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Leukemia - Acute


B cell acute lymphoblastic leukemia (ALL) / lymphoblastic lymphoma (LBL)

Reviewer: Daniela Mihova, M.D. (see Reviewers page)
Revised: 20 March 2013, last major update September 2012
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.


● Current 2008 WHO classification: B lymphoblastic leukemia / lymphoma, NOS or B lymphoblastic leukemia / lymphoma with recurrent genetic abnormalities
● See also lymphomas: B cell chapter
● Also called B cell acute lymphoblastic leukemia / lymphoblastic lymphoma, pre B ALL / LBL
● 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
● 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)

Prognostic features

● Favorable prognosis: age 1-10 years, female, white; preB phenotype, hyperdiploidy>50, t(12,21), WBC count at presentation <50x108/L, 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 1 (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 WBC at presentation, hypodiploidy, near tetraploidy, 17p- and MLL rearrangements t(v;11q23); CD10-; non-traumatic tap with > 5% blasts or traumatic tap (7%); also increased microvessel staining using CD105 in children (Leuk Res 2007;31:1741), MDR1 expression in children (Oncol Rep 2004;12:1201) and adults (Blood 2002;100:974), 25%+ blasts on morphology on day 15, remission status after induction ≥ 5% blasts on morphology and ≥ 0.1% blasts on flow or PCR

Case reports

● 12 month old girl and 13 month old boy with mature phenotype but no translocations (Arch Pathol Lab Med 2003;127:1340)
● 56 year old man with ALL arising from follicular lymphoma (Arch Pathol Lab Med 2002;126:997)
● 76 year old man with basal cell carcinoma (Diagn Pathol 2007;2:32)
● With hemophagocytic lymphohistiocytosis (Pediatr Blood Cancer 2008;50:381)


● Chemotherapy cures more children than adults; adolescents benefit from intensive regimens (Hematology Am Soc Hematol Educ Program 2005:123)

Micro 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
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
Other tissues: may have “starry sky” appearance similar to Burkitt lymphoma; collagen dissection, periadipocyte growth pattern and single cell linear filing

Micro images

Peripheral blood:
Blasts with scant cytoplasm  Blasts have L1 morphology,  L1 type has smaller blasts with minimal cytoplasm,
but prominent nucleoli       but mature phenotype      coarse chromatin, some cleaved nuclei or irregular
                              contours and no distinct nucleoli

Lymphoblastic lymphoma:
TdT negative cases     Figure a: H&E; b: CD179b; c/d: CD179a
              (FF is frozen tissue, PF is paraffin fixed)

Lymphoblastic lymphoma with basal cell carcinoma:
                       TdT+          CD79a+        CD34+

Kidney involvement

19 year old man with hypertension and renal insufficiency

Positive stains

● TdT (negative in 3%, Am J Clin Pathol 2004;121:810), CD19, CD22, CD79a, PAX5
● CD34 (75%), usually cytoplasmic (not surface) immunoglobulin, but rarely surface immunoglobulin (Am J Clin Pathol 2004;121:512)
● Also CD9, CD24, CD38, CD45 and HLA-DR; variable CD10 and CD20 (Blood 2006;108:3302)
● Myeloid antigens CD13 or CD33 in 27% (Exp Mol Pathol 2007;83:471), particularly pediatric cases with Philadelphia chromosome or 11q23 rearrangements (Am J Clin Pathol 1999;111:467)

Negative stains

● Surface IgM, CD15, CD30

Flow cytometry images

Patient with relapse of precursor B-ALL illustrating multiple antigenic aberrancies

Molecular description

● Usually chromosomal abnormalities

Differential diagnosis

Based on morphology:
AML - prominent nucleoli, delicate chromatin and fine azurophilic cytoplasmic granules
Blastic variant of mantle cell lymphoma
Burkitt lymphoma
Ewing sarcoma: negative for CD79a, CD43, TdT and immunoglobulin or T cell receptor rearrangement, vimentin++
Granulocytic sarcoma
Hodgkin lymphoma

End of Leukemia - Acute > PreB ALL > B cell acute lymphoblastic leukemia (ALL) / lymphoblastic lymphoma (LBL)

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