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Step 1 Miscellanous > Pathoma White Blood Cell Disorders > Flashcards

Pathoma White Blood Cell Disorders Flashcards

1
Q

What count defines Leukopenia vs Leukocytosis?

A

Leukopenia - WBC count <5k

Leukocytosis - WBC count >10k

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2
Q

What effect does excess cortisol have on leukocyte count and why?

A

Causes neutrophilia -> downregulation of P-selectin so they can’t exit tissues

Lymphopenia -> induces apoptosis of lymphocytes

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3
Q

What is the most sensitive cell in the body to whole body radiation?

A

Lymphocytes

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4
Q

What marker will be decresaed on neutrophils during a left shift?

A

Immature neutrophils have impaired expression of CD16

  • > CD16 = Fc receptor.
  • > Don’t function as well for phagocytosis and antibody-dependent cell meated cytotoxicity
  • > also present on NK cells
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5
Q

What bacteria causes a lymphocytic leukocytosis and how does it cause this?

A

Bordetella pertussis

  • > produces lymphocytosis-promoting factor
  • > blocks circulating lymphocytes from leaving the blood and entering the lymph node
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6
Q

What part of the spleen and lymph node are enlarged in Infectious Mononucleosis?

A

Spleen - PALS
Lymph node - Paracortex

Due to increased reactive population of CD8+ T cells

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7
Q

Why are patients with HBV at increased risk of B cell lymphoma throughout their life?

A

The virus lays dormant in the B cells.

-> can reactivate in AIDS patients and predispose to B cell lymphoma, especially in the CNS

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8
Q

What is the most critical marker for ALL? Who tends to get it?

A

TdT+ - Terminal deoxynucleotidyl transferase - a DNA polymerase
-> not present in mature lymphocytes or the myeloid line

Tends to occur in children, or in Down syndrome patients >5.

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9
Q

What is the most common subtype of ALL and what markers are expressed?

A

B-ALL

CD10!!!!!!! (not a T cell marker),CD19,CD20

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10
Q

Where must chemotherapy by given for ALL?

A

Requires prophylaxis to CNS and scrotum - immunoprivileged areas

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11
Q

What cytogenetic markers indicate good and poor prognosis for B-ALL? What populations are they seen in?

A

Good -> t(12;21) - seen in children

Poor -> t(9;22) - similar to CML, but this one is 190 kD. Seen in adults

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12
Q

Who gets T-ALL?

A

Disease of T’s
Teenagers
Thymic mass - Lymphoma
T-cell ALL

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13
Q

What leukemias are associated with Down syndrome and at what ages?

A

Before age 5: Acute megakaryoblastic anemia (type of AML)

After age 5: Acute lymphoblastic leukemia (ALL)

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14
Q

What tissue infiltration is characteristic of acute monocytic leukemia?

A

Gingival hypertrophy -> monoblasts have a tropism for the gums

Keep in mind this is a type of AML

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15
Q

What is the most common acute leukemia in adults and what are the risk factors?

A

Acute myeloid leukemia (AML)

  • Down syndrome
  • Radiation and alkylating chemotherapy -> myelodysplastic syndromes
  • Myeloproliferative disorders
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16
Q

What must be seen in bone marrow for diagnosis of MDS?

A

Hypercellular, abnormal maturation of cells, increased blasts (<20%, or would be leukemia)

Evidence of dysplasia in one or more cell lineages, affecting >10% of cells

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17
Q

What is seen on peripheral blood smear of MDS in general?

A

Cytopenias - with variable reduction RBCs, platelets, and granulocytes, some with functional defects.

RBCs = normocytic or **macrocytic**
WBCs = abnormal nuclear lobation and granules with impaired killing activity
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18
Q

What is one commonly tested WBC anomaly seen in peripheral smear in MDS?

A

Pseudo-Pelger-Huet anomaly

  • neutrophils with bilobed nuclei, and hypogranularity
  • will have impaired killing activity
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19
Q

Who tends to get chronic lymphoid leukemias and what are the most typical clinical features?

A

Older adults, diseases have indolent course (except ATLL)

Lymphadenopathy, hepatosplenomegaly (like ALL)

Constitutional symptoms - fever, night sweats, weight loss, fatigue

Abnormal CBC with bone marrow infiltration

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20
Q

What is the most common leukemia and what type of cell is it overall? Who gets it? What are the flow cytometry markers?

