A 38-year-old woman presents with a rapidly enlarging abdominal mass and B symptoms (fever, night sweats, weight loss) for 6 weeks. Imaging shows a large retroperitoneal lymph node mass. Fine-needle aspiration cytology shows large cells with high mitotic activity. Which investigation is most appropriate to confirm the diagnosis of diffuse large B-cell lymphoma (DLBCL) and assess for prognostic markers?

Explanation

## Confirmatory Investigation for DLBCL Diagnosis **Key Point:** Excision biopsy with histopathology and immunohistochemistry (IHC) is the gold standard for confirming DLBCL diagnosis and assessing prognostic markers (GCB vs ABC subtype, Ki-67 proliferation index, TP53 status). ### Why Excision Biopsy is Required for DLBCL DLBCL is an aggressive lymphoma that requires: 1. **Morphologic confirmation** — large cells with high mitotic rate, necrosis, and effaced architecture 2. **Immunophenotypic profiling** — CD20+, CD19+, CD10 (GCB) vs CD10− (ABC/non-GCB) 3. **Prognostic markers** — Ki-67 (>80% = poor prognosis), TP53 mutations, MYC/BCL2 status (double-hit lymphoma) 4. **Tissue architecture assessment** — essential for distinguishing DLBCL from other high-grade lymphomas ### Diagnostic Algorithm for Aggressive Lymphoma ```mermaid flowchart TD A[Large cell lymphoma suspected]:::outcome --> B{Tissue diagnosis available?}:::decision B -->|FNAC only| C[Perform excision biopsy]:::action B -->|Core/excision biopsy| D[Histopathology + IHC]:::action D --> E[Confirm DLBCL diagnosis]:::outcome E --> F[Assess prognostic markers]:::action F --> G[GCB vs ABC subtype]:::outcome F --> H[Ki-67, TP53, MYC/BCL2]:::outcome G --> I[Risk stratification & treatment planning]:::action ``` ### Comparison of Diagnostic Modalities | Modality | Diagnostic Yield | Prognostic Info | Subtype Classification | Best Use | |---|---|---|---|---| | **FNAC** | Suggestive only | No | No | Screening; inadequate for DLBCL | | **Core biopsy** | Good | Partial | Yes | Alternative if excision not feasible | | **Excision biopsy + IHC** | Definitive | Complete | Yes | **Gold standard for DLBCL** | | **Flow cytometry** | Limited in tissue | No | Partial | Better for indolent lymphomas | | **PET-CT** | No tissue diagnosis | Staging only | No | Post-diagnosis staging | **High-Yield:** FNAC is inadequate for DLBCL diagnosis because it cannot assess tissue architecture, perform adequate IHC, or evaluate prognostic markers. Excision biopsy is mandatory. **Clinical Pearl:** The presence of B symptoms and rapid growth in this case suggests an aggressive lymphoma. DLBCL is the most common aggressive NHL. Excision biopsy not only confirms diagnosis but also determines whether the tumor is GCB (better prognosis) or ABC (worse prognosis), which guides intensity of chemotherapy.