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PA19.1-6 | Lymphomas — Hodgkin vs Non-Hodgkin — Part 2

Hodgkin Lymphoma — Spread, Staging, and B Symptoms

Infographic showing Hodgkin lymphoma spreading contiguously through lymph node groups, Ann Arbor stages I to IV, B symptoms, and EBV association in Reed-Sternberg cells. — **Panel A:** Anterior torso map with cervical lymph nodes, supraclavicular lymph nodes, mediastinal lymph nodes, hilar lymph nodes, para-aortic lymph nodes, abdominal lymph nodes, diaphragm, contiguous numbered spread arrows, and haematogenous dissemination note.. **Panel B:** Ann Arbor Stage I single lymph node region, Stage II two or more regions on same side of diaphragm, Stage III regions on both sides of diaphragm, Stage IV diffuse extralymphatic involvement including liver and bone marrow.. **Panel C:** B symptoms: unexplained fever greater than 38 °C, drenching night sweats, unexplained weight loss greater than 10% body weight in 6 months; suffix A absent and suffix B present.. **Panel D:** Stylized Reed-Sternberg cell, EBV particles, EBER positivity in RS cells, EBV association in classical Hodgkin lymphoma, mixed cellularity Hodgkin lymphoma, and lymphocyte-depleted Hodgkin lymphoma..

HL has a characteristic contiguous, orderly spread along adjacent lymph node groups. Starting in a single node region, it spreads step-by-step to neighbouring regions before haematogenous dissemination occurs. This behaviour makes early-stage disease highly curable with localised radiation and/or chemotherapy.

Ann Arbor Staging:

Stage	Definition
I	Single lymph node region
II	Two or more regions, same side of diaphragm
III	Regions on both sides of diaphragm
IV	Diffuse involvement of extralymphatic organs (liver, bone marrow)

Suffix A = no constitutional symptoms; suffix B = B symptoms present.

B symptoms (clinically and prognostically important):
- Fever >38 °C (unexplained, often Pel-Ebstein cyclical pattern)
- Drenching night sweats
- Unexplained weight loss >10% body weight in 6 months

B-symptom positivity upstages prognosis and intensifies treatment. The opening case had all three.

EBV association: EBV-encoded RNA (EBER) is detectable in RS cells in ~40% of cHL overall, highest in MCHL (~70%) and LDHL. EBV likely contributes by activating NF-κB and providing anti-apoptotic signals in the RS cell precursor.

Non-Hodgkin Lymphoma — Overview

Four-panel infographic summarizing non-Hodgkin lymphoma classification, non-contiguous spread, common extranodal sites, leukaemic phase, and indolent versus aggressive behaviour. — **Panel A:** Central lymph node, B-cell NHL ~85%, T-cell NHL, NK-cell NHL, cell of origin, clinical behaviour, indolent, aggressive, absent Reed-Sternberg cell.. **Panel B:** Simplified lymphatic map, cervical nodes, axillary nodes, mediastinal nodes, abdominal nodes, inguinal nodes, non-contiguous spread, skip lesions, unpredictable pattern.. **Panel C:** Extranodal involvement sites: Waldeyer ring / MALT, gut, skin, CNS, liver, bone marrow.. **Panel D:** Leukaemic phase with lymphoma cells in blood, SLL/CLL, follicular lymphoma, indolent NHL slow growth, aggressive NHL rapid growth, chemotherapy curability concept..

Non-Hodgkin lymphoma (NHL) is a heterogeneous group of >60 distinct lymphoid malignancies. Key characteristics that distinguish NHL from HL as a category:

Cell of origin: Predominantly B-cell (~85%); remainder T-cell or NK-cell
Spread: Non-contiguous, unpredictable — skip lesions common; disease can present anywhere without following lymphatic drainage pathways
Extranodal involvement: Common and early — gut (Waldeyer's ring, MALT), skin, CNS, liver, bone marrow
Leukaemic phase: Many NHL subtypes spill into blood and can mimic leukaemia (e.g., follicular lymphoma, SLL/CLL — see H7)
No RS cell: Absence of RS cells is a negative criterion for classification

NHL is classified on two axes:

Cell of origin (B vs T/NK)
Clinical behaviour (indolent vs aggressive)

Indolent NHLs grow slowly, are often incurable but manageable for years. Aggressive NHLs grow fast but many are curable with chemotherapy.

