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Pathology > Diseases Of White Blood Cells, Lymph Nodes, Spleen, And Thymus > Flashcards

Diseases Of White Blood Cells, Lymph Nodes, Spleen, And Thymus Flashcards

1
Q

What is the ratio fat cells/ hemopoietic elements in the bone marrow of normal adults?

A

1:1

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2
Q

What is the general classification of the disorders of white blood cells?

A
  1. Proliferative disorders (reactive and neoplastic)

2. Leukopenias

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3
Q

What is the pathogenetic basis of agranulocytosis (neutropenia)?

A
  1. Inadequate or ineffective granulopoiesis

2. Accelerated removal of neutrophils from the blood.

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4
Q

When is inadequate or ineffective granulopoiesis observed?

A
  1. Suppression of hematopoietic stem cells.
  2. Suppression of committed granulocytic precursors.
  3. Diseases associated with ineffective hematopoiesis.
  4. Rare congenital conditions (Kostmann syndrome).
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5
Q

When does accelerated removal or destruction of neutrophils occur?

A
  1. Immunologically mediated injury to neutrophils.
  2. Splenomegaly
  3. Increased peripheral utilization.
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6
Q

What are the factors that influence the peripheral blood leukocyte count?

A
  1. The size of the myeloid and lymphoid precursor and storage cell pools in the bone marrow.
  2. The rate of release of cells from the storage pools into the circulation.
  3. The proportion of cells that are adherent to blood vessels at any time.
  4. The rate of extravasation of the cells from the blood into the tissues.
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7
Q

What are the Döhle bodies?

A

Patches of dilated ER that appear as sky-blue cytoplasmic “puddles” - morphologic change of the neutrophils in leukocytosis.

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8
Q

What are the cases in which it is difficult to distinguish reactive from neoplastic leukocytoses?

A
  1. Acute viral infection (in children)

2. Severe infections : many immature granulocytes appear in the blood.

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9
Q

What are the morphologic features in acute nonspecific lymphadenitis?

A
  1. Nodes are swollen, gray-red and engorged.
  2. Large reactive germinal centers containing numerous mitotic figures.
  3. Appearance of pus.
  4. Neutrophilic infiltration and endothelial hyperplasia.
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10
Q

In follicular hyperplasia, what are the two main regions in the germinal center?

A
  1. A dark zone, containing proliferating blastlike B cells (centroblasts).
  2. A light zone composed of B cells with irregular or cleaved nuclear contours (centrocytes).
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11
Q

What are the main causes for follicular hyperplasia?

A
  1. Rheumatoid arthritis
  2. Toxoplasmosis
  3. Early stages of HIV infection
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12
Q

What is sinus histiocytosis (also reticular hyperplasia)?

A

Refers to an increase in the number and size of the cells that line lymphatic sinusoids.

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13
Q

What is the general classification of malignancies of WBC?

A
  1. Lymphoid neoplasms
  2. Myeloid neoplasms : acute myeloid leukemia + myelodysplastic syndromes + chronic myeloproliferative disorders.
  3. Histiocytoses
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14
Q

What are the main general genetic abnormalities that occur in the pathogenesis of white cell neoplasms?

A
  1. Nonrandom chromosomal abnormalities (mostly translocations).
  2. Mutated genes are important for development, growth, differentiation of WBCs.
  3. Oncoproteins often block normal maturation.
  4. Proto-oncogenes are often activated in lymphoid cells by errors that occur during antigen receptor rearrangement and diversification.
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15
Q

What are the three lymphotropic viruses that have been implicated as causative agents in particular lymphomas?

A
  1. EBV
  2. HTLV-1 (human T-cell leukemia virus)
  3. Kaposi sarcoma herpesvirus / HHV-8.
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16
Q

What are the five broad categories of lymphoid neoplasms?

A
  1. Precursor B-cell neoplasms
  2. Peripheral B-cell neoplasms
  3. Precursor T-cell neoplasms
  4. Peripheral T-cell and NK-cell neoplasms
  5. Hodgkin lymphoma (neoplasms of Reed-Sternberg cells and variants)
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17
Q

Mention 6 important principles relevant to the lymphoid neoplasms.

A
  1. Histologic examination required for diagnosis.
  2. In most lymphoid neoplasms, antigen receptor gene rearrangement precedes transformation.
  3. Vast majority are B cell neoplasms.
  4. Lymphoid neoplasms are often associated with immune abnormalities.
  5. Neoplastic T and B cells tend to recapitulate the behavior of their normal counterparts.
  6. Hodgkin lymphoma spreads in an orderly fashion.
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18
Q

What is acute lymphoblastic leukemia/lymphoma (ALL)?

A

Neoplasms composed of immature B or T cells, which are referred to as lymphoblasts.

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19
Q

What is the most common cancer in children?

A

ALL

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20
Q

Describe briefly the immunophenotype of ALLs?

A

TdT - specialized DNA polymerase expressed only in pre-B and pre-T.
B-ALL : CD19 and PAX5.
T-ALL : CD1-2-5-7.

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21
Q

What is the basis of molecular pathogenesis in ALLs?

A

90% have numerical or structural chromosomal changes (hyperploidy, hypoploidy, or balanced chromosomal translocations).

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22
Q

What are the main clinical features in ALL (very close to AML clinically)?

A
  1. Abrupt stormy onset (days to few weeks of the first symptom).
  2. Symptoms related to depression of marrow function.
  3. Mass effects caused by neoplastic infiltration.
  4. CNS manifestations
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23
Q

Mention 4 factors that are associated with a worse prognosis in ALL.

A
  1. Age under 2.
  2. Presentation in adolescence or adulthood.
  3. Peripheral blood blast counts greater than 100.000, which probably reflects a high tumor burden.
  4. The presence of particular cytogenetic aberrations (such as t(9;22) - Philadelphia chromosome).
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24
Q

Mention 5 favorable prognostic markers in ALL.

A
  1. An age of 2-10 years.
  2. Low white cell count.
  3. Hyperploidy
  4. Trisomy of chromosomes 4,7,10
  5. Presence of a t(12;21).
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25
Q

What is the difference between chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL) (both peripheral B-cell neoplasms)?

A

Only in the degree of peripheral blood lymphocytosis. (>4000 per mm3).

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26
Q

What are the morphologic features in CLL/SLL?

A
  1. Infiltration of lymph nodes with small lymphocytes admired with variable larger activated lymphocytes.
  2. These cells often gather in loose aggregates, the proliferation centers.
  3. These centers are pathognomonic for CLL/SLL.
  4. Smudge (disrupted) cells in the smear.
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27
Q

What is the immunophenotype in CLL/SLL?

A
  1. Classic : CD19-20 as well as CD23-5 (CD5 on a small subset of normal B cells).
  2. Low level Ig expression is also typical.
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28
Q

What does most commonly happen in the molecular pathogenesis of CLL/SLL?

