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PA19.1-6 | Lymphomas — Hodgkin vs Non-Hodgkin — Part 3

Aggressive B-Cell NHLs — DLBCL and Burkitt Lymphoma

A four-panel medical diagram comparing DLBCL and Burkitt lymphoma by histology, MYC translocation, immunophenotype, clinical variants, and treatment. — **Panel A:** DLBCL diffuse sheets of large B cells, vesicular nuclei, prominent nucleoli, non-follicular growth; Burkitt starry-sky pattern, dark lymphoma cells, pale macrophages, apoptotic debris, high mitotic rate. **Panel B:** Chromosome 8 MYC, chromosome 14 IgH, t(8;14)(q24;q32), IgH promoter/enhancer activation, uncontrolled proliferation. **Panel C:** DLBCL: CD20+, CD10±, MUM1±, BCL2 overexpression, BCL6 rearrangement; Burkitt: CD20+, CD10+, BCL6+, BCL2−, Ki-67 approximately 100%. **Panel D:** DLBCL nodal disease, R-CHOP, long-term remission; Burkitt endemic jaw/facial bones EBV nearly 100%, sporadic abdominal mass EBV about 20%, immunodeficiency-associated HIV EBV about 30%, intensive short-duration chemotherapy.

Diffuse Large B-Cell Lymphoma (DLBCL) is the commonest NHL overall (~30–35%):

Large B cells with vesicular nuclei and prominent nucleoli, growing diffusely (not follicular)
CD20+, CD10± (germinal-centre origin ~60%), MUM1± (activated B-cell origin ~40%)
Aggressive but potentially curable: ~60% achieve long-term remission with R-CHOP
Can arise de novo or by transformation from FL or SLL
BCL2 overexpression (via translocation or amplification) and/or BCL6 rearrangements are common

Burkitt Lymphoma — the most rapidly proliferating human tumour (doubling time ~24 hours):

Hallmark: t(8;14)(q24;q32) — places MYC proto-oncogene under the IgH promoter → massive uncontrolled proliferation
High mitotic rate + high apoptosis → macrophages engulf apoptotic debris → "starry-sky" pattern on H&E (dark lymphoma cells = sky; pale macrophages = stars)
Three clinical variants:
Endemic (African): jaw/facial bones; EBV+ in nearly 100% of cases
Sporadic: abdominal mass; EBV+ in ~20%
Immunodeficiency-associated: HIV; EBV+ ~30%
CD20+, CD10+, BCL6+; BCL2−; Ki-67 ~100% (near-total proliferative fraction)
Treatment: intensive short-duration chemotherapy; highly curable in children if diagnosed promptly

Three-panel histological illustration of Burkitt lymphoma showing starry-sky pattern with annotated macrophages and lymphoma cells at different magnifications. — **Panel A:** 20× H&E section showing starry-sky pattern, tingible-body macrophages scattered among dense lymphoma cells, overall tissue architecture. **Panel B:** High-magnification tingible-body macrophage with pale cytoplasm, engulfed apoptotic debris, nuclear morphology. **Panel C:** Magnified lymphoma cell population showing uniform small cells, scant cytoplasm, mitotic figures, nuclear characteristics.

T-Cell and NK-Cell NHLs — Brief Overview

A four-panel medical infographic summarizes T-cell and NK-cell non-Hodgkin lymphomas, their major subtypes, key markers, and why excision or core biopsy is needed for diagnosis. — **Panel A:** Big-picture lymph node cross-section showing malignant T-cell clone, preserved nodal architecture, T/NK-cell NHLs approximately 15% of NHL, and B-cell NHLs as higher exam-weight contrast.. **Panel B:** Major entities: PTCL-NOS, ALCL, ATLL, and Mycosis Fungoides/Sézary Syndrome with concise hallmark notes.. **Panel C:** Diagnostic markers and hallmarks: CD3, CD4 > CD8, CD30, ALK fusion from t(2;5), CD25, and HTLV-1.. **Panel D:** Biopsy imperative comparing fragmented fine-needle aspiration with architecture-preserving excision/core biopsy and tissue allocation for flow cytometry, cytogenetics, and IHC..

