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Org Path Exam 2 > Heme > Flashcards

Heme Flashcards

1
Q

How many RBCs does the average 70 kg man have?

A

25 Trillion

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2
Q

Average lifespan of RBCs, neutrophilic granulocytes and platelets

A

RBC-120 days
neutrophils-7 hours
platelets-8.5 days

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3
Q

Average number of RBCs, neutrophilic granulocytes and platelets produced by a 70 kg man per day

A

RBC-175 billion
neutrophils-70 billion
platelets-200 billion

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4
Q

Where are the general sites of HEMATOPOIESIS for EMBRYO, FETUS, and POST-NATAL?

A

1) YOLK SAC- EMBRYONIC – Yolk sac, until 3 mos. gestational age
2) LIVER AND SPLEEN-FETAL – Liver and spleen, (2 mos. to 7 mos. gestational age)
3) BONE MARROW –POST-NATAL- by time of birth

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5
Q

Where are the general sites of HEMATOPOIESIS for child vs. adult?

A

YOUNG CHILDREN – (“red marrow” because it looks red)
Most of marrow cavity throughout skeletal system

ADULTS – (hematopoiesis shrinks only in certain bones) 90% in marrow cavities of vertebrae, pelvis, sternum, ribs, and calvarium

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6
Q

Describe hematopoietic stem cells (HSCs) and what is so unique about them? What CDs do they express?

A
  • Very rare in marrow
  • Not morphologically recognizable
  • Express CD34, CD117
  • Unique function of ASYMMERTRIC CELL DIVISION: 1 HSC daughter and 1 multipotent progenitor cell

(these are the cells that make a lineage commitment)

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7
Q

What is the role of progenitor cells (one of the by-products of the HSC)?

A
  • Multipotent – can differentiate into all lymphoid and myeloid lineages
  • Oligopotent – common myeloid progenitor cells and common lymphoid progenitor cells
  • Lineage-restricted progenitor cells–as they gradually differentiate, they are eventually committed to one blood cell type
    (differentiation commitment)
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8
Q

Give an example of amplification in hematopoiesis.

A
  • One lineage-restricted progenitor cell, e.g. a blast forming unit-erythroid (BFU-E), gives rise to 2000 RBCs
  • Similar with WBCs
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9
Q

What is in common for all hematologic malignancies, even though there is such a wide array of them?

A

***presence of a CLONAL malignant population of cells derived from a TRANSFORMED CELL OF MARROW DERIVATION
-The transforming event may occur anywhere, but most commonly:
- a stem cell or progenitor cell in the marrow for
acute leukemias and myeloid neoplasms
- a lymphocyte in peripheral lymphoid tissues for
most lymphomas

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10
Q

Where do the transforming events most commonly occur?

A
  • may occur anywhere, but most commonly:
    • stem cell or progenitor cell –> marrow
    • lymphocyte –> peripheral lymphoid tissues
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11
Q

Why do the clonal populations of malignancies tend to have a variety of cell lineages in the neoplasm?

A

transforming event n a multipotent cell–> the clonal population includes cells of different lineages

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12
Q

What is the difference between leukemia vs. lymphoma vs. extra medullary myeloid tumor?

A

-this is terminology for how the condition manifests

Leukemia – “condition of white blood”;
chief manifestation: involvement of the BLOOD AND MARROW
-includes diseases of lymphoid and myeloid cells, both mature and immature.

Lymphoma – derived from LYMPHOCYTES or their precursors, which chiefly manifests as a solid mass
-may be nodal (e.g. enlarged lymph node(s)) or extra nodal (e.g. at sites like skin, brain, or GI tract), or both

(Note Marrow and blood usually interconnected so if one wrong then it affects other and vice versa)

Extra medullary myeloid tumor-myeloid cells or their precursors (e.g. granulocytes, monocytes, myeloblasts) which presents primarily as a solid mass

  • much less common than leukemia and lymphoma
  • Often referred to as ‘granulocytic sarcoma’ or ‘chloroma,’
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13
Q

What is an extramedullary myeloid tumor?

