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PA19.1-6 | Approach to Lymphadenopathy — Part 2

Differentiating Features: Clinical Discriminators

When you palpate a lymph node, six clinical features create the differential framework:

1. Distribution: Localised vs Generalised
• Localised (one region) → suggests a regional cause: local infection (dental, scalp, tonsil), or metastatic disease draining from a known primary.
• Generalised (≥ 2 non-contiguous regions) → suggests systemic disease: viral infection (EBV, CMV, HIV), autoimmune (SLE, RA), disseminated malignancy (leukaemia, advanced NHL), drug reaction, or sarcoidosis.

2. Tenderness
• Tender → inflammatory/infective (rapid capsular stretch from oedema). Pyogenic lymphadenitis, early viral infections.
• Non-tender → neoplastic (slow growth, no inflammation) or granulomatous (TB, sarcoid — fibrosis suppresses pain). Painless lymphadenopathy in a young adult = lymphoma until proven otherwise.

3. Consistency
• Soft — acute inflammation, abscess formation.
• Firm — reactive hyperplasia, early lymphoma.
• Rubbery — classic for lymphoma (HL particularly). The word to remember: rubber-ball feel.
• Hard/stony — metastatic carcinoma. Desmoplastic stroma from the tumour makes the node rock-hard.

4. Mobility and Matting
• Mobile — reactive nodes (capsule intact, no extra-nodal spread).
• Fixed/matted (nodes fused together) — neoplastic infiltration (lymphoma, metastasis) or TB (periadenitis from caseation and fibrosis).

5. Site Significance
• Virchow's node (left supraclavicular) — via the thoracic duct; metastasis from GI (gastric, colon, pancreatic), lung, or pelvic primaries. Troisier's sign = palpable Virchow's node.
• Right supraclavicular — lung, oesophagus, mediastinal primaries.
• Epitrochlear — normally impalpable; when enlarged → sarcoidosis, syphilis (secondary), cat-scratch disease, lymphoma.
• Posterior cervical — EBV, toxoplasmosis, TB (posterior triangle).
• Anterior cervical — dental, tonsillar, thyroid pathology.

6. Age as Discriminator
• < 14 years: reactive/infective cause is overwhelmingly more likely (> 90%).
• 15–35 years: infectious mononucleosis + lymphoma both on the list; Hodgkin lymphoma peaks here.
• > 50 years: malignancy (NHL, metastasis, CLL) probability rises sharply.

Lymph Node Groups and Drainage Territories: Clinical Anatomy

Diagnostic Approach: FNAC vs Excision Biopsy

Once clinical assessment raises concern, tissue diagnosis is required. Two options exist:

Fine-Needle Aspiration Cytology (FNAC)
What it does: Aspirates individual cells; cytology shows cell morphology but NOT tissue architecture.
When to use:
• Suspected metastatic carcinoma (cell type, e.g., adenocarcinoma vs squamous) — architecture irrelevant.
• Tuberculous lymphadenitis — caseous material, epithelioid granulomas identifiable on smear, ZN stain for AFB.
• Reactive lymphadenopathy — polymorphous population of lymphocytes supports benign diagnosis.
Limitations: Cannot subclassify lymphoma reliably (requires architecture, immunohistochemistry, flow cytometry on intact tissue).

Excision Biopsy (or core biopsy with IHC)
What it does: Provides the entire node with architecture intact; allows immunohistochemistry (IHC), flow cytometry, cytogenetics (FISH for translocations), and molecular studies.
When to use:
• Suspected lymphoma — ALWAYS excision biopsy. This is non-negotiable. Lymphoma subclassification (Hodgkin vs NHL, and the specific subtype of NHL) is ONLY possible with intact architecture. Reed-Sternberg cells in Hodgkin lymphoma, follicular vs diffuse pattern in NHL — all require histology.
• Persistent lymphadenopathy > 6 weeks with no obvious cause after FNAC.
• Failed FNAC (insufficient material, atypical cells).

The key principle: Architecture = lymphoma diagnosis. Cytology alone cannot classify lymphoma.

Practical sequence for a suspicious node:
1. Clinical history + examination (distribution, consistency, B symptoms, age).
2. Blood work: CBC, ESR, LDH, LFT, viral serology (EBV/CMV/HIV) if clinically indicated.
3. Imaging: CECT to characterise node and look for primary (for suspected metastasis) or mediastinal/abdominal disease (for suspected lymphoma).
4. FNAC first if rapid confirmation needed (for clinically obvious TB or metastatic carcinoma).
5. Excision biopsy if lymphoma suspected, FNAC inconclusive, or persistence > 6 weeks.

Putting It Together: A Framework for the Clinic

Use this mental checklist at the bedside:

Step 1 — Age bracket?
< 14 → reactive most likely. 15–35 → EBV, lymphoma. > 50 → malignancy prominent.

Step 2 — Localised or generalised?
Generalised → systemic cause (viral, autoimmune, haematological malignancy).

Step 3 — Consistency and mobility?
• Rubbery + non-tender + mobile → lymphoma.
• Hard + fixed → metastatic carcinoma.
• Soft + tender → acute infection.
• Matted + firm + central softening → TB (with caseation).

Step 4 — Site?
Left supraclavicular (Virchow's) → abdominal/thoracic primary. Epitrochlear → sarcoid, syphilis.

Step 5 — B symptoms?
Present → lymphoma workup mandatory.

Step 6 — Duration?
< 2 weeks + tender + localised after obvious infection → observe with antibiotics.
> 6 weeks + unexplained → biopsy.

Stepwise Diagnostic Flowchart for Lymphadenopathy

Bridge to SDL2, SDL3, and SDL4

This module has given you the framework. The next three SDLs apply it to specific diseases:

SDL2 — Tuberculous Lymphadenitis:
The commonest cause of lymphadenopathy in India. You will learn the morphological spectrum (follicular hyperplasia → epithelioid granulomas → caseation → collar-stud abscess), Langhans giant cells, ZN staining, and the paradox of lymphocyte trapping that masks positive FNAC.

SDL3 — Hodgkin Lymphoma:
The prototype rubbery, non-tender, localised lymphadenopathy of the young adult. You will learn Reed-Sternberg cells, the Ann Arbor staging, and the four histological subtypes. Paracortical destruction by the malignant process builds on the paracortical hyperplasia you learned today.

SDL4 — Non-Hodgkin Lymphoma:
The heterogeneous group — from indolent follicular lymphoma (bcl-2 you saw today) to aggressive DLBCL and Burkitt lymphoma. The concept of follicular architecture mimicking follicular hyperplasia you learned here will be the diagnostic challenge in SDL4.

The architecture of a lymph node you reviewed in the Recall block is the lens through which all four SDLs are read.