patoloji-ders-notlari

Title

Serdar Balcı

Nomenclature and Classification of Neoplasia

Serdar BALCI, MD

What is Cancer?

• “A neoplasm is an abnormal mass of tissue, the growth of which exceeds and is uncoordinated with that of the normal tissues and persists in the same excessive manner after cessation of the stimuli which evoked the change.”
  • British oncologist R.Willis, 1952

Cancer is a genetic disease

Genetic changes allow excessive and unregulated proliferation that becomes autonomous (independent of physiologic growth stimuli), although tumors generally remain dependent on the host for their nutrition and blood supply.

Karkinos: Crab like

http://en.wikipedia.org/wiki/Cancer#mediaviewer/File:BreastCancer.jpg

Rosai and Ackerman’s Surgical Pathology

The field of Cancer Research is broad

• Pathology
• Morphology
• Pharmacology
• Genetics
• Epidemiology
• Biochemistry
• System Biology
• Evolution
• Population dynamics
• …
• AS WELL AS
  • Quackery, fraudulency, charlatan, cheating ….

When will there be a cure for cancer?

Which cancer?

Hodgkin lymphoma is highly curable

Pancreas Cancer is nearly always fatal

Cancer is a genetic disorder

• DNA mutations
  • acquired spontaneously
  • induced by environmental insults
• Epigenetic changes
  • DNA methylation
  • Histone modifications
• Genetic instability
• Genetic changes affect the ability of
  • Growth, survival, senescence

Genetic alterations are heritable

Passed to daughter cells via cell division

Cells with growth and survival advantages dominate the population

One single cell ultimately gives rise to the tumor → all tumors are clonal

Hallmarks of Cancer - Properties of Cancer

• self-sufficiency in growth signals
  • whereby the growth of cancers becomes autonomous and is unregulated by physiologic cues
• lack of response to growth inhibitory signals that control non-neoplastic cellular proliferations such as hyperplasias
• evasion of cell death, allowing cancer cells to survive under conditions that induce apoptosis in normal cells
• limitless replicative potential, thus making cancer cells immortal
  • He-La ** **Cell __ Line__
• development of angiogenesis to sustain the growth of cancer cells
• ability to invade local tissues and spread to distant sites
• reprogramming of metabolic pathways—specifically, a switch to aerobic glycolysis even when there is abundant oxygen
• ability to evade the immune system

NOMENCLATURE

Some Terminology

Aplasia

Hyperplasia

Metaplasia

Neoplasia

Dysplasia

Tumor

Mass

Oncology (oncos: tumor)

Neoplasia “new growth”

• Neoplastic
  • Transformed
• Continue to replicate
  • does not take into account the control of normal regulatory influences of growth
  • Autonomy
    • Not complete some still require endocrine stimulation, treated as such
• Increase in size
  • Depend on the host for nutrition, blood supply

Benign Tumors

Microscopic and gross characteristics are considered to be relatively innocent

remain localized, local surgical removal

patient generally survives

sometimes they are responsible for serious disease

Malignant Tumors

Cancers

From the Latin word for “crab”

Adhere to any part that they seize in an obstinate manner, similar to a crab’s behavior

#

Cancer

Carcinoma

Malignant Epithelial Tumor

Malignant Mesenchymal Tumor

Small Blue Round Cell Tumor

Leukeima

Lymphoma

Malignant

Invade and destroy adjacent structures

**Spread to distant sites (metastasize) **

Cause death

Not all cancers go into a deadly course

Most aggressive are also some of the most curable

Tumors have two components

• Parenchyma
  • Transformed or neoplastic cells
• Stroma
  • Supporting, host-derived, non-neoplastic stroma
  • Connective tissue, blood vessels, and host-derived inflammatory cells
• Parenchyma
  • determines its biologic behavior
  • tumors named according to parenchmal cells
• Stroma
  • crucial to the growth of the neoplasm
  • blood supply
  • support for the growth
• A two-way conversation
  • Epithelial Mesenchymal Interactions / Transitions

Nomenclature of Neoplasms

• A problem of Taxonomy
• Classification of Neoplasms
• Subject to change over time
• Different classification schemes and proposals for each group of tumor
  • Schools are different:
    • Japanese, European, North American, South American
  • Authors from same country also have different opinions