A

heme malignancy: composed of myeloid cells or precursors (e.g. granulocytes, monocytes, myeloblasts) which presents primarily as a solid mass
-much less common than leukemia and lymphoma

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14
Q

What happens if a neoplasm has both a leukemic and a lymphomatous component? What do you call it?

A

-may be called by different names depending on which component predominates

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15
Q

What is acute leukemia?

A
  • rapidly progressive; failed production of normal marrow cells due to the predominance of the leukemic cells
  • often presents due to problems associated with any combination of: low platelets – bleeding, bruises, hemorrhagic stroke; low neutrophils – fever, infections, malaise; low RBC – fatigue
  • RAPIDLY FATAL WITHOUT THERAPY
  • the leukemic cells are often, not always, blasts, which are often accumulating due to a block in maturation
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16
Q

What are the two chronic leukemia diseases?

A

chronic lymphocytic leukemia (CLL) or chronic myelogenous leukemia (CML)

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17
Q

How are the two chronic leukemia diseases similar?

A
  • increased WBC count (accumulation of normal blood cells)
  • insidious onset, often with no symptoms (often diagnosed incidentally)
  • natural course of disease is prolonged; small risk of transformation to higher grade disease
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18
Q

How do high grade heme malignancies present? (lymphoma and leukemia)

A

A high grade lymphoma–> rapidly enlarging mass

A high grade (acute) leukemia–> very high WBC count; near replacement of a normal cells in marrow and blood

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19
Q

How do low grade heme malignancies present? (lymphoma and leukemia

A

low grade lymphoma–> mildly enlarged lymph nodes

A low grade (chronic) leukemia–> often noted incidentally by increased WBC count on a CBC

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20
Q

How do genetic abnormalities affect the etiology of heme malignancies?

A
  • thought to be caused by MULTIPLE GENETIC INSULTS – even if a single genetic abnormality defines the disease
  • might be chromosomal abnormalities demonstrable by cytogenetic studies but many require molecular testing,
  • detecting genetic abnormalities helps with developing specific therapies
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21
Q

What type of chromosomal abnormalities are detectable in a majority of heme malignancies? e.g. MOST COMMON CHROMOSOMAL ABNORMALITY?

A

BALANCED TRANSLOCATIONS

  • Many abnormalities are persistently seen in certain heme malignancies, such as the t(9;22) in CML
  • can be a diagnostic marker
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22
Q

Are the vast majority of heme malignancies associated with a virus?

A

NO!

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23
Q

Even though the vast majority of heme malignancies are not associated with a virus, which viruses are involved in the development of some lymphomas?

A

1) Epstein-Barr virus (EBV) – some Hodgkin lymphoma, some Burkitt lymphoma, and some other B-cell NHLs
2) Human T cell leukemia virus-1 (HTLV-1) – adult T cell leukemia/lymphoma
3) Kaposi sarcoma herpesvirus/Human herpesvirus 8 (KSV/HHV-8) – primary effusion lymphoma

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24
Q

Besides viruses, chromsome abnormalities, etc. what are some predisposing factors for heme malignancies?

A
  • Primary or acquired immunodeficiencies
  • Inherited conditions of genomic instability, such as Fanconi anemia and ataxia-telangiectasia
  • Ionizing radiation exposure
  • Exposure to certain DNA-damaging chemotherapies
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25
Q

How prominent is leukemia and lymphoma regarding childhood cancers?

A
  • Leukemia=most common childhood cancer

- Lymphoma=third most common childhood cancer

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26
Q

What is the difference for classification of myeloid vs. lymphoid vs. other classification?

A

Myeloid – Resemble cells of the granulocytic, monocytic, erythroid, megakaryocytic, and/or mast cell lineages
Lymphoid – Resemble cells of the B cell, T cell, and NK cell lineages
Other – Resemble histiocytes, dendritic cells, Langerhans cells

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27
Q

What type of classification system does the WHO use for heme malignancies?

A

MULTI PARAMETER CLASSIFICATION SYSTEM to classify them into as many clinically distinct entities as possible

28
Q

What types of data does the WHO use to classify the heme malignancies?

A
  • microscopic appearance of the malignant cells
  • histologic growth patterns
  • presence/absence of specific cytogenetic/molecular findings
  • relative amount of malignant cells present in marrow or blood
  • presence or absence of certain cell surface markers, cytoplasmic markers, and/or nuclear markers
29
Q

What is the functional classification of acute leukemias?

