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Hodgkin Lymphoma (HL)
Definition
A group of lymphoid neoplasms characterized by Reed-Sternberg (RS) cells or their variants, set in a background of inflammatory and reactive components.
WHO Classification - 5 Subtypes
| Subtype | Morphology | Immunophenotype | Reactive Background | Prognosis |
|---|---|---|---|---|
| Nodular sclerosis | Fibrous bands; few classical + more lacunar RS cells | CD15+, CD30+, EBV- | T-lymphocytes, eosinophils, macrophages | Excellent |
| Mixed cellularity | Frequent mononuclear classical RS cells | CD15+, CD30+, EBV+ (70%) | T-lymphocytes, eosinophils, macrophages, plasma cells | Very Good |
| Lymphocyte rich | Classic RS cells | CD15+, CD30+, EBV+ (40%) | T-lymphocytes | Very Good |
| Lymphocyte depleted | Reticular variant | CD15+, CD30+, Most EBV+ | Few T-lymphocytes | Worst |
| Lymphocyte predominance | Popcorn variant | CD15-, CD30-, CD20+, EBV- | Follicular dendritic cells + reactive B cells | Excellent |
Key memory tip: Lymphocyte predominance is the odd one out - it is CD15 negative and CD30 negative, unlike all other subtypes.
Types of Reed-Sternberg Cells
| Variant | Features | Associated Subtype |
|---|---|---|
| Classical (Owl eye) | Large (15-40 µm), mirror-image nucleus, acidophilic nucleoli | Mixed cellularity, Nodular sclerosis |
| Popcorn | Large cell, single nucleus, popcorn shape | Lymphocyte predominance |
| Lacunar | Large cell, multilobulated nuclei, lacuna (empty space) around it | Nodular sclerosis |
| Pleomorphic | Pleomorphic + atypical nuclei | Lymphocyte depletion |
Etiopathogenesis
- Epstein-Barr virus (EBV) or genetic mutation
- Overexpression of NF-kB → proliferates B-lymphocytes and inhibits apoptosis
Staging - Ann Arbor Classification
| Stage | Description |
|---|---|
| I | Single lymph node region (I) or single extra-lymphatic organ/site (IE) |
| II | Two or more LN regions on the same side of the diaphragm (II), or + localized extra-lymphatic involvement (IIE) |
| III | LN regions on both sides of the diaphragm, without (III) or with extra-lymphatic (IIIE) |
| IV | Diffuse involvement of one or more lymphatic organs/sites |
'B' symptoms (add suffix B if present, A if absent):
- Fever (Pel-Ebstein fever - cyclical)
- Unexplained weight loss
- Night sweats
Non-Hodgkin Lymphoma (NHL)
Definition
A lymphoid neoplasm that is non-contiguous in nature (spreads in a disorganized, non-sequential fashion) - contrasted with HL which spreads contiguously.
NHL Working Formulation
| Grade | Types |
|---|---|
| Low grade | Small lymphocytic lymphoma; Follicular, predominantly small cleaved cell; Follicular, mixed (large + cleaved) |
| Intermediate grade | Follicular predominantly large cell; Diffuse mixed; Diffuse large cell (most common overall) |
| High grade | Large cell immunoblastic; Lymphoblastic; Small non-cleaved cell (Burkitt) |
Summary Table of NHL Types
| Type | Cell of Origin | Key Genotype | Immunophenotype | Key Clinical Features |
|---|---|---|---|---|
| Small lymphocytic lymphoma / CLL | Naive or memory B cell | Trisomy 12; del(11q), del(13q), del(17p) | CD10, CD19, CD20, CD21, CD5 (T cell marker anomalously expressed) | Bone marrow failure; liver/spleen disease; autoimmune disease; thrombocytopenia; indolent, elderly |
| Follicular lymphoma | Germinal center B cell | t(14;18) BCL2-IgH fusion | CD19, CD20, CD21, CD23 | Older adults; generalized lymphadenopathy; marrow involvement; indolent |
| Mantle cell lymphoma | B cell in mantle zone | t(11;14) Cyclin D-IgH fusion | CD5, CD10, CD19, CD20 | Older males; disseminated disease; moderately aggressive |
| Diffuse large B-cell lymphoma (DLBCL) | Germinal center or post-GC B cell | BCL-6 (30%), BCL-2 (10%), C-MYC (5%) | CD19, CD20, CD21, CD22 | All ages; rapidly growing mass; 30% extra-nodal; aggressive |
| Burkitt lymphoma | Germinal center B cell | t(8;14) MYC + Ig loci, EBV+ | CD19, CD20, CD21, CD22 | Adolescents/young adults; extra-nodal mass; uncommon leukemia presentation; aggressive |
| Extra-nodal marginal zone lymphoma (MALT) | Memory B cell / MALT tissue | t(11;18), t(1;14), t(14;18) - MALT1-IAP2, BCL10-IgH, MALT-IgH | CD10, CD19, CD20, CD21, CD22 | Extra-nodal sites; chronic inflammatory background (e.g., H. pylori gastritis); may be localized; indolent |
Key Distinguishing Points for Exams
- Only subtype CD15- CD30-: Lymphocyte predominance (Nodular lymphocyte predominant HL)
- Worst prognosis in HL: Lymphocyte depletion
- Best prognosis in HL: Nodular sclerosis / Lymphocyte predominance (both Excellent)
- Most common NHL: Diffuse large B-cell lymphoma
- Starry sky pattern: Burkitt lymphoma (t(8;14), c-MYC rearrangement)
- BCL-2 overexpression (anti-apoptotic): Follicular lymphoma - t(14;18)
- Cyclin D1 overexpression: Mantle cell lymphoma - t(11;14)
- CLL = SLL: Same disease, different presentation (blood vs. lymph node)
- MALT lymphoma arises in the setting of chronic inflammation (H. pylori, Sjogren's, Hashimoto's)
- B symptoms in HL staging = Fever + Weight loss + Night sweats (suffix B); absent = suffix A
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