General Pathology: Oncology and Molecular Pathology

Introduction to Pathology

• Determining the correct diagnosis of a disease relies on clear classification, which is the core of pathology.
• A correct classification is crucial to determine therapy and prognosis.
• Classical pathology deals with morphological changes of histology, specific stainings, and expression of proteins as detected by immunohistochemistry.

Molecular Pathology

• The analysis of nucleic acids is integrated in regular pathology diagnostics and is used to confirm diagnosis and determine treatment options.
• Molecular analysis is of particular importance in the diagnosis and treatment of cancer.
• Classification of tumors is performed using histological examination, location in the body, and identification of specific DNA mutations.
• The quality of the tissue is not always optimal, which may be formalin fixed, partly necrotic, and contaminated with non-diseased tissue.

Distant Metastasis (M)

• MX: Metastasis cannot be measured.
• M0: Cancer has not spread to other parts of the body.
• M1: Cancer has spread to other parts of the body.

Molecular Profile Tumor DNA

Copy Number Variation > Genomic Instability

• Gain or loss of chromosomes, resulting in aneuploidy and nuclear hyperchromasia.
• Gain or loss of parts of chromosomes/focal.

Nucleotide Variation

• Single Nucleotide Polymorphism (SNP), silent variation.
• Variants with unknown significance (VUS).
• Pathogenic variants: driver mutations in oncogene, frameshift/non-sense mutations in tumor-suppressor genes, and passenger mutations.

Genomic Alterations

• Nucleotide variations: single nucleotide polymorphism, frameshift variants, or in-frame deletions of insertions.
• Pathogenic variants: activating or inactivating.
• Variants with unknown significance (VUS).
• Copy number variations: amplification (activating), deletion (inactivating).
• Gene rearrangements: fusion genes (activating), loss of inhibitory domain (activating).

Oncogenes: Therapeutic Targets

• Activation of proto-oncogene > abnormal activation > cancer.
• Proto-oncogenes are dominant on a cellular level, and abnormal activation is achieved with activation of 1 allele.

Activities

• Study the reading list in advance.
• Perform the SSA-test (Brightpace) before attending the work group.
• Keep your course book (Robbins and Cotran Pathologic Basis of Disease) available during the work group.
• The work group is on campus with a tutor.

Reading List and Study Guidelines

• Read the indicated pages from Robbins and Cotran Pathologic Basis of Disease, 10th edition, 2020.
• Chapter 5, page 180-187, molecular genetic diagnosis.
• Chapter 7, page 267-338, chapter 7: neoplasia.

Molecular Pathology: R-Assignment

• Develop an application in R for the analysis of next generation sequencing data.

General Pathology: Introducing Pathology

• Pathology = study of disease (study of functional and structural changes in cells, tissues, and organs that cause disease).
• Histology = tissue.
• Cytology = cells.
• Etiology = cause.
• Pathogenesis = mechanism of its development.
• Morphologic and molecular changes = structural alterations induced in cells and organs of the body.
• Clinical significance = relation to the clinical picture.

Detection Methods

• Standard histology (such as HE staining).
• Special stains (such as histochemical stains and immunohistochemical stains).
• Molecular assays.
• Electron microscopy.

General Pathology: Oncology

• Unifying nomenclature of neoplasia.
• Learning objectives: being able to use the oncologic terminology regarding benign and malignant tumors and their pre-malignant stages.

This quiz covers the basics of general pathology, focusing on oncology and molecular pathology, including disease classification, diagnosis, and prognosis.