Whole pathology of bone tumors and MSC differentiation
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Questions and Answers

What is the result of a promoter swap in Ewing sarcoma?

  • Next generation sequencing
  • Deregulated signaling (correct)
  • Altered expression
  • Genetic testing

    • The break in EWSR1 is specific to Ewing sarcoma.

    False

    What are the two main techniques used for translocation detection in Ewing sarcoma?

    Conventional cytogenetic (fresh tissue) and RT-PCR (frozen tissue, paraffin)

    Ewing sarcoma is typically found in young people, in _______ and soft tissue.

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

    Match the following techniques with their descriptions:

    <p>Conventional cytogenetic = Examines fresh tissue RT-PCR = Designs primers at both ends of the fusion (no fusion, no PCR product) FISH = Uses paraffin material, not decalcified! Immunohistochemistry = Uses antibodies to detect protein expression</p> Signup and view all the answers

    What is the characteristic of osteochondroma?

    <p>It is not entirely clonal</p> Signup and view all the answers

    Ewing sarcoma can occur in older people.

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

    What are the three main components used in pathological diagnosis of bone tumors?

    <p>Immunohistochemistry, Molecular analysis, and Morphology (with Clinical and radiological information)</p> Signup and view all the answers

    IDH mutants convert ____________ to D2HG.

    <p>α-KG (alpha-ketoglutarate)</p> Signup and view all the answers

    Match the following bone tumors with their characteristic features:

    <p>Chondrosarcoma = Requires an accumulation of mutations Ewing Sarcoma = Specific translocations (e.g. EWSR1-ETS fusion proteins) Osteochondroma = Forms a niche for normal cells to acquire mutations</p> Signup and view all the answers

    What is the effect of LWD treatment on growth?

    <p>Gain of 7-10 cm</p> Signup and view all the answers

    DNA analysis is always necessary in making a diagnosis of syndromic growth disorder.

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

    What is the importance of recognizing the inheritance pattern of a specific syndrome?

    <p>It is important for the patient and their family to understand the implications of the syndrome.</p> Signup and view all the answers

    The presence of giant cells in bone tumors is not unique to _______________________.

    <p>Giant Cell Tumor</p> Signup and view all the answers

    Match the following characteristics with the correct diagnosis:

    <p>Lytic lesion, less mineral = Giant Cell Containing Tumor of Bone Growth hormone, Gain of 7-10 cm = LWD treatment Short stature, Gain of 3-5 cm = Turner syndrome Giant cells, mononuclear cells = Mesenchymal tumors</p> Signup and view all the answers

    What is the most common chromosomal cause of short stature?

    <p>Down syndrome</p> Signup and view all the answers

    Turner syndrome only occurs in boys.

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

    What is the mean IQ of individuals with Noonan syndrome?

    <p>86</p> Signup and view all the answers

    The frequency of skeletal dysplasia is approximately ______________ live births.

    <p>1:3000</p> Signup and view all the answers

    Match the following syndromes with their characteristics:

    <p>Turner syndrome = Girls only, heart condition, infertile Noonan syndrome = Developmental delay, facial features, coagulation defect Achondroplasia = Short stature, large head, short arms and legs</p> Signup and view all the answers

    What is the frequency of Achondroplasia?

    <p>1:15,000 to 1:40,000</p> Signup and view all the answers

    What is the definition of tall stature in terms of standard deviation?

    <p>Height &gt; 2 SDS</p> Signup and view all the answers

    Short stature is defined as a height less than -1 SDS.

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

    What are the factors that influence height, aside from genetics?

    <p>Feeding, health, and medication</p> Signup and view all the answers

    Armspan measurement is typically the same as ______________ in adults.

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

    Match the following measurements with their descriptions:

    <p>Height = Weight Measurement from finger to finger = Measurement taken when laying down</p> Signup and view all the answers

    What is the effect of upregulation of PDGF-C, CCDN1, c-MYC in cell proliferation?

    <p>Stimulation of cell proliferation</p> Signup and view all the answers

    Tall stature is always a sign of overgrowth.

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

    What is the difference between syndromic and non-syndromic growth disorders?

    <p>Syndromic growth disorders have additional features or anomalies besides short stature, whereas non-syndromic growth disorders only have short stature.</p> Signup and view all the answers

    Downregulation of cyclin-dependent kinase inhibitors (p21, p57) leads to ______________ of growth inhibition.

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

    Match the following features with their corresponding syndromic growth disorders:

    <p>Short stature = Syndromic growth disorder Tall stature = Non-syndromic growth disorder Additional features or anomalies = Syndromic growth disorder</p> Signup and view all the answers

    VEGF expression is a characteristic of evading growth inhibition.

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

    What is the role of hTERT in escaping from senescence?

    <p>Upregulation of hTERT leads to increased telomerase activity, which helps escape from senescence.</p> Signup and view all the answers

    Repression of IGFBP-3 promoter leads to ______________ of apoptosis.

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

    Study Notes

    Osteochondroma and Chondrosarcoma

    • Mutant cells grow out and form an osteochondroma with some normal cells.
    • Osteochondroma is not entirely clonal.
    • Osteochondromas can progress to secondary peripheral chondrosarcoma.
    • Chondrosarcoma is clonal, and some cells may not have EXT mutations.
    • Other mutations that inactivate cell cycle genes, such as INK4 or Trp53, can also occur.

