Podcast
Questions and Answers
What is the primary usage of FISH technique in translocation detection?
What is the primary usage of FISH technique in translocation detection?
Rhabdomyosarcoma is ruled out by IHC.
Rhabdomyosarcoma is ruled out by IHC.
True
What is the name of the fusion protein involved in Ewing sarcoma?
What is the name of the fusion protein involved in Ewing sarcoma?
EWSR1-FLI1
The EWSR1-FLI1 fusion protein orchestrates a list of other genes involved in ______________________.
The EWSR1-FLI1 fusion protein orchestrates a list of other genes involved in ______________________.
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Match the following techniques with their corresponding tissue requirements:
Match the following techniques with their corresponding tissue requirements:
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What is the approximate 5-year survival rate for Ewing sarcoma?
What is the approximate 5-year survival rate for Ewing sarcoma?
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Next generation sequencing is used to detect translocations in tumors.
Next generation sequencing is used to detect translocations in tumors.
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What is the name of the technique used to detect translocations by using primer on both chromosomes?
What is the name of the technique used to detect translocations by using primer on both chromosomes?
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The EWSR1-FLI1 fusion protein is involved in the regulation of ______________________ in Ewing sarcoma.
The EWSR1-FLI1 fusion protein is involved in the regulation of ______________________ in Ewing sarcoma.
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What is the primary treatment for Ewing sarcoma?
What is the primary treatment for Ewing sarcoma?
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What is the result of a promoter swap in tumor formation?
What is the result of a promoter swap in tumor formation?
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A break in EWSR1 is specific to Ewing sarcoma.
A break in EWSR1 is specific to Ewing sarcoma.
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What is the common location where Ewing sarcoma is likely to occur?
What is the common location where Ewing sarcoma is likely to occur?
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The EWSR1-FLI1 fusion protein orchestrates a list of other genes involved in _______________________.
The EWSR1-FLI1 fusion protein orchestrates a list of other genes involved in _______________________.
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What is the purpose of using conventional cytogenetics in translocation detection?
What is the purpose of using conventional cytogenetics in translocation detection?
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Immunohistochemistry is a technique used to detect translocations.
Immunohistochemistry is a technique used to detect translocations.
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Match the following techniques with their corresponding diagnostic uses:
Match the following techniques with their corresponding diagnostic uses:
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What is the role of hTERT in Ewing sarcoma?
What is the role of hTERT in Ewing sarcoma?
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The EWSR1-FLI1 fusion protein is involved in the upregulation of _______________________.
The EWSR1-FLI1 fusion protein is involved in the upregulation of _______________________.
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What is the treatment approach for Ewing sarcoma?
What is the treatment approach for Ewing sarcoma?
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Study Notes
Autopsy
- Hospital autopsy: performed by a clinical pathologist, requires permission from relatives, and is done in almost every hospital in the Netherlands
- Medico-legal autopsy: performed by a forensic pathologist, ordered by a district attorney, and does not require permission from relatives
Pathology
- Study of disease: focuses on functional and structural changes in cells, tissues, and organs
- Aspects of disease:
- Etiology: cause of disease
- Pathogenesis: mechanism of disease development
- Morphologic and molecular changes: structural alterations in cells and organs
- Clinical significance: relation to clinical picture
Histology and Cytology
- Histology: study of tissue structure
- Cytology: study of individual cells
- Formalin fixation: denatures DNA, making it unusable for analysis
- Target genes: examples include HER2 in breast cancer, KRAS/BRAF in colon cancer, and EGFR/KRAS in lung cancer
Nomenclature of Disease
- Importance of uniform nomenclature: enables accurate epidemiological studies and communication
- Eponymous names: commemorate discoverers or signify ignorance of cause or mechanism
- Neoplasm: literally means "new growth", can be benign or malignant
Prefixes and Suffixes in Terminology
- Prefixes:
- Ana-: absence
- Dys-: disordered
- Hyper-: excess
- Hypo-: deficiency
- Meta-: change
- Suffixes:
- -itis: inflammatory process
- -oid: resembling
- -penia: lack of
- -ectasis: dilatation
- -opathy: abnormal state
Neoplasia
- Definition: abnormal mass of tissue, growth exceeds and is uncoordinated with normal tissues