A

Unlike most other lymphoid malignancies, not translocations, but deletions.

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29
Q

What are the principal clinical features of CLL/SLL?

A
  1. Asymptomatic at diagnosis
  2. Nonspecific symptoms when appear.
  3. Lymphadenopathy and hepatosplenomegaly.
  4. Highly variable leukocyte count
  5. Variable course and prognosis
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30
Q

Mention 4 facts in patients with CLL/SLL that favor a worse outcome.

A
  1. Deletions of 11q and 17p
  2. Lack of somatic hypermutation
  3. Expression of ZAP-70 (protein that augments signals produced by Ig receptor.
  4. Tendency to progress to more aggressive tumors - richter syndrome.
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31
Q

What is the most common form of indolent NHL ?

A

Follicular lymphoma

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32
Q

What happens briefly in follicular lymphoma ?

A

The tumor likely arises from germinal center B cells and is strongly associated with chromosomal translocation of BCL2.

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33
Q

What are the two principal cell types that are present in follicular lymphoma in varying proportions?

A
  1. Small cells with irregular or cleaved nuclear contours and scant cytoplasm, referred to as centrocytes (small cleaved cells).
  2. Larger cells with open nuclear chromatin, several nucleoli and modest amount of cytoplasm (centroblasts).
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34
Q

What is the hallmark of follicular lymphoma?

A

A 14;18 translocation that juxtaposes the IgH locus on chromosome 14 and the BCL2 locus on chromosome 18 - leading to overexpression of BCL2.

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35
Q

What are the major clinical features of follicular lymphoma?

A
  1. Painless generalized lymphadenopathy.
  2. Extra nodal involvement is uncommon.
  3. Survival 7-9 years.
  4. Histologic transformation occurs in 30% to 50% (commonly to diffuse large B-cell lymphoma).
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36
Q

What is the most common form of NHL?

A

Diffuse large B-cell lymphoma

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37
Q

What is the most common morphologic feature of diffuse large B-cell lymphoma?

A

Relatively large size (usually four to five times the diameter of a small lymphocyte) and diffuse pattern of growth.

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38
Q

Mention a frequent pathogenic event in the molecular pathogenesis of large diffuse B-cell lymphoma.

A

Dysregulation of BCL6 (DNA zinc finger transcriptional repressor required for the formation of normal germinal centers).

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39
Q

Mention two important subtypes of DLBCL.

A
  1. Immunodeficiency-associated large B-cell lymphoma.

2. Primary effusion lymphoma

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40
Q

What are the main clinical features of DLBCL?

A
  1. Typically presents as a rapidly enlarging mass as a nodal or extranodal site.
  2. It can arise anywhere - lymphoid tissue involved commonly.
  3. Aggressive tumor, rapidly fatal without treatment.
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41
Q

What types of Burkitt lymphoma exist?

A
  1. African (endemic) Burkitt lymphoma
  2. Sporadic (nonendemic) Burkitt lymphoma
  3. Subset of aggressive lymphomas occurring in individuals infected with HIV.
    All histologically identical, but differ in some clinical, genotypic, and virologic characteristics.
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42
Q

What are the main morphologic feature of Burkitt lymphoma?

A
  1. Diffuse infiltrate of intermediate-sized lymphoid cells.
  2. High mitotic index and numerous apoptotic cells.
  3. Starry sky pattern - abundant clear cytoplasm of phagocytes.
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43
Q

What is the main pathogenic event in the molecular pathogenesis of Burkitt lymphoma?

A

Translocations of the c-MYC gene on chromosome 8.

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44
Q

What is the most common plasma cell neoplasm?

A

Multiple myeloma

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45
Q

What terms are used to describe abnormal Igs in plasma cell neoplasms?

A
  1. Monoclonal gammopathy
  2. Dysproteinemia
  3. Paraproteinemia
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46
Q

What are the 5 principal clinicopathologic entities associated with monoclonal gammopathies?

A
  1. Multiple myeloma
  2. Waldenström macroglobulinemia
  3. Heavy chain disease
  4. Primary or immunocyte-associated amyloidosis.
  5. Monoclonal gammopathy of undetermined significance.
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47
Q

What is multiple myeloma?

A

A plasma cell neoplasm that is characterized by multifocal involvement of the skeleton.

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48
Q

What cytokine plays a critical role in multiple myeloma for the proliferation and survival of myeloma cells?

A

IL-6

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49
Q

How myeloma cells lead to bone destruction (main pathologic feature of multiple myeloma)?

A

Via the myeloma derived MIP-1α - induces RANKL - osteoclasts.

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50
Q

What are the most commonly affected bones in multiple myeloma?

A
  1. Vertebral column
  2. Ribs
  3. Skull
  4. Pelvis
  5. Femur
  6. Clavicle
  7. Scapula
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51
Q

From where are the main clinical features of multiple myeloma stem?

A
  1. Effect of plasma cell growth in tissues (particularly bones)
  2. Production of excessive Igs - abnormal physicochemical properties.
  3. Suppression of normal humoral immunity.
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52
Q

What are the main clinical features of multiple myeloma?

A
  1. Bone absorption : lead to pathologic fractures and chronic pain.
  2. Hypercalcemia
  3. Recurrent bacterial infections
  4. Renal insufficiency - multifactorial - Bence-Jones proteinuria.
  5. Certain light chains are prone to amyloidosis.
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53
Q

What other myelomas progress inevitably to multiple myeloma?

A
  1. Solitary myeloma (plasmacytoma)
  2. Smoldering myeloma
  3. MGUS
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54
Q

What is the most common plasma cell dyscrasia?

A

Monoclonal gammopathy of uncertain significance (MGUS).

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55
Q

What happens in lymphoplasmacytic lymphoma?

A
  1. B-cell neoplasm of older adults.
  2. Superficial resemblance with CLL/SLL - but the tumor cells differentiate to plasma cells.
  3. Secretion of IgM
  4. Hyperviscosity syndrome (Waldenström macroglobulinemia)
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56
Q

What are the main clinical features of lymphoplasmacytic lymphoma?

A
  1. Nonspecific complaints (weakness, fatigue)
  2. Half the patients : lymphadenopathy, hepatomegaly and splenomegaly.
  3. Autoimmune hemolysis: cold agglutinins
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57
Q

What characterizes the hyperviscosity syndrome?

A
  1. Visual impairment
  2. Neurologic problems
  3. Bleeding
  4. Cryoglobulinemia
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58
Q

What is the major immunophenotype in mantle cell lymphoma?

A
  1. High levels of cyclin D1.
  2. CD19
  3. CD20
  4. Moderately high levels of surface Ig.
  5. CD5+ and CD23- distinguish from CLL/SLL.
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59
Q

What is the basis Of the molecular pathogenesis in mantle cell lymphoma?

