Diffuse Large B Cell Lymphoma
Differential Diagnosis
- Non-neoplastic processes
- Blastic lymphomas
- Other B lineage lymphomas
- Other lymphomas
Reactive immunoblastic processes may simulate DLBCL
- Most common causes are mononucleosis, other viruses, vaccination and drug reaction
- Any of the following favor a reactive process
- History or clincal evidence of any of the above causes
- Age under 20 years
- Polymorphous infiltrate with immunoblastic large cells
- Partial node involvement
- Mixed B and T phenotype of large cells
- Light chain polytypia in large cells
- CD30 may be seen in both neoplastic and reactive processes
- EBV is rare in DLBCL except in immunosuppressed patients
- Its presence suggests mononucleosis or other reactive conditions
- Immunoglobulin gene rearrangement study may be neccesary in difficult cases
Kikuchi lymphadenitis may simulate DLBCL
- Patchy pale foci composed of histocytes and karyorrhectic debris
- Atypical activated large lymphocytes predominantly peripheral
- Most large cells T lineage
- Plasmacytoid dendritic cells (plasmacytoid monocytes) may be present
- No sheets of large B cells on CD20 stain
- Extracapsular extension rare
| Burkitt Lymphoma | Diffuse Large B Cell Lymphoma |
|---|---|
| Starry sky macrophages present | Starry sky pattern infrequent |
| Fine chromatin | Vesicular chromatin |
| Multiple small nucleoli | Few, prominent nucleoli |
| Uniform cells | Heterogeneous cells |
| Ki67 nearly 100% | Ki67 moderately high |
| Translocation involving myc gene | 15% of cases have myc translocation |
| Lymphoblastic Lymphoma, B or T | DLBCL |
|---|---|
| Median age 17-20 years | Median age 60 years |
| 90% T lineage, 10% B lineage | B lineage |
| Starry sky macrophages present | Starry sky pattern infrequent |
| Fine chromatin | Vesicular chromatin |
| None or small nucleoli | May have prominent nucleoli |
| Uniform cells | Heterogeneous cells |
| Diffuse Mixed Lymphoma | DLBCL |
|---|---|
| 50-75% of cells are small atypical B cells | Over 50% large atypical B cells |
| No confluent foci of large cells | Confluent foci of large cells |
| Diffuse Large B Cell Lymphoma | Paraimmunoblastic SLL/CLL |
|---|---|
| Nuclear shape variable | Nuclei round, uniform |
| Nucleoli frequently multiple | Nucleoli single |
| Cytoplasm may be basophilic | Cytoplasm pale |
| Node capsule frequently destroyed | Node capsule preserved even if overrun |
| CD5 rare | CD5 80% |
| Sporadic Diffuse Large B Cell Lymphoma | SLL/CLL with Large Cell Transformation |
|---|---|
| No history of SLL/CLL | History or concurrent SLL/CLL |
| CD23 negative | CD23 85% |
| CD5 negative | CD5 80% |
| CD43 rare | CD43 60-80% |
| Plasmablastic Lymphoma | Immunoblastic DLBCL |
|---|---|
| Typically oral cavity mass in HIV+ patient | Wide variety of presentations, including HIV |
| LCA negative or minimal + | LCA >90% |
| CD20 minimal to negative, CD79a positive | Both CD20 and CD79a >90% |
| Ki67 >95% | Ki67 moderately high, variable |
| EBV in situ 50% | EBV in situ rare in de novo cases; frequent in immunodeficiency cases |
| CD138 positive | CD138 negative |
Both may partially replace the node and be negative or minimally reactive for CD20 and CD45RB
| Diffuse Large B Cell Lymphoma | KSHV-associated Germinotropic Lymphoproliferative Disorder |
|---|---|
| Typically effaced architecture | Overall nodal architecture preserved |
| Typically sheets of large atypical cells | Follicular pattern |
| HHV8 and EBV negative except in immunosuppressed patients | HHV8 and EBV positive |
| Diffuse Large B Cell Lymphoma | True Histiocytic Lymphoma |
|---|---|
| Variable cytoplasm | Abundant cytoplasm with erythrophagocytosis |
| Most over 30 years of age | Most under 30 years |
| CD20, CD79a positive | CD20, CD79a negative |
| CD68, CD15, CD163, Lysozyme, CD138 negative or rare | CD138+ or at least two of: CD68, CD15, CD163, Lysozyme |
| Classical Hodgkin Lymphoma | Diffuse Large B Cell Lymphoma |
|---|---|
| CD45RB, CD20 and CD79a 10-20% | CD45RB, CD20 and CD79a >90% |
| CD15 80% | CD15 5% |
| CD30 90% | CD30 30% |
| Light chains polytypic or negative | Light chains monotypic or negative |
| Lymphocyte Predominant Hodgkin Lymphoma | Diffuse Large B Cell Lymphoma, T Cell Rich B Cell Variant |
|---|---|
| Background small cells B lineage | Background small cells T lineage |
| CD57+ small cells increased | No increase in CD57+ small cells |
| CD57+ rosettes around large cells | No CD57+ rosettes |
| Large cells EMA 50% | Large cells EMA negative |
- One report questions this clear distinction describing a subset of TCRBCL that had bcl6 positive large cells with increased numbers of CD57+ small cells and rosette formation (EMA not tested). In this same report, some LPHL cases showed 50% of small cells to be T lineage. (Kraus et al.)
- Some consider cases reported as diffuse LPHL to fall in the spectrum of TCRBCL as the background population in diffuse LPHL is enriched for T cells
| Primary Systemic Anaplastic Large Cell Lymphoma | Anaplastic Variant Large B Cell Lymphoma | ALK Positive Large B Cell Lymphoma |
|---|---|---|
| Marked anaplasia | Marked anaplasia | Monomorphic with round nuclei |
| Frequently sinusoidal | Frequently sinusoidal | Frequently sinusoidal |
| CD30 >90% | CD30 variable | CD30 negative |
| EMA 60% | EMA 33% | EMA positive |
| T lineage | B lineage | B lineage |
| ALK immunohistology 60-85% positive | ALK immunohistology negative | ALK immunohistology 100% positive |
| Majority of ALK positive cases show ALK translocation such as t(2;5) or t(1:2) | Lack ALK translocation | Rare cases reported with clathrin-ALK t(2:17) gene rearrangement |
