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Neoplasia Overview Characteristics of neoplasms compared to normal tissues Types of neoplasms Benign vs malignant Cellular differentiation Genetic basis for neoplasia What is a “neoplasm”? Lay term of “tumor” conveys usual connotations – ie a new growth or mass Definition revolves around these features: Monoclonal proliferation of cells with specific mutations Excessive and unregulated growth of these cells, often at the expense of surrounding normal tissue Terms to know about when discussing neoplasia Metastasis - spread of a malignant tumor from one site to another via blood or lymph Benign – typically refers to those tumors incapable of metastasis and having a good clinical outcome (prognosis) Malignant – those tumors capable of invasive growth and/or metastasis, often fatal if not treated effectively Parenchyma – these are the tumor cells themselves, usually referring to epithelial cells in organs. Stroma – connective tissue cells that support the parenchymal cells – not actually tumor cells, but are stimulated to grow by the tumor via growth factors, eg angiogenesis Cellular differentiation Tumors are often “graded” as to how closely they resemble the normal parent tissue that they are derived from. Well-differentiated means the cells are very similar in appearance and architectural arrangement to normal tissue of that organ Differentiation “Poorly-differentiated” refers to tumors that show only minimal resemblance to the normal parent tissue they are derived from. “Anaplastic” means the tumor shows no obvious similarity to it’s parent tissue, usually associated with aggressive behavior So what?????? Differentiation often provides clues as to the clinical aggressiveness of the tumor Tumors often lose differentiation features over time as they become more “malignant” and as they acquire more cumulative genetic mutations Differentiation often predicts responsiveness to certain therapies, eg estrogen receptors and Tamoxifen in breast cancers Benign – circumscribed, often encapsulated, pushes normal tissue aside Malignant – infiltrative growth, no capsule, destructive of normal tissues Classification of neoplasms Epithelial tumors Benign forms – adenoma , papilloma Malignant forms – carcinoma, eg adenocarcinoma, squamous cell carcinoma Mesenchymal tumors Benign forms – fibroma, leiomyoma, Malignant forms – sarcoma, eg fibrosarcoma, leiomyosarcoma Classification continued Tumors of lymphocytes are always malignant – called lymphoma Tumors of melanocytes Benign – nevus Malignant - melanoma Precursors of neoplasia Hyperplasia Metaplasia Chronic inflammation dysplasia Metaplasia, dysplasia, neoplasia
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Neoplasia
Overview Characteristics of neoplasms compared to
normal tissues Types of neoplasms
Benign vs malignant Cellular differentiation
Genetic basis for neoplasia
What is a “neoplasm”? Lay term of “tumor” conveys usual
connotations – ie a new growth or mass Definition revolves around these features:
Monoclonal proliferation of cells with specific mutations
Excessive and unregulated growth of these cells, often at the expense of surrounding normal tissue
Biology of tumor growth
Terms to know about when discussing neoplasia Metastasis - spread of a malignant tumor
from one site to another via blood or lymph Benign – typically refers to those tumors
incapable of metastasis and having a good clinical outcome (prognosis)
Malignant – those tumors capable of invasive growth and/or metastasis, often fatal if not treated effectively
More terms…. Parenchyma – these are the tumor cells
themselves, usually referring to epithelial cells in organs.
Stroma – connective tissue cells that support the parenchymal cells – not actually tumor cells, but are stimulated to grow by the tumor via growth factors, eg angiogenesis
Cellular differentiation Tumors are often “graded” as to how
closely they resemble the normal parent tissue that they are derived from.
Well-differentiated means the cells are very similar in appearance and architectural arrangement to normal tissue of that organ
Normal cervical “Pap smear”
Malignant cervical “Pap smear”
Colonic “adenoma” illustrating a “well-differentiated” neoplasm similar to normal colon mucosa
Differentiation “Poorly-differentiated” refers to tumors
that show only minimal resemblance to the normal parent tissue they are derived from.
“Anaplastic” means the tumor shows no obvious similarity to it’s parent tissue, usually associated with aggressive behavior
So what?????? Differentiation often provides clues as to the
clinical aggressiveness of the tumor Tumors often lose differentiation features over
time as they become more “malignant” and as they acquire more cumulative genetic mutations
Differentiation often predicts responsiveness to certain therapies, eg estrogen receptors and Tamoxifen in breast cancers
Gross (macroscopic) features of two breast neoplasms
Benign – circumscribed, often encapsulated, pushes normal tissue aside
Malignant – infiltrative growth, no capsule, destructive of normal tissues
Classification of neoplasms Epithelial tumors
Benign forms – adenoma , papilloma Malignant forms – carcinoma, eg
adenocarcinoma, squamous cell carcinoma Mesenchymal tumors
Benign forms – fibroma, leiomyoma, Malignant forms – sarcoma, eg fibrosarcoma,
leiomyosarcoma
Classification continued Tumors of lymphocytes are always
malignant – called lymphoma Tumors of melanocytes
Benign – nevus Malignant - melanoma
Microscopic features of tumors Loss of normal architectural arrangement –
Microscopic features of tumors Pleomorphism – variation in size and shape
of cells within the neoplasm
Microscopic features of tumors Mitotic activity - Increased in more
malignant tumors and often abnormal in shape
Precursors of neoplasia Hyperplasia Metaplasia Chronic inflammation dysplasia
Metaplasia, dysplasia, neoplasia Metaplasia – an adaptive
change in differentiation, reversible, no mutations necessary. Eg- change of esophageal
mucosa from squamous to gastric type in the setting of acid reflux (“heartburn”). Better able to withstand the corrosive effects of the acid.
Metaplasia is fertile ground for development of “dysplasia” (disordered growth)
Metaplasia, dysplasia, neoplasia Dysplasia refers to recognizable morphologic changes in
cells that indicate the presence of genetic mutations beginning the development of a neoplasm
Often graded, eg PAP smears for uterine cervical cancer are low and high grade
Causes of Cancer Most cancer arises as the result of somatic
mutations in the genome resulting from: Chance (ie, we don’t know) Environmental factors – chemical, radiation,
viruses Ageing
Inherited cancer syndromes- defect in germline DNA
Environmental carcinogens Chemicals capable of DNA damage Initiators vs Promoters Common denominator is “electrophilic
intermediates” forming adducts with DNA Some are direct acting, others are activated
in the body, usually in the liver by cytochrome P-450 enzymes
Radiation Ionizing radiation – x-rays, gamma rays,
radioactive materials such as Radon gas – all cause a variety of defects to DNA
UV light (non-ionizing) – primarily sun-exposure and T-T dimerization – skin cancers
Common features of viral carcinogenesis Oncogenic viruses typically integrate their
genomes into host cells and enter a period of “latency”
May be of DNA or RNA type DNA viruses include EBV, HPV and
Hepatitis B virus RNA viruses include retroviruses like
HTLV-1 and indirectly HIV
Viral carcinogenesis Human papilloma virus (HPV) prototype
Cause warts Some types have stronger cancer causing
associations, esp 16 and 18 with uterine cervix cancer - Pap smears of cervix can detect precursor lesions of infection – Rx
Viral genes interact with human genes concerned with cell division
How does HPV cause cancer? Gene products of certain sub-type (eg 16
and 18) interfere with normal cellular proteins
Early viral proteins E6 and E7 bind p53 and RB proteins respectively
Other oncogenic viruses Epstein-Barr virus (EBV) associated with
some lymphomas and nasopharyngeal carcinoma
Hepatitis B virus associated with malignant liver tumors
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