Types of Autopsies and Pathology
106 Questions
0 Views

Choose a study mode

Play Quiz
Study Flashcards
Spaced Repetition
Chat to lesson

Podcast

Play an AI-generated podcast conversation about this lesson

Questions and Answers

What type of autopsy requires permission from relatives?

  • Clinical autopsy
  • Forensic autopsy
  • Hospital autopsy (correct)
  • Medico-legal autopsy

    • Formalin fixation preserves DNA for analysis.

    False

    What is the study of disease that involves the study of functional and structural changes in cells, tissues, and organs?

    Pathology

    Eponymous names commemorate, for example, the ______________________ of a disease.

    <p>discoverer</p> Signup and view all the answers

    Match the following types of autopsies with their corresponding professionals:

    <p>Hospital autopsy = Clinical pathologist Medico-legal autopsy = Forensic pathologist Clinical autopsy = Not applicable</p> Signup and view all the answers

    What is the term for the study of the structure of tissue and cells together?

    <p>Histology</p> Signup and view all the answers

    Neoplasm always means a malignant tumor.

    <p>False</p> Signup and view all the answers

    The term "tumor" literally means ______________________.

    <p>swelling</p> Signup and view all the answers

    What is the type of necrosis that involves the destruction of fat cells and the formation of calcium soap?

    <p>Fat necrosis</p> Signup and view all the answers

    Chronic inflammation always leads to tissue regeneration.

    <p>False</p> Signup and view all the answers

    What are the five classic signs of inflammation?

    <p>Heat, Redness, Swelling, Pain, Loss of function</p> Signup and view all the answers

    During inflammation, the first leukocytes to arrive at the site are ____________________.

    <p>neutrophils</p> Signup and view all the answers

    What is the primary function of cytokines in inflammation?

    <p>To regulate the inflammation process</p> Signup and view all the answers

    Granulomatous inflammation is a type of chronic inflammation.

    <p>True</p> Signup and view all the answers

    What is the term for the deposition of calcium at injured or necrotic locations?

    <p>Dystrophic calcifications</p> Signup and view all the answers

    The process of tissue repair involves the formation of ____________________ tissue.

    <p>granulation</p> Signup and view all the answers

    Match the following types of necrosis with their descriptions:

    <p>Liquefactive = Tissue liquefaction Caseous = Mummified tissue Fibrinoid = Immune-mediated necrosis Fat = Fat destruction and calcium soap formation</p> Signup and view all the answers

    What is the primary function of bones?

    <p>All of the above</p> Signup and view all the answers

    What is the purpose of Ki-67 marker in IHC?

    <p>To detect proliferating cells</p> Signup and view all the answers

    Gleason grading system is used for breast cancer.

    <p>False</p> Signup and view all the answers

    What does the TNM system stand for in cancer staging?

    <p>Tumor size and extent of the primary tumor, affected nodes, and metastasis</p> Signup and view all the answers

    Aneuploidy refers to the presence of an abnormal number of _____________________ in a cell.

    <p>chromosomes</p> Signup and view all the answers

    What is the purpose of molecular analysis in cancer diagnosis?

    <p>To detect both chromosomal translocations and gene alterations</p> Signup and view all the answers

    Tumor grade is based on the degree of maturity or differentiation under the microscope.

    <p>True</p> Signup and view all the answers

    Match the following terms with their definitions:

    <p>Genomic instability = Gain or loss of chromosomes or parts of chromosomes Nuclear hyperchromasia = Increased DNA content Driver mutations = Activating mutations in oncogenes Passage mutations = Loss of function caretakers</p> Signup and view all the answers

    What is the difference between a proto-oncogene and a tumor suppressor gene?

    <p>A proto-oncogene only needs one allele mutation for gain of function, while a tumor suppressor gene needs loss of heterozygosity to be inactivated and oncogenic.</p> Signup and view all the answers

    The term 'hallmark of cancer' refers to the molecular profile of ______________________ DNA.

