L28. Neoplasia 1 Flashcards
What proportion of deaths in Australia is due to malignancy?
30% of deaths
What group of people account for the 68% of all diagnosed with malignancy?
Aged >60
What is meant by Neoplasia?
“New Growth”
An Excessive and Unregulated cell proliferation
What is the process of neoplasia?
A multi-step process starting with a SINGLE cell that has abnormalities that develop from aberrant genetic and epigenetic control mechanisms on the
- CELL CYCLE
- APOPTOSIS
- DNA REPAIR
What does neoplastic tissue comprise of?
Neoplastic cells and reactive stroma
What does the reactive stroma of neoplastic tissue usually include?
Inflammatory cells
Fibroblasts
Endothelial cells
Blood vessels
What are the 2 main groups of neoplasia?
Benign and Malignant
What is the definition of a tumour?
Any mass lesion
Can be inflammatory, hyperplastic, neoplastic or any accumulation of mass
But it is a VAGUE term that often implies a neoplasm (but not strictly speaking)
What is the definition of a tumour?
Any mass lesion
Can be inflammatory, hyperplastic, neoplastic or any accumulation of mass
But it is a VAGUE term that often implies a neoplasm (but not strictly speaking)
What are the six classical characteristics/hallmarks that malignant cells possess?
- Resist Cell Death
- Induce Angiogenesis
- Sustain proliferative signalling
- Evade growth suppression
- Activate invasion and metastasis
- Enable a replicative imortality
What are some emerging hallmarks of cancer?
Immune system involvement
Metabolism
Paediatric Cancer doesn’t occur as commonly. They often have a certain characteristic/type called Blastoma. What does this mean?
Blastomas are consistent of primitive and less differentiated cells (called blasts) and these are what form the embryo.
List some common paediatric cancers
Certain leukaemias Certain brain tumours Neuroblastoma Certain lymphomas Retinoblastoma Certain Bone Cancers Wilm's Tumour
What are the characteristics of a Benign tumour?
LOCAL expansile
SLOW growth
well CIRCUMSCRIBED (sometimes encapsulated)
well DIFFERENTIATED (looks like normal cells)
UNABLE TO METASTASISE
rarely life threatening
These cancers have NO evasion or destruction of surrounding tissue and instead tends to pus it aside
What are the characteristics of a Malignant tumour?
LOCALLY INVASIVE
DESTRUCTIVE growth
Often poorly circumscribed with IRREGULAR MARGINS
Frequently induce DESMOPLASIA in the stroma
Sometimes NECROSIS (tumour cells outgrow their blood supply)
Variable DIFFERENTIATION
Potential to METASTASISE
What are the three major ways that malignant tumours can metastasise? Describe each one.
Lymphatic: tumour extends along the lymphatic vessels into the draining lymph nodes
Haematogenous (blood): Tumour can enter the draining veins and the systemic circulation (or can also enter via invasion into the bloodstream)
Transcoelomic (through body cavities): the tumour migrates along the body cavity space
What are uncertain malignant/ potential/borderline tumours?
Lesions with histologically intermediate features between benign and malignant. Difficult to predict what they are but are often not aggressive and have a slow course (some do metastasise)
What are the clinical features of benign tumours?
Benign tumours are rarely symptomatic (depends on where and what it is)
They rarely cause death and rarely become malignant
Is local spread considered metastasis?
No - the tumour growth needs to be completely SEPARATE from the original primary cancer
What are some common sites of metastasis?
Liver
Brain
Ling
Bone
Note: lymphadenopathy is local metastasis
Are metastasise usually multiple of single? What does this mean for treatment?
Usually multiple (sometimes single) and to multiple sites. This means it is very difficult to treat
Are metastasise usually multiple of single? What does this mean for treatment?
Usually multiple (sometimes single) and to multiple sites. This means it is very difficult to treat
What are the histopathological features of neoplasia?
Cytological atypia
Architectural Disorganisation
What is meant by Cytological Aytpia?
Larger Nuclei
Pleomorphic nuclei: varied size and shape
Coarser nuclear chromatin
Hyperchromatic nuclei (more haematoxylin due to more DNA)
Larger, more prominent nucleoli (high activity)
More mitotic activity (sometimes see abnormal mitotic features)
Do benign neoplastic cells show more or less atypia?
Less
What is a histopathological feature of malignant cells that is rarely seen in benign? Describe this feature
Necrosis
It doesn’t fit any pattern (eg. not caseous or coagulative)
The nuclei become shrunken, dark staining, fragmented and condensed nuclear chromatin
What does desmoplastic mean?
The growth fibrous or connective tissue: dense fibroblast proliferation and collagen.
The more desmoplastic a tumour, the more firm the cancer is
What is meant by Cytological Aytpia?
- Larger Nuclei
- Pleomorphic nuclei: varied size and shape
- Coarser nuclear chromatin
- Hyperchromatic nuclei (more haematoxylin due to more DNA)
- Larger, more prominent nucleoli (high activity)
- More mitotic activity (sometimes see abnormal mitotic features)
What does desmoplastic mean?
The growth fibrous or connective tissue: dense fibroblast proliferation and collagen.
The more desmoplastic a tumour, the more firm the cancer is
Tumour cells originate from normal cells and generally show a PHENOTYPE that RESEMBLES the normal counterpart histologically. What are the 3 main groups?
- Epithelial Cells (glandular, squamous, urothelial, endocrine)
- Mesenchymal Cells (osteoblasts, endothelial, smooth muscle, skeletal, adipocytes)
- Other (melanocytes, myeloid cells, lymphoid cells, astrocytes)
Tumour cells originate from normal cells and generally show a PHENOTYPE that RESEMBLES the normal counterpart histologically. What are the 3 main groups?