A
  • rapidly growing malignancy, usually with a block in maturation resulting in the accumulation of immature cells in the marrow, often replacing normal marrow cells, are often accumulating in the blood as well.
  • The immature cells are often, but not always, blasts.
30
Q

What is the functional classification of MYELODYSPLASTIC SYNDROME?

A
  • group of conditions– marrow is overtaken by neoplastic clone that is incapable of making normal effective blood cells in one or more myeloid lineages (dysplasia).
  • Usually persistently low blood cell counts in one or more lineages.
31
Q

What is the functional classification of MYELOPROLIFERATIVE NEOPLASMS ?

A

0Marrow overtaken by a neoplastic clone that makes normal functioning myeloid cells, usually in multiple lineages, but makes too many in one or more lineages.

32
Q

What is the functional classification of CLASSIC HODGKIN LYMPHOMA ?

A

(now known to be derived from B cells); so unique that it remains its own broad category of heme malignancy

33
Q

What is the functional classification of NON-HODGKIN LYMPHOMA ?

A

-ALL the different malignancies of mature lymphocytes, EXCLUDING classical Hodgkin lymphoma and plasma cell malignancies
subdivided into:
- B cell NHLs (much more common)

         -T cell / NK cell NHLs (much less common)
34
Q

What is the functional classification of PLASMA CELL NEOPLASMS ?

A

includes MGUS, plasmacytoma, and multiple myeloma

35
Q

What are other types of classifications of heme neoplasms?

A

Histiocytoses, dendritic cell tumors, and other rare entities

36
Q

Are patients likely to die fast if they have a low grade heme malignancy? What is the treatment?

A

No. They are more likely to die WITH their disease than due to their disease, thus therapy might include: - no therapy

  • treating of symptoms
  • surveillance for significant disease progression
37
Q

What are treatments like for aggressive, high grade heme malignancies?

A
  • based on age, the patient’s performance status (i.e. how healthy they are), and the stage of the disease:
  • Chemotherapy alone
  • Chemotherapy with radiation therapy
  • Stem cell transplant (w/ conditioning chemotherapy)
  • Palliative treatments
38
Q

Is surgery appropriate for heme malignancies?

A

ONLY IN RARE SITUATIONS

39
Q

What type of heme malignancies may be present in in oral/dental areas?

A
  • NON-HODGKIN LYMPHOMA: Many different types (B cell, T cell, NK cell); high grade and low grade
  • ACUTE LEUKEMIA: Both AML and ALL, usually with blood/marrow involvement (i.e. actual leukemia) but sometimes just with oral lesions
  • PLASMA CELL NEOPLASMS
  • CLASSICAL HODGKIN LYMPHOMA (rarely)
  • OTHER WEIRD HEMATOLOGIC MALIGNANCIES
    (e. g. histiocytoses, dendritic cell tumors)
40
Q

Why do we use bone marrow biopsies for heme malignancies?

A
  • -helps determine the cellularity of the marrow, as well as for performing a marrow cell differential
  • May detect focal lesions in the marrow, e.g. granulomas or metastatic carcinoma
  • May evaluate how well the different lineages appear to be developing/maturing
  • Done for staging with a new diagnosis of lymphoma
  • Done to follow disease status in patient’s believed to be in remission, or to monitor the efficacy of a treatment
41
Q

What are the most common clinical presentations of acute leukemias? What causes these symptoms?

A

-usually result from replacement of the normal marrow cells by leukemic cells.

The they might include:

  • Symptoms of anemia: fatigue, malaise, pallor, dyspnea
  • symptoms of thrombocytopenia: bruising, petechiae, hemorrhage
  • Symptoms of neutropenia: fever, infections
42
Q

On the rare occasions that clinical presentations of acute leukemia is attributable to leukemic cells themselves (rather than replacement of normal bone marrow cells), what are the clinical signs and symptoms?

A
  • thrombotic events due to increased blood viscosity in patients with very high WBC counts (leukostasis) –disseminated intravascular coagulation (DIC), which can be initiated by the leukemic cells in some types of AML - direct infiltration of skin, gums, and/or lymph nodes by leukemic cells
43
Q

What is acute lymphoblastic leukemia (epidemiology)?

