The role of pathology in diagnosis and treatment of cancer

11 important questions on The role of pathology in diagnosis and treatment of cancer

What is tumor budding?

The presence of single cells or small clusters of up to five cells at the invasive front of tumors. These budding cells are thought to represent a more aggressive, invasive phenotype of cancer cells, undergoing a process known as epithelial-mesenchymal transition (EMT).

What are passenger mutations?

Passenger mutations have no effect on the fitness of a cell but may be associated with a clonal expansion because it occurs in the same genome with a driver mutation.

What are the 4 different morphologies in cancer development?

Hyperplasia, dysplasia, carcinoma in situ and invasive cancer.
Hyperplasia: increase number of cells
Dysplasia: disordered growth and maturation of cellular components
Carcinoma in situ: severe dysplasia
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What describes the TNM classification of cancer?

The amount and spread of cancer in a patient's body.
T: size of tumor and any spread of cancer into nearby tissue
N: spread of cancer to nearby lymph nodes
M: metastasis, spread of cancer to other parts of the body.

T, N and M are subdivided in stages, whereby I is the beginning and stage IV is an advanced stage

What are the steps that are needed for invasion and metastasis of cancer?

  • Binding of components of the extracellular matric
  • Epithelial-mesenchymal transition (EMT)
  • Extracellular matrix degradation by proteolytic enzymes
  • Intravasation
  • Survival in blood vessels or lymphatics
  • Extravasation
  • Establishment of micrometastases
  • Growing out

Explain the 'homing' phenomenon in cancer

Homing describes the recruitment of circulating tumor cells back to a previously excised primary tumor location, contributing to tumor recurrence as well as their migration to established metastatic lesions. Homing is due to the expression of certain receptors on the tumor cells that lead to migration to organs which express high levels of its ligand (chemotaxis).

What is the 'mechanical hypothesis' in cancer?

The mechanical hypothesis states that the metastatis is determined by the pattern of blood flow and is based on the anatomy of dissemination routes (lymphogenous metastases and hematogenous metastases). The organs where hematogenous metastases can be expected are determined by the blood flow; tumor cells are transported here and get stuck in the first vascular capillary they encounter.

What is the 'seed and soil' hypothesis in cancer?

The seed and soil hypothesis sthates that metastatic tumor cells will metastasize to a site where the local microenvironment is favorable. Just like a seed will only grow if it lands on fertile soil. The relative frequencies of metastatic locations differ between organs, a high % in liver and low in spleen.

Why is the timing of metastases important?

If the metastases happens in a later stage it is possible that treatment and surgical excision of a local tumor can prevent the development of the cancer becoming metastatic. Furthermore, the primary and metastatic tumors share the majority of clinically relevant mutations, and therefore analysis of the primary tumor will suffice for treatment planning.

What are the two distinct mechanisms of colon cancer metastases + explain them

  • Common origin: organ metastases descends from a cancerous lymph node deposit or that both originate from a common subclone disseminated from the primary tumor (35% of cases).
  • Distinct origins: Organ metastases and lymph node deposits each directly descend from a different parental subclone within the primary tumor (65% of cases).

What are the histopathological risk factors that could be used to indicate metastasis?

- TNM: size, lymph node metastatis, vascular invasion)
- Perineural growth
- Grade (does the tumor still look like the original tissue or is it differentiating, tells something about aggresiveness
- Histological subtype (e.g. Mucus production)
- Growth pattern/tumor budding (where does the tumor grow into other tissue, is this in one strand or multiple individual tumor cells (buds)).
- Infiltrating lymphocytes (is the immune system responding?).

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