- Epithelial Cells (glandular, squamous, urothelial, endocrine)
- Mesenchymal Cells (osteoblasts, endothelial, smooth muscle, skeletal, adipocytes)
- Other (melanocytes, myeloid cells, lymphoid cells, astrocytes)
What are some important features of Glandular (Adeno-) Carincomas?
They often form lumina (lumens) around a stroma
Creates a lot of mucous production: MUCIN
- the lumen
- inside the cells themselves (signent ring cells):
What are some important features of Glandular (Adeno-) Carincomas?
They often form lumina (lumens) around a stroma
Creates a lot of mucous production: MUCIN
- the lumen
- inside the cells themselves (signet ring cells):
What are some important features of Glandular (Adeno-) Carincomas?
They often form lumina (lumens) around a stroma
Creates a lot of mucous production: MUCIN
- the lumen
- inside the cells themselves (signet ring cells):
What are some features of Squamous Cancers?
Show features of stratified squamous epithelium
Highly eosinophilic cytoplasms
Intercellular bridges (like the stratus spinosum) with desmosomes holding cells together
May see areas of keratinisation and loss of nuclei within a whirl INSIDE the tissue (not on the surface)
What are some features of Squamous Cancers?
Show features of stratified squamous epithelium
Highly eosinophilic cytoplasms
Intercellular bridges (like the stratus spinosum) with desmosomes holding cells together
May see areas of keratinisation and loss of nuclei within a whirl INSIDE the tissue (not on the surface)
What are the main questions to ask when deciding between differential diagnosis of mass lesions?
- Neoplastic vs. Non-neoplastic
- Is it Benign or Malignant?
- What type is it? (Epithelial, Mesenchymal?)
- If is it malignant: is it the primary or a metastatic lesion?
What are you looking for in a HISTOPATHOLOGICAL ASSESSMENT?
Cytological features
Architectural Organisation (necrosis)
Stroma
Cell Lineages
What are you looking for in a HISTOPATHOLOGICAL ASSESSMENT?
Cytological features
Architectural Organisation (necrosis)
Stroma
Cell Lineages
Describe the general rules for Tumour Type Terminology?
The PREFIX gives the line of differentiation or cell lineage Adeno = glandular Squamous Cell Leiomyo = smooth muscle Osteo = Osteblastic
The SUFFIX Benign = OMA Malignant Epithelial = Carcinoma Mesenchymal = Sarcoma
Describe the general rules for Tumour Type Terminology?
The PREFIX gives the line of differentiation or cell lineage Adeno = glandular Squamous Cell Leiomyo = smooth muscle Osteo = Osteblastic
The SUFFIX Benign = OMA Malignant Epithelial = Carcinoma Mesenchymal = Sarcoma
What is meant by the degree of differentiation of tumours?
The extent to which tumour cells resemble their normal counterparts histologically
What is the difference between well differentiated vs. poorly differentiated tumour cells?
Well Differentiated:
- more Closely resemble mature cells of origin
- Less cytologic atypia
- architecturally more organised
Poorly Differentiated:
- Poorly resemble mature cells
- More cytologic atypia
- Less architecturally organised
What is the grade of a tumour?
The degree of differentiation of a malignant tumour
Why is the tumour microenvironment important?
It is important for tumour growth: remodelling via cell-cell and cell-matrix communication or via secretion of cytokines and growth factors.
Important for establishment and growth of metastases
What are two major theories regarding how neoplasms arise?
- Adult stem cells which are normally proliferating and able to differentiate via different pathways. These can become mutated in one cell and then replicate
- Cancer from mature cells that don’t normally divide but for some unknown reason the cell begins to proliferate uncontrollably
What is epithelial dysplasia?
An abnormality in the development: alteration of size, shape and organisation of cells
Also called intraepithelial neoplasia and non-invasive precursor epithelial lesions
What is epithelial dysplasia?
An abnormality in the development: alteration of size, shape and organisation of cells
Also called intraepithelial neoplasia and non-invasive precursor epithelial lesions
Describe the grading of the Dysplasia or Intraepithelial Neoplasia
Mild, moderate, severe (grades 1,2,3)
Low grade often regress but sometimes progress. Moderate and Severe are more likely to progress.
In situ carcinoma (because it sits in the epithelium) generally refers to grade 3 or severe dysplasia
What is important about diagnosing intraepithelial neoplasia?
They can be used to prevent malignancy (eg. cervical screening)
What is intraepithelial neoplasia?
A process that start carcinoma formation
Changes down a microscope before it becomes invasive.
- An epithelial cell (or basal cell) develops mutations and this cell proliferates
- Pleomorphisms begin to occur and dysplasia
- Severe change leads to in situ carcinoma (no longer any organisation)
- Acquisition of more mutations that can lead to expression of MMPs or other proteins that enable migration out of the epithelium itself - but STAYS in the layer. ie. NON-INVASIVE
What do glandular dysplastic lesions arising from lining epithelia (lining tubular structures) often form?
Polyps
What do the terms hyperplasia and metaplasia mean? Are they the same as neoplasia?
They are adaptive changes that are regulated and controlled by cytokine or growth factor driven changes. They are NOT NEOPLASIA.
Neoplasia arises from genetic dysregulations. Hyperplasia MAY confer an increased risk of malignancy due to increased risk of mutations occurring.
What do the terms hyperplasia and metaplasia mean? Are they the same as neoplasia?
They are adaptive changes that are regulated and controlled by cytokine or growth factor driven changes. They are NOT NEOPLASIA.
Neoplasia arises from genetic dysregulations. Hyperplasia MAY confer an increased risk of malignancy due to increased risk of mutations occurring.
What is the risk of benign lesions becoming malignant?
It is very low risk (except intraepithelial neoplasia which has a relatively higher risk)
