Table 2.

Diagnostic clues and pitfalls in small B-cell lymphomas.

Lymphoma SubtypeDiagnostic CluesPitfalls
Abbreviations: LEL, lymphoepithelial lesion; SLL, small lymphocytic lymphoma; CLL, chronic lymphocytic leukemia; MZL, marginal zone lymphoma; PB, peripheral blood; BM, bone marrow; FL, follicular lymphoma; PCR, polymerase chain reaction; FISH, fluoresence in situ hybridization; RFH, reactive follicular hyperplasia; FDC, follicular dendritic cell 
Follicular lymphoma Follicle formation, admixed centroblasts, presence of tight FDC meshworks
 –CD10 +/− Bcl-6 expression between follicles
 –Low proliferative rate in contrast to RFH
 –PCR/FISH presence of t(14;18) Not all FLs express Bcl-2 protein
 –BCL2 PCR can be negative (inherent high false- negative rate)
 –Discordance between morphology and proliferative rate in some cases 
MALT lymphoma Reactive follicles, LELs and centrocyte-like cells
 –Presence of light chain restriction
 –Absence of CD5/CD10 expression
 –FISH detection of characteristic translocations Classic cytomorphology not always present
 –Small biopsies may produce false-positive PCR for IGH clonality
 –Distinction from LPL may be difficult 
SLL Presence of growth centers
 –Co-expression of CD5 and CD23
 –Absence of t(11;14) Growth centers may be ill-defined 
Splenic MZL Biphasic splenic morphology
 –Uncommon red pulp pattern
 –Frequent PB/BM involvement, may be intrasinusoidal in BM
 –Cells fail to express CD5, CD10, CD23 and CD43 Occasional SMZL cases express CD5
 –Some may weakly express CD23
 –Diagnosis can be difficult without a splenectomy 
Nodal MZL Distinct marginal zone architecture
 –Rule out adjacent mucosal disease
 –B cells do not co-express CD5 or CD10 Almost a diagnosis of exclusion
 –Absence of characteristic cytogenetic alterations found in MALT lymphomas 
Lymphoplasmacytic lymphoma Mature plasma cell component +/−
 Russell/Dutcher bodies
 –Usually not leukemic
 –Absence of growth centers and CD5 expression
 –Increased mast cells in BM
 –Presence of serum/urine monoclonal protein Subtle inter-follicular pattern in some cases
 –Grey-zone cases with SLL/CLL occur
 –Clinical information often not available 
Mantle cell lymphoma Monomorphic appearance, absence of centroblasts; epithelioid histiocytes and mitoses
 –PB & BM often involved
 –CD5+, CD23
 –Expression of cyclin D1
 –Presence of t(11;14) Blastoid variants may be pleomorphic
 Rare cases mimic MZL architecture
 –5% to 7% may be CD5
 –Rare cases lack t(11;14) and cyclin D1
 overexpression 
Lymphoma SubtypeDiagnostic CluesPitfalls
Abbreviations: LEL, lymphoepithelial lesion; SLL, small lymphocytic lymphoma; CLL, chronic lymphocytic leukemia; MZL, marginal zone lymphoma; PB, peripheral blood; BM, bone marrow; FL, follicular lymphoma; PCR, polymerase chain reaction; FISH, fluoresence in situ hybridization; RFH, reactive follicular hyperplasia; FDC, follicular dendritic cell 
Follicular lymphoma Follicle formation, admixed centroblasts, presence of tight FDC meshworks
 –CD10 +/− Bcl-6 expression between follicles
 –Low proliferative rate in contrast to RFH
 –PCR/FISH presence of t(14;18) Not all FLs express Bcl-2 protein
 –BCL2 PCR can be negative (inherent high false- negative rate)
 –Discordance between morphology and proliferative rate in some cases 
MALT lymphoma Reactive follicles, LELs and centrocyte-like cells
 –Presence of light chain restriction
 –Absence of CD5/CD10 expression
 –FISH detection of characteristic translocations Classic cytomorphology not always present
 –Small biopsies may produce false-positive PCR for IGH clonality
 –Distinction from LPL may be difficult 
SLL Presence of growth centers
 –Co-expression of CD5 and CD23
 –Absence of t(11;14) Growth centers may be ill-defined 
Splenic MZL Biphasic splenic morphology
 –Uncommon red pulp pattern
 –Frequent PB/BM involvement, may be intrasinusoidal in BM
 –Cells fail to express CD5, CD10, CD23 and CD43 Occasional SMZL cases express CD5
 –Some may weakly express CD23
 –Diagnosis can be difficult without a splenectomy 
Nodal MZL Distinct marginal zone architecture
 –Rule out adjacent mucosal disease
 –B cells do not co-express CD5 or CD10 Almost a diagnosis of exclusion
 –Absence of characteristic cytogenetic alterations found in MALT lymphomas 
Lymphoplasmacytic lymphoma Mature plasma cell component +/−
 Russell/Dutcher bodies
 –Usually not leukemic
 –Absence of growth centers and CD5 expression
 –Increased mast cells in BM
 –Presence of serum/urine monoclonal protein Subtle inter-follicular pattern in some cases
 –Grey-zone cases with SLL/CLL occur
 –Clinical information often not available 
Mantle cell lymphoma Monomorphic appearance, absence of centroblasts; epithelioid histiocytes and mitoses
 –PB & BM often involved
 –CD5+, CD23
 –Expression of cyclin D1
 –Presence of t(11;14) Blastoid variants may be pleomorphic
 Rare cases mimic MZL architecture
 –5% to 7% may be CD5
 –Rare cases lack t(11;14) and cyclin D1
 overexpression 

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