Neoplasia and Metaplasia Flashcards
what are Epithelial neoplasms?
derived from epithelia or glandular structures
what are Mesenchymal neoplasms?
derived from tissues descended from mesenchyme: muscle, fibroblasts, bone, cartilage, fat, etc.
what are Haemopoietic neoplasms?
derived from cells descended from the pluripotent bone marrow stem cell
what are Nervous system neoplasms?
derived from cells of the central and peripheral nervous system
what are Primitive embryonal neoplasms?
derived from immature cells
what are Germ cell neoplasms?
derived from germ cells in the ovary and testis
how does a tumour begin as the tumour parenchyma?
Clonal expansions of neoplastic cells
what are Supporting stroma composed of?
non neoplastic connective tissue, blood vessels and variable numbers of cells of the adaptive and innate immune system.
what is a desmoplasia?
Abundant collagenous stroma
such tumours will be rock hard or scirrhous.
Differentiation or anaplasia of malignant vs benign
BENIGN - Well differentiated; structure sometimes typical of tissue of origin
MALIGNANT - Some lack of differentiation (anaplasia); structure often atypical
Growth rate of malignant vs benign
BENIGN - Usually progressive and slow; may come to a standstill or regress; mitotic figures rare and normal.
MALIGNANT - Erratic, may be slow to rapid; mitotic figures may be numerous and abnormal.
Local invasion of benign vs malignant
BENIGN - Usually cohesive, expansile, well demarcated masses that do not invade or infiltrate surrounding normal tissues
MALIGNANT - Locally invasive, infiltrating surrounding tissue; sometimes may be misleadingly cohesive and
expansile
Metastasis of benign vs malignant
BENIGN - Absent
MALIGNANT - Frequent; more likely with large undifferentiated primary tumours
what is Metaplasia defined as?
the transformation of one differentiated cell type to another differentiated cell type;
often associated with tissue damage, repair, and regeneration.
AN example in the oesophagus?
gastroesophageal reflux damages the squamous epithelium of the oesophagus,
leading to its replacement by glandular (gastric or intestinal) epithelium more suited to an
acidic environment.
Barrett’s oesophagus
why is metaplasia reversible?
there is no intrinsic gene defect
Can metaplasia progress nto neoplasia
Metaplasia per se does not progress to neoplasia,
but because the metaplastic tissues are less genetically stable than their normal counterparts,
they are prone to undergo further transformation to dysplasia and neoplasia.
what does Dysplasia refers to?
a failure of normal maturation that occurs prior to the development of malignancy.
what is Dysplasia is often preceded by?
metaplasia
what is the main contrast from metaplasia?
it is usually irreversible.
where are Features of dysplasia are more easily recognised?
in epithelia than in mesenchymal or other tissues.
what is a carcinoma in situ?
When dysplastic changes involve the entire thickness of an epithelium,
the lesion is considered a preinvasive neoplasm and is referred to as carcinoma in situ.
Once the tumor cells breach the basement membrane, the tumor is said to be … ?
invasive.
what are the Morphological changes of dysplasia?
- Pleomorphism
- Abnormal nuclear morphology
- Abundant and/or atypical mitoses
- Loss of polarity
- Tumour giant cells
- Ischemic necrosis
how do Nearly all benign tumours grow?
Benign tumours grow and expand slowly,
as cohesive expansile masses that remain localised to their site of origin.
what is meant by a capsule?
they usually develop a rim of compressed fibrous tissue called a capsule that separates them from the host tissue.
what are Malignant neoplasms are typically?
invasive and infiltrative, destroying surrounding normal tissues.
Why is surgery difficult in malignant neoplasms?
They commonly lack a well defined capsule and cleavage plane, making simple excision impossible.
Surgery requires removal of a considerable margin of healthy and apparently uninvolved tissue.
what is Metastasis?
secondary growth of a neoplasm at one or more locations distant from the primary site .
what is the single most important feature distinguishing benign from malignant?
Metastasis
how does Spread may occur?
via lymphatics, blood vessels, across coelomic cavities, within cerebrospinal fluid,
through implantation of neoplastic cells following biopsy or surgery.
where are the most common metastasis locations from solid tumours?
The lungs, liver, brain, and bones
what is a common symptom In lymph nodes metastasis?
lymphadenopathy
what are common symptoms in Lung metastasis?
cough, haemoptysis and dyspnoea (shortness of breath)
what are common symptoms in Liver metastasis?
hepatomegaly (enlarged liver), nausea and jaundice
what are common symptoms in Bone metastasis?
bone pain, fracture of affected bones
what are common symptoms in Brain metastasis?
neurological symptoms such as headaches, seizures, and vertigo
is pain a symptom of cancer?
Although advanced cancer may cause pain, it is often not the first symptom.
when does Transcoelomic spread occur?
May occur whenever a malignant neoplasm penetrates a natural “open field” lacking physical barriers.
where can it occur?