WHO Classification of Neoplasms

• Updated every 5-7 years
• Aim is:
  • To form a unified terminology
  • Define distinct diseases in terms of morphological, clinical, genetic features
  • Started adding therapeutic subgroups as well

http://www.iarc.fr/en/publications/list/bb/

Tumors are named according to embryologic origin

Endoderm derived → Epithelial

Ectoderm derived → Epithelial, Neuronal

Mesoderm derived → Epithelial, Mesenchymal and Hematolymphoid

Tumors are named according to normal cell type they resemble or derived from

Squamous cell, Urothelial cell

Fibroblast, Chondrocyte

Lymphocyte

Astrocyte

…

Nomenclature of Benign Tumors

Tumor cell type + oma

Fibroblast + oma → Fibroma

Chondrocyte + oma → Chondroma

Robbins Basic Pathology

Nomenclature of Benign Tumors

• Growth type is also used in naming
• Adenoma
  • Tumors forming glands
• Papilloma
  • Tumors forming papillary (finger-like) features
• Polyp
  • Finger like projection on the mucosal surface
  • General term, does not mean neoplastic (nasal polyp is not neoplastic, but inflammatory)
• Cystadenoma
  • Tumors forming cysts

Thyroid Follicular Adenoma

Tumor is Forming Glands that resemble normal tissue

Robbins and Cotran’s Pathological Basis of Diseases

Tubular Adenoma of Colon

Polyp

Stalk

Benign

Gland forming tumor/mass

Projecting into the lumen

Connected to mucosa with a stalk

Robbins Basic Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Papilloma

Finger like projections

Robbins Basic Pathology

Urologic Surgical Pathology, Chapter 6, 228-316.e23

Ovary, Serous Cystadenoma

Benign Neoplasm forming Cyst

Rosai and Ackerman’s Surgical Pathology

Nomenclature of Malignant Tumors

• Cancer is the general term
• Carcinoma
  • Epithelial Malignant Tumor
• Sarcoma
  • Mesenchymal Malignant Tumor

Chondrocyte + Sarcoma → Chondrosarcoma

Fibroblast + Sarcoma → Fibrosarcoma

Epithelial tumors forming glands → Adenocarcinoma

Epithelial tumors forming squamous cells → Squamous cell carcinoma

Papillary carcinoma

Papillary cystadenocarcinoma

Ovarian Cystadenocarcinoma

Rosai and Ackerman’s Surgical Pathology

Nomenclature of Malignant TumorsDifferentiation

How much the tumor cell resemble the normal counterpart

Well differentiated

Moderately differentiated

Poorly differentiated

Undifferantiated

Elsevier’s Integrated Pathology

Robbins Basic Pathology

Robbins Basic Pathology

Malignant tumors ending with -oma

Seminoma

Melanoma

Glioma

Lymphoma

Insulinoma, gastrinoma, somatostatinoma, glucagonoma

Hepatoblastoma

Tumors with more than one cell type

• Divergent Differentiation
• Mixed Tumors
• Mixed tumor of salivary gland
  • Epithelial component
  • Fibromyxoid stroma, sometimes islands of cartilage or bone
  • Also called pleomorphic adenoma of salivary gland

Mixed tumor of salivary gland, Pleomorphic Adenoma

Robbins Basic Pathology

Fibroadenoma of Breast

Robbins Basic Pathology

Wilms tumor (nephroblastoma)

Rosai and Ackerman’s Surgical Pathology

Teratoma

Mixed tumor

Mature, immature cells

More than one germ layer

Originate from totipotent germ cells

Ovary, testis

give rise to neoplasms that mimic, in helter-skelter fashion, bits of bone, epithelium, muscle, fat, nerve, and other tissues

Mature Csytis Teratoma of Ovary

Robbins Basic Pathology

Robbins and Cotran’s Pathological Basis of Diseases

Mixed Tumors

Robbins Basic Pathology

Blastoma

Tumors composed of immature cells resembling those that form the fetal anlage or primordia of adult organs.

Retinoblastoma is a tumor of the eye

Neuroblastoma is a tumor composed of nerve precursors cells (neuroblasts)

Hepatoblastoma is a tumor composed of fetal hepatocytes

Nephroblastoma: Wilms tumor

Eponyms

Hodgkin disease: a special form of malignant lymphoma

Ewing sarcoma: a malignant bone tumor

Wilms tumor: a malignant kidney tumor of childhood, also known as nephroblastoma

Kaposi sarcoma: a blood vessel tumor of the skin and internal organs

Burkitt lymphoma: a form of malignant lymphoma

Hamartoma

• Mass of disorganized tissue
• Composed of cells that are normally found in that tissue
  • In liver: mass of mature but disorganized hepatic cells, blood vessels, and possibly bile ducts
  • In lung islands of cartilage, bronchi, and blood vessels
• Developmental malformations
• Little evidence of acquired translocations, suggesting a neoplastic origin

Bile Duct Hamartoma in Liver

Pulmonary Hamartoma in Lung

Robbins and Cotran’s Pathological Basis of Diseases

Choristoma

A congenital anomaly

Heterotopic rest of cells

A small nodule of well-developed and normally organized pancreatic tissue in the submucosa of the stomach, duodenum, or small intestine

May contain islets of Langerhans and exocrine glands

Heterotopic exocrine pancreas tissue in stomach

Rosai and Ackerman’s Surgical Pathology