B-Lymphoblastic Leukemia/Lymphoma NOS

Question 1

What is the definition of B-ALL ?

Answer 1

• typically composed of small to medium-sized blasts with scant cytoplasm
• fine chromatin and inconspicuous nucleoli
• occasionally presenting with primary involvement of nodal or extranodal sites
• most treatment protocols have a requirement of >25% blasts but you need minimum 20%
  
  • low blast count presentations are very rare

Question 2

What cases should NOT be diagnosed as

B-ALL NOS ?

Answer 2

• Burkitt lymphoma with leukemic cells
• Genetically defined B-ALL
  
  • there are 9 separate genetic mutations associated with this
  • those should be diagnosed by their genetics

Question 3

What is the epidemiology of B-ALL NOS?

Answer 3

• primarily a disease of children (75% of cases in kids < 6 years old)
• most ALL cases are B cell type
• lymphomatous presentation in B-ALL is rare and represents only 10% of cases
  
  • most of them are of T cell lineage

Question 4

What is the etiology of B-ALL ?

Answer 4

• etiology is unknown
• increased incidence in Down syndrome and other constitutional disorders
• Increased incidence with certain SNPs but true familial ALL is very rare
  
  • SNPs: GATA3, ARID5B, IKZF1, CEBPE and CDKN2A/B
  • Familial associated mutations
    
    • PAX5
    • ETV6
    • TP53

Question 5

What is the localization of B-ALL ?

Answer 5

• bone marrow and peripheral blood usually involved
• extramedullary involvement is common:
  
  • CNS, spleen liver and testes (particularly)
  • Common sites it is seen in:
    
    • skin
    • soft tissue
    • bone
    • lymph nodes
• IMP:
  
  • mediastinal masses are very rare

Question 6

What is the clinical presentation for

B-ALL ?

Answer 6

• often present with consequences of bone marrow failure:
  
  • thrombocytopenia
  • anemia
  • neutropenia
  • leukocyte count may be normal, decreased or increased
• Lymphadenopathy, splenomegay and hepatomegaly are frequent
• limited LBL presentations are usually asymptomatic
  
  • common in head and neck of kids
  • marrow can be involved by by definition for LBL <25%

Question 7

What is the morphology of B lymphoblasts in the

aspirate smear ?

Answer 7

• vary in morphology from small blats with scant cytoplasm, condense nuclear chromatin and indistinct nucleoli or larger cells with moderate amounts of light-blue to blue-grey cytoplasm (with occasional vacuoles), dispersed chromatin and multiple, nucleoli
• nuclei can be round or show convolutions
• 10% of cases have coarse azurophilic granules
• some have cytoplasmic pseudopods (hand-mirror cells)

Question 8

How are hematogones morphologically

different from B lymphoblasts ?

Answer 8

• typically have even higher N:C ratios
• more homogeneous chromatin
• no discernible nucleoli

Question 9

What is the morphology of B-ALL in

the bone marrow ?

Answer 9

• relatively uniform with round to oval nuclei
  
  • can be indented or convoluted though
• nucleoli range from inconspicuous to prominent
• chromatin is finely dispersed
• LBL
  
  • usually diffuse pattern of involvement but rarely can be paracortical
  • in soft tissue single filing is common
  • mitotic figures are usually numerous and can have a starry sky pattern

Question 10

What is the immunophenotype of B-ALL ?

Answer 10

• CD19, cCD79a, and cCD22 - usually in combination and high intensity
• Note: CD79a IHC is frequently positive in T-ALL
• CD10, sCD22, CD24, Pax-5, and TDT (most cases)
  
  • Pax-5 is the most sensitive B cell lineage marker in tissues but can also be positive in AML with t(8;21)
• variable for CD34 and CD20
• CD45 when present is dim
• CD13 and CD33 (myeloid associated markers)
  
  • may be expressed but does not rule out a B-ALL

IMP: strong to moderate MPO indicates an AML or MPAL with B and myeloid differentiation

Question 11

What is the immunophenotype of early,

pre-cursor B-ALL ?

Answer 11

• positive for:
  
  • CD19, cCD79a, cCD22 and nuclear TdT
• this is the so-called pro-B-ALL

Question 12

What is the immunophenotype of B-ALL

intermediate stage/common type ?

Answer 12

• CD19, cCD79a, cCD22
• CD10 **

Note:

• in the most mature precursor B-ALL blasts express cytoplasmic mu chain and occasional heavy chain without light chains
• IMP: clonal surface immunoglobulins are characteristically absent but their presence does NOT exclude a B-ALL

Question 13

What are the findings of the

antigen receptor genes ?

Answer 13

• nearly all cases of B-ALL have clonal rearrangements of IGH
• IMP:
  
  • T-cell receptor gene rearrangments may be seen in up to 70% of cases
  • so not helpful for lineage determination

Question 14

What are some cytogenetic abnormalities

that are frequently seen in B-ALL but

not disease defining entities ?

Answer 14

• del(6q)
• del(9p)
• del(12p)
• these are often seen but do not have an impact on prognosis

Question 15

What is a rare cytogenetic abnormality with

very poor prognosis ?

Answer 15

• t(17;19)(q22;p13.3)
  
  • results in the TCF3-HLF fusion
  • very poor prognosis
  • not enough cases to make it it’s own designated entity but may be one in the future

Question 16

What are the prognosis and predictive factors

for B-ALL, NOS ?

Answer 16

• B-ALL has a good prognosis in children but less favorable prognosis in adults
  
  • overall complete remission rate > 95% in kids
  • vs. 60-85% in adults
• more intensive therapy improves cure rates
  
  • some data suggesting younger adults should receive the pediatric regimens as they may improve outcome
• prognosis of B-LBL
  
  • similar to B-ALL
  • relatively favorable

Question 17

What are associated with adverse prognosis ?

Answer 17

• infancy
• older patient age
• higher WBC count
• slow response to initial therapy as assessed by morphologic examination of blood and bone marrow
• presence of minimal residual disease after therapy