    <p>tumor</p> Signup and view all the answers

    P53 mutated in benign tumors.

    <p>False</p> Signup and view all the answers

    What is the meaning of the prefix 'Meta-' in terminology?

    <p>Change from one state to another</p> Signup and view all the answers

    Benign tumors are always small.

    <p>False</p> Signup and view all the answers

    What is a Papilloma?

    <p>A tumor with finger-like projections.</p> Signup and view all the answers

    The suffix '-ectasis' means _______________.

    <p>dilatation</p> Signup and view all the answers

    What is the name of the disease characterized by the presence of Reed-sternberg cells?

    <p>Hodgkin disease</p> Signup and view all the answers

    All malignant tumors are fast-growing.

    <p>False</p> Signup and view all the answers

    What is the main difference between benign and malignant tumors?

    <p>Benign tumors are non-invasive and do not metastasize, while malignant tumors are invasive and can metastasize.</p> Signup and view all the answers

    What is the name of the tumor that can be comprised of cells from more than one germ layer?

    <p>Teratoma</p> Signup and view all the answers

    The suffix '-sarcoma' refers to a _______________ neoplasm.

    <p>malignant mesenchymal</p> Signup and view all the answers

    Match the following tumors with their descriptions:

    <p>Adenoma = Tumor forming glands Papilloma = Tumor with finger-like projections Lipoma = Fat neoplasm Carcinoma = Malignant epithelial neoplasm</p> Signup and view all the answers

    Which protein is most involved in DNA repair?

    <p>BRCA1</p> Signup and view all the answers

    Formalin-fixed tissues do not contain DNA-DNA crosslinks.

    <p>False</p> Signup and view all the answers

    What type of cell death occurs when there is a lack of oxygen due to a clot in the blood flow?

    <p>Necrosis</p> Signup and view all the answers

    HER2 can be detected by IHC with ______________ staining.

    <p>silver</p> Signup and view all the answers

    Which of the following is NOT a cause of cell injury?

    <p>Hormonal regulation</p> Signup and view all the answers

    Autophagy is a type of cell death.

    <p>False</p> Signup and view all the answers

    What is the result of reperfusion injury?

    <p>More cell damage due to reactive oxygen species</p> Signup and view all the answers

    Match the following cellular adaptations to stress:

    <p>Hypertrophy = Increase in cell- and organ size Hyperplasia = Increase in cell number Atrophy = Decrease in cell size and number Metaplasia = Reversible change in cells</p> Signup and view all the answers

    EGFR is a type of ______________ receptor.

    <p>tyrosine kinase</p> Signup and view all the answers

    Coagulative necrosis shows a loss of tissue morphology.

    <p>False</p> Signup and view all the answers

    What is the function of CBFA1/RUNX2 in bone development?

    <p>Induces RANK ligand</p> Signup and view all the answers

    Mutations in AXIN2 can lead to osteoporosis.

    <p>False</p> Signup and view all the answers

    What is the purpose of classification in mesenchymal tumors?

    <p>To predict how the tumor should be treated and give the best outcome for the patient</p> Signup and view all the answers

    MSCs are present in the _______________________.

    <p>bone marrow</p> Signup and view all the answers

    Match the following types of chondrosarcoma with their locations:

    <p>Peripheral chondrosarcoma = Bone surface Central chondrosarcoma = In marrow Endochondroma = Hands and feet</p> Signup and view all the answers

    What is the function of HSPG in signaling?

    <p>As a co-receptor for FGF and VEGF</p> Signup and view all the answers

    Mouse MSCs can become sarcomas when administered intravenously.

    <p>True</p> Signup and view all the answers

    What is the hallmark of cancer?

    <p>Multistep progression model</p> Signup and view all the answers

    Osteochondromas are most frequent in _______________________ patients.

    <p>young</p> Signup and view all the answers

    What is the function of EXT proteins?

