Bone marrow neoplastic
Bone marrow - plasma cell and lymphoid neoplasms
Precursor lymphoid neoplasms
B cell lymphoblastic lymphoma / leukemia NOS


Topic Completed: 1 March 2013

Minor changes: 19 April 2020

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PubMed Search: B lymphoblastic leukemia [title]

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Cite this page: Mihova D. B cell lymphoblastic lymphoma / leukemia NOS. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowneoplasticBLL.html. Accessed August 8th, 2020.
Definition / general
  • 6050 cases / year in US in 2012 (National Cancer Institute), peaks at age 4; usually age 15 years or less
  • 80% of childhood leukemia is ALL
  • Higher incidence in whites, males and advanced (not developing) countries
  • 85% are B cell, 15% are T cell, but both often express aberrant myeloid or lymphoid associated antigens
  • Note that only 10 - 20% of lymphoblastic lymphoma is B cell lineage
  • Risk factors: in utero radiation, Down syndrome, ataxia telangiectasia, but most cases have no known cause
  • Symptoms: abrupt stormy onset, symptoms related to bone marrow depression (fatigue, fever, bleeding), bone pain and tenderness (due to marrow expansion), joint pain, generalized lymphadenopathy, hepatosplenomegaly, testicular involvement, CNS manifestations
  • Atypical presentation: hypercalcemia, bone lesions and no circulating blasts
  • Laboratory: anemia common, platelet count < 100K in 75% and < 10K in 15%; leukopenia (25%), WBC > 100K (10%)
  • Diagnosis: immunostains required for diagnosis
  • Relapse: blasts usually unchanged; may progress from L1 to L2, TdT positive to negative (25%), gain or lose an antigen (CD10, HLA-DR), evolve clonally (75%) or evolve to AML; CNS relapse common
  • Pathophysiology
    • Tumors are derived from pre-germinal center naive B cells with unmutated VH region genes
    • Have multiple immunophenotyping aberrancies relative to normal B cell precursors (hematogones); at relapse, 73% show loss of 1+ aberrance and 60% show new aberrancies (Am J Clin Pathol 2007;127:39)
    Clinical features
    • Usually children
    • B acute lymphoblastic leukemia presents with pancytopenia due to extensive marrow involvement, stormy onset of symptoms, bone pain due to marrow expansion, hepatosplenomegaly due to neoplastic infiltration, CNS symptoms due to meningeal spread and testicular involvement
    • B acute lymphoblastic lymphoma often presents with cutaneous nodules, bone or nodal involvement, < 25% lymphoblasts in bone marrow and peripheral blood; aleukemic cases are usually asymptomatic
    • Depending on specific leukemia, arises in either hematopoietic stem cell or B-cell progenitor
    WHO classification
      Precursor B lymphoblastic leukemia / lymphoblastic lymphoma:
    • ALL with t(9;22)(q34;q11.2); BCR-ABL (Philadelphia chromosome)
    • ALL with t(v;11q23) (MLL rearranged)
    • ALL with t(1;19)(q23;p13.3); TCF3-PBX1 (E2A-PBX1)
    • ALL with t(12;21)(p13;q22); ETV6-RUNX1 (TEL-AML1)
    • Hyperdiploid > 50
    • Hypodiploid
    • t(5;14)(q31;q32); IL3-IGH
    Prognostic factors
    • Cytogenetics / FISH is single most important prognostic factor for adults (Blood 2008;111:2563)
    • Favorable prognosis: age 1 - 10 years, female, white; preB phenotype, hyperdiploidy > 50, t(12,21), normal WBC count at presentation, non-traumatic tap with no blasts in CNS, rapid response to chemotherapy < 5% blasts on morphology on day 15, remission status after induction < 5% blasts on morphology and < 0.01% blast on flow or PCR, CD10+
    • Intermediate prognosis: hyperdiploidy 47 - 50, diploid, 6q- and rearrangements of 8q24
    • Unfavorable prognosis: under age 2 (usually have 11q23 translocations) or over age 10; t(9;22) (but not if age 59+ years, Am J Clin Pathol 2002;117:716); male, > 50x108/L, hypodiploidy, near tetraploidy, 17p-, MLL rearrangements and t(v;11q23); CD10- preB ALL; non-traumatic tap with > 5% blasts or traumatic tap with 7%+ blasts, also increased microvessel staining using CD105 in children (Leuk Res 2007;31:1741), MDR1 expression in children (Oncol Rep 2004;12:1201) or adults (Blood 2002;100:974)
    Case reports
    Treatment
    Microscopic (histologic) description
    • Bone marrow biopsy: usually markedly hypercellular with reduction of trilinear maturation; cells have minimal cytoplasm, medium sized nuclei that are often convoluted, moderately dense chromatin and indistinct nucleoli, brisk mitotic activity
    • Blasts have scant agranular cytoplasm, no Auer rods, coarse to fine chromatin, often indistinct nucleoli and no dysplastic myeloid cells
    • Bone marrow: hypercellular, high percentage of lymphoblasts
    • Children: 80% are L1, 10 - 20% L2 and < 5% L3
    • Adults: 35% are L1, 60% L2 and < 5% L3
    • Other tissues: may have "starry sky" appearance similar to Burkitt lymphoma; collagen dissection, periadipocyte growth pattern and single cell linear filing
    Microscopic (histologic) images