A

CLL - always older adults

Phenotype by flow cytometry:
CD19+,CD20+ (B-cell), CD5+ (T cell marker)
-> these are naive B cells which co-express B and T cell markers

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21
Q

What is the cell morphology of chronic lymphocytic leukemia (CLL)?

A
  1. Small, mature-looking lymphocytes indistinguishable from normal
  2. Smudge cells - ruptured lymphocytes (cells are fragile in CLL) CLL = crushed little lymphocytes
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22
Q

What is the most common cause of death in CLL? What does this do to blood counts as well?

A

Infections due to hypogammaglobulinemia - neoplastic B cells do not want to produce useful antibody

If they do, often causes autoimmune hemolytic anemia (leads to thrombocytopenia (Evan’s syndrome) and anemia) -> usually a Warm (IgG), but rarely Cold (IgM)

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23
Q

What is Richter’s syndrome / transformation?

A

Transformation of SLL / CLL into an aggressive lymphoma, most commonly a diffuse large B-cell lymphoma

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24
Q

Why does CLL cause generalized lymphadenopathy?

A

Small Lymphocytic Lymphoma is the sister disease. obviously these mature B cells are going to hone into lymph nodes..

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25
Q

What are the lab staining features of hairy cell leukemia? How do they look on peripheral smear? What is the mnemonic?

A

Mature B cells with hairy cytoplasmic processes (appear fuzzy on LM with indistinct borders)

Lab features - TRAP + (tartrate resistant acid phosphatase)

Remember these hairy cells are TRAPPED in the bone marrow (causing fibrosis) and TRAPPED in the red pulp causing splenomegaly

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26
Q

What will physical exam and CBC show with HCL? Why do these things happen? Will there be lymphadenopathy?

A

Massive splenomegaly due to accumulation of hairy cells in red pulp

NO lymphadenopathy -> cells are TRAPPED in the bone marrow and cannot make it to LN’s

Pancytopenia will be the rule
-> due to massive fibrosis of bone marrow

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27
Q

What two drugs are used in the treatment of hairy cell leukemia and what is their mechanisms of action?

A

Cladribine, pentostatin

Both are purine analogs.
Cladribine accumulates due to resistance to adenosine deaminase and prevents DNA polymerase activity

Pentostatin inhibits of adenosine deaminase
-> adenosine toxically accumulates in neoplastic B cells

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28
Q

What is the presentation of Adult T-cell leukemia/lymphoma? Where is it most common?

A

Most common in Caribbean and Japan (endemic areas)

A diffuse erythematous rash due to skin infiltration, generalized lymphadenopathy with hepatosplenomegaly
-> these T cell lymphomas love to go to skin

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29
Q

What can Adult T cell leukemia/lymphoma be easily confused with and how do you differentiate?

A

Easily confused with multiple myeloma, since it also causes lytic bone lesions and hypercalcemia
-> differentiate based on presence of rash

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30
Q

What cells are seen in Mycosis fungoides and what is the characteristic intraepidermal finding?

A

CD4+ T cells with “cerebriform” nuclei

  • > this is cutaneous T cell lymphoma (CD4 cells love to go to the skin, like ATLL)
  • > Pautrier microabscesses (P doesn’t go with P)
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31
Q

What is Sezary syndrome?

A

Progression of mycosis fungoides to T cell leukemia -> sezary cells in blood.

Will lead to generalized erythroderma / exfoliative dermatitis

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32
Q

What are the features of CML on peripheral smear and bone marrow CML? What will happen to RBCs and platelets?

A

Uncontrolled production of ALL granulocytes; remember this is the characteristic disorder where basophils are increased

RBCs -> generally anemia because bone marrow is hypercellular
Platelets -> develop okay -> thrombocytosis

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33
Q

What are the phases of CML infection and when are most patients diagnosed?

A

Chronic phase - most patients diagnosed here by CBC when asymptomatic
Accelerated phase - increased output of mature myeloid cells, marked by enlargement of the spleen
Terminal blast crisis - right before it becomes an acute leukemia

34
Q

What does CML progress to? How does this relate to where the driving mutation is? Treatment?

A

AML in 2/3 of cases and ALL in 1/3 of cases. Mutation must be in the Hematopoietic stem cell (CD34+) since there is no other way it could also progress to an ALL.

Treatment: imatinib, since CML is always driven by the Philadelphia chromosome (9;22)

35
Q

What mutations are associated with each of the four main Myeloproliferative neoplasms?

