Bcl

CLASSIFICAZIONE DEI LINFOMI

Caratteristiche immunofenotipiche e genotipiche delle forme incluse nella classificazione WHO

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LINFOMI B

Precursor B-lymphoblastic leukemia/lymphoma:

slg-, cytoplasmic µ chain 30%, CD19+, CD20-/+, CD22+, CD79a+, TdT+, HLA-DR+, CD10+/-, CD34+/-, CD13-/+, CD33-/+, IgH gene rearrangement +/-, IgL gene rearrangement -/+, TCR gene rearrangement -/+, variable cytogenetic abnormalities

B-cell chronic lymphocytic leukemia (B-CLL)/prolymphocytic leukemia (B-PLL)/small lymphocytic lymphoma: (B-CLL)

Faint SIgM+, SIgD+/-, CIg-/+, panB+, CD5+, CD10-, CD23+, CD43+, CD11c-/+, CD25-/+ (B-PLL) More likely strong SIg+, CD22+, and CD5-. All of above - IgH and IgL gene rearrangements; trisomy 12-/+; 13q abnormalities-/+

Lymphoplasmacytic lymphoma:

SIgM+, SIgD-/+, CIg+, PanB+, CD5-, CD10-, CD43+/-, CD25-/+; IgH and IgL gene rearrangements

Mantle cell lymphoma:

SIgM+, SIgD+, lambda>kappa, PanB+, CD5+, CD10-/+, CD23-, CD43+, CD11c-, CD25-; IgH and IgL gene rearrangements, t(11;14); bcl-1 gene rearrangements (CCND1/cyclinD1/PRAD1) common

Follicular center lymphoma, follicular:

SIg+ (usually IgM +/- IgD, IgG, IgA), PanB+, CD10+/-, CD5-, CD23-/+, CD43-, CD11c-, CD25-; overexpression of bcl-2 protein useful in distinction to reactive follicles; IgH and IgL gene rearrangements, t(14;18) with rearranged bcl-2 gene in 70-95% of cases

Extranodal marginal zone B-cell lymphoma (low-grade B-cell lymphoma of MALT type):

SIg+ (IgM or IgA or IgG), SIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD43-/+; IgH and IgL gene rearrangements, bcl-1 and bcl-2 germline, trisomy 3 or t(11;18)(q21;q21) may be seen

Nodal marginal zone B-cell lymphoma:

SIgM+, SIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD43-/+; IgH and IgL gene rearrangements, bcl-1 and bcl-2 germline

Splenic marginal zone B-cell lymphoma:

CIgM+, CIgD-, CIg-/+, PanB+, CD5-, CD10-, CD23-, CD25-, IgH and IgL gene rearrangements

Hairy cell leukemia:

SIg+ (IgM, IgD, IgG, or IgA), PanB+, DBA44+, CD11c++, CD25+, CD103+ (mucosal lymphocyte antigen as detected by B-ly7), tartrate-resistant acid phosphatase+; IgH and IgL gene rearrangements

Plasmacytoma/myeloma:

CIg+ (IgG, IgA, rare IgD, IgM, or IgE or light chain only), PanB-, (CD19, CD20, CD22), CD79a+/-, CD45-/+, HLA-DR-/+, CD38+, CD56+/-, EMA-/+, CD43+/-; IgH and IgL gene rearrangements or deletions, occasional cases t(11;14)

Diffuse large B-cell lymphoma:

SIg+/-, CIg-/+, PanB+, CD45+/-, CD5-/+, CD10-/+ (weak); IgH and IgL gene rearrangements; bcl-2 gene rearranged in 30% of cases, bcl-6/LAZ3 gene (chromosome 3q27) rearranged in 30% of cases, c-myc gene rearrangement uncommon

Primary mediastinal large B-cell lymphoma:

SIg-/+, PanB+, (especially CD20, CD79a), CD45+/-, CD15-, CD30-/+ (weak); IgH and IgL gene rearrangements