Most often involved is the peritoneal cavity, but can include any other cavity:
pleural, pericardial, subarachnoid, and joint spaces.
how can cancer spread Within the peritoneal cavity>
cancer can spread from one organ to another e.g. carcinoma of stomach to ovary
how can cancer spread Within the pleural cavity?
a primary lung cancer can spread the pleura to the other lung.
what is Lymphatic Spread?
Transports tumour cells to regional nodes and ultimately throughout the body.
why are Lymph nodes draining tumours are frequently enlarged?
this can result from metastatic tumour cell proliferation or from reactive hyperplasia to tumour antigens.
How to accurately assessment of tumour metastasis?
Biopsy of the proximal sentinel lymph node draining a tumour
how is A sentinel lymph node is defined?
as the first lymph node to which cancer cells are most likely to spread from a primary tumour.
what is A sentinel lymph node biopsy?
is a procedure in which the sentinel lymph node is identified, removed, and examined to determine whether cancer cells are present.
which cancers show Hematogenous Spread?
Typical of sarcomas but also is the favored route for certain carcinomas (e.g., renal).
Why?
Because of their thinner walls, veins are more frequently invaded than arteries, and metastasis follows the pattern of venous flow.
what are the are the most common sites of hematogenous metastases?
The lung and liver
first step in Mechanism of invasion and metastasis
- Detachment of neoplastic cells from each other (through downregulation of cadherin expression).
second?
- Attachment to extracellular matrix (ECM) via specific receptors.
third?
- Degradation of the ECM through secretion of collagenases and proteases.
fourth?
- Locomotion through the ECM via secretion of motility factors
5th?
- Vascular intravasation
6th?
- Interaction of tumour cells with host lymphocytes
7th?
- Formation of tumour embolus
8th?
- Adhesion to endothelium at a distant site via adhesion molecules
9th?
- Vascular extravasation
10th?
- Regrowth of the metastatic clone.
what do E cadherins mediate?
the homotypic adhesion of epithelial cells,
serving to both hold the cells together and to relay signals between the cells.
what is the result of Downregulation of E cadherin?
reduces the ability of cells to adhere to each other and facilitates their detachment from the primary tumour
how can tumours degradate ECM?
Tumours elaborate proteases or can induce stromal cell to produce them.
ECM degradation releases a host of growth factors.
Matrix metalloproteinase 9 (MMP9) degrades epithelial and vascular basement membrane type IV collagen, in addition to releasing ECM sequestered pools of VEGF.
how do Tumor cells embolize in the bloodstream?
as self aggregates and by adhering to circulating leukocytes and platelets.
Exactly where tumor cell emboli eventually lodge and begin growing is influenced by what?
- Vascular and lymphatic drainage from the site of the primary tumor.
- Interaction with specific receptors.
- The microenvironment of the organ or site.
what is Organ Tropism?
Organ specific targets
how are Adhesion molecules involved?
whose ligands are expressed preferentially on the endothelial cells of the target organ.
what do chemokines have an important role in?
in determining the target tissues for metastasis.
E.g. some breast cancer cells express the chemokine receptors CXCR4 and CCR7.
examples of Target tissues that may be a nonpermissive environment (“unfavourable)?
E.g. skeletal muscle and spleen are rarely sites of metastasis.
How does the clonal evolution model suggests only some tumors metastasise?
that as mutations accumulate in genetically unstable cancer cells
and the tumour become heterogenous,
a rare subset of tumour cell subclones acquires a pattern of gene expression that is permissive for all steps involves in metastasis.
Tumour cells interact with stromal elements. why important?
Host stromal cells, ECM, and inflammatory cells can modulate (inhibit and augment) tumour growth
(e.g., by secreting matrix degrading proteases and cleaving ECM to release angiogenic and growth factors).
what are Metastasis Oncogenes?
Specific “metastases suppressor genes” or “metastases promoter genes” (e.g., miRNA)
have been described that also impact the capacity of primary lesions to develop secondary tumor spread.
what are TWIST and SNAIL?
Genes that promote epithelial mesenchymal transitions, may be important metastasis genes in epithelial tumours.
what is immune surveillance?
the immune system is normally capable of recognising and eliminating malignant cells
role of Lymphocytes of immune surveillance?
infiltrate tumors, and there is reactive hyperplasia of lymph nodes that drain cancers.
what has been Directly demonstrated?
tumor specific T cells and antibodies in patients.
Response of malignancies to immune modulation.
What are some Mechanisms of evasion of the immune system used by tumour cells?
- Loss or reduced expression of MHC molecules
- Activation of immunoregulatory pathways
- Downregulation of co stimulators or upregulation of surface proteins that induce lymphocyte cell death (PD L1 or PD L2).
- Secretion of immunosuppressive factors by cancer cells.
- E.g. TGF β, interleukin 10, and prostaglandin E 2
- Induction of regulatory T cells (Tregs)