T-cell NHLs (~15% of NHL) are generally more aggressive and harder to treat than their B-cell counterparts:

Peripheral T-cell lymphoma, NOS (PTCL-NOS): Most common T-NHL; heterogeneous; CD3+, CD4 > CD8; poor prognosis
Anaplastic Large Cell Lymphoma (ALCL): CD30+ (mimics RS cells); t(2;5) → ALK fusion protein in systemic form; ALK+ form has better prognosis; ALK− has poor prognosis
Adult T-cell Leukaemia/Lymphoma (ATLL): caused by HTLV-1 retrovirus; endemic in Japan and Caribbean; CD4+, CD25+; lytic bone lesions, hypercalcaemia
Mycosis Fungoides/Sézary Syndrome: cutaneous T-cell lymphoma; indolent skin patches → plaques → tumours; Sézary syndrome = leukaemic phase with cerebriform nuclei

For the PA19.3 examination, the B-cell lymphomas carry more weight; T-cell NHLs are a supporting contrast.

CLINICAL PEARL

The biopsy imperative: Fine-needle aspiration cannot diagnose lymphoma reliably — it fragments the architecture. Excision biopsy (or core biopsy in difficult sites) preserves the nodal architecture essential for subtype classification. Always send fresh tissue for flow cytometry and cytogenetics in addition to standard formalin-fixed sections for IHC. A delay in biopsy for a patient with Burkitt lymphoma can be fatal within days; for follicular lymphoma, a few weeks rarely matters. Clinical urgency guides timing, not the histological subtype you suspect.

Hodgkin vs Non-Hodgkin Lymphoma — Differentiating Framework

A three-panel comparison diagram contrasts Hodgkin lymphoma and Non-Hodgkin lymphoma by spread pattern, hallmark cells, extranodal disease, and key examination differences. — **Panel A:** Orderly contiguous lymph node spread in Hodgkin lymphoma versus scattered non-contiguous nodal and extranodal involvement in Non-Hodgkin lymphoma.. **Panel B:** Reed-Sternberg cell with bilobed owl-eye nuclei and CD15+/CD30+ markers contrasted with variable lymphoid cells without Reed-Sternberg cells.. **Panel C:** Key differentiating framework: cell of origin, hallmark cell, spread pattern, extranodal involvement, leukaemic phase, and typical clinical clue..

This is the core table for PA19.3 examinations. Commit the key differences:

Parameter	Hodgkin Lymphoma	Non-Hodgkin Lymphoma
Cell of origin	B cell (RS cell, aberrant)	B cell (85%), T/NK cell (15%)
Hallmark cell	Reed-Sternberg cell (CD15+/CD30+)	No RS cell; varies by subtype
Spread pattern	Contiguous, orderly (node-to-node)	Non-contiguous, unpredictable
Extranodal involvement	Rare (late, haematogenous)	Common and early
Leukaemic phase	Very rare	Common in indolent subtypes (FL, SLL)
Age at presentation	Bimodal (15–35 yr + >55 yr)	Any age; peaks in older adults
Mediastinal mass	Common (especially NSHL)	Less common; seen in DLBCL, mediastinal large B-cell
B symptoms	Prominent; staged formally (A/B)	Less systematically staged by symptoms
EBV association	Yes — MCHL (70%), NSHL (~30%)	Yes — Burkitt endemic (100%), PTLD
Prognosis	Generally good; early-stage curable >90%	Wide range; DLBCL curable ~60%; FL incurable but indolent

IMPORTANT PATTERN: When given a clinical vignette with a young woman + mediastinal mass + B symptoms → think NSHL. Young African child + jaw mass + rapidly growing → think endemic Burkitt. Elderly patient + indolent generalised lymphadenopathy + CLL-like blood picture → think FL or SLL.

Side-by-side comparison showing orderly contiguous lymph node spread in Hodgkin lymphoma versus random skip pattern with extranodal involvement in non-Hodgkin lymphoma — **Panel A:** Hodgkin lymphoma showing contiguous spread through cervical, mediastinal, para-aortic, iliac, and inguinal node groups with sequential arrows. **Panel B:** Non-Hodgkin lymphoma showing non-contiguous skip lesions in lymph nodes plus extranodal sites including liver, spleen, GI tract, bone marrow, and CNS.

SELF-CHECK

Which of the following features MOST strongly favours Non-Hodgkin lymphoma over Hodgkin lymphoma in a patient presenting with lymphadenopathy?

A. Non-contiguous spread with early extranodal involvement

B. Presence of B symptoms (fever, night sweats, weight loss)

C. Bimodal age distribution with a peak in young adults

D. Ann Arbor Stage II disease at presentation

Reveal Answer

Answer: A. Non-contiguous spread with early extranodal involvement

Non-contiguous spread and early extranodal involvement are hallmarks of NHL. Hodgkin lymphoma characteristically spreads in an orderly, contiguous fashion along adjacent node groups, which is why localised radiation was historically effective. B symptoms and Ann Arbor staging are used in both HL and NHL. The bimodal age peak describes HL (NSHL at 15–35, MCHL/>55), not NHL.