Flow cytometric approach to the diagnosis and classification of T- and NK-cell lymphoid neoplasms
| Disease entities to consider . | Distinguishing phenotypic features . | Additional diagnostic information . |
|---|---|---|
| CD4+ CD8− | ||
| CTCL/Sézary syndrome | Often CD7−, CD26−, CD25+/− (with heterogeneous staining intensity). | Confirm characteristic morphology and clinical presentation. HYLV-1− |
| T-PLL | Usually lacks significant phenotypic aberrancy. CD16−, CD56−, CD57−. | 80% t(14;14)(q11;q32) or inv(14)(q11;q32). TCL1 protein overexpression. |
| Adult T-cell leukemia/lymphoma | CD7−, CD25+ (uniform bright intensity). | HTLV-1+, endemic to Japan and Caribbean. |
| Anaplastic large cell lymphoma | Often loss of many pan–T-cell antigens. Strong uniform CD30+, Alk-1 protein+/−. CD56+/−, CD13+/−, CD15+/−, CD33+/−. Cytotoxic granule–associated protein (+). | Anaplastic morphology, except in small cell/monomorphic variant. ALK gene rearrangement. |
| Angioimmunoblastic TCL | Often aberrant phenotype (eg, decreased intensity CD7 and CD3). CD10+/−. | Characteristic morphology. Proliferative follicular dendritic meshwork, CXCL13+, scattered EBV+ B cells. |
| Peripheral TCL, NOS | Variable phenotype, often aberrant loss of CD5 and/or CD7. | Diagnosis by exclusion of other distinct disease entities. |
| CD4−/CD8+ | ||
| T-cell large granular lymphocyte leukemia | Frequent aberrant expression CD5 and/or CD7. CD16+/−, CD56+/−,CD57+. TIA-1+, granzyme-B+, perforin+. | Often LGL morphology. Usually indolent course, associated with rheumatoid arthritis and cytopenias (eg, neutropenia and anemia). EBV−. |
| Subcutaneous panniculitis-like TCL | Usually only focal CD56, EBV−, TCR α/β, TIA-1+, granzyme-B+, perforin+ | Infiltrate in subcutis with rimming fat droplets, beanbag histiocytes. Must distinguish from lupus profundus. |
| Hepatosplenic TCL | Usually CD5− and CD7+. CD16+/−, CD56+, CD57−, TIA-1+, granzyme-B−, perforin−. | Often TCR γ/δ but may be TCR α/β, EBV−. Frequent isochromosome 7q. Usually aggressive clinical course. |
| CD4+/CD8+ | ||
| T-PLL | Usually lacks significant phenotypic aberrancy. CD16−, CD56−, CD57−. | 80% t(14;14)(q11;q32). TCL1 protein overexpression. |
| Adult T-cell leukemia/lymphoma | CD7−, CD25+ (uniform bright). | HTLV-1+, endemic to Japan and Caribbean. |
| Peripheral TCL, NOS | Variable phenotype, often aberrant loss of CD5 and/or CD7. | Diagnosis by exclusion of other distinct disease entities. |
| CD4−/CD8− | ||
| Enteropathy-associated TCL | CD5−, CD3+, CD7+, CD103+, CD56+/−. TIA-1+, granzyme-B+, perforin+. | CD30+/−, EBV−. FISH for gains 9q33–34. History of celiac disease. |
| Hepatosplenic TCL | Usually CD5− and CD7+. CD16+/−, CD56+, CD57−. TIA-1+, granzyme-B−, perforin−. | Often TCR δ but may be TCR α/β, EBV−. Frequent isochromosome 7q. Usually aggressive clinical course. |
| Nonhepatosplenic γ/δ TCL | CD5−, CD56+, mostly CD57−, TCR γ/δ. TIA-1+, granzyme-B+, perforin+. | Skin, mucosal sites, and other extranodal locations. EBV often positive in mucosal and negative in cutaneous lymphoma. |