Indolent B-Cell NHLs — Follicular and SLL

Four-panel medical diagram comparing follicular lymphoma histology with reactive follicles and summarizing BCL2-driven pathogenesis, immunophenotype, clinical behavior, and SLL presentation. — **Panel A:** Low-power follicular lymphoma: lymph node capsule, back-to-back neoplastic follicles, absent mantle zones, uniform follicle distribution, effaced nodal architecture.. **Panel B:** High-power follicular lymphoma: neoplastic germinal center, centrocytes, centroblasts, absent mantle zone, BCL2-positive follicle, CD10+, CD20+ B cells.. **Panel C:** Reactive follicle comparison: germinal center, mantle zone, light zone, dark zone, polarization, normal interfollicular area, BCL2-negative germinal center.. **Panel D:** Pathogenesis and clinical summary: germinal-centre B cell, t(14;18)(q32;q21), IgH promoter, BCL2 overexpression, failure of apoptosis, relapsing course, marrow involvement, transformation to DLBCL, SLL lymph node inset..

Follicular Lymphoma (FL) is the commonest indolent NHL (~20% of all NHL):

Arises from germinal-centre B cells (centrocytes and centroblasts)
Architecture: neoplastic follicles throughout the node, replacing normal architecture
Hallmark translocation: t(14;18)(q32;q21) — places BCL2 under the IgH promoter → constitutive BCL2 overexpression → failure of apoptosis in germinal-centre cells
Cells: BCL2+, CD10+, CD20+ (BCL2 positivity in follicles distinguishes FL from reactive germinal centres, which are normally BCL2-negative)
Clinical: median age 60; bone marrow involved in 85% at diagnosis; responds to treatment but relapses; transformation to DLBCL in ~30% over 10 years

Three-panel histological comparison showing follicular lymphoma characteristics versus normal reactive follicle structure in H&E stained lymph node tissue. — **Panel A:** Low-power view showing back-to-back neoplastic follicles, absent mantle zones, uniform distribution, lymph node capsule. **Panel B:** High-power follicular lymphoma showing neoplastic germinal center cells, lack of mantle zone, follicular architecture. **Panel C:** Normal reactive follicle with germinal center, mantle zone, polarization, and normal interfollicular areas.

Small Lymphocytic Lymphoma (SLL): Identical clone to CLL but presents as solid lymph node disease rather than peripheral blood involvement. See H7 for detail. Indolent; may transform to DLBCL (Richter transformation).

SELF-CHECK

A 58-year-old man has generalised lymphadenopathy and splenomegaly. Lymph node biopsy shows a nodular proliferation of small lymphoid cells. IHC: CD20+, CD10+, BCL2+ within follicles. Cytogenetics: t(14;18). What is the underlying molecular consequence of this translocation?

A. BCL2 overexpression leading to failure of apoptosis in germinal-centre B cells

B. MYC overexpression causing rapid cell proliferation

C. BCL6 suppression causing loss of germinal-centre identity

D. ABL kinase activation causing constitutive cell-cycle entry

Reveal Answer

Answer: A. BCL2 overexpression leading to failure of apoptosis in germinal-centre B cells

The t(14;18) translocation juxtaposes BCL2 (chromosome 18) with the IgH locus (chromosome 14), placing BCL2 under the constitutively active immunoglobulin promoter. BCL2 is an anti-apoptotic protein; its overexpression prevents programmed cell death of germinal-centre B cells, allowing their clonal accumulation. MYC/t(8;14) is characteristic of Burkitt lymphoma; ABL/t(9;22) is seen in CML/ALL.