Histopathology

Question 1

What tools does a pathologist use?

Answer 1

• Morphology (pattern recognition)
• Immunohistochemistry (protein expression)
• Molecular pathology (abnormalities in the DNA)
• In situ hybridization
• Fluorescence immunohistology

Question 2

In order for pathology to make a diagnosis a combination of what is used?

Answer 2

1. Macroscopy (what did the tumour/ organ look like to the naked eye?)
2. Microscopy (what is the morphology of the tumour under the microscope?)
3. Immunohistochemistry (what is the protein expression?)
4. Molecular pathology (what mutations does the tumour have?)

Question 3

What considerations are taken into account for tissue selection?

Answer 3

• Select the invasive component with the worst prognosis
• If multiple growth patterns, then try to select most or all components
• Select the primary tumour or distant metastasis
• Lesion resistant to targeted therapy

Question 4

What factors are considered for tissue selection macro/microdissection and mutation status testing?

Answer 4

• Select the invasive component with the worst prognosis
• If multiple growth patterns, then try to select most or all components
• Select the primary tumour or distant metastasis
• Lesion resistant to targeted therapy

Question 5

What considerations are taken into account for tissue assessment (tumour percentage and cellularity)?

Answer 5

• Significant interobserver variability in assessing tumour percentage and cellularity of the HE slides
• Factors such as experience and non-neoplastic cells may lead to over and underestimation of the tumour percentage.
• To overcome sample assessment variability correlation with sequencing results is essential
• The latter would also allow for more accurate results and recommendations for possible further testing.

Question 6

How is the final data interpreted?

Answer 6

• The quantitative analytical performance of a test does not necessarily predict performance on a clinical level because of the intrinsic biological variability of the disease.
• The main concern: differentiate between the analytical and clinical performance of your mutational results in the context of the histomorphology.
• An explanation of the clinical implications of the results should be stated if appropriate.

Question 7

Presence of a what should be interpreted with care in poorly differentiated tumours?

Answer 7

Mutation

Question 8

What are the challenges within Histopathology?

Answer 8

• Pathologists also very often subspecialise in very specific organ systems and areas within oncology.
• The most challenging aspects within diagnostic pathology is just getting the diagnosis right.
• There is great variation in cancer with multiple sub-classifications within the different tumour types.
• Final say in the diagnosis, staging and prognosticators.

Question 9

Mutations may be present as part of cancer evolution but does not necessarily mean what?

What is needed to be relied upon?

Answer 9

It is a driving mutation/amenable to therapy. PDL1 dubiously predictive in this case.

The WHO histological criteria as this will guide behaviour

Question 10

What is advocated in situations with tumour with specify WHO morphology and tumours known to harbour clinically active mutations

Answer 10

Molecular tests and subsequent therapy at molecular tumour boards/ MDTs