A

Neoplasms of PRECURSOR LYMPHOID CELLS (ALL); less commonly manifest as a solid mass, referred to as lymphoblastic lymphoma.

  • ALL is divided into two types:
    • B-lymphoblastic ALL (B-ALL) (85%)
    • T-lymphoblastic ALL (T-ALL) (15%)
  • ALL has an incidence of 1-5 cases / 100K person/ yr
44
Q

75% of cases for ALL (acute lymphoblastic leukemia) occurs in what age group?

A

CHILDREN LESS THAN 6 years old

45
Q

How do you diagnose acute lymphoblastic leukemia(ALL)?

A
  • usually see blasts as a majority of marrow cells (“packed marrow”), thus there is no set percentage of blasts required to diagnosis ALL
  • Peripheral WBC count may be markedly increased, mildly increased, normal, or decreased
  • Determination of blast type (myeloblast v. lymphoblast, as well as B-lymphoblast v. T-lymphoblast) requires IMMUNOPHENOTYPING
46
Q

Describe B-LYMPHOBLASTIC ALL (B-ALL) and what percentage of ALL cases is it?

A

-80-85% of cases of ALL
Besides expressing B cell-lineage antigens, B-lymphoblasts usually lack markers of mature B cells, such as CD20 and surface immunoglobulin
-B-ALL is the typical ALL of childhood

47
Q

Describe T-LYMPHOBLASTIC ALL (T-ALL) and what percentage of ALL cases is it?

A
  • 25% of cases of ALL
    When compared to B-ALL…..
    1) T-ALL more in adolescents and young adults 2) T-ALL more frequently presents with a component of T-lymphoblastic lymphoma (T-LBL),
    –> OFTEN PRESENT AS MEDIASTINAL MASS
    3) T-ALL is more likely to have markedly elevated WBC count than B-ALL
    4) T-ALL FAVORS MALES over females
48
Q

What is the therapy/prognosis for acute lymphoblastic leukemia (ALL)?

A

Children: “good prognosis disease,” with…

  • complete remission rates of >95%
  • cure rates around 80%

In adults, the prognosis is worse than for children, with …

  • complete remission rates of 60-80%
  • cure rates of
49
Q

Describe acute myeloid leukemia generally and contrast with ALL?

A

-much more heterogeneous disease than ALL

AML is typically a disease of adults:

  • average age at diagnosis of AML: 65
  • only ~10% of childhood leukemias are AML
  • AML incidence is around 3 cases per 100K persons per year (similar to ALL)
50
Q

Describe the diagnosis of acute myeloid leukemia–how is it identified?

A

-Most cases diagnosed from the presence of ≥20% myeloblasts in the marrow and/or peripheral blood.

This can be done by: - -IDing blasts by morphologic appearance and performing a differential count on marrow or peripheral smear

  • flow cytometry of marrow aspirate or peripheral blood
  • immunohistochemistry on a marrow core biopsy
51
Q

How is acute myeloid leukemia categorized?

A
  • priorly categorized based on how blasts looked
  • NOW categorized by recurrent cytogenetic findings of prognostic importance, though cases lacking these findings are still categorized based on what the blasts look like
52
Q

For purposes of identifying AML, what do myeloblasts look like?

A

-typically have the generic appearance of a blast, and cannot be definitely differentiated from lymphoblasts based on morphology alone

53
Q

What do some cases of AML (acute myeloid leukemia) show for their myeloblasts?

A

AUER RODS–in some cases—allowing their identification as myeloblasts by morphology alone

54
Q

What is the dental correlation for acute myeloid leukemia?

A

AML with monocytic differentiation is often associated with skin and/or gingival lesions due infiltration of the leukemic monoblasts/monocytes

55
Q

What is the therapy and prognosis for acute myeloid leukemia?