A

Cyclin D1 overexpression caused by an (11;14) translocation involving the IgH locus on chromosome 14 and the cyclin D1 locus on chromosome 11.

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60
Q

What are the three exceptional characteristics of the marginal zone lymphomas occurring at extranodal sites?

A
  1. Often in tissue with chronic inflammation disorders of autoimmune or infectious etiology (Sjögren salivary gland, Hashimoto thyroiditis).
  2. Remain localized for prolonged periods - only terminally spreading.
  3. They may regress if the inciting agent is eradicated.
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61
Q

Describe briefly what is a peripheral T-cell lymphoma?

A
  1. Tumors of the mature T cells
  2. Efface lymph nodes diffusely
  3. Composed of pleomorphic mixture of variable sized malignant T cells.
  4. Infiltrate of eosinophils, macrophages
  5. Brisk angiogenesis
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62
Q

What is the immunophenotype of peripheral T cell lymphoma?

A
  1. That of mature T cells.
  2. CD2-3-5
  3. Either αβ or γδ T cell receptors.
  4. Some also CD4-8 (helper or cytotoxic origin)
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63
Q

What are the symptoms in peripheral T cell lymphoma, unspecified?

A
  1. Generalized lymphadenopathy
  2. Eosinophilia
  3. Pruritus (sort of itching)
  4. Fever
  5. Weight loss
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64
Q

What is the genetic aberration in anaplastic large-cell lymphoma (ALK positive)?

A

This uncommon entity is defined by the presence of rearrangements in the ALK gene on chromosome 2p23.

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65
Q

What is the reliable indicator in anaplastic large-cell lymphoma?

A

The presence of ALK protein in tumor cells, because ALK is not expressed in normal T cells or other lymphomas.

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66
Q

What virus is associated with adult T cell leukemia/lymphoma?

A

This neoplasm of CD4+ T cells is only observed in adults infected by human T cell leukemia retrovirus type I (HTLV-1).

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67
Q

What are the common findings in adult T cell leukemia/lymphoma?

A
  1. Skin lesions
  2. Generalized lymphadenopathy
  3. Hepatosplenomegaly
  4. Peripheral blood lymphocytosis
  5. Hypercalcemia
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68
Q

Describe briefly what is mycosis fungoides?

A
  1. Tumor of CD4+ T cells that home to skin.
  2. Three-stage progression : premycotic - plaque - tumor.
  3. Infiltration of epidermis and upper dermis by neoplastic T cells.
  4. Cerebrifrom appearance of T cells.
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69
Q

Describe briefly what is Sezary syndrome?

A
  1. A variant of mycosis fungoides - generalized exfoliative erythroderma.
  2. Leukemia of “Sezary” cells with characteristic cerebriform nuclei.
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70
Q

What is the immunophenotype in mycosis fungoides/Sezary syndrome ?

A
  1. Adhesion molecule CLA.

2. Chemokine receptors CCR4 and CCR10

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71
Q

Describe briefly what is large granular lymphocytic leukemia.

A
  1. Rare neoplasm of T cell/NK cells.
  2. Mild/moderate lymphocytosis and splenomegaly (T cell variant).
  3. Absent lymphadenopathy and hepatomegaly.
  4. Tumor cells : large lymphocytes with abundant blue cytoplasm and a few coarse azurophilic granules.
  5. T cell variant : CD3+
  6. NK cell variant : CD3- and CD56+.
  7. Neutropenia and anemia dominate the clinical picture.
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72
Q

What is the hallmark morphologic feature of Hodgkin lymphoma?

A

The presence of neoplastic giant Reed-Sternberg cells.

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73
Q

What are the 4 principal differences between NHL and HL?

A
  1. HL is more often localized to a single axial group of nodes (cervical, mediastinal, para-aortic).
  2. HL spreads orderly by contiguity.
  3. In HL mesenteric nodes and Waldeyer ring rarely involved.
  4. Extra-nodal presentation rare in HL.
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74
Q

What are the 5 subtypes of HL?

A
  1. Nodular sclerosis
  2. Mixed cellularity
  3. Lymphocyte-rich
  4. Lymphocyte depletion
  5. Lymphocyte predominance
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75
Q

Describe briefly the morphologic features of Reed-Sternberg cells.

A
  1. Large cells (>45μm)
  2. Multiple nuclei or single nucleus with multiple lobes.
  3. Large inclusion-like nucleolus about the size of a small lymphocyte.
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76
Q

Describe briefly the features of nodular sclerosis type of HL.

A
  1. Most common (65-70%)
  2. Presence of lacuna variant Reed-Sternberg cells.
  3. Deposition of collagen in bands that divide involved lymph nodes into circumscribed nodules.
  4. Fibrosis may be scant or abundant.
  5. Reed-Steinberg cells are found in a polymorphous background of inflammatory cells.
  6. Positive for PAX5, CD15-30.
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77
Q

What is the basis of the molecular pathogenesis in HL ?

A

The Ig genes of Reed-Sternberg cells have undergone both V(D)J recombination and somatic hypermutation, establishing an origin from a germinal center or post-germinal-center B cell.
+ activation of NF-kB is common.

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78
Q

Mention some important clinical features of HL.

A
  1. Presents as painless lymphadenopathy.
  2. Stages III and IV are more likely to have fever, night sweats and weight loss.
  3. Immune dysregulation
  4. Stereotyped spreading : nodal disease - splenic disease - hepatic disease - marrow and other tissues.
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79
Q

What is the common feature of myeloid neoplasms?

A

An origin from hematopoietic progenitor cells.

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80
Q

What are the three main categories of myeloid neoplasms?

A
  1. Acute myeloid leukemias : accumulation of immature myeloid forms (blasts) in the bone marrow suppresses normal hematopoiesis.
  2. Myelodysplastic syndromes : ineffective hematopoiesis leads to cytopenias.
  3. Myeloproliferative disorders : increased production of one or more types of blood cells.
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81
Q

What factors influence principally the specific manifestations of different myeloid neoplasms?

A
  1. The position of the transformed cells within the hierarchy of progenitors.
  2. The effect of the transforming events on differentiation.
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82
Q

What is acute myeloid leukemia?

A

A tumor of hematopoietic progenitors caused by acquired oncogenic mutations that impede differentiation, leading to the accumulation of immature myeloid blasts in the marrow.

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83
Q

On what is the diagnosis of AML based?

A

The presence of at least 20% myeloid blasts in the bone marrow.

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84
Q

What is the basis in the molecular pathogenesis of AML?

A

Genetic aberrations that disrupt genes encoding transcription factors that are required for normal myeloid differentiation.

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85
Q

Mention some important clinical features of AML.