Burkitt’s lymphoma:

SIgM+, PanB+, CD5-, CD10++, CD23-; IgH and IgL gene rearrangements, t(8;14) and variants t(2;8) and t(8;22); rearranged c-myc gene. EBV common (95%) in endemic cases and infrequent (15-20%) in sporadic cases, intermediate incidence (30-40%) in HIV-positive cases

High grade B-cell lymphoma, Burkitt-like:

SIg+/- (IgM or IgG), CIg-/+, PanB+, CD5-, CD10-/+; IgH and IgL gene rearrangements, infrequent rearrangment of c-myc gene, bcl-2 gene rearranged in 30% of cases

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LINFOMI T

Precursor T-lymphoblastic lymphoma/leukemia:

TdT+, CD7+, CD3+/-, variable expression of other PanT antigens, CD1a+/-, often CD4 and CD8 double positive or negative, Ig-, PanB-; variable rearrangement of TCR genes; IgH gene rearrangement -/+, most common chromosomal abnormalities involve 14q11-14 or 7q35; variable cytogenetic abnormalities reported

T-cell CLL/prolymphocytic leukemia:

TdT-, PanT+, (CD2, CD3, CD5, CD7) CD25-, CD4+/CD8->CD4+/CD8+>CD4-/CD8-; TCR gene rearrangements, 75% of cases show inv 14(q11;q32)

Large granular lymphocytic leukemia, T-cell type:

TdT-, PanT+ (CD2, CD3+, CD5+/-, CD7-), TCR+, CD4-, CD8+, CD16+, CD56-, CD57+, CD25-; most cases show clonal rearrangements of TCR genes

Large granular lymphocytic leukemia, NK cell type:

TdT-, CD2+, CD3-, TCR-, CD4-, CD8+/-, CD16+/-, CD56+/-, CD57+/-, CD25-; TCR and Ig genes are germline

Mycosis fungoides/Sézary syndrome:

TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-/+), most cases CD4+/CD8-, CD25-/+; TCR gene rearrangements

Peripheral T-cell lymphomas, unspecified:

TdT-, PanT variable (CD2+/-, CD3+/-, CD5+/-, CD7-/+), most cases CD4+, some cases CD8+, CD4-/CD8-, or CD4+/CD8+; TCR gene rearrangements usual

Hepatosplenic g-d T-cell lymphoma (provisional):

CD2+, CD3+, TCRgd+, TCRab-, CD5-, CD7+, CD4-, CD8-/+, CD56+/-, CD25-; TCR- gene rearrangements, variable TCR- gene rearrangements

Angioimmunoblastic T-cell lymphoma:

TdT-, PanT+ (often with variable loss of some PanT antigens), usually CD4+; TCR gene rearrangements in 75%; IgH gene rearrangements in 10%, EBV often positive, but usually only in isolated neoplastic or reactive cells

Nasal/nasal type T/NK cell (angiocentric) lymphoma:

TdT-, CD2+, CD5-/+, CD7-/+, CD3-/+, may be CD4+ or CD8+, CD56+/-; usually no rearranged TCR or Ig genes; often EBV positive

Intestinal T-cell lymphoma:

TdT-, CD3+, CD7+, CD4-, CD8+/-, CD103+ (mucosal lymphocyte antigen, such as detection by HML-1)

Adult T-cell lymphoma/leukemia:

TdT-, PanT+ (CD2+, CD3+, CD5+, CD7-) CD4+, CD8-, CD25+; TCR gene rearrangements, clonally integrated HTLV1

Anaplastic large cell lymphoma, T- and null-cell types:

TdT-, CD30+, EMA+/-, PanT-/+, CD45+/-, CD25+/-, CD15-/+, CD68-, lysozyme-, BNH9+/-; primary cutaneous form is EMA- and cutaneous lymphocyte antigen+; TCR gene rearrangements > germline, 12-50% of adult cases show t(2;5) resulting in a fusion on NPM gene (5q35) with ALK gene (2q23)