- Classification:
- Behavioural: benign or malignant
- Histogenetic: cell of origin
- Precise classification of individual tumors
- Benign vs malignant:
- Benign: small, slow-growing, non-invasive, well-differentiated
- Malignant: large/small, fast-growing, invasive, poorly differentiated
Morphological and Cytological Features of Cancer
- Microscopic appearance:
- Large, variably shaped nuclei
- Increased number and abnormal mitoses
- Benign features:
- Looks like normal cells
- Low proliferation rate
- No necrosis
- Malignant features:
- Cells look "very" abnormal
- Polymorphic cells
- High N/C rate
- High proliferation rate
- Often necrosis
Staging of Cancer
- Definition: extent of cancer, such as tumor size and spread
- Purpose: understand seriousness of cancer and chances of survival
- TNM system:
- T: tumor size and extent
- N: affected nodes
- M: metastasis
Molecular Pathology
- Diagnosis: detection of mutations, specific translocations, or amplifications
- Prognostic: detection of specific changes associated with prognosis
- Predictive: detection of mutations or amplifications that are druggable targets
- Hereditary syndromes: detection of (epigenetic) changes associated with somatic variations
Hallmarks of Cancer
- Molecular profile: tumor DNA
- Genomic alterations: copy number variations, nucleotide variations, and gene rearrangements
- Tumor microenvironment: surrounded by various cell types
Cellular Pathology and Inflammation
- Homeostasis: balance between cellular growth and death
- Cellular adaptations to stress:
- Hypertrophy: increase in cell size
- Hyperplasia: increase in cell number
- Atrophy: decrease in cell size and number
- Metaplasia: reversible change in cell type and function
- Cell death: necrosis, apoptosis, and autophagy
Inflammation
- Components:
- Vascular
- Cellular
- Mediators
- Outcome:
- Acute inflammation: resolution or abscess formation
- Chronic inflammation: prolonged duration of inflammation
Tissue Repair
- Regeneration or scar formation
- Dependent on tissue, stem cells, and growth factors
- Scar formation: replacement with connective tissue (fibrosis)### Bone Structure and Formation
- Osteoblasts, osteoclasts, hematopoietic supportive stroma, marrow adipocyte, and hematopoietic stem cells are present in bone.
- Cortical bone has a dense layer with osteoblasts on the inside, osteocytes within the matrix, and canaliculi connecting them.
- Osteons are organized in a ring shape within cortical bone, with a canal for blood vessels.
Ossification
- There are two types of ossification:
- Intramembranous ossification: direct bone formation without a cartilage step (minority of bone formation).
- Endochondral ossification: cartilage model is replaced by bone.
- Intramembranous ossification occurs in the cranial vault, facial bones, clavicles, and cortical bone, mainly for appositional bone growth.
- Endochondral ossification occurs in the axial and appendicular skeleton, resulting in longitudinal bone growth, joint cartilage, and fracture healing.
Regulation of Longitudinal Growth
- Regulation of longitudinal growth is complex and involves paracrine and systemic regulation.
Differences between Articular and Growth Plate Cartilage
- Articular cartilage:
- Located at distal ends of bones.
- Involved in joint formation and motility.
- Resistant to resorption.
- Associated with osteoarthritis (osteoarthritis).
- Growth plate cartilage:
- Entrapped between epiphyseal and metaphyseal bone.
- Involved in longitudinal bone growth.
- Disappears at the end of puberty.
- Associated with growth disorders.
Non-Neoplastic Pathology of Bone
- Bone fracture:
- Loss of bone integrity due to mechanical injury and/or diminished bone strength.
- Types: normal (acute trauma), stress or fatigue fracture (repetitive mechanical stress), and pathological fracture (weakened bone due to pre-existing lesion/tumor).
- Fracture healing:
- Involves the formation of a callus, which unites the fractured bone ends.
- Stages: inflammatory, soft callus, and hard callus formation.
Mesenchymal Stem Cell Differentiation
- Mesenchymal stem cells (MSCs):
- Multipotent progenitor cells.
- Reside in bone marrow, adipose tissue, and cord blood.
- Undifferentiated, with self-renewal capacity.
- Can differentiate into bone, cartilage, and adipose tissue.
- Identification of MSC markers:
- CD73, CD90, CD105.
- Osteoblast differentiation:
- CBFA1/RUNX2 transcription factor induces RANK ligand, blocking adipocyte differentiation.
- RUNX2 is essential for osteoblast differentiation and bone formation.
Wnt Signaling
- Wnt signaling pathway:
- Important for bone development and homeostasis.
- Defects in Wnt genes lead to hereditary bone pathologies.
- β-Catenin translocation into the nucleus activates genes.
Mesenchymal Stem Cells in Research and Therapy
- MSCs are present in bone marrow, easy to obtain, and can differentiate in vitro.
- MSCs can be transfected with foreign DNA and frozen for later use.
- MSCs are immunosuppressive and can inhibit alloreactive T-cell proliferation.
Cartilage Tumors of Bone
- Classification of cartilage tumors:
- Benign: osteochondroma, enchondroma.
- Malignant: peripheral chondrosarcoma, central chondrosarcoma.
- Histological grading:
- ACT/grade I: low cellularity, lot of matrix, mitoses absent.
- Grade II: increased cellularity, cytonuclear atypia, mitoses sparse.
