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Summary Principles and Practice of Human Pathology NWI-BB025B

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This is a summary of the course Principles and Practice of Human Pathology (NWI-BB025B). It contains information from the lectures, but also included images for better visualization and a summary of the concerned chapter in Junqueira's Basic Histology. Good luck!

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  • Hoofdstuk 19
  • November 12, 2022
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  • 2021/2022
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Principles and Practice of Human
Pathology



NWI-BB025B


6 EC




Year 3
Quarter 3
Biology – Bachelor

,L1 – Pathology of primary skin tumours 1

Neoplasm = a genetically driven growth of cells (benign, pre-malignant or malignant)

From neoplasm to tumor

Tumor is always a mass, mostly due to genetics but also due to other things such as large scars




Benign neoplasm:
- Often slowly growing
- Only local growth
- No metastases
- Cells without atypia (look less for precursor cells)
- Examples: mole or warts

Malignant neoplasm:
- Often rapid growth/proliferation
- Infiltration in other tissues
- Can metastasize
- Atypical cells

A benign tumor can be premalignant but usually is not.
Benign tumors stick to their own location and there is no atypia.

The development of cancer is a multistep process, multiple genetic aberrations in different genes:
usually at least 6
1. Autonomous cell proliferation: growth
2. New vessels formation: growth
3. Loss of programmed cell death (apoptosis): growth, survival
4. Loss of differentiation: loss of function
5. Loss of cell contact inhibition: invasion
6. Growth into and out of vessels: metastasis

,Genes involved in formation of cancer:
- (Proto)oncogenes:
o Function: involved in promotion of cell growth
o Alteration: gain of function = activation/gain of expression
- Tumor suppressor genes:
o Function: inhibition of cell proliferation or induction of apoptosis
o Alteration: loss of function mutation/loss of gene/loss of expression (in both alleles,
2x)
- DNA repair genes:
o Function: control of genome/repair of DNA replication errors
o Alteration: loss of function/loss of gene/loss of expression (in both alleles, 2x) (→
accumulation of DNA errors)
- Viral genes (usually act as oncogenes)

3 types of genetic alterations:
- Mutations (small change):
o Activation of oncogenes
o Loss of function/expression of tumor suppressor genes
▪ Substitution: activation of oncogene (usually hotspot mutation) or loss of
function of tumor suppressor (e.g., stopcodon)
▪ Insertion/deletion: with frameshift: loss of function of tumor suppressor or
without frameshift: gain or loss of function
- Copy number variations (large change):
o Gains of oncogenes
o Loss of tumor suppressor genes
- Chromosomal translocations:
o Expression or activation of oncogenes


Mutations in cancer:
- Somatic mutation:
o Acquired (throughout life)
o Present only in certain cells of the body, dependent on carcinogen: e.g., UVB induced
TP53 mutation in epithelial cells of the skin
- Germline mutations (often family history):
o Congenital
o Present in all cells of the body
o Can give susceptibility for cancer

Skin cancer is by far the most common cancer
Incidence skin cancer is rising fast = epidemic
Causes:
- The skin is our largest organ (largest number of cells)
- Ageing of the population
- Life long exposure to UV light (most common cause of skin cancer)
- Viral infection (e.g., human papilloma virus)
- Hereditary

Tanning bed: very bad!

Mutation signature of UV light: mutation/replacement CC → TT in a certain gene

, Pathological investigation of (skin) tumors:
1. Assessment of line of differentiation: from which tissue/cells is the tumor derived?
2. Establish whether the tumor is benign or malignant
→ Diagnosis
3. Determine the stage of tumor (invasion depth)
4. Establish whether the margins are free of tumor

Why is pathological examination necessary? Because pathological examination determines clinical
management
Diagnosis, stage and margins determine:
- Necessity of (re)excision
- Margins of (re)excision (0-2 cm)
- Adjuvant radiotherapy
- Sentinel node excision
- Adjuvant systemic therapy

Example routing of a patient with a skin tumor:
1. Clinician takes a biopsy of a lesion
2. Pathologist determines the diagnosis
3. Excision: margins depend on diagnosis
4. Pathological examination of skin excision: marked skin excision: margins marked with
different ink colors and cut with bread loaf technique (in lamels)

Diagnosis of a tumor:
- Routine histology (H&E staining) is sufficient in most cases
- Immunohistochemistry (10-15%)
- Molecular pathology (<2%)
- Example of diagnosis purely based on histology:




Immunohistochemistry (IHC):
- Method for determining type of tumor/cell of origin and for determining malignant character
of tumor (for example staining of P16 (tumor suppressor) and in the melanoma there is no
P16 staining visible anymore)
- Usage of an antibody directed against an antigen on a (tumor) cell
- The binding is subsequently visualized with a chromogen

Molecular pathology:
- Method for determining treatment options
- For example, determining the gene BRAF V600E mutations, BRAF mutated melanoma can be
treated with targeted therapy

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