Hodgkin Lymphoma

Overview

HD = arises in lymph nodes, extranodal secondary. ~8% of lymphoid neoplasms. Bimodal peaks (15-35yr, >5th decade), more in young males. Diagnostic: Reed-Sternberg (RS) cell.

Classification

Rye classification (4 subtypes): lymphocyte-predominance, nodular sclerosis, mixed cellularity, lymphocyte-depletion. WHO regroups into: nodular lymphocyte-predominant HD (new entity) + classic HD (all 4 Rye types).

Reed-Sternberg cell

The real neoplastic cell but scarce (<5% of tumour mass) — rest is reactive infiltrate. Monoclonal B-cell (germinal centre) origin. Classic HD: CD15+, CD30+. Lymphocyte-predominance type: CD15-, CD30-, CD20+.

Variants: Classic (bilobed mirror-image nucleus, owl-eye nucleolus) — mixed cellularity. Lacunar (pericellular halo) — nodular sclerosis. Popcorn/L&H (lobulated) — lymphocyte-predominance. Pleomorphic — lymphocyte-depletion.

Subtypes (WHO)

Nodular sclerosis: collagen bands + lacunar RS cells, more in women, commonest overall.

Clinical features

Painless firm movable lymphadenopathy (cervical, mediastinal commonest). Splenomegaly ~half. B symptoms (fever, night sweats, weight loss) in 25-40%.

Lab findings

Normocytic normochromic anaemia. ↓Serum iron+TIBC but normal/↑marrow iron. Leukaemoid reaction, eosinophilia (if pruritus), lymphopenia (advanced). Platelets normal/↑. ESR always ↑. ↓T-cell immunity, reversed CD4:CD8.

Staging (Ann Arbor)

I: single node region. II: ≥2 regions, same side diaphragm. III: both sides diaphragm. IV: disseminated extralymphatic. Suffix A (no symptoms)/B (constitutional symptoms), E (extranodal), S (spleen).

Prognosis

Stage I/IIA ~100% 5yr survival; advanced ~50%. Order: lymphocyte-predominance > nodular sclerosis > mixed cellularity > lymphocyte-depletion (worst).

HD vs NHL

HD: mostly B-cell, localised spread, extranodal/marrow rare, constitutional symptoms common, aneuploidy, never spills to blood, better prognosis (75-85% cure). NHL: 90% B/10% T, disseminated spread, extranodal/marrow common, translocations, may spill to blood, worse prognosis (30-40% cure).

Clinical relevance

RS cell being <5% of tumour mass while defining the diagnosis is unusual among malignancies — most of what’s seen microscopically is the body’s reaction, not the tumour. RS variant correlating with subtype (and matching immunophenotype) is a reliable pattern. HD’s orderly, contiguous nodal spread (vs NHL’s unpredictable dissemination) is why localised radiotherapy and staging laparotomy mattered more historically for HD.

Overview

Hodgkin lymphoma (Hodgkin’s disease, HD) primarily arises within lymph nodes, involving extranodal sites only secondarily — about 8% of all lymphoid neoplasms. Incidence shows bimodal peaks: young adults (15–35 years) and again after the 5th decade; overall more prevalent in young adult males. The classical diagnostic feature is the Reed-Sternberg (RS) cell (also called the Dorothy-Reed-Sternberg cell).

Classification

Diagnosis requires biopsy, usually of lymph node. Unlike NHL, HD has only one universally accepted classification — the Rye classification (since 1966), with 4 subtypes:

1. Lymphocyte-predominance type
2. Nodular-sclerosis type
3. Mixed-cellularity type
4. Lymphocyte-depletion type

The WHO classification regroups these into two main categories:

• Nodular lymphocyte-predominant HD (a distinct, newer entity)
• Classic HD (encompassing all 4 Rye subtypes)

The Reed-Sternberg Cell

RS cells are the actual neoplastic cells, but are surprisingly scarce (under 5% of the cellular population) — the bulk of the tumour mass is a reactive infiltrate. This is why identification requires a thorough search, and why architectural/cellular context matters as much as finding an individual cell (similar-appearing cells can occur in infectious mononucleosis and some other lymphomas). Immunophenotyping shows RS cells are of monoclonal B-cell (germinal centre) origin in most subtypes; in classic HD they are CD15+, CD30+, while in lymphocyte-predominance type they are CD15−, CD30−, CD20+.