- Grade III: high cellularity, atypia, myxoid, mitoses.
Osteochondroma
- Benign cartilage tumor:
- Located at the bone surface.
- Has a cartilage cap and marrow cavity continuous with the underlying bone.
- Multiple osteochondromas (MO):
- Hereditary, autosomal dominant.
- Mutations in EXT1 and EXT2.
Ewing Sarcoma and Molecular Diagnostics
- Sarcoma genesis:
- Ewing sarcoma: specific translocation.
- Chondrosarcoma: specific mutation, multistep model.
- Osteosarcoma: complex karyotype.
- Age-specific incidence of bone sarcomas:
- Ewing sarcoma: peaks in adolescence and young adulthood.
- Chondrosarcoma: peaks in adulthood.
- Osteosarcoma: peaks in adolescence and young adulthood.
Case Study: Ewing Sarcoma
- Diagnosis:
- Small blue round cell tumor in bone.
- Immunohistochemistry: CD99, FLI1.
- Molecular diagnostics: EWSR1-FLI1 fusion (NGS analysis).
- Treatment:
- Resection, chemotherapy, radiation.
- 5-year survival: about 60-65%.
- EWSR1-ETS target genes:
- Involved in cell proliferation, evading growth inhibition, escape from senescence, angiogenesis, and invasion and metastases.
Autopsy
- Hospital autopsy: performed by a clinical pathologist, requires permission from relatives, and is done in almost every hospital in the Netherlands
- Medico-legal autopsy: performed by a forensic pathologist, ordered by a district attorney, and does not require permission from relatives
Pathology
- Study of disease: focuses on functional and structural changes in cells, tissues, and organs
- Aspects of disease:
- Etiology: cause of disease
- Pathogenesis: mechanism of disease development
- Morphologic and molecular changes: structural alterations in cells and organs
- Clinical significance: relation to clinical picture
Histology and Cytology
- Histology: study of tissue structure
- Cytology: study of individual cells
- Formalin fixation: denatures DNA, making it unusable for analysis
- Target genes: examples include HER2 in breast cancer, KRAS/BRAF in colon cancer, and EGFR/KRAS in lung cancer
Nomenclature of Disease
- Importance of uniform nomenclature: enables accurate epidemiological studies and communication
- Eponymous names: commemorate discoverers or signify ignorance of cause or mechanism
- Neoplasm: literally means "new growth", can be benign or malignant
Prefixes and Suffixes in Terminology
- Prefixes:
- Ana-: absence
- Dys-: disordered
- Hyper-: excess
- Hypo-: deficiency
- Meta-: change
- Suffixes:
- -itis: inflammatory process
- -oid: resembling
- -penia: lack of
- -ectasis: dilatation
- -opathy: abnormal state
Neoplasia
- Definition: abnormal mass of tissue, growth exceeds and is uncoordinated with normal tissues
- Classification:
- Behavioural: benign or malignant
- Histogenetic: cell of origin
- Precise classification of individual tumors
- Benign vs malignant:
- Benign: small, slow-growing, non-invasive, well-differentiated
- Malignant: large/small, fast-growing, invasive, poorly differentiated
Morphological and Cytological Features of Cancer
- Microscopic appearance:
- Large, variably shaped nuclei
- Increased number and abnormal mitoses
- Benign features:
- Looks like normal cells
- Low proliferation rate
- No necrosis
- Malignant features:
- Cells look "very" abnormal
- Polymorphic cells
- High N/C rate
- High proliferation rate
- Often necrosis
Staging of Cancer
- Definition: extent of cancer, such as tumor size and spread
- Purpose: understand seriousness of cancer and chances of survival
- TNM system:
- T: tumor size and extent
- N: affected nodes
- M: metastasis
Molecular Pathology
- Diagnosis: detection of mutations, specific translocations, or amplifications
- Prognostic: detection of specific changes associated with prognosis
- Predictive: detection of mutations or amplifications that are druggable targets
- Hereditary syndromes: detection of (epigenetic) changes associated with somatic variations
Hallmarks of Cancer
- Molecular profile: tumor DNA
- Genomic alterations: copy number variations, nucleotide variations, and gene rearrangements
- Tumor microenvironment: surrounded by various cell types
Cellular Pathology and Inflammation
- Homeostasis: balance between cellular growth and death
- Cellular adaptations to stress:
- Hypertrophy: increase in cell size
- Hyperplasia: increase in cell number
- Atrophy: decrease in cell size and number
- Metaplasia: reversible change in cell type and function
- Cell death: necrosis, apoptosis, and autophagy
Inflammation
- Components:
- Vascular
- Cellular
- Mediators
- Outcome:
- Acute inflammation: resolution or abscess formation
- Chronic inflammation: prolonged duration of inflammation
Tissue Repair
- Regeneration or scar formation
- Dependent on tissue, stem cells, and growth factors
- Scar formation: replacement with connective tissue (fibrosis)### Bone Structure and Formation
- Osteoblasts, osteoclasts, hematopoietic supportive stroma, marrow adipocyte, and hematopoietic stem cells are present in bone.
