Definition
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
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)
Score
B-lymphoid
T-lymphoid
Myeloid
2
Cytoplasmic CD79a*
CD3 (membrane/cytoplasmic)
MPO
Cytoplasmic IgM
Anti-TCR
Cytoplasmic CD22
1
CD19
CD2
CD117
CD20
CD5
CD13
CD10
CD8
CD33
CD10
CD65
0.5
TdT
TdT
CD14
CD24
CD7
CD15
CD1a
CD64
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
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)
Clinical
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
Lists
Blastic lymphomas
Precursor lymphoid lesions
Bibliography
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.
Authors
Dita Gratzinger MD PhD
Last Update: September 30, 2007
