Precursor B and T Cell Neoplasms and Mature B Cell Neoplasms Flashcards by Adam Shaver

PreT ALL is usually…

lymphomic

ex- you may see a mediastinal mass

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Epidemiology of Precursor B and T Cell Neoplasms: how common? Race? Gender? Age for each?

Precursor B and T Cell Neoplasms are the most common cancer of children; 5/100,000 age 2-5
Hispanics > Whites >&raquo_space; Blacks
Boys > Girls
Pre B incidence is highest at 4yrs; Pre T incidence is highest at adolescence

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Describe the morphology of Precursor B and T Cell Neoplasms

Both look similar
Small cells, high N/C Ratio, irregular nuclear contours, immature nuclear chromatin, +/- nucleoli (look similar to a “hand mirror”)
No peroxidase granules (MPO negative)

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Immunophenotype of immature lymphocytes

CD34 and TdT positive; surface light chain negative

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Immunophenotype of Pre-B Cells

CD19, CD22, CD10

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Immmunophenotype of Pre-T Cells

Early cell- CDIa, CD2, CD5, CD7

Other T cell antigens- cCD3, CD4/8

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Genetics of Pre-B Neoplasms

Loss of fxn mutations
translocation 12,22 involving ETV6 and RUNXI genes
translocation 9,22 involving BCR and ABL genes
Hyperdiploidy or Hypodiploidy

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Genetics of Pre-T Neoplasms

NOTCHI mutations (gain of fxn)

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Favorable prognostic factors for Precursor B and T Cell Neoplasms include

Age 2-10
Low WBC count
Early Pre-B Phenotype (CD19/CD10)
Hyperdiploidy
Trisomy of 4, 7, 10
12,21 translocation

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Poor prognostic risk factors for Precursor B and T cell neoplasms

Less than 2yrs old
MLL gene on chromosome 11
Adult
Peripheral Blast count > 100,000

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Clinical Features of Chronic Lymphocytic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) (5)

Patient older than 50
Typically asymptomatic
Adenopathy, hepatosplemomegaly
May have monoclonal serum spike
Immune disruption

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Morphology of CLL

Peripheral Blood- increase in small mature lymphocytes with hyperclumped nuclear chromatin; smudge cells

BM- Lymphoid aggregates
Spleen/Liver- red and white pulp; portal tracts

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Morphology of SLL

Lymph nodes effaced diffusely by small round cells, proliferation centers mimic germinal centers

BM- lymphoid aggregates
Spleen/Liver- red and white pulp; portal tracts

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In CLL/SLL, what are the pale regions observed in the lymph nodes that have replaced the follicles?

Proliferation centers that are sites of neoplastic proliferation and diffuse replacement of normal tissue by small lymphocytes

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Pre-B ALL is usually…

Leukemic

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Immunophenotype of CLL/SLL

CD19, CD5, CD23 and dim CD20 and dim light chain restricted

CLL dimly express kappa and not lambda

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Genetics of CLL/SLL

Deletions: 13q14, 11q and 17p
Trisomy 12

Severity (Good –>Bad) 13q14, tris12, 11q, 17p

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What is Richter Syndrome?

The transformation of CLL to Diffuse Large B Cell Leukemia (which has a poor prognosis and a higher grade)

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Follicular Lymphoma is associated with what translocation?

Translocations involving BCL2

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Morphology of Follicular Lymphoma

Nodular pattern in lymph nodes
Centrocytes and Centroblasts
Paratubular aggregates seen in bone marrow
Portal tracts in the white pulp of the spleen and liver

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How can you distinguish follicular lymphoma from follicular hyperplasia?

Follicular Lymphoma has no tingable macrophages and the nodules are basically taking over the lymph node

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Immunophenotype of Follicular Lymphoma

CD19, CD20, CD10, BCL2 positive

bcl6

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Genetics of Follicular Lymphoma

translocation of 14,18

14 = IgH
18 = BCL2

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If Follicular Lymphoma transforms it becomes what higher grade cancer?

Diffuse Large B Cell Leukemia

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Describe the morphology of Mantle Cell Lymphoma

Can have nodular or diffuse pattern small round, slightly irregular lymphocytes Surround and infiltrate normal germinal center Cells are small with cleaved nuclear contours similar to SLL but expres cyclin D Blastoid variant is more aggressive

Immunophenotype of Mantle Cell Lymphoma

CD19, CD20, CD5, bright surface light chain | CD23 negative

Genetics of Mantle Cell Lymphoma

11, 14 translocation 11= cyclin D; 14 = IgH

What are the treatment options for Mantle Cell Lymphoma?

1. Chemotherapy + Retuximab (anti-CD20) | 2. BM transplant

What type of cancer arises from chronic inflammatory disorders?