    Central Cartilaginous Tumors

    • Enchondromatosis (Ollier disease) is a rare, non-hereditary condition with a unilateral predominance.
    • It occurs during skeletal formation in young patients and has a 40% risk of malignant transformation.
    • IDH1 or IDH2 mutations are often found in Ollier, secondary chondrosarcoma, and primary central chondrosarcoma.
    • These mutations convert α-KG to D2HG, affecting DNA methylation and histone modifications.

    Ewing Sarcoma and Molecular Diagnostics

    • Pathological diagnosis involves immunohistochemistry, molecular analysis, morphology, and clinical and radiological information.
    • Ewing sarcoma has a specific translocation, EWSR1-ETS, which is essential for tumor formation.
    • Immunohistochemistry is used to detect antigens in tissue sections, determine diagnosis, and predict prognosis.
    • Molecular testing is necessary to confirm the diagnosis, as immunohistochemical profiles may overlap.
    • Techniques for translocation detection include conventional cytogenetic, RT-PCR, FISH, and next-generation sequencing.

    Molecular Alterations in Small Blue Round Cell Tumors

    • Ewing sarcoma specific translocations involve EWSR1-ETS fusion proteins.
    • Specific translocations in sarcomas involve chimeric gene formation, promoter swap, and truncation.
    • These translocations lead to transcriptional deregulation, deregulated signaling, and altered expression.

    Diagnosis and Treatment

    • Diagnosis involves a combination of immunohistochemistry, molecular analysis, and radiological information.
    • Treatment for Ewing sarcoma involves resection, chemotherapy, and radiation, with a 5-year survival rate of about 60-65%.
    • Genetic testing is essential for diagnosis, but not sufficient on its own, as some tumors share the same fusion but are entirely different.
    • Antibodies against chimeric proteins, such as SS18-SSX, can be used for diagnosis.

    Giant Cell Containing Tumors of Bone

    • Giant cells in bone tumors are not necessarily indicative of a giant cell tumor.
    • GCTB (giant cell containing tumors of bone) is a specific type of tumor with a distinct biology and therapy.
    • GCTB is characterized by the presence of giant cells and mononuclear cells.
    • Treatment for GCTB involves understanding its biology and therapy.

    Height Measurement and Definition

    • Height is measured in relation to the standard deviation (SDS) from the mean height
    • Tall stature: height > 2 SDS or > 1.6 SDS above target height based on parent's height
    • Short stature: height < -2 SDS or > 1.6 SDS under target height based on parent's height

    Guideline for Measuring

    • Measure height, weight, head circumference, arm span, and sitting height
    • Measure parents' height only when armspan and sitting height are abnormal in the child

    Height Determinants

    • 60-80% of height is determined by genetics
    • Feeding, health, and medication are other important factors influencing height

    Syndrome Definition and Recognition

    • A syndrome is a group of signs and symptoms that occur together and characterize a particular abnormality or condition
    • Syndrome recognition involves pattern recognition

    Causes of Short Stature

    Primary Growth Disorders

    • Syndromes
    • SGA (small for gestational age) without catch-up growth
    • Skeletal dysplasia
    • Disorders of bone metabolism

    Secondary Growth Disorders

    • Malnutrition
    • Celiac disease
    • Hormonal disorders
    • Metabolic disorders
    • Idiopathic short stature (unknown cause)

    Syndromes with Short Stature

    • Down syndrome (trisomy 21)
    • Turner syndrome
    • Noonan syndrome

    Turner Syndrome

    • Occurs only in girls
    • Characterized by a single X chromosome or an isochromosome X (missing short arm)
    • Often have heart conditions and are infertile
    • Benefit from growth hormone therapy

    Noonan Syndrome

    • Caused by a gene mutation, affecting both boys and girls
    • Short stature (mean height: 169 cm in males, 154 cm in females)
    • Developmental delay (mean IQ: 86)
    • Facial features: hypertelorism, ptosis, low-set ears, and broad neck
    • Congenital cardiac anomaly, pectus deformity, lymphatic abnormalities, coagulation defects, and cryptorchidism
    • Genetics: mutations in genes in the RAS-MAPK pathway

    Skeletal Dysplasia

    • Frequency: 1:3000 live births, 1:110 perinatal mortality
    • Characterized by short limbs for trunk, epiphysis, metaphysis, and/or diaphysis abnormalities
    • Causes disproportionate short stature
    • Heterogeneity (clinical and genetic), non-uniform terminology

    Skeletal Dysplasia: Achondroplasia

    • Frequency: 1:15,000 - 1:40,000
    • Clinical features: short stature with large head, short arms and legs, skin creases, pronounced lumbar lordosis, and short hands with trident fingers
    • X-ray features: normal or small bone size, no increase in bone width with age

    Objectives

    • Define short stature and tall stature
    • Recognize and describe the clinical features of common syndromes with short stature
    • Understand the molecular background of specific syndromes
    • Interpret the inheritance pattern of a specific syndrome and its implications for the patient and their family

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    3_Mesenchymal differentiation and pathology of bone.docx

    Description

    This quiz covers the growth of mutant cells, formation of osteochondroma, and its progression to secondary peripheral chondrosarcoma. It also explains how normal cells can acquire mutations leading to malignancy.

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