## Investigation of Choice for NHL Diagnosis and Classification **Key Point:** Flow cytometry with immunophenotyping is the gold standard for diagnosing and classifying Non-Hodgkin lymphomas. It identifies the cell of origin (B-cell vs T-cell) and specific markers that define lymphoma subtypes. ### Why Flow Cytometry is Essential Flow cytometry provides: 1. **Cell lineage determination** — distinguishes B-cell from T-cell lymphomas 2. **Clonality assessment** — identifies monoclonal populations (malignant) vs polyclonal (reactive) 3. **Immunophenotypic profile** — CD19, CD20, CD5, CD23, surface immunoglobulin, and other markers that define specific entities (e.g., CLL/SLL, follicular lymphoma, DLBCL) 4. **Rapid turnaround** — results available within 24–48 hours ### Role of Other Investigations | Investigation | Purpose | Timing | |---|---|---| | **Flow cytometry** | Diagnosis & classification | Initial | | **Histopathology + IHC** | Morphology, subtype confirmation, prognostic markers | Concurrent with flow | | **LDH level** | Prognostic marker (elevated = poor prognosis) | After diagnosis | | **CT chest/abdomen** | Staging (extent of disease) | After diagnosis confirmed | | **Bone marrow biopsy** | Staging, assess marrow involvement | After diagnosis confirmed | **High-Yield:** While histopathology (excision biopsy) remains the gold standard for definitive diagnosis, flow cytometry on tissue or blood is the fastest, most specific initial test to confirm NHL and guide further workup. **Clinical Pearl:** In this case, the combination of lymphadenopathy + small lymphocytes on smear suggests a low-grade lymphoma (e.g., CLL/SLL, follicular lymphoma). Flow cytometry will rapidly identify the phenotype and confirm clonality. 
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