A
  1. Within weeks or few months with complaints about anemia, neutropenia, thrombocytopenia.
  2. Fatigue, fever
  3. Spontaneous mucosal and cutaneous bleeding.
  4. Findings similar to ALL.
  5. Frequent infections.
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86
Q

What are the myelodysplastic syndromes?

A

A group of clonal stem cell disorders characterized by maturation defects that are associated with ineffective hematopoiesis and a high risk of transformation to AML.

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87
Q

Mention the most important morphologic features of myelodysplastic syndromes?

A
  1. Marrow is usually hypercellular (it can also be normocellular, and rarely hypocellular).
  2. Disordered (dysplastic) differentiation affecting all cell lineages to varying degrees.
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88
Q

Describe briefly the clinical course of myelodysplastic syndromes.

A
  1. Age of onset is 70 years.
  2. Up to half patients is discovered incidentally on routine blood testing.
  3. When symptomatic : weakness, infections, hemorrhages, all due to pancytopenia.
  4. Median survival varies from 9-29 months.
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89
Q

What is the common pathogenic feature of myeloproliferative disorders?

A

The presence of mutated, constitutively activated tyrosine kinases.

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90
Q

What is the major result of the mutated tyrosine kinases found in the myeloproliferative disorders?

A

They circumvent normal and lead to the growth-factor independent proliferation and survival of marrow progenitors. They do not impair differentiation.

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91
Q

What are the 4 main common features among the myeloproliferative disorders?

A
  1. Increased proliferative drive in the bone marrow.
  2. Extramedullary hematopoiesis - homing of neoplastic stem cells to secondary hematopoietic organs.
  3. Marrow fibrosis and peripheral blood cytopenias.
  4. Variable transformation to acute leukemia.
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92
Q

What is more common? Lymphopenia or granulocytopenia?

A

Lymphopenia

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93
Q

Under what circumstances is lymphopenia observed?

A
  1. In advanced HIV infection.
  2. In congenital immunodeficiency diseases.
  3. Following therapy with glucocorticoids / cytotoxic drugs.
  4. In autoimmune disorders.
  5. In malnutrition.
  6. In certain acute viral infections (induced production of type I interferon).
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94
Q

What is the most common cause of agranulocytosis?

A

Drug toxicity

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95
Q

What drugs can result in agranulocytosis?

A
  1. Aminopyrine
  2. Chloramphenicol
  3. Sulfonamides
  4. Thiouracil
  5. Phenylbutazone
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96
Q

What is observed in acquired idiopathic neutropenia ?

A

Autoantibodies directed against neutrophil-specific antigens are detected.

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97
Q

What is the common consequence of agranulocytosis ?

A

Infections

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98
Q

What is the neutrophil count for serious infections to occur?

A

Below 500 per mm3.

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99
Q

What can cause increased production of leukocytes in the marrow?

A
  1. Chronic infection/inflammation.
  2. Paraneoplastic (Hodgkin lymphoma).
  3. Myeloproliferative disorders (CML).
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100
Q

What can cause increased release of leukocytes from marrow stores?

A
  1. Endotoxemia
  2. Infection
  3. Hypoxia
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101
Q

What can lead to decreased margination of leukocytes?

A
  1. Exercise

2. Catecholamines

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102
Q

What can lead to decreased extravasation of leukocytes?

A

Glucocorticoids

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103
Q

What can cause neutrophilia ?

A
  1. Acute bacterial infections, especially those caused by pyogenic organisms.
  2. Sterile inflammation caused by, for example, tissue necrosis (myocardial infarction, burns).
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104
Q

What can cause eosinophilia?

A
  1. Allergic reactions - asthma, hay fever.
  2. Certain skin diseases - pemphigus, dermatitis herpetiformis.
  3. Parasitic infestations.
  4. Drug reactions.
  5. Certain malignancies (Hodgkin and some NHL).
  6. Collagen vascular disorders + some vasculitides.
  7. Transient atheroembolic disease.
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105
Q

What can cause basophilia?

A

It is rare, often indicative of a myeloproliferative disease (CML).

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106
Q

What can cause monocytosis?

A
  1. Chronic infections (TB).
  2. Bacterial endocarditis.
  3. Rickettsiosis and malaria.
  4. Collagen vascular diseases (SLE).
  5. Inflammatory bowel diseases (ulcerative colitis).
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107
Q

What can cause lymphocytosis?

A
  1. Accompanies monocytosis in many chronic immunological disorders.
  2. Viral infections (hep A, CMV, EBV).
  3. Bordetella pertussis infection.
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108
Q

Are the lymph nodes in adults normal? :)

A

No, the lymph nodes are never “normal” or “resting”.

Trivial injuries and infections induce subtle changes.

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109
Q

What is the most common cause of acute nonspecific lymphadenitis in the cervical/inguinal-axillary regions?

A

Cervical region : most often due to microbial drainage from the teeth, tonsils.
Axillary/inguinal regions : due to infections in the extremities.

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110
Q

What is follicular hyperplasia?

A

It is defined by the presence of large oblong germinal centers (secondary follicles), which are surrounded by a collar of small resting naive B cells (the mantle zone).
It is caused by stimuli that activate humoral immune responses.

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111
Q

What are the tingible-body macrophages?

A

Interspersed between the germinal B centers is an inconspicuous network of antigen presenting follicular dendritic cells and macrophages (tingible-body macrophages).
These macrophages contain the nuclear debris of B cells, which undergo apoptosis, if they fail to produce an antibody with a high affinity for antigen.

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112
Q

What observations favor a follicular hyperplasia instead of a follicular lymphoma?

A
  1. Preservation of the lymph node architecture.
  2. Marked variation in the shape and size of the follicles.
  3. Presence of frequent mitotic figures, phagocytic macrophages, and recognizable light and dark zones (all of which tend to be absent from neoplastic follicles).
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113
Q

In what malignant tumor is sinus histiocytosis (also called reticular hyperplasia) observed?

A

Although non specific, this form of hyperplasia may be prominent in lymph nodes draining cancers, such as carcinoma of the breast.

114
Q

Mention one classic example of chronic immune reaction that promotes the appearance of organized collections of immune cells in non lymphoid tissues.

A

Chronic gastritis causes by Helicobacter pylori.

115
Q

What cytokine is probably involved in the formation of these extranodal inflammation-induced collections of lymphoid cells.

A

Lymphotoxin

116
Q

What is the genetic abnormality in MALTomas (B cell lymphomas occurring in extranodal mucosal sites)?

A

Translocations involving the MALT1 or the BCL10 gene.

Dysregulation of the MALT1/BCL10 complex that causes constitutive activation of NF-kB.

117
Q

What is the AID (activation-induced cytosine deaminase)?

A

A specialized DNA-modifying enzyme.

It is up-regulated after antigen stimulation in the germinal B cells.

