What: Nature and name of disease, Grading and staging, Comments
Benign vs Malignant neoplasm
Invasive and metastasis
Grading and Staging
Definition of Neoplasm
Dr. DA Willis
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.
Terms for Neoplasm
Neoplasm — the new growth
Neoplasia — the process of “new growth”
Tumor — the term was originally applied to the swelling caused by inflammation, but by long precedent, the term is now equated to neoplasm
Cancer — the common term for all malignant tumors
Oncology — the study of tumors or neoplasm
More Terms …
Dysplasia — recognizable morphologic changes in cells that indicate the presence of genetic mutations beginning the development of a neoplasm. Usually grading dysplastic changes based on the thickness of the involved epithelium: less than 1/3 mild atypical proliferation. less than 2/3 moderate atypical proliferation. more than 2/3 severe atypical proliferation.
eg: Dysplastic change of cervical epithelium infected by HPV
Anaplasia — recognizable morphologic changes in the tumor cells lack of differentiation; literally means “to form backward”, implying a ‘reverse differentiation’ of mature normal cells. It is considered a hallmark of malignant transformation.
eg: Anaplastic Rhabdomyosarcoma
Dysplasia Dysplastic change in cervical epithelium
Anaplastic tumor showing cellular pleomorphism
Rhabdomyosarcoma: Anaplastic cells
Proliferative Terms (Not Neoplastic)
METAPLASIA: One cell type is replaced by another cell type .
eg: cigarette smoking induced change of bronchial epithlelial cells to squamous; Barrett’s esophagitis--where the squamous epithelium of the esophagus is replaced by columnar epithelium.
HYPERPLASIA: An increase in the number of cells in an organ or tissue, which may then have an increased volume.
Physiologic hyperplasia: Proliferation of mammary glandular epithelium at pregnancy, compensatory hyperplasia of the liver after partial hepatectomy
HYPERTROPHY: An increase in size of cells and thus an increase in the size of the organ
eg: physiologic hypertrophy of uterus during pregnancy, hypertrophy of the cardiac muscle in hypertension or valvular disease, hypertrophy of skeletal muscles due to heavy exercise
Differentiation — refers to the extent which neoplastic cells resemble comparable normal cells, both morphologically and functionally.
Tumors are often “ graded ” as to the extent of cellular differentiation or how closely they resemble the normal parent tissue that they are derived from.
Grading of Differentiation
Well-differentiated means the cells are very similar in appearance and architectural arrangement to normal tissue of that organ
“ Poorly-differentiated” refers to tumors that show only minimal resemblance to the normal parent tissue they are derived from.
“ Anaplastic” (undifferentiated) means the tumor shows no obvious similarity to it’s parent tissue, usually associated with aggressive behavior
Structure of Neoplasm
Parenchyma: Neoplastic cells.
Stroma: Non-neoplastic (Fibrous connective tissue and vasculature )
Fast growth less stroma
Less stroma more necrosis
Loss of normal architectural arrangement and polarity
Morphological features of tumors Late Adenoma Normal Crypt Early Adenoma Adenocarcinoma
Pleomorphism – variation in size and shape of cells and nuclei within the neoplasm
Morphological features of tumors
Mitotic activity - Increased in more malignant tumors and often abnormal in shape
Morphological features of tumors
Functional Alterations of Neoplastic cells
Loss of functions
Loss of responsiveness to and dependence upon normal regulatory pathways
Nomenclature of Neoplasm
Cell of origin + Suffix
Neoplasms are named according to a binomial system denoting their histogenetic origin of the parenchymal component and biological behavior
Histogenetic origin refers to the tissue or cell type from which the tumor arose
Biological behavior includes the degree of tumor cell deffirentiation and patterm of growth: benign and malignant
Tumors of lymphocytes are always malignant – called lymphoma
Tumors of melanocytes
Benign – nevus
Malignant - melanoma