A
  1. Polycythemia Vera (PV) - JAK2 always
  2. Essential Thrombocythemia (ET) - JAK2 50%
  3. Primary Myelofibrosis (MF) - JAK2 50%
  4. Chronic Myelogenous Leukemia (CML) - philadelphia chromosome
36
Q

What is polycythemia vera / what are the usual symptoms for a patient presenting? Why do they have these symptoms?

A

Disorder of increased RBCs due to Jak-2 mutation, primary polycythemia

Usually asymptomatic, but often has headaches, visual disturbances, and dizziness due to increased blood viscosity

Also present with venous / portal thrombosis -> Budd-Chiari syndrome, and arterial thrombosis

37
Q

What are the rarer but classic symptoms of polycythemia vera?

A
  1. Intense pruritis (itching) following a shower due to increased mast cells (WBCs can also go up in this condition)
  2. Erythromelalgia - pain and red-blue discoloration in hands and feet
38
Q

What cell lines are also increased in P. vera?

A

All cell lines -> RBCs, WBCs, and platelets

39
Q

How does PV differ from secondary polycythemia?

A

Erythropoietin levels will be decreased -> stem cells are proliferating without growth signal

Secondary polycythemia is a reactive process
-> EPO production would be increased secondary to decreased SaO2

40
Q

What is the treatment for polycythemia vera?

A
  1. Phlebotomy - to reduce hyperviscosity

2. Hydroxyurea - a ribonucleotide reductase inhibitor (chemotherapy)

41
Q

What would be an example of a secondary polycythemia where SaO2 is normal?

A

Ectopic EPO production secondary to renal cell carcinoma (classically), or hepatocellular carcinoma

42
Q

What are the criteria for essential thrombocytopenia? This includes bone marrow biopsy and mutations.

A

Chronic elevated non-reactive platelet count (>450k) not accounted for by other MPNs

Bone marrow biopsy showing mainly megakaryocytes, especially with hyperlobulated nuclei

Absence of a philadelphia chromosome, and presence of a characteristic mutation (i.e. JAK2)

43
Q

In what other condition can the platelet count also be massively elevated?

A

Iron deficiency anemia

44
Q

What are classical symptoms of essential thrombocytopenia? Will it cause gout?

A

Usually asymptomatic, but may present with bleeding and thrombosis events, headache, lightheadedness, syncope

Classically does not cause hyperuricemia / gout like P. vera or CML -> not that much nuclear material in megakaryotes, just membrane blebbing which makes platelets.

45
Q

What is primary myelofibrosis (PMF)? Give the pathophys

A

Chronic proliferation of myeloid stem cells in marrow leads to progressive reactive fibrosis of bone marrow
-> due to PDGF from megakaryocytes especially stimulating fibroblasts to cause fibrosis

46
Q

What systemic symptoms are likely to develop in primary myelofibrosis and why?

A
  1. Massive hepatosplenomegaly due to extramedullary hematopoesis in liver and spleen since there’s no room in bone marrow to do this anymore
  2. Hypermetabolic state due to cytokines secreted by platelets, leading to fever, bone pain, and night sweats
  3. Anemia is also common
47
Q

How do you distinguish primary myelofibrosis from hairy cell leukemia?

A
  1. Primary myelofibrosis is more likely to have normal WBC and platelet counts.
  2. Dacrocytes / tear drop cells will also be seen due to RBCs being squeezed out of fibrosed bone marrow in PMF, but are NOT seen in HCL.
  3. Hairy cell leukemia will show hairy B cells which are TRAP+.
48
Q

What does the peripheral blood smear show for PMF? Why?

A

Leukoerythroblastic smear - spleen is not built to hold all this hematopoesis so immature cells leak out, includes immature LEUKOBLASTS and ERYTHROBLASTS

Includes nucleated RBCs, and immature neutrophils

49
Q

What type of lymph node hyperplasia happens in early HIV?

A

Expansion of follicular dendritic cells which are presenting antigens to CD4+ T cells
-> follicular hyperplasia

50
Q

What are the causes of painless lymphadenopathy?

A
  1. Chronic inflammation - i.e. due to RA / SLE
  2. Metastatic carcinoma
  3. Lymphoma
51
Q

What is the cause of hyperplasia of sinus histiocytes?

A

Lymph node draining a region of cancer
-> medullary region hyperplasia

Can also be seen idiopathic in Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)

52
Q

How is follicular lymphoma differentiated from follicular hyperplasia (reactive)?