118
Q

What is the importance of AID?

A

It is essential for two types of Ig gene modifications :

  1. Class switching.
  2. Somatic hypermutation - create point mutations within the Ig genes that may by chance increase antibody affinity for antigen.
119
Q

Mention some inherited genetic conditions that increase the risk of leukemias.

A
  1. Bloom syndrome
  2. Fanconi anemia
  3. Ataxia telangiectasia
  4. Down syndrome
  5. Type 1 neurofibromatosis
120
Q

What is the most common clinical presentation of NHLs? (Briefly)

A

2/3 of NHLs (and virtually all HLs) present as enlarged nontender lymph nodes (often >2cm).
The remaining 1/3 of NHLs presents with symptoms related to extranodal sites (skin, stomach, brain).

121
Q

How do the lymphocytic leukemias most often come to attention?

A

Because of signs and symptoms related to the suppression of normal hematopoiesis by tumor cells in the bone marrow.

122
Q

What percentage of acute lymphoblastic leukemias are B-ALL?

A

85% - typically childhood acute leukemias.

123
Q

When do the less common T-ALL tend to present?

A

In adolescent males as thymic “lymphomas”.

124
Q

What ethnicity has the highest incidence for ALL?

A

Hispanics

125
Q

When do B-ALL and T-ALL peak, respectively ?

A

B-ALL : age of 3.

T-ALL : in adolescence.

126
Q

What is the main morphology of ALL?

A
  1. The marrow is hypercellular and packed with lymphoblasts.
  2. Mediastinal thymic masses occur in 50-70% of T-ALLs.
  3. The tumor cells have scant basophilic cytoplasm and nuclei somewhat larger than those of small lymphocytes.
  4. High mitotic rate (aggressive).
  5. As with other rapid growing tumors - starry sky appearance.
127
Q

Why it is important to distinguish ALL from AML?

A

Because of differing response to chemotherapy.

128
Q

What histochemical stains can be helpful in order to distinguish ALL from AML?

A
  1. MPO negative

2. PAS positive cytoplasmic material.

129
Q

What is the prognosis of ALL?

A

Pediatric ALL is one of the great success stories of oncology.

130
Q

What is the most common leukemia of adults in the western world?

A

CLL

131
Q

What are the most common deletions in CLL/SLL?

A

13q14.3 (miR-15a and miR-16-1)
11q
17p
Trisomy 12q

132
Q

What may be the cell of origin in CLL/SLL ?

A

Either a postgerminal center memory B cell or a naive B cell.

133
Q

What is the median survival in patients with CLL/SLL?

A

4-6 years, but over 10 in individuals with minimal tumor burdens at diagnosis.

134
Q

What is the percentage of patients with CLL in which a transformation to diffuse large B cell lymphoma occur (Richter syndrome)?

A

5-10%

135
Q

What is the cell of origin in follicular lymphoma?

A

Germinal center B cells.

136
Q

What is the immunophenotype of the follicular lymphoma cells?

A
  1. CD 19
  2. CD 20
  3. CD 10
  4. Surface Ig
  5. BCL6
    Close resemblance of normal germinal center B cells.
  6. BCL2 is expressed in more than 90% of cases, in distinction to normal follicular center B cells, which are BCL2 negative.
137
Q

What is the usual approach in patients with follicular lymphoma?

A

Not improved by aggressive therapy.
The usual approach is to palliate patients with low dose chemotherapy or immunotherapy (anti-CD20 antibody) when they become symptomatic.

138
Q

What is the most common form of NHL?

A

Diffuse large B-cell lymphoma

139
Q

Mention some morphologic variations that are seen in DLBCL.

A
  1. Large multilobated or cleaved nuclei are prominent in some cases.
  2. Cytoplasm is usually moderately abundant and may be pale or basophilic.
  3. More anaplastic tumors - multinucleated cells with large inclusion-like nucleoli that resemble Reed-Sternberg cells.
140
Q

What is the immunophenotype of DLBCL ?

A
  1. CD19
  2. CD20
  3. Variable expression of germinal center B cell markers : CD10 and BCL6.
  4. Most have surface Ig.
141
Q

What percentage of DLBCLs are associated with the t(14;18) (follicular lymphoma), leading to overexpression of BCL2?

A

10-20% - distinctive form from the DLBCLs with BCL6 rearrangements.

142
Q

Describe briefly what happens in immunodeficiency-associated large B-cell lymphoma (subtype of DLBCL).

A
  1. Occurs in severe T cell immunodeficiency.

2. Usually neoplastic B cells are infected by EBV.

143
Q

Describe briefly what happens in primary effusion lymphoma (subtype of DLBCL).

A
  1. Presents as malignant pleural or ascetic effusion - in HIV patients.
  2. Anaplastic - only have clonal IgH gene rearrangements.
  3. In all cases the tumors are infected with HHV8 - causal role.
144
Q

What is the prognosis of DLBCL ?

A
  1. Aggressive tumor - rapidly fatal without treatment.
  2. With intensive combination chemotherapy :
    60-80% - complete remission.
    40-50% - cured.
145
Q

What is the immunophenotype of Burkitt lymphoma cells?

A

Mature B cells that express :

  1. IgM
  2. CD19
  3. CD20
  4. CD10
  5. BCL6
  6. Unlike other tumors of germinal center origin - NO BCL2 expression.
146
Q

What percentage of DLBCLs have c-MYC translocations - therefore, are difficult to be distinguished from Burkitt lymphomas?

A

5%

147
Q

Where is Burkitt lymphoma mainly found?

A

In children and young adults.

148
Q

Where does endemic Burkitt lymphoma often present?

A
  1. As a mass involving the mandible.

2. Unusual involvement of abdominal viscera - kidneys, ovaries, adrenals.

149
Q

Where does sporadic Burkitt lymphoma often present?

A

As a mass involving the ileocecum and peritoneum.

150
Q

What is the prognosis for Burkitt lymphoma?

A

Very aggressive, but responds well to intensive chemotherapy. Most children and young adults can be cured.

151
Q

What is the main difference between normal plasma cells and neoplastic plasma cells?

A

The latter often synthesize excess light (excreted as Bence-Jones proteins) or heavy chains along with complete Igs.

152
Q

How are the bone lesions appear radiographically ?

A

As punched-out defects, usually 1-4cm in diameter.

153
Q

In multiple myeloma, what percentage of the marrow’s cellularity consists of plasma cells?

A

Usually more than 30%.

154
Q

What are the Russel and Dutcher bodies that are seen in multiple myeloma plasma cells?

A

Globular inclusions that contain proteins, fibrils, crystalline rods, and globules.
Cytoplasmic - Russel bodies.
Nuclear - Dutcher bodies.

155
Q

What is the rouleaux formation that is observed in multiple myeloma?