    <p>To elongate sugar chains on heparan sulfate proteoglycan</p> Signup and view all the answers

    What is the percentage of organic component in bone?

    <p>35%</p> Signup and view all the answers

    Osteocytes are responsible for producing the matrix.

    <p>False</p> Signup and view all the answers

    What is the role of osteoclasts in bone formation?

    <p>Resorb bone</p> Signup and view all the answers

    The RANK receptor gets stimulated, leading to differentiation towards _______________________.

    <p>osteoclast</p> Signup and view all the answers

    Match the following types of bone with their characteristics:

    <p>Osteoid = Non-mineralized bone Woven bone = Random deposition of collagen Lamellar bone = Orderly deposition of collagen</p> Signup and view all the answers

    Which of the following pathways is important in the normal growth plate?

    <p>All of the above</p> Signup and view all the answers

    What is the purpose of the osteoprotegerin (OPG)?

    <p>Inhibit osteoclast precursor</p> Signup and view all the answers

    Inactivation of hedgehog signaling leads to excessive bone formation.

    <p>False</p> Signup and view all the answers

    Hematopoietic stem cells are found in the cortical bone.

    <p>False</p> Signup and view all the answers

    What is the name of the disease where patients have multiple enchondromas that can progress to sarcoma?

    <p>Ollier disease</p> Signup and view all the answers

    What is the main difference between intramembranous and endochondral ossification?

    <p>Cartilage step in between</p> Signup and view all the answers

    The mutation in IDH1 or IDH2 genes leads to the production of _______________, an onco-metabolite.

    <p>D2HG</p> Signup and view all the answers

    Osteoblasts and osteoclasts are involved in the _______________________ of bone.

    <p>remodeling</p> Signup and view all the answers

    Match the following bone sarcomas with their characteristic features:

    <p>Ewing sarcoma = Specific translocation Chondrosarcoma = Specific mutation Osteosarcoma = Complex karyotype</p> Signup and view all the answers

    What is the term for the process by which osteoclasts resorb bone to initiate the healing process after microdamage?

    <p>Bone resorption</p> Signup and view all the answers

    What is the name of the gene that is mutated in patients with Ollier disease?

    <p>IDH2</p> Signup and view all the answers

    The use of IDH inhibitor is promising for the treatment of chondrosarcoma patients.

    <p>False</p> Signup and view all the answers

    What is the name of the test used to determine the line of differentiation in small blue round cell tumors?

    <p>Immunohistochemistry</p> Signup and view all the answers

    The diagnosis of Ewing sarcoma can be confirmed by the presence of a specific ______________________.

    <p>translocation</p> Signup and view all the answers

    IHC profiles never overlap in small blue round cell tumors.

    <p>False</p> Signup and view all the answers

    What is the primary function of articular cartilage?

    <p>Weight bearing</p> Signup and view all the answers

    Growth plate cartilage is resistant to resorption.

    <p>False</p> Signup and view all the answers

    What is the name of the process by which bone is formed within muscle tissue?

    <p>Myositis ossificans</p> Signup and view all the answers

    The process of bone formation in which cartilage is replaced by bone is called _______________ ossification.

    <p>endochondral</p> Signup and view all the answers

    Match the following types of fractures with their descriptions:

    <p>Normal fracture = Due to acute trauma Stress or fatigue fracture = Due to repetitive mechanical stress Pathological fracture = In weakened bone due to pre-existing lesion/tumor</p> Signup and view all the answers

    What is the role of RANKL in MSC differentiation?

    <p>Produced by osteoblast</p> Signup and view all the answers

    Osteoclasts are derived from Mesenchymal Stem Cells (MSCs).

    <p>False</p> Signup and view all the answers

    What is the name of the protein marker used to identify MSCs?

    <p>CD73/90/105</p> Signup and view all the answers

    The process of bone formation in which a hard mass of skeletal repair tissue forms is called a _______________.

    <p>callus</p> Signup and view all the answers

    Endochondral ossification is seen only in fracture healing.

