A 52-year-old woman from Mumbai presents with a 6-week history of painless swelling of bilateral cervical and axillary lymph nodes. She reports night sweats and a 4 kg weight loss over 2 months. On examination, lymph nodes are firm, rubbery, and matted. Laboratory work shows hemoglobin 10.8 g/dL, WBC 7.2 × 10⁹/L, and LDH 920 U/L. A lymph node biopsy reveals a diffuse infiltrate of large atypical cells with abundant cytoplasm and multiple nuclei or multilobated nuclei ("mirror-image" or "owl-eye" appearance). Immunohistochemistry shows CD20+, CD10+, BCL6+, BCL2−. What is the most likely diagnosis?

Explanation

## Diagnosis: Germinal Center B-Cell Type DLBCL ### Clinical Presentation The patient presents with features typical of aggressive non-Hodgkin lymphoma: - **B symptoms**: night sweats, weight loss (>10% body weight over 2 months) - **Rapid onset**: 6 weeks of progressive lymphadenopathy - **Elevated LDH**: 920 U/L (very high, indicates high tumor burden and aggressive behavior) - **Cytopenias**: anemia (Hb 10.8 g/dL) ### Pathology and Immunophenotype | Feature | Finding | Interpretation | |---------|---------|----------------| | **Morphology** | Large atypical cells with abundant cytoplasm, multilobated nuclei ("mirror-image"/"owl-eye") | Consistent with centroblasts and immunoblasts | | **CD20** | Positive | B-cell origin | | **CD10** | Positive | Germinal center marker (present in GCB-DLBCL) | | **BCL6** | Positive | Germinal center transcription factor | | **BCL2** | Negative | Absence of t(14;18) translocation; argues against follicular lymphoma | ### Key Point: **CD10+ BCL6+ BCL2− = Germinal Center B-cell type DLBCL (GCB-DLBCL).** This is one of two molecular subtypes of DLBCL (the other being activated B-cell type, ABC-DLBCL, which is CD10−/BCL6−/BCL2+). ### High-Yield: **GCB-DLBCL has a better prognosis than ABC-DLBCL.** The CD10+/BCL6+ signature indicates origin from germinal center B cells, which carries a more favorable outcome with standard R-CHOP therapy compared to ABC-DLBCL (which has worse prognosis and may benefit from intensified regimens). ### Clinical Pearl: DLBCL is the most common non-Hodgkin lymphoma (30–40% of NHL). The presence of **CD10+ BCL6+ BCL2−** phenotype is crucial for prognostic stratification and treatment planning. GCB-DLBCL typically has 5-year OS >70% with R-CHOP, whereas ABC-DLBCL has 5-year OS ~50%. ### Mnemonic: **GCB-DLBCL = CD10 + BCL6 + BCL2−** **ABC-DLBCL = CD10− BCL6− BCL2+** --- ## Why Other Options Are Incorrect ### Diffuse Large B-Cell Lymphoma (DLBCL) — Non-Specific - This is the **correct entity** but lacks the molecular subtype specification - The question asks for the "most likely diagnosis," and the immunophenotype allows us to specify **GCB-DLBCL**, which is more precise and carries prognostic significance - A more general "DLBCL" answer would be incomplete without subtyping ### Burkitt Lymphoma - Presents with **very high LDH** (often >1000 U/L) — this patient's LDH is elevated but not extreme - Morphology shows **small to medium-sized cells with basophilic cytoplasm and "starry-sky" pattern**, NOT large cells with "owl-eye" nuclei - Immunophenotype: CD20+, CD10+, **BCL6−, BCL2−** (BCL6 is typically negative in Burkitt) - t(8;14) translocation (MYC rearrangement) is hallmark; would be detected on FISH - Typically affects children and young adults; this patient is 52 years old ### Hodgkin Lymphoma, Nodular Sclerosis Subtype - **Does NOT express CD20** (B-cell marker); Hodgkin cells are typically CD30+, CD15+, CD45− - Pathology shows **Reed-Sternberg cells and Hodgkin cells** (not the large atypical B cells seen here) - Histology includes collagen bands and nodular sclerosis pattern - The CD20+ immunophenotype definitively excludes Hodgkin lymphoma