A

The high levels of M proteins causes red cells in peripheral blood smears to stick to one another in linear arrays, a finding called rouleaux formation.

156
Q

What are the laboratory findings in patients with multiple myeloma?

A
  1. In 99% - increased levels of Igs in the blood and/or light chains (Bence-Jones proteins) in the urine.
  2. Firstly, the Igs are detected as spikes in electrophoresis.
  3. Most are associated with more than 3gm/dL of serum Ig(IgG followed by IgA) and/or more than 6gm/dL of urine Bence-Jones protein.
157
Q

What is the prognosis of multiple myeloma?

A
  1. Generally poor.
  2. Median survival : 4-6 years.
  3. If untreated : 6-12 months.
  4. Myeloma cells are sensitive to inhibitors of the proteasome.
158
Q

What percentage of patients with MGUS develop a symptomatic plasma cell neoplasm (usually multiple myeloma), per year?

A

1%

159
Q

What is a smoldering myeloma?

A

A middle ground between multiple myeloma and MGUS.

Patients are asymptomatic, but 75% progress to multiple myeloma over a 15-year period.

160
Q

What is the cellularity of the marrow in lymphoplasmacytic lymphoma?

A 
The marrow contains :
1. Lymphocytes 
2. Plasma cells
3. Plasmacytoid lymphocytes 
in varying proportions often accompanied by MAST cell hyperplasia.
161
Q

At diagnosis, what are the main sites of lymphoplasmacytic lymphoma dissemination ?

A
  1. Lymph nodes
  2. Spleen
  3. Liver
  4. Infiltration of nerve roots, meninges.
  5. Rarely the brain.
162
Q

What is the immunophenotype in lymphoplasmacytic lymphoma?

A 
B cell markers :
1. CD20
2. Surface Ig 
Plasma cell components :
3. Secretion of the same Ig that is on B cells (IgM, but also IgG and IgA).
163
Q

What is the molecular basis of lymphoplasmacytic lymphoma?

A

Lack of translocations - most common is a deletion involving chromosome 6q.

164
Q

What is the prognosis of lymphoplasmacytic lymphoma?

A
  1. Incurable progressive disease.
  2. Symptoms caused by high IgM - plasmapheresis.
  3. Median survival is about 4 years.
165
Q

Is mantle cell lymphoma male predominant ?

A

YES

166
Q

Is mantle cell lymphoma common in USA and Europe ?

A

NO - 2.5% of NHLs in USA and 7-9% of NHLs in Europe.

167
Q

In mantle cell lymphoma, what are the morphologic features of the neoplastic cells?

A
  1. Homogeneous population of small lymphocytes with irregular to occasionally deeply cleaved nuclear contours.
  2. Nodal tumor cells may surround reactive germinal centers or diffusely efface the node.
168
Q

How is mantle cell lymphoma being distinguished from follicular lymphoma and CLL/SLL?

A
  1. Absence of large cells resembling centroblasts.

2. Absence of proliferation centers.

169
Q

At diagnosis of mantle cell lymphoma, what does the majority of the patients have?

A
  1. Generalized lymphadenopathy

2. 20-40% have peripheral blood involvement.

170
Q

In mantle cell lymphoma, what are the frequent sites of extranodal involvement?

A
  1. The bone marrow
  2. The spleen
  3. Liver
  4. Gut (lymphatoid polyposis)
171
Q

What is the prognosis for patients with mantle cell lymphoma?

A
  1. Poor
  2. Median survival : 3-4 years.
  3. Not curable with conventional chemotherapy.
172
Q

Mention some general features of hairy cell leukemia.

A
  1. Rare but distinctive B cell neoplasm.
  2. Median age of 55.
  3. Male to female ratio 5:1
173
Q

How can the hairy cell leukemia cells be seen?

A

Only in marrow biopsies - enmeshed in ECM - “dry tap”.

174
Q

What happens in spleen and liver in hairy cell leukemia?

A
  1. Splenic red pulp is usually heavily infiltrated, leading to obliteration of white pulp and a beefy red gross appearance.
  2. Frequent involvement of hepatic portal triads.
175
Q

What is the immunophenotype in hairy cell leukemias?

A
  1. Typical B cell markers : CD19, CD20, surface Ig (usually IgG).
  2. Certain relative distinctive markers : CD11c, CD25, CD103.
  3. Cell of origin : post-germinal center memory B cell.
176
Q

What is the prognosis for patients with hairy cell leukemia?

A
  1. Excellent.

2. Response to “gentle” chemotherapeutic agents, which produce long lasting remissions.

177
Q

What is practically the peripheral T-cell lymphoma, unspecified?

A

A wastebasket diagnosis - no morphologic feature is pathognomonic.

178
Q

Describe ruefully the main features of the hallmark cells of anaplastic large cell lymphoma (ALK positive).

A
  1. Anaplastic cells - horseshoe-shaped nuclei and voluminous cytoplasm.
  2. Often cluster about venules and infiltrate lymphoid tissues - mimicking metastatic carcinoma.
179
Q

Who is the main target of T-cell lymphomas with ALK rearrangements?

A

Children or young adults.

180
Q

What is the prognosis in anaplastic large cell lymphoma?

A

Very good - 75-80% cure rate from chemotherapy.

Poor - when ALK rearrangements are absent.

181
Q

Besides adult T-cell leukemia/lymphoma, to what else can sometimes HTLV-1 give rise?

A

To a progressive demyelinating disease of the CNS and spinal cord.

182
Q

What is the prognosis of mycosis fungoides?

A
  1. Indolent tumors : median survival 8-9 years.

2. Transformation to T-cell lymphoma occurs occasionally as terminal event.

183
Q

Describe briefly the appearance of the neoplastic cells in large granular lymphocytic leukemia.

A
  1. Large lymphocytes
  2. Abundant blue cytoplasm
  3. A few coarse azurophilic granules
    Best seen in peripheral blood smears.
184
Q

What dominates the clinical picture in large granular lymphocytic leukemia?

A

Despite the relative paucity of the marrow infiltration, neutropenia and anemia dominate the clinical picture.

185
Q

What is Felty syndrome?

A

A triad of :

  1. Rheumatoid arthritis
  2. Splenomegaly
  3. Neutropenia
186
Q

What is the prognosis of large granular lymphocytic leukemia?

A

In general :
Tumors of T-cell origin : indolent course.
Tumors of NK-cell origin : more aggressive.

187
Q

Is extranodal NK/T-cell lymphoma rare in the USA and Europe?

A

Yes, but in Asia : 3% of NHLs.

188
Q

How does extranodal NK/T-cell lymphoma usually present?

A

As a destructive nasopharyngeal mass.

189
Q

Is extranodal NK/T-cell lymphoma associated with a virus?

A

Highly associated with EBV !

190
Q

What is the immunophenotype of extranodal NK/T-cell lymphoma?

