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  • Surgical Pathology Criteria

    Precursor T Lymphoblastic Leukemia / Lymphoma


    • Neoplasm of T-lineage lymphoblasts which may form lymphomatous masses and/or involve the blood and bone marrow

    Alternate/Historical Names

    • Acute lymphoblastic leukemia, FAB L1 and L2

    Diagnostic Criteria

    • May present as leukemia, lymphoma, or both
      • Lymphoma characteristically presents in anterior mediastinum (less commonly lymph nodes), < 25% lymphoblasts in bone marrow
      • Leukemia if > 25% lymphoblasts in bone marrow or lack of mass lesion
    • Histology is high grade
      • Tissue biopsies are often effaced
      • Tingible body macrophages may impart “starry sky appearance”
    • Cytology is quite variable
      • Small to medium-sized round blasts with high N:C ratio, inconspicuous nucleoli, and finely stippled chromatin
      • Large blasts with convoluted nuclei, abundant clear cytoplasm, and prominent nucleoli
      • Range of blast sizes in any one patient is typical
    • Precursor T immunophenotype

    Supplemental studies

    Immunohistology and Flow Cytometry

    • Non-lineage specific markers
      • TdT > 95%
      • CD10 subset of cases
      • CD34 subset of cases
    • T lineage markers
      • Usually positive:
        • CD3 (highly lineage-specific)
          • cytoplasmic CD3 >95% of cases
          • surface CD3 infrequent
        • CD7 >95% of cases
      • Subset of cases positive:
        • CD1a
        • CD2
        • CD5
        • CD4
        • CD8
        • CD4, CD8 double positive ~50%
    • Aberrant lineage markers expressed in a minority of cases
      • B-lineage
        • CD79a (10%)
      • Myeloid
        • CD13, CD33 and others (~15%)
      • These markers alone are not sufficient for a leukemia to be considered biphenotypic (e.g. combined B and T lineage or combined T and myeloid lineage)
        • See the scoring criteria below for further information
    • Scoring system for lineage assignment of leukemias by the European Group for the Immunologic Classification (EGIL)






      Cytoplasmic CD79a*

      CD3 (membrane/cytoplasmic)



      Cytoplasmic IgM




      Cytoplasmic CD22







































      • A score of 2.5 is considered sufficient to assign a lineage
      • CD79a may also be expressed in a subset of T lymphoblastic leukemia/lymphoma

    Genetic study

    • Cytogenetic/molecular studies show abnormalities in > 50% of cases
      • May be useful in monitoring for residual disease, but unlike in B-lymphoblastic lymphoma/leukemia,  do not add prognostic information
    • May show clonal T cell receptor rearrangement

    Differential Diagnosis

    Type B1 Thymoma Precursor T Lymphoblastic Leukemia / Lymphoma
    Scattered epithelial cells (may require anti-keratin stain) Only keratin positive cells should be overrun thymus
    Scattered pale medullary foci Lacks medullary foci
    Thick fibrous capsule and septa produce large lobules Lacks thick fibrous capsule and septa and lobular growth pattern
    Typically older adult but may occur in children Typically adolescent or pediatric
    No circulating blasts Circulating blasts
    Variable expression of surface CD3, CD4, CD8 in a given case Uniform phenotype in a given case
  • Lymphocytes have same basic phenotype in both: predominantly immature T cells with mature T cells restricted to medullary foci
  • May be a significant problem on small biopsies and in cases analyzed by flow

    Normal Thymus Precursor T Lymphoblastic Leukemia / Lymphoma
    No circulating blasts Circulating blasts
    Histopathology shows normal epithelial component No neoplastic epithelial component on histopathology (effaced epithelial component may be present)
    Histopathology shows lobularity with cortical / medullary differentiation Histopathology shows no normal architecture
    Flow cytometry of normal thymus will show a preponderance of precursor T cells with a phenotype that may be indistinguishable from leukemia / lymphoma


    Precursor B Lymphoblastic Leukemia / Lymphoma Precursor T Lymphoblastic Leukemia / Lymphoma
    10% of precursor lymphoblastic lymphomas 90% of precursor lymphoblastic lymphomas
    Frequently involves skin and bone Frequent mediastinal mass
    B lineage (usually CD19+, CD79a+ at a minimum) T lineage (usually CD3+, CD7+ at a minimum)
    Both are TdT+ and may be CD34+


    Burkitt Lymphoma Precursor T Lymphoblastic Leukemia / Lymphoma
    Presents as soft tissue mass, rarely mediastinal Frequently presents as mediastinal mass
    B cell phenotype (usually CD19+, CD20+, CD79a+) T cell phenotype (usually CD3+, CD7+ at a minimum)
    Mature phenotype (TdT and CD34 negative) Immature phenotype (usually TdT+, sometimes CD34+)
    Translocation involving myc gene No myc translocation


    CD4+ CD56+ Hematodermic Neoplasm (Blastic NK Cell Lymphoma) Precursor T Lymphoblastic Leukemia / Lymphoma
    Skin lesions usually predominate Frequently presents as mediastinal mass
    Usually negative for T cell markers (rare cases may be positive for TdT) Immature T cell phenotype (usually CD3+, CD7+, TdT+ at a minimum)


    • Seen across both pediatric and adult age groups
      • Most common in adolescent/young adult male
    • Most common presentation is anterior mediastinal mass
      • May present acutely with superior vena cava syndrome
      • Other lymphoid sites (lymph nodes, Waldeyer’s ring) or soft tissue sites may also be involved
      • Peripheral blood often shows high blast count
    • High risk disease treated with aggressive chemotherapy and radiation
      • Prognosis is best in the pediatric age group

    Grading / Staging / Report

    Grading and Staging are not applicable

    The pathology report should contain the following information:

    • Diagnosis in the World Health Organization (WHO) classification
      • Equivalent diagnosis in other classifications used by relevant clinicians
    • Results of supplementary studies if performed
    • Relationship to other specimens from the same patient
    • Information relevant to staging if available


    Blastic lymphomas

    Precursor lymphoid lesions


    • Warnke RA, Weiss LM, Chan JKC, Cleary ML, Dorfman RF . Tumors of the Lymph Nodes and Spleen, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 14, 1995
    • Jaffe ES, Harris NL Stein H, Vardiman JW . Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues, World Health Organization Classification of Tumours 2001
    • Han X and CE Bueso-Ramos. Precursor T acute lymphoblastic leukemia/ lymphoblastic lymphoma and acute biphenotypic leukemias. Am J Clin Pathol 2007 Apr;127(4):528-544.
    • European Group for the Immunological Characterization of Leukaemias (EGIL). The value of c-kit in the diagnosis of biphenotypic acute leukemia.  Leukemia 1998; 12: 2038.
    • Li S, Juco J, Mann KP, Holden JT. Flow cytometry in the differential diagnosis of lymphocyte-rich thymoma from precursor T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma. Am J Clin Pathol. 2004 Feb;121(2):268-74. 
    • Thalhammer-Scherrer R, Mitterbauer G, Simonitsch I, Jaeger U, Lechner K, Schneider B, Fonatsch C, Schwarzinger I.The immunophenotype of 325 adult acute leukemias: relationship to morphologic and molecular classification and proposal for a minimal screening program highly predictive for lineage discrimination. Am J Clin Pathol. 2002 Mar;117(3):380-9.


    Dita Gratzinger MD PhD
    Yasodha Natkunam MD PhD

    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Last Update: September 30, 2007

    Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/
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