A
  1. No tingible body macrophages in follicular lymphoma because no apoptosis is occurring, vs follicular hyperplasia where tingible body macrophages will be present due to somatic hypermutation and apoptosis.
  2. Any expression of Bcl-2 (normally Bcl-2 is not expressed at all in follicles to allow for apoptosis)
  3. Cells will be monoclonal
  4. Normal lymph node architecture will be disrupted
53
Q

What is the feared complication of follicular lymphoma?

A

Same as CLL -> development of a diffuse large B cell lymphoma (Richter transformation)

54
Q

What type of B cell lymphoma expands the region immediately adjacent to the follicle? What translocation does it express?

A

Mantle cell lymphoma. t(11;14), cyclin D

Note that the follicle is surrounded by the mantle.

55
Q

Why do marginal zones classically arise in chronic inflammatory states? Give a few examples of these states.

A

Marginal zone only exists in post-germinal center B cells -> can only arise in states of chronic inflammation.

Examples:

  1. Hashimoto thyroiditis
  2. Sjogren syndrome - unilateral enlargement of the parotid late in the disease course
  3. H. pylori gastritis - MALToma.
56
Q

What is the most common form of NHL?

A

Diffuse large B cell lymphoma

  • > very common since it is the endstage of follicular lymphoma (the most common indolent type) as well as chronic lymphocytic leukemia (CLL / SLL)
  • > also arises sporadically
57
Q

Is DLBCL aggressive? What alterations are common?

A

Very aggressive since large, poorly differentiated

Bcl-2 / Bcl-6 mutations are common - make sense since it arises from follicular lymphoma very often (Bcl-2 overexpressed)

58
Q

What is the malignant cell in Hodgkin lymphoma? What do they look like? What is this illness are some forms associated with?

A

Reed-Sternberg cells

  • > They look like “owl-eyed nuclei” - large B cells with bilobed nuclei and prominent nucleoli
  • > associated with EBV
59
Q

How is the RS cell of HL identified and why? What markers are used?

A

Identified by immunohistochemistry (not flow cytometry) because majority of cells are reactive to the cancerous RS cells -> lymphocytes, plasma cells, macrophages, eosinophils

15 * 2 owl eyes = 30

Identified by CD15,CD30, they are actually CD20- despite being B cells

60
Q

Give the salient features of each type of HL in terms of what makes them unique.

A
  1. Nodular sclerosis - most common, especially females
  2. Lymphocyte-rich - best prognosis
  3. Mixed cellularity - high eosinophils due to RS cells producing IL-5
  4. Lymphocyte depleted - seen in immunocompromised, worst prognosis (elderly and HIV positive)

more lymphs -> better prognosis

61
Q

What are the “B” symptoms of lymphomas and how do they relate to prognosis?

A

Patients are “B”othered by constitutional “B” symptoms. At least one of:

  1. Fever
  2. Night sweats
  3. Weight loss

Indicates poorer prognosis
-> often due to cytokines, i.e. produced by RS cells

62
Q

Who is HL most common in overall and what is the age distribution?

A

Most common in men overall, but the nodular sclerosing subtype is the most common subtype, more common in women

Bimodal distribution - more common in young adulthood, then >55 years.

63
Q

What is the special name given for the Reed-Sternberg cells in nodular sclerosing subtype?

A

“Lacunar cells” - RS cells with an empty space around them

Lymph node surrounded will be seen divided by bands of sclerosis (nodular sclerosing)

64
Q

What HL subtype is associated with eosinophilia and why? Why is this one super special

A

Mixed cellularity subtype, the one associated with EBV

-> RS cells produce IL-5

65
Q

What is the definition of multiple myeloma? Is it common? Why cytokine is characteristically elevated?

A

Most common PRIMARY malignancy of bone - Driven by IL-6 (like castleman disease)

Expansion of malignant plasma cells in bone marrow, characterized by lytic bone lesions, manifestations of marrow failure, and consequences of secreted proteins

Incase you’re wondering: -> most common malignancy of bone overall is metastasis. Nonhematopoietic primary would be osteosarcoma.

66
Q

What are the classic symptoms of symptomatic myelomas? Give why all these symptoms happen.

A

CRAB
Calcemia - hypercalcemia due to plasma cells activating RANK on osteoclasts, increasing bone resorption

Renal impairment - Free light chain excreted in urine damages kidney tubules, renal failure

Anemia - normo-cytic or macrocytic - Rouleaux formation

Bone disease - lytic lesions due to increased bone resorption (osteoclast-activating factor produced by plasma cells)

67
Q

What happens to the ESR in multiple myeloma and why?