A
  1. CD3-
  2. Lack of T-cell receptor rearrangements
  3. Expression of NK cell markers
191
Q

What is the prognosis in extranodal NK/T-cell lymphoma?

A

Poor - highly aggressive neoplasms, resistant to chemotherapy.

192
Q

What is the origin of Reed-Sternberg cells in Hodgkin lymphoma?

A

From germinal center or post-germinal center B cells.

193
Q

What is the average age at Hodgkin lymphoma diagnosis?

A

32

194
Q

What was the first successfully treated human cancer?

A

Hodgkin lymphoma

195
Q

What are the classical forms of HL?

A

The first 4 (nodular sclerosis, mixed cellularity, lymphocyte-rich, lymphocyte depletion) - similar immunophenotype.

196
Q

Besides HL, in what other conditions do the cells resemble the Reed-Sternberg cells?

A
  1. Infectious mononucleosis
  2. Solid tissue cancers
  3. Large-cell NHLs
    Must excluded for HL diagnosis.
197
Q

On what depends the diagnosis of HL ?

A

On the identification of Reed-Sternberg cells in a typical prominent background of NON-neoplastic inflammatory cells. (Also have specific immunoprofile)

198
Q

What are the components of the polymorphous background in which RSCs are found in nodular sclerosis?

A
  1. T cells
  2. Eosinophils
  3. Plasma cells
  4. Macrophages
199
Q

What is the immunophenotype of RSCs in nodular sclerosis (and other HL classical subtypes)?

A
  1. PAX5
  2. CD15
  3. CD30
  4. CD45- (leukocyte common antigen)
200
Q

Is nodular sclerosis associated with EBV?

A

No

201
Q

What percentage of HLs are of mixed cellularity subtype?

A

20-25%

202
Q

What are the components of the heterogeneous cellular infiltrate in mixed cellularity HL ?

A
  1. RSCs
  2. Eosinophils
  3. Plasma cells
  4. Benign macrophages
203
Q

Is there an association with EBV in mixed cellularity HL?

A

Yes, 70% of RSCs are infected.

204
Q

Is mixed cellularity HL more common in men?

A

Yes

205
Q

What is the major components of cellular infiltrate in lymphocyte rich HL?

A

Uncommon - reactive lymphocytes make up the vast majority of the infiltrate.

206
Q

How is lymphocyte rich HL being distinguished from the lymphocyte predominance HL?

A
  1. Presence of mononuclear variants.

2. Classical immunophenotypic RSCs.

207
Q

Is there an association of lymphocyte rich HL with EBV?

A

Yes, 40% of cases.

208
Q

What is the least common form of HL?

A

Lymphocyte depletion HL - <5%.

209
Q

What is the major cellular characteristic of lymphocyte depletion HL?

A
  1. Paucity of lymphocytes

2. Relative abundance of RSCs or their pleomorphic variants

210
Q

Why is immunophenotyping ESSENTIAL for the diagnosis of lymphocyte depletion HL?

A

Since most tumors suspected of being lymphocyte depletion HL actually prove to be large cell NHLs !

211
Q

Is there an association between lymphocyte depletion HL and EBV?

A

YES - over 90%!

212
Q

What are the target groups of lymphocyte depletion HL ?

A
  1. Elderly
  2. HIV +
  3. In non industrialized countries
213
Q

In contrast to the other HLs, what is the prognosis in lymphocyte depletion subtype ?

A

Less favorable - advanced stage and systemic symptoms are frequent.

214
Q

What is the major difference in cellular level between lymphocyte predominance HL and the “classical” HLs?

A

RSCs are usually DIFFICULT to find!

215
Q

What is the major cellular component in lymphocyte predominance HL?

A
  1. L&H (lymphocytic and histiocytic) variants - multilobed nucleus resembling popcorn kernel (popcorn cell)!
  2. Eosinophils and plasma cells are absent.
216
Q

What is the immunophenotype in lymphocyte predominance HL?

A

In contrast to classical HLs :

  1. CD20
  2. BCL6
  3. CD15-
  4. CD30-
217
Q

What percentage of lymphocyte predominance HL transforms into a tumor resembling DLBCL ?

A

3-5%

218
Q

Is there an association between lymphocyte predominance HL and EBV ?

A

NO!!!

219
Q

What is the typical patient with lymphocyte predominance HL ?

A

A male, usually younger than 35, presenting with cervical/axillary lymphadenopathy.

220
Q

What is the major problem in HL long term survivors of chemo and radiation therapy ?

A

Increased risk for developing second cancers.

221
Q

What are the main features of myeloblasts in AML?

A
  1. Delicate nuclear chromatin.
  2. 2-4 nucleoli.
  3. More voluminous cytoplasm than lymphoblasts.
222
Q

What are the Auer rods ?

A

In AML : distinctive needle-like azurophilic granules.

223
Q

In what specific form of AML are Auer rods particularly present?

A

In AML with the t(15;17) - acute promyelocytic leukemia.

224
Q

What are the main features of monoblasts in AML?

A
  1. Folded/lobulated nuclei.
  2. Lack Auer rods.
  3. Non specific esterase positive.
225
Q

In AML, what happens to the number of leukemic cells (blasts) in the blood?

A

HIGHLY VARIABLE!

  1. May be more than 100.000/mm3.
  2. Under 10.000/mm3 (50% of cases).
  3. Occasionally : blasts are absent (aleukemic leukemia!).
226
Q

What we do to surpass the difficulty to distinguish myeloblasts from lymphoblasts (AML from ALL)?

A

Perform stains for myeloid specific antigens.

227
Q

What is the central role of cytogenetics in AML?

A

In the classification.

228
Q

With what genetic abnormalities is AML arising de novo in younger adults commonly associated?

A

Balanced chromosomal translocations :

  1. t(8;21)
  2. Inv(16)
  3. t(15;17)
229
Q

What is the basis of the molecular pathogenesis in AML?

A

Many recurrent genetic aberrations seen in AML disrupt genes encoding transcription factors that are required for normal myeloid differentiation.

230
Q

Are the genetic lesions that merely block the maturation of myeloid progenitors, by themselves sufficient to cause AML?

A

NO!!!

231
Q

What is the prognosis for AML?

A
  1. Difficult to treat.
  2. 60% complete remission after chemotherapy.
  3. t(8;21) and inv(16) : relatively good prognosis.
  4. Dismal prognosis : AML following MDS or genotoxic therapy in the elderly.
232
Q

All forms of MDS can transform to AML. In what condition is this transformation particularly frequent?

A

In secondary to previous genotoxic drug or radiation therapy MDS (t-MDS).

233
Q

Both primary MDS and t-MDS are associated with similar clonal chromosomal abnormalities. Mention some important ones.