| Disease entities to consider . | Distinguishing phenotypic features . | Additional diagnostic information . |
|---|---|---|
| CD4+ CD8− | ||
| CTCL/Sézary syndrome | Often CD7−, CD26−, CD25+/− (with heterogeneous staining intensity). | Confirm characteristic morphology and clinical presentation. HYLV-1− |
| T-PLL | Usually lacks significant phenotypic aberrancy. CD16−, CD56−, CD57−. | 80% t(14;14)(q11;q32) or inv(14)(q11;q32). TCL1 protein overexpression. |
| Adult T-cell leukemia/lymphoma | CD7−, CD25+ (uniform bright intensity). | HTLV-1+, endemic to Japan and Caribbean. |
| Anaplastic large cell lymphoma | Often loss of many pan–T-cell antigens. Strong uniform CD30+, Alk-1 protein+/−. CD56+/−, CD13+/−, CD15+/−, CD33+/−. Cytotoxic granule–associated protein (+). | Anaplastic morphology, except in small cell/monomorphic variant. ALK gene rearrangement. |
| Angioimmunoblastic TCL | Often aberrant phenotype (eg, decreased intensity CD7 and CD3). CD10+/−. | Characteristic morphology. Proliferative follicular dendritic meshwork, CXCL13+, scattered EBV+ B cells. |
| Peripheral TCL, NOS | Variable phenotype, often aberrant loss of CD5 and/or CD7. | Diagnosis by exclusion of other distinct disease entities. |
| CD4−/CD8+ | ||
| T-cell large granular lymphocyte leukemia | Frequent aberrant expression CD5 and/or CD7. CD16+/−, CD56+/−,CD57+. TIA-1+, granzyme-B+, perforin+. | Often LGL morphology. Usually indolent course, associated with rheumatoid arthritis and cytopenias (eg, neutropenia and anemia). EBV−. |
| Subcutaneous panniculitis-like TCL | Usually only focal CD56, EBV−, TCR α/β, TIA-1+, granzyme-B+, perforin+ | Infiltrate in subcutis with rimming fat droplets, beanbag histiocytes. Must distinguish from lupus profundus. |
| Hepatosplenic TCL | Usually CD5− and CD7+. CD16+/−, CD56+, CD57−, TIA-1+, granzyme-B−, perforin−. | Often TCR γ/δ but may be TCR α/β, EBV−. Frequent isochromosome 7q. Usually aggressive clinical course. |
| CD4+/CD8+ | ||
| T-PLL | Usually lacks significant phenotypic aberrancy. CD16−, CD56−, CD57−. | 80% t(14;14)(q11;q32). TCL1 protein overexpression. |
| Adult T-cell leukemia/lymphoma | CD7−, CD25+ (uniform bright). | HTLV-1+, endemic to Japan and Caribbean. |
| Peripheral TCL, NOS | Variable phenotype, often aberrant loss of CD5 and/or CD7. | Diagnosis by exclusion of other distinct disease entities. |
| CD4−/CD8− | ||
| Enteropathy-associated TCL | CD5−, CD3+, CD7+, CD103+, CD56+/−. TIA-1+, granzyme-B+, perforin+. | CD30+/−, EBV−. FISH for gains 9q33–34. History of celiac disease. |
| Hepatosplenic TCL | Usually CD5− and CD7+. CD16+/−, CD56+, CD57−. TIA-1+, granzyme-B−, perforin−. | Often TCR δ but may be TCR α/β, EBV−. Frequent isochromosome 7q. Usually aggressive clinical course. |
| Nonhepatosplenic γ/δ TCL | CD5−, CD56+, mostly CD57−, TCR γ/δ. TIA-1+, granzyme-B+, perforin+. | Skin, mucosal sites, and other extranodal locations. EBV often positive in mucosal and negative in cutaneous lymphoma. |
+ indicates usually positive; −, usually negative; +/−, may be positive or negative; d, dim or weak intensity; I, intermediate intensity; b, bright or strong intensity.