Intestine:

meningiomameningioma

Lung carcinomaLung carcinoma

Hepatic Adenoma:Hepatic Adenoma:

Carcinoma Breast:Carcinoma Breast:

Carcinoma Lung:Carcinoma Lung:

Osteo - sarcoma:Osteo - sarcoma:

Biopsy – Slide Biopsy – Slide preparationpreparation