A
  1. Monosomies 5 and 7.
  2. Deletions of 5q, 7q, and 20q.
  3. Trisomy 8.
234
Q

What are the Pseudo-Pelger-Hüet cells?

A

Neutrophils with only two nuclear lobes observed in MDS.

235
Q

What are the principal components of the blood in MDS ?

A
  1. Pseudo-Pelger-Hüet cells.
  2. Giant platelets.
  3. Macrocytes.
  4. Poikilocytes.
  5. Accompanied by a relative or absolute monocytosis.
236
Q

What is the target group of primary MDS?

A

The elderly.

237
Q

What is the mean age of onset in primary MDS ?

A

70

238
Q

What distinguishes CML from other myeloproliferative disorders?

A

The presence of the chimeric BCR-ABL gene.

Portions of BCR gene (22) and ABL gene (9).

239
Q

What is the specific genetic abnormality in 90% of CMLs?

A 
The Philadelphia chromosome ! 
Reciprocal translocation (9;22)(q34;q11).
240
Q

What is the cell of origin in CML?

A

A pluripotent hematopoietic stem cell.

241
Q

What are the types of cells that, for unknown reasons, BCR-ABL preferentially drives the proliferation in CML?

A
  1. Granulocytic progenitors.
  2. Megakaryotic progenitors.
  3. Causes abnormal release of immature granulocytopenia forms from the marrow into the blood.
242
Q

Is the marrow hypercellular in CML?

A

YES

243
Q

What are the major components of the marrow in CML?

A
  1. Massive numbers of maturing granulocytic precursors.
  2. Elevated proportion of eosinophils / basophils.
  3. Dysplastic megakaryocytes.
  4. Sea-Blue histiocytes (characteristic - macrophages with abundant green-blue cytoplasm).
244
Q

What is the level of leukocytosis in CML?

A

Often exceeding 100.000/mm3.

245
Q

What is the target group of CML?

A

Primarily, adults, but also children and adolescents.

246
Q

What are the initial symptoms in CML?

A
  1. Insidious onset.
  2. Mild/moderate anemia
  3. Hyper metabolism due to increased cell turnover - leading to fatigue, anorexia, weakness.
247
Q

What can sometimes be the first symptom of CML?

A

A dragging sensation in the abdomen caused by splenomegaly.

Or the acute onset of left upper quadrant pain due to splenic infarction.

248
Q

How is CML best differentiated?

A

By detection of the BCR-ABL fusion gene through chromosomal analysis or PCR-based tests.

249
Q

Is CML fast or slow progressing?

A

Slow progression. After 3 years enters an accelerated phase…

250
Q

What is the median survival in CML without treatment?

A

About 3 years.

251
Q

What is the Ikaros transcription factor?

A

A regulator of hematopoietic differentiation that appears to be mutated in 85% of CMLs.

252
Q

What characterizes polycythemia Vera?

A

Increased marrow production of red cells, granulocytes, and platelets (panmyelosis).

253
Q

In polycythemia Vera, what cells are responsible for most of the symptoms?

A

The red blood cells.

254
Q

With what mutations is PCV strongly associated?

A

With activating point mutations in the tyrosine kinase JAK2.

255
Q

What is the basis of the molecular pathogenesis in PCV ?

A

The progenitor cells do not need erythropoietin and other factors for growth due to constitutive activation of JAK2 signaling.

256
Q

What is the specific mutation in JAK2 (97% of cases)?

A

A valine to phenylalanine substitution at residue 617.

257
Q

Is the marrow hypercellular in PCV?

A

Yes, but some residual fat is also present.

258
Q

What happens during the spent phase, late in the course of PCV?

A

Extensive marrow fibrosis that displaces hematopoietic cells.
Increased extramedullary hematopoiesis.

259
Q

What percentage of PCV transforms to AML?

A

About 1%

260
Q

What is the incidence of PCV ?

A

1-3/100.000 per year.

261
Q

What is the target group of PCV?

A

Adults of late middle age. (Insidiously)

262
Q

What is the major risk resulting from abnormalities in blood flow and platelet function in patients with PCV ?

A

Increased risk for both major bleeding and thrombosis.

263
Q

What percentage of PCV patients come to attention due to DVT, MI, or stroke?

A

25%

264
Q

What is the hemoglobin concentration in PCV ?

A

14-28gm/dL

265
Q

What is the Ht in PCV ?

A

Usually 60% or more.

266
Q

What happens with chronic bleeding in PCV ?

A

Iron DEFICIENCY!

Suppresses erythropoiesis and thus LOWERS the abnormally high Ht.

267
Q

What is the WBC count in PCV?

A

12.000-50.000/mm3

268
Q

What is the platelet count in PCV?

A

Greater than 500.000/mm3.

269
Q

What is the prognosis for PCV?

A

Without treatment, death from bleeding or thrombosis occurs within months of diagnosis.

270
Q

What has extended survival with treatment revealed?

A

PCV tends to evolve into a spent phase - features of primary myelofibrosis develop.

271
Q

What is the time needed for PCV to transform in primary myelofibrosis?

A

In about 15-20% of patients after an average period of 10 years.

272
Q

What are the two principal mutations in essential thrombocytosis?

A
  1. Activating point mutations in JAK2 (50% of cases).

2. MPL (5-10%) - a receptor of tyrosine kinase that is normally activated by thrombopoietin.

273
Q

What happens to marrow in ET?

A
  1. Mild cellularity increase.
  2. Megakaryocytes often markedly increased in number and include abnormally large forms.
  3. Overt fibrosis of primary myelofibrosis is absent.
274
Q

What is the incidence of ET?

A

Same as for PCV - 1-3/100.000 per year.

275
Q

What is the major clinical manifestation of ET?

A

Thrombosis and hemorrhage - stem from dysfunction of platelets from the neoplastic clone.

276
Q

What is the characteristic symptom of ET (May also be seen in PCV) - (damn there are too many!) ?

A

Erythromelalgia : throbbing and burning of hands and feet caused by occlusion of small arterioles by platelet aggregates.

277
Q

What is the median survival for ET?

A

12-15 years.

278
Q

What is the hallmark of primary myelofibrosis?

A

The development of obliterative marrow fibrosis - suppression of hematopoiesis - cytopenias and extensive neoplastic extramedullary hematopoiesis.

279
Q

What is the basis of the molecular pathogenesis of primary myelofibrosis?

A

50-60% - JAK2 mutations.

1-5% - MPL mutations.

280
Q

What are the two factors synthesized by megakaryocytes that have been implicated in primary myelofibrosis?

A
  1. PDGF

2. TGF-β

281
Q

What is leukoerythroblastosis?

A

Abnormal release of immature precursor cells into the peripheral blood - usually result from diseases that distort the marrow architecture (deposits of metastatic cancer or granulomatous disease).

Pathology (16 decks)

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