A

It increases, because increased immunoglobulins affect the electrical surface charge of RBCs and cause them to form Rouleaux formations. Rouleaux formation settle faster in the test tube.

68
Q

What is Serum Protein Electrophoresis (SPEP)? How do you tell if something is monoclonal or polyclonal?

A

A way to analyze proteins in the serum

Polyclonal gamma globin peaks will be broad

Monoclonal peaks will be narrow-based (usually about the width of the albumin peak)

69
Q

What types of antibody are responsible for the M spike in multiple myeloma? Most common cause of death in this disease?

A

IgG - 60% of cases
IgA - 20-25% of cases

Death - infection, due to lack of diversity in Ig’s

70
Q

What causes renal injury in MM?

A
  1. Bence Jones protein - kappa or lamda light chains deposit in renal tubules and in urine
  2. Amyloid deposition - in glomeruli and blood vessels (myeloma kidney)
  3. Calcium deposition - nephrocalcinosis due to hypercalcemia
  4. Pyelonephritis - from inflammatory cells
  5. Uric acid crystal deposition (hyperuricemia from cell turnover)
71
Q

What type of amyloidosis does MM possibly cause and what are some possible clinical manifestations?

A

AL primary amyloidosis

  1. Macroglossia
  2. Cardiomegaly, CHF, arrhythmia - pressure atrophy and conduction disturbances
  3. Peripheral neuropathy
  4. Renal failure
  5. Absorptive abnormalities
72
Q

What is MGUS? Why is it relevant?

A

Monoclonal gammopathy of undetermined significance
-> M spike - monoclonal spike on SPEP, but plasma cells are <10% in bone marrow and no CRAB symptoms

  • MGUS is common in older patients, and progresses to multiple myeloma at a rate of 1% per year (precursor to MM)
73
Q

What is the definition of Waldenstrom macroglobulinemia?

A

Malignant proliferation of IgM-secreting plasmacytoid B lymphocytes in bone marrow
-> M spike = IgM accumulations. Macro since IgM is big.

74
Q

How does Waldenstrom macroglobulinemia differ from MM?

A

It is associated with soft tissue disease rather than bone disease

  • > generalized lymphadenopathy, no lytic bone lesions
  • > defects are due to high IgM levels and tissue invasion of neoplastic cells
75
Q

What are the clinical features of hyperviscosity syndrome?

A

All due to engorgement of small vessels with impaired platelet aggregation due to effects of IgM:

Visual disturbances and retinal changes due to retinal hemorrhages / occlusion

Lethargy, confusion, weakness - stroke symptoms due to poor blood flow

Epistaxis - bleeding due to small vessels in nose and poor platelet function

CHF due to increased afterload

76
Q

How is hyperviscosity syndrome treated?

A

Plasmapheresis, and treat underlying cause

77
Q

How do cells appear in peripheral smear in Waldenstrom?

A

Lymphoplasmacytoid -

Features in between small lymphocytes and plasma cells

78
Q

What are the principles of benign vs malignant when trying to remember Langerhans cell histiocytoses? What markers are positive in these disease?

A

CD1a+ - very specific
S-100 positive - just indicates neural crest derivation (i.e. Schwannoma)

If it has someone’s name in it, it’s malignant (i.e. Letterer-Siwe, Hand-Schuller-Christian Disease), and will involve the skin

If it does not, it’s benign (i.e. eosinophilic granuloma), and will not involve the skin

79
Q

What is Letterer-Siwe disease? Prognosis?

A

The most severe form of Langerhans cell histiocytosis
Two names so it happens before age 2.

  • > Acute disseminated
  • > skin rash and cystic skeletal defects in an infant, with systemic involvement and rapid progression
80
Q

What is Hand-Schuller-Christian disease and what is it associated with?

A

Langerhans cell histocytosis seen in age >2 (greater than 2 names)
-> scalp rash, skull defects, exophthalmos, and diabetes insipidus (due to posterior pituitary involvement)

81
Q

How does eosinophilic granuloma typically present? What will biopsy show?

A

Benign lesion causing a pathologic bone fracture in an adolescent, skin is not involved (since benign)

Biopsy shows Langerhans cells with abundant eosinophils.

Step 1 Miscellanous (40 decks)

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