A 38-year-old woman presents with a 2-month history of painless lymphadenopathy involving cervical and axillary nodes. Physical examination reveals firm, rubbery, non-tender lymph nodes. Complete blood count shows mild lymphocytosis. Chest X-ray reveals mediastinal widening. Which investigation is most appropriate to establish a definitive diagnosis?

Question

Accepted Answer

A. Excisional lymph node biopsy with immunohistochemistry. ## Diagnosis of Non-Hodgkin Lymphoma: Investigation of Choice

### Clinical Context
The patient presents with constitutional features suggestive of lymphoma: painless lymphadenopathy, mediastinal involvement, and systemic symptoms. While imaging and laboratory tests provide supportive evidence, **tissue diagnosis is mandatory** before initiating treatment.

### Why Excisional Lymph Node Biopsy is the Gold Standard

**Key Point:** Excisional (complete) lymph node biopsy with immunohistochemistry is the investigation of choice for definitive diagnosis of non-Hodgkin lymphoma (NHL).

Excisional biopsy offers:
1. **Architectural preservation** — allows assessment of nodal architecture, which is critical for NHL classification (follicular vs. diffuse patterns)
2. **Immunophenotyping** — flow cytometry and immunohistochemistry identify B-cell or T-cell lineage and specific markers (CD20, CD5, CD10, etc.)
3. **Cytomorphology** — permits accurate histological grading and subtyping (e.g., follicular lymphoma grade, DLBCL vs. Burkitt)
4. **Clonality assessment** — identifies monoclonal lymphoid populations

### Role of Other Investigations

| Investigation | Role | Limitation |
|---|---|---|
| Flow cytometry (peripheral blood) | Identifies immunophenotype; useful for leukemic phase | Cannot assess nodal architecture; misses tissue-based diagnosis |
| CT chest/abdomen | Staging after diagnosis confirmed | Does not establish diagnosis; used for staging (TNM) |
| Serum LDH, β2-microglobulin | Prognostic markers; assess tumor burden | Not diagnostic; supportive only |
| Core needle biopsy | Acceptable if excisional biopsy not feasible | Lower diagnostic yield than excisional; less architectural detail |

**Clinical Pearl:** Fine-needle aspiration (FNA) is inadequate for NHL diagnosis because it cannot preserve nodal architecture and does not allow adequate immunophenotyping.

**High-Yield:** The WHO classification of NHL requires integration of morphology, immunophenotype, and clinical features — all best obtained from excisional biopsy.

### Staging After Diagnosis
Once NHL is confirmed histologically, staging investigations (CT, PET-CT, bone marrow biopsy) are performed to determine extent of disease and guide therapy.

[cite:Robbins 10e Ch 13]

![Lymphomas — Non-Hodgkin diagram](https://mmcphlazjonnzmdysowq.supabase.co/storage/v1/object/public/blog-images/explanation/2652.webp)

Answer

B. Flow cytometry of peripheral blood

Answer

C. Serum LDH and beta-2 microglobulin levels

Answer

D. CT chest and abdomen with contrast

Explanation

Diagnosis of Non-Hodgkin Lymphoma: Investigation of Choice

Clinical Context

Why Excisional Lymph Node Biopsy is the Gold Standard

Role of Other Investigations

Staging After Diagnosis

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Investigation	Role	Limitation
Flow cytometry (peripheral blood)	Identifies immunophenotype; useful for leukemic phase	Cannot assess nodal architecture; misses tissue-based diagnosis
CT chest/abdomen	Staging after diagnosis confirmed	Does not establish diagnosis; used for staging (TNM)
Serum LDH, β2-microglobulin	Prognostic markers; assess tumor burden	Not diagnostic; supportive only
Core needle biopsy	Acceptable if excisional biopsy not feasible	Lower diagnostic yield than excisional; less architectural detail