Ihc report for non hodkings lymphoma
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"non-Hodgkin lymphoma"[MeSH Terms] AND "immunohistochemistry"[MeSH Terms]
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I now have comprehensive data. Let me compile the complete, detailed IHC report for Non-Hodgkin Lymphoma.
IHC (Immunohistochemistry) Report for Non-Hodgkin Lymphoma (NHL)
IHC is the cornerstone of NHL classification. It establishes lineage, subtype, cell of origin, grade, and prognosis - and directly guides targeted therapy selection. The WHO classification requires IHC as a mandatory component of diagnosis.
1. INITIAL LINEAGE PANEL
The first step is always to determine whether the lymphoma is B-cell, T-cell, or NK-cell origin.
| Marker | B-Cell NHL | T/NK-Cell NHL |
|---|---|---|
| CD20 | + | - |
| CD79a | + | - |
| PAX5 | + | - |
| CD3 | - | + |
| CD5 | - (except MCL, CLL) | + (most) |
| CD45 (LCA) | + | + |
| TdT | - (except B-LBL) | - (except T-LBL) |
2. B-CELL NHL SUBTYPES - DETAILED IHC PROFILES
A. Diffuse Large B-Cell Lymphoma (DLBCL)
DLBCL is the most common NHL. IHC is required not just for diagnosis but for cell-of-origin (COO) subgrouping, which has prognostic and therapeutic implications.
Core panel:
| Marker | Result | Significance |
|---|---|---|
| CD20 | + (strong) | Confirms B-cell lineage; target for rituximab |
| CD79a | + | Pan-B marker |
| CD19 | + | Pan-B marker |
| CD22 | + | Pan-B marker |
| CD30 | +/- (variable) | Present in subset; target for brentuximab |
| Ki-67 | >40%, often >70% | High proliferative index |
| BCL2 | +/- | Adverse prognosis if co-expressed with MYC ("double expressor") |
| BCL6 | +/- | GCB subtype marker |
| CD10 | +/- | GCB subtype marker |
| MUM1/IRF4 | +/- | ABC (non-GCB) subtype marker |
| MYC | + in ~40% | "Double-hit" if co-expressed with BCL2 or BCL6 |
| EBV (EBER-ISH) | +/- | Relevant in immunosuppressed patients |
Hans Algorithm - COO Subgrouping (using IHC):
| Profile | Subtype |
|---|---|
| CD10+ (>30% cells) | GCB type |
| CD10-, BCL6+, MUM1- | GCB type |
| CD10-, BCL6+, MUM1+ | Non-GCB (ABC) type |
| CD10-, BCL6- | Non-GCB (ABC) type |
GCB type has better response to RCHOP therapy than ABC type. - Henry's Clinical Diagnosis and Management by Laboratory Methods
B. Follicular Lymphoma (FL)
| Marker | Result | Notes |
|---|---|---|
| CD20 | + | Strong pan-B marker |
| CD19 | + | Pan-B |
| CD10 | + | Germinal center origin marker |
| BCL6 | + | GC marker |
| BCL2 | + (hallmark) | Distinguishes from reactive follicles (BCL2-) |
| CD5 | - | Negative - helps exclude MCL and CLL |
| CD23 | + | Positive in FDCs and sometimes tumor cells |
| Cyclin D1 | - | Negative - excludes MCL |
| Ki-67 | Low-intermediate | Inversely correlates with grade |
Grading by IHC/morphology:
| Grade | Centroblasts per 40x field |
|---|---|
| 1 | 0-5 |
| 2 | 6-15 |
| 3A | >15, with residual centrocytes |
| 3B | >15, no centrocytes - behaves like DLBCL |
Note: BCL2 and CD10 are negative in primary cutaneous FL and pediatric FL - these are important exceptions. BCL2 positivity in skin FL should raise suspicion for systemic disease. - Quick Compendium of Clinical Pathology
C. Mantle Cell Lymphoma (MCL)
MCL has a characteristic IHC profile that is nearly pathognomonic. Definitive diagnosis requires t(11;14) by FISH or cyclin D1 overexpression by IHC.