    L1 type (blood smears):
    Missing Image

    Blasts have minimal cytoplasm, variable
    nuclear size and chromatin density, irregular
    nuclear contour, some small nucleoli

    Missing Image

    Blasts have moderate cytoplasm, round
    nuclei of variable size, coarse chromatin and
    some resemble mature lymphocytes



    L1 type (bone marrow smears):
    Missing Image

    Blasts contain large cytoplasmic azurophilic
    granules (uncommon), but were B
    cells by IHC and cytochemistry



    L1 type (bone marrow biopsy):
    Missing Image

    Markedly hypercellular marrow
    with lymphoblasts replacing
    normal marrow elements

    Missing Image

    Lymphoblasts occupy marrow,
    have minimal cytoplasm and
    indistinct cell borders, convoluted
    nuclei, angulated borders

    Missing Image

    Lymphoblasts are small with
    more condensed chromatin

    Missing Image

    Marrow contains lymphoblasts,
    one megakaryocyte, normoblasts in
    upper half and occasional eosinophils
    and eosinophil precursors



    L1 type (stains):
    Missing Image

    Lymphoblasts have block and
    coarse granular PAS staining



    L2 type (blood smears):
    Missing Image

    Three large lymphoblasts have
    moderate cytoplasm, large nuclei
    with coarsely reticular chromatin
    and 1 - 3 prominent nucleoli

    Missing Image

    Lymphoblasts have variable size,
    moderate cytoplasm, markedly
    irregular nuclei with coarse
    chromatin and distinct nucleoli

    Missing Image

    Most lymphoblasts have variable
    size, reticular chromatin with
    prominent nucleoli and some
    have L1 features

    Missing Image

    Blasts have cytoplasmic
    azurophilic granules (uncommon)



    L2 type (bone marrow smears):
    Missing Image

    Large lymphoblasts with cytoplasm that has numerous,
    sharply defined clear vacuoles similar to L3, non-L3 features
    are reticular chromatin, prominent nucleoli, TdT+ and CD10+



    L2 type (bone marrow biopsy):
    Missing Image

    Relatively large lymphoblasts with
    variable nuclear shape, dispersed
    chromatin and prominent nucleoli



    L3 type (bone marrow smears):
    Missing Image

    No prominent vacuoles, dispersed chromatin and
    more obvious nucleoli than usually observed in L3,
    diagnosed as ALL-L3 and non-Burkitt type



    L3 type (stains):
    Missing Image

    Strong cytoplasmic staining by methyl green pyronine (left),
    vacuoles are Oil Red O positive (right)

    Cytology description
    • Bone marrow smears: small to intermediate blast-like cells with scant, variably basophilic cytoplasm, round / oval or convoluted nuclei, fine chromatin and indistinct nucleoli; frequent mitotic figures; may have "starry sky" appearance similar to Burkitt lymphoma; may have large lymphoblasts with 1 - 4 prominent nucleoli resembling myeloblasts; usually no sclerosis
    • Peripheral smear: leukoerythroblastosis common with granulocyte precursors and nucleated RBCs, lymphoblasts, occasionally reactive lymphocytes and rarely marked eosinophilia
    Cytology images
    Peripheral blood:
    Missing Image

    L1 type has smaller blasts with minimal
    cytoplasm, coarse chromatin, some
    cleaved nuclei or irregular contours
    and no distinct nucleoli


    Images hosted on other servers:

    Peripheral smear images:
    Missing Image

    Blasts with scant cytoplasm
    and prominent nucleoli

    Enzyme cytochemistry
    • Negative for myeloperoxidase, chloroacetate esterase, nonspecific esterase (usually) and only rarely positive for Sudan Black B (Mod Pathol 1992;5:68)
    • Positive for PAS (75%, coarse clumping corresponds to glycogen), acid phosphatase (T-ALL has focal paranuclear staining)
    • Only L3 stains for glycogen with Sudan Black B and PAS
    Positive stains
    Negative stains
    Molecular / cytogenetics description
    • 90% have cytogenetic abnormalities, usually hyperdiploidy (> 50 chromosomes), also pseudodiploidy (46 chromosomes but structural anomalies), t(12,21); t(9,22) [Philadelphia chromosome] and t(4,11)
    Electron microscopy images

    Images hosted on PathOut server:

    L1 type:
    Missing Image

    Cytoplasm has small mitochondria, small Golgi region, scattered polyribosomes and
    occasional strands of round endoplasmic reticulum, nucleus is indented with a small
    nucleolus, chromatin is condensed and concentrated at nuclear periphery



    L2 type:
    Missing Image

    Large lymphoblast with moderate cytoplasm, dispersed chromatin
    with peripheral condensation and large prominent nucleolus



    L3 type:
    Missing Image

    Abundant cytoplasm with numerous polyribosomes and large lipid vacuoles (arrow)
    nuclei have peripherally condensed chromatin and 1+ prominent nucleoli

    Differential diagnosis
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