- Cortical bone has a dense layer with osteoblasts on the inside, osteocytes within the matrix, and canaliculi connecting them.
- Osteons are organized in a ring shape within cortical bone, with a canal for blood vessels.
Ossification
- There are two types of ossification:
- Intramembranous ossification: direct bone formation without a cartilage step (minority of bone formation).
- Endochondral ossification: cartilage model is replaced by bone.
- Intramembranous ossification occurs in the cranial vault, facial bones, clavicles, and cortical bone, mainly for appositional bone growth.
- Endochondral ossification occurs in the axial and appendicular skeleton, resulting in longitudinal bone growth, joint cartilage, and fracture healing.
Regulation of Longitudinal Growth
- Regulation of longitudinal growth is complex and involves paracrine and systemic regulation.
Differences between Articular and Growth Plate Cartilage
- Articular cartilage:
- Located at distal ends of bones.
- Involved in joint formation and motility.
- Resistant to resorption.
- Associated with osteoarthritis (osteoarthritis).
- Growth plate cartilage:
- Entrapped between epiphyseal and metaphyseal bone.
- Involved in longitudinal bone growth.
- Disappears at the end of puberty.
- Associated with growth disorders.
Non-Neoplastic Pathology of Bone
- Bone fracture:
- Loss of bone integrity due to mechanical injury and/or diminished bone strength.
- Types: normal (acute trauma), stress or fatigue fracture (repetitive mechanical stress), and pathological fracture (weakened bone due to pre-existing lesion/tumor).
- Fracture healing:
- Involves the formation of a callus, which unites the fractured bone ends.
- Stages: inflammatory, soft callus, and hard callus formation.
Mesenchymal Stem Cell Differentiation
- Mesenchymal stem cells (MSCs):
- Multipotent progenitor cells.
- Reside in bone marrow, adipose tissue, and cord blood.
- Undifferentiated, with self-renewal capacity.
- Can differentiate into bone, cartilage, and adipose tissue.
- Identification of MSC markers:
- CD73, CD90, CD105.
- Osteoblast differentiation:
- CBFA1/RUNX2 transcription factor induces RANK ligand, blocking adipocyte differentiation.
- RUNX2 is essential for osteoblast differentiation and bone formation.
Wnt Signaling
- Wnt signaling pathway:
- Important for bone development and homeostasis.
- Defects in Wnt genes lead to hereditary bone pathologies.
- β-Catenin translocation into the nucleus activates genes.
Mesenchymal Stem Cells in Research and Therapy
- MSCs are present in bone marrow, easy to obtain, and can differentiate in vitro.
- MSCs can be transfected with foreign DNA and frozen for later use.
- MSCs are immunosuppressive and can inhibit alloreactive T-cell proliferation.
Cartilage Tumors of Bone
- Classification of cartilage tumors:
- Benign: osteochondroma, enchondroma.
- Malignant: peripheral chondrosarcoma, central chondrosarcoma.
- Histological grading:
- ACT/grade I: low cellularity, lot of matrix, mitoses absent.
- Grade II: increased cellularity, cytonuclear atypia, mitoses sparse.
- Grade III: high cellularity, atypia, myxoid, mitoses.
Osteochondroma
- Benign cartilage tumor:
- Located at the bone surface.
- Has a cartilage cap and marrow cavity continuous with the underlying bone.
- Multiple osteochondromas (MO):
- Hereditary, autosomal dominant.
- Mutations in EXT1 and EXT2.
Ewing Sarcoma and Molecular Diagnostics
- Sarcoma genesis:
- Ewing sarcoma: specific translocation.
- Chondrosarcoma: specific mutation, multistep model.
- Osteosarcoma: complex karyotype.
- Age-specific incidence of bone sarcomas:
- Ewing sarcoma: peaks in adolescence and young adulthood.
- Chondrosarcoma: peaks in adulthood.
- Osteosarcoma: peaks in adolescence and young adulthood.
Case Study: Ewing Sarcoma
- Diagnosis:
- Small blue round cell tumor in bone.
- Immunohistochemistry: CD99, FLI1.
- Molecular diagnostics: EWSR1-FLI1 fusion (NGS analysis).
- Treatment:
- Resection, chemotherapy, radiation.
- 5-year survival: about 60-65%.
- EWSR1-ETS target genes:
- Involved in cell proliferation, evading growth inhibition, escape from senescence, angiogenesis, and invasion and metastases.
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Description
This quiz covers the different types of autopsies, including hospital autopsy and medico-legal autopsy, and their respective procedures and requirements.