| Marker | Result | Notes |
|---|---|---|
| CD20 | + (mod-bright) | Pan-B, brighter than CLL |
| CD19 | + | Pan-B |
| CD5 | + | Co-expressed (shared with CLL) |
| Cyclin D1 (BCL1) | + (hallmark) | Most important distinguishing marker from CLL |
| SOX11 | + | High sensitivity/specificity; useful in cyclin D1-negative MCL |
| CD23 | - | Key difference from CLL (which is CD23+) |
| CD10 | - | Negative |
| BCL6 | - | Negative |
| BCL2 | + (strong) | Due to strong Bcl-2 expression, resistant to apoptosis |
| Ki-67 | Variable | >30% correlates with adverse prognosis |
| FMC7 | + | Bright, unlike CLL |
Cytogenetics: t(11;14)(q13;q32) - translocation of IgH (14q32) to CCND1 (11q13), causing cyclin D1 overexpression. Confirmed by FISH. - Quick Compendium of Clinical Pathology; Robbins Pathologic Basis of Disease
D. Burkitt Lymphoma (BL)
| Marker | Result | Notes |
|---|---|---|
| CD20 | + | Pan-B |
| CD19 | + | Pan-B |
| CD22 | + | Pan-B |
| CD10 | + | GC marker |
| BCL6 | + | GC marker |
| BCL2 | - (hallmark) | Absence = high apoptosis rate; "starry sky" pattern |
| TdT | - | Distinguishes from B-LBL (TdT+) |
| Ki-67 | ~100% | Extremely high proliferative index |
| MYC | + (all cases) | t(8;14), t(2;8), or t(8;22) - MYC rearrangement required |
| Surface IgM | + | Monotypic light chain restriction |
Key diagnostic feature: Nearly 100% Ki-67 + BCL2 negativity in a mature B-cell lymphoma is essentially diagnostic of Burkitt lymphoma. MYC FISH confirmation is required. - Henry's Clinical Diagnosis and Management; Robbins Pathologic Basis of Disease
E. Marginal Zone Lymphoma (MZL) / MALT Lymphoma
| Marker | Result | Notes |
|---|---|---|
| CD20 | + | Pan-B, moderate-bright |
| CD19 | + | Pan-B |
| CD79a | + | Pan-B |
| CD5 | - (usually) | Occasionally weakly + |
| CD10 | - | Negative - excludes FL |
| CD23 | -/+ | Usually negative |
| BCL6 | - | Negative |
| Cyclin D1 | - | Excludes MCL |
| BCL2 | + | Positive; helps exclude cutaneous FL |
An IHC panel is essential to exclude FL, MCL, and CLL in MALT lymphoma. - Fishman's Pulmonary Diseases and Disorders
F. CLL/SLL (Chronic Lymphocytic Leukemia / Small Lymphocytic Lymphoma)
| Marker | Result |
|---|---|
| CD20 | + (dim) |
| CD5 | + |
| CD23 | + (key differentiator from MCL) |
| CD10 | - |
| Cyclin D1 | - |
| Surface Ig | + (dim) |
3. T-CELL AND NK-CELL NHL
| Subtype | Key Positive Markers | Key Negative Markers | Notes |
|---|---|---|---|
| Peripheral T-cell lymphoma, NOS (PTCL-NOS) | CD3, CD4 or CD8, TCR | CD20, TdT | Diagnosis of exclusion |
| Anaplastic Large Cell Lymphoma (ALCL) | CD30 (strong), ALK (ALK+), CD3 (variable), EMA, CD43 | CD20, often CD3- | ALK+ has better prognosis |
| Angioimmunoblastic T-cell lymphoma (AITL) | CD3, CD4, CD10, CXCL13, PD-1, ICOS | CD8, CD20 | GC T-helper origin; BCL6+ |
| Adult T-cell Leukemia/Lymphoma (ATLL) | CD3, CD2, CD4, CD25 | CD8, CD7 | HTLV-1 associated |
| Extranodal NK/T-cell lymphoma, nasal type | CD2, CD56, cytoplasmic CD3, TIA-1, Granzyme B | Surface CD3, CD5 | EBV+ (EBER-ISH); not B-cell |
| T-LGL Leukemia | CD3, CD8, CD57, TCR-γδ | CD4 | NK variant: CD56+, surface CD3- |
| Aggressive NK-cell Leukemia | CD2, CD56, cytoplasmic CD3 | Surface CD3, CD5 | Clonal EBV |
Source: Henry's Clinical Diagnosis and Management by Laboratory Methods, Table 34.7
4. COMPARISON TABLE - B-CELL NHL DIFFERENTIAL
| Disease | CD5 | CD10 | CD23 | Cyclin D1 | BCL2 | BCL6 | Ki-67 |
|---|---|---|---|---|---|---|---|
| CLL/SLL | + | - | + | - | + | - | Low |
| MCL | + | - | - | + | + | - | Variable |
| FL | - | + | +/- | - | + | + | Low-mod |
| DLBCL | - | +/- | - | - | +/- | +/- | High (>40%) |
| Burkitt | - | + | - | - | - | + | ~100% |
| MZL/MALT | -/+ | - | -/+ | - | + | - | Low |
5. SPECIAL / ADDITIONAL MARKERS
| Marker | Application |
|---|---|
| ALK (CD246) | ALCL - positive in ALK+ variant (better prognosis) |
| CD138 / MUM1 | Plasma cell differentiation; ABC-DLBCL |
| EBV (EBER-ISH) | EBV-associated lymphomas (endemic BL, PTLD, ENKTL) |
| HHV-8 (LANA-1) | Primary effusion lymphoma, HHV8+ DLBCL |
| CD21 / CD23 | Mark follicular dendritic cell (FDC) meshwork |
| TdT | Lymphoblastic lymphoma/leukemia (precursor B or T) |
| SOX11 | MCL (especially cyclin D1-negative cases) |
| PD-L1 | Some DLBCL, PMBCL; guides checkpoint inhibitor therapy |
| MYC protein | DLBCL "double expressor" (MYC+/BCL2+); adverse prognosis |
6. REPORTING STRUCTURE SUMMARY
A complete IHC report for NHL should include:
- Lineage determination - B-cell vs T/NK-cell (CD20, CD3, CD79a, PAX5)
- Subtype-specific panel - Based on morphology and lineage
- Cell of origin (for DLBCL) - GCB vs non-GCB via Hans algorithm
- Proliferative index - Ki-67% (mandatory)
- Prognostic markers - BCL2, MYC, BCL6 co-expression; ALK status
- Viral markers if indicated - EBV/EBER, HHV-8
- Cytogenetics correlation - FISH for t(14;18) FL, t(11;14) MCL, t(8;14) BL, ALK rearrangement
Sources:
- Henry's Clinical Diagnosis and Management by Laboratory Methods - Lymphoma classification and IHC profiles
- Robbins, Cotran & Kumar: Pathologic Basis of Disease - Burkitt lymphoma and MCL morphology and immunophenotype
- Quick Compendium of Clinical Pathology, 5th edition - Detailed MCL and FL IHC panels
- Goldman-Cecil Medicine - B-cell malignancy IHC comparison table
- Fishman's Pulmonary Diseases - MALT lymphoma IHC
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