Morphologic variants (each characterising a different subtype):

The number of RS cells is generally inversely proportional to the number of reactive lymphocytes in a given subtype.

Morphologic Subtypes (WHO Classification)

Nodular sclerosis — most frequent overall, more common in women; defined by two essential features: bands of collagen (occasionally replacing the entire node with dense hyalinised collagen) and lacunar-type RS cells.

Mixed cellularity — heterogeneous infiltrate replacing the entire node, with frequent typical RS cells, some fibrosis, focal necrosis.

Lymphocyte-depletion — two variants: diffuse fibrotic (hypocellular, homogeneous hyaline fibrosis) and reticular (more cellular, numerous atypical pleomorphic histiocytes, scanty lymphocytes).

Gross appearance of HD and NHL is largely indistinguishable — cervical, supraclavicular, and axillary nodes most commonly affected; initially discrete nodes, later matted masses; cut surface grey-white, “fishflesh”-like.

Clinical Features

• Painless, movable, firm lymphadenopathy — most common presentation; cervical and mediastinal nodes most frequently involved.
• Splenomegaly in roughly half of patients over the disease course; hepatomegaly may also occur.
• Constitutional (type B) symptoms in 25–40%: low-grade fever with night sweats and weight loss, plus fatigue, malaise, weakness, pruritus.
• All histologic subtypes except nodular sclerosis are more common in males.

Laboratory Findings

• Moderate normocytic normochromic anaemia.
• Low serum iron and TIBC, but normal or increased marrow iron stores (anaemia of chronic disease pattern).
• Marrow infiltration can cause marrow failure with a leucoerythroblastic reaction.
• Moderate leukaemoid reaction on routine counts; peripheral eosinophilia in patients with pruritus; absolute lymphopenia in advanced disease.
• Platelet count normal or increased.
• ESR invariably elevated.
• Immunologic: progressive fall in immunocompetent T-cells, defective cellular immunity, reversed CD4:CD8 ratio, anergy to skin tests; humoral antibody production remains normal until late disease.

Staging (Ann Arbor Classification)

Suffixes: A (asymptomatic) or B (constitutional symptoms — fever, night sweats, unexplained weight loss >10%); E (extranodal); S (splenomegaly).

Prognosis

Overall 5-year survival for stage I/IIA approaches 100%; advanced-stage disease up to 50%. Prognosis follows subtype: lymphocyte-predominance (excellent, usually localised) > nodular sclerosis (very good, though large mediastinal mass responds poorly) > mixed cellularity (intermediate) > lymphocyte-depletion (poor, usually disseminated at diagnosis, most aggressive).

Hodgkin vs Non-Hodgkin Lymphoma

Clinical Relevance

• The scarcity of the actual neoplastic cell (RS cell, under 5% of the tumour mass) against a background of reactive cells is what makes HD diagnostically distinctive among malignancies — most of what is seen under the microscope is the host’s own immune response to a small population of transformed cells, not the tumour itself.
• The RS-cell morphologic variant (classic, lacunar, popcorn, pleomorphic) correlating tightly with a specific histologic subtype is a genuinely reliable pattern-recognition tool, and each variant’s immunophenotype (CD15/CD30 status) reinforces rather than contradicts the morphologic call.
• The contiguous, orderly pattern of nodal spread in HD (versus the disseminated, unpredictable spread of NHL) is the biological basis for why staging laparotomy and localised radiotherapy have historically played a larger role in HD management than in NHL.

No Rendered Diagram for This Topic

Hodgkin lymphoma is fundamentally a classification topic (Rye/WHO subtypes, RS cell variants, Ann Arbor staging) rather than a multi-step disease mechanism — the tables in notes.md already carry the structure that matters, and a rendered diagram would just be a redrawing of a table.

Hand-Draw Suggestion

Draw a single table by hand with four columns (Subtype / RS cell variant / Key histology / Prognosis) and fill in the four Rye subtypes plus nodular lymphocyte-predominant HD — this is the single most testable structure in the topic and benefits more from active recall of the table than from a process diagram.

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