Benign vs Malignant Tumor Characteristics Benign Malignant Morphology and Differentiation Well-differentiated appearance Structure similar to tissue origin Little or no anaplasia Usually some lack of differentiation Structure often atypical Variable degree of anaplasia Rate and pattern of growth Slow, progressive expansion Rare mitotic figures Normal-appearing mitotic figures Slow to rapid growth; erratic growth rate Mitotic figures often numerous Mitotic figures sometimes abnormal Local invasion No Invasion Cohesive and expansile growth Capsule often present Local Invasion Infiltrative growth Usually no capsule Metastasis No metastasis Frequent metastasis (definitive criteria for malignancy) Damage to human body Relatively smaller Relatively bigger Prognosis Good Bad
Features of tumor spread
invasion and metastasis
Invasion and metastasis are biologic hallmarks of malignant tumors
Invasion and Metastasis
Pathways of tumor spread
Metastatic cascade: two phases
Invasion of Extracellular Matrix
Vascular Dissemination and Homing of Tumor Cells
Invasion and Metastasis
loss of tumor cell-cell adhesion
invasion of basement membrane and extracellular matrix
invasion of blood vessels and lymphatics
Steps of invasion Steps of Extravasation
circulating tumor cells
formation of tumor clumps
adhesion to endothelium
penetration of basement membrane
Metastatic deposit and growth
Invasion and Metastasis Mammary carcinoma in a lymphatic in the lung
Grading & Staging of neoplasm
Grading – Cellular Differentiation (Microscopic)
Staging – Progression or Spread (clinical)
Grading of neoplasms
Grade I: Well-differentiated, cells look like normal cells
Grade II: Moderately differentiated
Grade III: Poorly-differentiated
Grade IV : Nearly anaplastic
Grading of neoplasms assigned by the pathologist to reflect the cancer's degree of differentiation, the four grades are generally divided for malignant tumors
Staging of neoplasms
The most common systems for staging employs the TNM classification.
"T" - based upon the size and/or extent of invasion.
"N" -indicates the extent of lymph node involvement.
"M" - indicates whether distant metastases are present.
The TNM forms are filled out using clinical and pathologic criteria and aid in determination of therapy, estimating the prognosis, and developing statistics useful for determining outcomes.
TNM : Staging of tumor
Staging of Malignant Neoplasms Stage Definition Tis In situ, non-invasive (confined to epithelium) T1 Small, minimally invasive within primary organ site T2 Larger, more invasive within the primary organ site T3 Larger and/or invasive beyond margins of primary organ site T4 Very large and/or very invasive, spread to adjacent organs N0 No lymph node involvement N1 Regional lymph node involvement N2 Extensive regional lymph node involvement N3 More distant lymph node involvement M0 No distant metastases M1 Distant metastases present
UICC( 国际抗癌联盟 ) TNM staging system
T 0 ～ 4 primary tumor size and invasive spectrum
N 0 ～ 3 lymph node metastasis
M 0 ， 1 organ metastasis
I ． T 1 N 0 M 0
II ． T 2 N 0 M 0
T 0-2 N 1 M 0
III ． T 3 N 0 M 0
T 0-3 N 2 M 0
V ． T 4 N 0 M 0
T 0-4 N 3 M 0
T 0-4 N 0-3 M 1
Hamartoma – disorganized but mature mesenchymal or epithelial tissues found their normal anatomic location. It represents an aberrant differentiation, not a true neoplasia.
Choristoma – normal mature tissue located at an ectopic site
Polyp – grossly visible nodule or mass projecting from a
mucosal or epidermal surface. It is a hyperplastic response to chronic inflammation or irritation. Also it is used to indicate a benign neoplasm in some cases.
– Nasal polyp, endometrial polyp, vaginal polyp, and fibroepithelial cutaneous polyp (acrochordon, skin tag) are considered a hyperplastic response to chronic irritation
– Intestinal polyps are benign neoplasm of mucosal epithelium
Pathogenesis of Neoplasia Normal Cell Neoplastic Cell DNA Damage Chemical or physical agents
Microscopic morphology : consisted of a cystic structure lined with keratinized stratified squamous epithelium and solid nests of parenchymal squamous cells, no mitotic figures, a dense lymphoid element with follicles in the stroma.
Immunohistochemistry : CK (+), CK5/6(+), p63(+), p53(+)
Pathological diagnosis ： keratocystoma of parotid gland.
XXX, M/37y,Pathological No: xxxxxx, the left parotid gland mass
Learning without thinking leads to confusion, thinking without learning ends in danger. 学而不思则罔 , 思而不学则殆 -Kong Zi Learning is like rowing upstream: not to advance is to drop back 学如逆水行舟 , 不进则退