A 48-year-old Indian woman presents with a 2-month history of rapidly enlarging left inguinal lymphadenopathy and constitutional symptoms. On examination, she has a 6 cm firm, matted lymph node. Laboratory findings: hemoglobin 10.1 g/dL, WBC 6,800/μL, LDH 1,200 U/L (markedly elevated). Lymph node biopsy shows effacement of normal architecture with a diffuse proliferation of medium to large cells with abundant cytoplasm, high mitotic rate, and scattered tingible-body macrophages creating a "starry-sky" appearance. Immunohistochemistry: CD20+, CD10−, BCL6+, MUM1+, Ki-67 80%. What is the most likely diagnosis?

Explanation

## Diagnosis: Diffuse Large B-Cell Lymphoma (DLBCL), Germinal Center B-Cell Type ### Clinical Presentation **Key Point:** Rapidly enlarging lymph node with markedly elevated LDH and B symptoms in a middle-aged adult is classic for aggressive lymphoma. **Clinical Pearl:** DLBCL is the most common non-Hodgkin lymphoma worldwide (~30% of all NHL). It presents acutely with large nodal masses and constitutional symptoms, distinguishing it from indolent lymphomas. ### Pathologic Hallmarks | Feature | DLBCL (GCB) | Burkitt | FL Grade 3B | PMBCL | |---------|-----------|---------|-----------|-------| | **Cell size** | Medium to large | Medium, uniform | Large cells | Large cells | | **Cytoplasm** | Abundant | Moderate | Moderate | Abundant | | **Mitotic rate** | High (40–80%) | Very high (>95%) | High | High | | **Starry-sky** | Present | Prominent | Absent | Absent | | **CD10** | Variable (GCB+) | Negative | Positive | Negative | | **BCL6** | Positive (GCB) | Negative | Positive | Positive | | **MUM1** | Positive (GCB) | Negative | Positive | Positive | | **Ki-67** | 40–80% | >95% | 40–80% | 40–80% | | **t(8;14)** | Absent | Present (90%) | Absent | Absent | | **Translocation** | BCL2 or BCL6 (variable) | t(8;14) | t(14;18) | Rare | **High-Yield:** DLBCL is subdivided by **cell-of-origin** (COO) classification: - **Germinal center B-cell (GCB) type:** CD10+/−, BCL6+, MUM1− (favorable prognosis) - **Activated B-cell (ABC) type:** CD10−, BCL6−, MUM1+ (unfavorable prognosis) This patient's immunophenotype (CD10−, BCL6+, MUM1+) is **intermediate** but leans toward **GCB-type DLBCL**. ### Morphology **Key Point:** Medium to large cells with: - Abundant cytoplasm - Irregular nuclear membranes - Prominent nucleoli - High mitotic rate (40–80%) - **"Starry-sky" appearance** — scattered tingible-body macrophages (histiocytes laden with apoptotic debris) creating a "starry" background The starry-sky pattern indicates high proliferation and apoptosis, typical of aggressive lymphomas. ### Immunophenotype - **CD20+** (B-cell marker) - **CD10−** (excludes follicular lymphoma as primary diagnosis) - **BCL6+** (germinal center marker) - **MUM1+** (activation marker) - **Ki-67 80%** (very high proliferation index, indicating aggressive disease) **Mnemonic: "DLBCL = Large cells + High Ki-67 + Starry-sky"** — the combination of morphology and proliferation rate is diagnostic. ### Why Not Burkitt Lymphoma? **Warning:** Burkitt lymphoma also shows starry-sky appearance and high mitotic rate, but: - **Uniform, medium-sized cells** (not medium-to-large as here) - **Ki-67 >95%** (higher than this case's 80%) - **CD10+, BCL6−, MUM1−** (different immunophenotype) - **t(8;14) translocation** (pathognomonic, absent in DLBCL) - **Extremely aggressive, often abdominal** (this patient has inguinal node) ### Prognostic Factors - **IPI score:** Age, stage, LDH, performance status, extranodal sites - **GCB vs. ABC:** GCB has better prognosis - **BCL2/BCL6 translocations:** "Double-hit" DLBCL (BCL2 + MYC or BCL6 + MYC) has worse prognosis This patient has high LDH (1,200 U/L) and B symptoms, indicating high-risk disease. ### Management **R-CHOP** (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) is the standard first-line therapy for DLBCL, with ~60–70% cure rates in favorable-risk patients [cite:Robbins 10e Ch 13].