Marginal Zone Lymphoma

Describe the morphology of Marginal Zone Lymphoma

-Monocytoid B cells and plasmactoid cells that infiltrate and destroy host tissue

Immunophenotype of Marginal Zone Lymphoma

CD20, CD19 and surface light chain restricted

Genetics of Marginal Zone Lymphoma

Inflammation --> acquisition of mutations 11,18 transposition 1,14 transposition Upregulation of BCL10 and MALT1

What cell population is largely neoplastic in lymphoplasmacytic lymphoma?

Plasma Cells

Secretion of IgM from Lymphoplasmacytic Lymphomas can cause what?

A hyperviscosity syndrome called Waldenstrom Macroglobulinemia

What are the symptoms of Waldenstrom's Macroglobulinemia from LPL?

1. Visual Symptoms 2. Neurologic Symptoms 3. Bleeding (because it interferes with the coagulation factors and platelets) 4. Cryoglobulinemia (IgM that precipitates at low temps in the fingers/toes)

A mutation in what gene is associated with LPL?

MYD88

BRAF mutation is associated with what?

Hairy Cell Leukemia

What are the clinical symptoms of Hairy Cell Leukemia?

Splenomegaly and Pancytopenia

Describe the morphology of Hairy Cell Leukemia

Diffuse, fried egg appearance in Bone Marrow Round hyperchromatic nuclei with pale blue cytoplasm which have hairs, making the borders indistinct Cells incite reticulin fibrosis on dry BM tap Causes obliteration of the white pulp and involves red pulp

Immunophenotype of Hairy Cell Leukemia

CD19, CD20, surface light chain restriction | CD11c/CD25/CD103

Treatment of Hairy Cell Leukemia

Use a purine analog chemo --> long remission | BRAF inhibitors

What is secreted by all plasma cell neoplasms?

M Component | Bruce Jones Protein (free light chain)

Immunophenotype of Plasma Cell Neoplasms

CD38, CD56 | No- CD20, CD19 and CD45

The weakness and fatigue of MM is caused by

Anemia

The recurrent infections seen with MM are caused by

Decreased IgG

The polyuria, constipation and confusion seen with MM is caused by

Hyercalcemia

The bone pain and fractures associated with MM are caused by

the tumor load

Renal Insufficiency seen in MM is caused by

Bence Jones Protein

Amyloidosis seen in MM is caused by

Light chain deposition in organs

Radiographic studies of Multiple Myeloma will reveal

Bony Lytic Lesions (vertebral column, ribs, skull and pelvis)

Multiple Myeloma is associated with what genetic changes?

translocations involving IgH, deletions of 17p (TP53) and rearrangements involving MYC Tumor Produces IL6

In MM, the increased serum immunoglobulins cause

RBC adhesion resulting in "rouleaux formation"

What are the common clinical features of Diffuse Large B Cell Lymphome (DLBCL)?

Rapidly enlargine lymph node or extranodal site; possible B type symptoms

Describe the morphology of DLBCL

Large lymphocytes with convoluted nuclear contours, 1-3 nucleoli, pale cytoplasm and indistinct cellular borders (mitotically active)

Immunophenotype of DLBCL

CD19, CD20, surface light chain restriction | +/- bcl2, CD10, BCL6

Genetics of DLBCL

- BCL6 (3q27) mutation --> represses normal B cell differentiation, growth arrest and apoptosis - BCL2 (18) mutation - MYC (8) mutation or translocation (patients with the translocation do better than those with the mutation)

Which mature B cell neoplasm has the highest grade?

Burkitt Lymphoma

Burkitt Lyphoma is strongly associated to what virus?

EBV

What are the clinical features of Burkitt Lymphoma?

Tumor Lysis Syndrome and CNS diseases

What is Tumor Lysis Syndrome?

Rapid cell turnover resulting in tumor cell death and the release of uric acid, K and Ca --> medical emergency requiring hydration, binding agents for electrolytes and hemodialysis Occurs in Burkitt Lymphoma

Describe the morphology of Burkitt Lymphoma

Diffuse infiltrate of medium size cells with round nuclear contours, basophilic cytoplasm and vacuoles, proliferation rate at 100% (measure by Ki-67) and many macrophages giving the appearance of a starry sky

Why does Burkitt Lymphoma grow so fast?

MYC translocation --> increased exp of genes for glycolysis so constantly making building blocks for growth and division

Immunophenotype of Burkitt Lymphoma

CD19, CD20, CD10, surface light chain restriction, bcl6 No bcl2, CD34 or TdT

The translocations involving MYC seen in Burkitt Lymphoma include

8, 14 2, 8 8, 22