A
  • Prognosis is heterogeneous/varied, with mean survival times ranging from 10 years for favorable risk AML
  • Approximate complete remission rate of 60%
  • If patients are healthy enough, hematopoietic stem cell transplant (SCT) is the best therapy for younger patients, patients with high risk, and relapsed patients
56
Q

What is MYELODYSPLASTIC SYNDROME? (MDS)

A
  • misnomer–disease–not a syndrome
  • group of clonal hematopoietic stem cell diseases characterized by one or more peripheral cytopenia(s), dysplasia in one or more myeloid cell line, and ineffective hematopoiesis
  • has a strong risk of progression to acute myeloid leukemia (AML) (In effect, a precursor to AML)
  • typically occurs in older patients
  • can be seen a few years after certain types of DNA-damaging chemotherapy, in which case it is referred to as therapy-related MDS
57
Q

What are the two main categories of MYELODYSPLASTIC SYNDROME?

A
  • various categories but two main ones
    1) Low grade MDSz: no significant increase in myeloblasts in blood or marrow
    2) High grade MDS: significant increase of myeloblasts in the blood an/or marrow but still less than 20% blasts
58
Q

What are the cytogenetics of MDS?

A

Monosomy 7 or del 7q and monosomy 5 are associated with therapy-related MDS, and have a bad prognosis

59
Q

What is the prognosis of MDS?

A

Low grade MDS –> median survival of several years

high grade MDS–>very poor prognosis; median survivals of around one year or less

60
Q

What is therapy related AML (t-AML) and/or MDS (t-MDS)? Is the prognosis good or bad?

A

-AML or MDS arising secondary to DNA damage from a prior therapy.
t-AML accounts for 10-20% of AML
-BAD PROGNOSIS

61
Q

Discuss MYELOPROLIFERATIVE NEOPLASMS generally

A
  • Clonal hematopoietic stem cell disorders with proliferation of one or more of the myeloid lineages (granulocytic, erythroid, megakaryocytic, or mast cell)
  • Early disease shows hypercellular marrow with hematopoietic maturation and increased numbers of cells of one or more lineages in the peripheral blood
  • Splenomegaly and hepatomegaly are common
  • May progress to marrow fibrosis with marrow failure, or may transform to an acute leukemia
  • transformation of an MPN to an acute leukemia in termed ‘blast phase’ or ‘blast crisis.’
62
Q

What is Chronic myelogenous leukemia (CML)?

A
  • MPN associated with the BCR-ABL1 fusion gene on the Philadelphia chromosome (t(9;22), leading to consistutive activation of the ABL tyrosine kinase protein
  • Diagnosis by increased WBCs, due to increased neutrophilic granulocytes
  • Most diagnosed in ‘chronic phase,’ where blasts represent less than 10% of blood and marrow cells.
  • CML with 10-19% blasts in the blood and/or marrow is termed ‘accelerated phase’; with more than 20% blasts in blood and/or marrow is termed ‘blast phase,’ and is essentially a transformation to an acute leukemia.
63
Q

What is the cell situation like in chronic myelogenous leukemia?

A
  • WBC count may range from 12,000 to 1,000,000 (median is about 100,000) (upper end of normal limit is 11,000)
  • Segmented (mature) neutrophils and myelocytes are the most frequent granulocyte types in the peripheral blood (unlike a leukemoid reaction, where segmented neutrophils and bands are the most common granulocyte types, with much fewer myelocytes)
  • There is also a prominent associated basophilia
64
Q

What is the drug breakthrough for chronic myelogenous leukemia?

A
  • Small molecular inhibitors of protein tyrosine kinases (PTKIs) are a major breakthrough (e.g.: imatinib (Gleevec))
  • With these, 5 year survival is around 90%
65
Q

What are some other myeloproliferative neoplasms?

A

Polycythemia vera – increased RBC mass (as well as increased WBCs and platelets), 100% with JAK2 mutation
Essential thrombocythemia – normal RBC, massively increased platelet count, 50% with JAK2 mutation
Primary myelofibrosis – initially increased WBCs and platelets, decrease as marrow becomes fibrotic

66
Q

What are the common end points of myeloproliferative neoplasms?

A
  • Severe marrow fibrosis -> pancytopenia -> complications of pancytopenia (infections, bleeding, etc.)
  • Transformation to acute leukemia
  • Death from unrelated cause
  • Death from related cause (thrombosis, hemorrhage, etc.)

Org Path Exam 2 (8 decks)

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