    <p>False</p> Signup and view all the answers

    What is the purpose of molecular testing in this case?

    <p>To look for specific genetic alterations within the tumor DNA</p> Signup and view all the answers

    A break in EWSR1 is specific for Ewing sarcoma.

    <p>False</p> Signup and view all the answers

    What is the function of the EWSR1-FLI1 fusion protein in Ewing sarcoma?

    <p>It orchestrates a list of other genes involved in cell proliferation, evading growth inhibition, escape from senescence, escape from apoptosis, angiogenesis, and invasion and metastases.</p> Signup and view all the answers

    The 5-year survival rate for Ewing sarcoma is approximately _______%.

    <p>60-65</p> Signup and view all the answers

    What is the primary technique used for translocation detection?

    <p>Next generation sequencing</p> Signup and view all the answers

    Ewing sarcoma is likely to occur in brain tissue.

    <p>False</p> Signup and view all the answers

    Match the following genes with their functions in Ewing sarcoma:

    <p>PDGF-C = Stimulation of cell proliferation p21 = Evasion of growth inhibition hTERT = Escape from senescence IGFBP-3 = Escape from apoptosis</p> Signup and view all the answers

    What is the term for the genetic alteration where half of one gene is attached to the other half of another gene?

    <p>Chimeric gene</p> Signup and view all the answers

    What is the purpose of molecular testing in tumor diagnosis?

    <p>To identify specific genetic alterations within the tumor DNA</p> Signup and view all the answers

    Truncation occurs when the promoter of a gene is swapped with another gene.

    <p>False</p> Signup and view all the answers

    What is the most common translocation detected in Ewing sarcoma?

    <p>EWSR1-FLI1 fusion</p> Signup and view all the answers

    FISH (Fluorescence In Situ Hybridization) is a technique used to detect translocations in _______________ material.

    <p>paraffin</p> Signup and view all the answers

    What is the 5-year survival rate for Ewing sarcoma?

    <p>60-65%</p> Signup and view all the answers

    EWSR1-ETS target genes stimulate cell proliferation.

    <p>True</p> Signup and view all the answers

    What is the primary treatment for Ewing sarcoma?

    <p>Resection, chemotherapy, and radiation</p> Signup and view all the answers

    The EWSR1-FLI1 fusion protein orchestrates a list of other genes involved in _______________, including stimulation of cell proliferation and evasion of growth inhibition.

    <p>tumor formation</p> Signup and view all the answers

    Match the following techniques with their descriptions:

    <p>Conventional cytogenetics = Uses fresh tissue to detect translocations RT-PCR = Uses probes that attach to chromosomes to detect translocations FISH = Uses primer on both chromosomes to detect translocations Immunohistochemistry = Uses staining to detect protein expression</p> Signup and view all the answers

    What is the function of the EWSR1-ETS target gene hTERT?

    <p>Increased telomerase activity</p> Signup and view all the answers

    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.

    Studying That Suits You

    Use AI to generate personalized quizzes and flashcards to suit your learning preferences.

    Quiz Team

    Description

    This quiz covers the different types of autopsies, including hospital and medico-legal autopsies, and the role of pathology in diagnosing diseases.

    More Like This

    Autopsy Procedures and Terminology Quiz
    20 questions

    Autopsy Procedures and Terminology Quiz

    LegendaryHill avatar
    LegendaryHill
    Forensic Pathology Concepts Quiz
    11 questions

    Forensic Pathology Concepts Quiz

    UnwaveringLynx avatar
    UnwaveringLynx
    Autopsy Procedures and Causes of Death
    10 questions

    Autopsy Procedures and Causes of Death

    LuxuriantConnotation avatar
    LuxuriantConnotation
    Autopsy Procedure Overview
    21 questions

    Autopsy Procedure Overview

    SophisticatedTulsa2777 avatar
    SophisticatedTulsa2777
    Use Quizgecko on...
    Browser
    Open
    Browser
    Browser