Histologies types of Hodgkin lyphoma from pathology mbbs
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Histological Types of Hodgkin Lymphoma
Source: Robbins & Cotran Pathologic Basis of Disease + Robbins & Kumar Basic Pathology
The Reed-Sternberg Cell - The Hallmark
The sine qua non of Hodgkin lymphoma is the Reed-Sternberg (RS) cell - a very large cell (15-45 µm diameter) with an enormous multilobate nucleus, exceptionally prominent nucleoli, and abundant slightly eosinophilic cytoplasm. The classic "owl-eye" appearance comes from two mirror-image nuclei, each with a large acidophilic nucleolus surrounded by a clear halo.
- Origin: Germinal center B cell (proven by clonal IGH gene rearrangements + somatic hypermutation in microdissected RS cells)
- Classic RS cell immunophenotype: CD15+, CD30+, PAX5 (dim)+, CD45-, CD20-, T-cell markers-
Below: RS cells and their variants (A = classic owl-eye, B = mononuclear variant, C = lacunar variant, D = lymphohistiocytic/popcorn variant)
WHO Classification: 5 Subtypes
The first four are grouped as Classic Hodgkin Lymphoma (cHL). The fifth is non-classic.
1. Nodular Sclerosis (NS-HL)
Most common - 65-70% of all HL
| Feature | Detail |
|---|---|
| RS cell variant | Lacunar cells - multilobed nucleus, multiple small nucleoli, abundant pale cytoplasm; nucleus retracts in formalin leaving an empty "lacune" |
| Background | T lymphocytes, eosinophils, plasma cells, macrophages |
| Key histology | Collagen bands dividing lymph node into nodules |
| Immunophenotype | CD15+, CD30+, CD45-, EBV usually negative |
| Demographics | Equal M:F, adolescents and young adults |
| Sites | Lower cervical, supraclavicular, mediastinal nodes |
| Stage at presentation | Usually stage I or II |
| Prognosis | Excellent |
2. Mixed Cellularity (MC-HL)
Second most common - 20-25% of cases
| Feature | Detail |
|---|---|
| RS cell variant | Classic diagnostic RS cells and mononuclear variants - plentiful |
| Background | Heterogeneous mix: T cells, eosinophils, plasma cells, macrophages |
| Key histology | Diffuse effacement of lymph node; no fibrosis |
| Immunophenotype | CD15+, CD30+; EBV+ in ~70% |
| Demographics | Male predominance; most common HL in >50 years; biphasic incidence |
| Stage at presentation | >50% present as stage III or IV |
| Symptoms | More likely to have B symptoms (fever, night sweats, weight loss) |
| Prognosis | Very good overall |
3. Lymphocyte-Rich (LR-HL)
Uncommon classic subtype
| Feature | Detail |
|---|---|
| RS cell variant | Frequent mononuclear and classic diagnostic RS cells |
| Background | Predominantly reactive T lymphocytes; eosinophils/plasma cells scanty |
| Key histology | Diffuse pattern; sometimes vague nodularity from residual B-cell follicles |
| Immunophenotype | CD15+, CD30+; EBV+ in ~40% |
| Demographics | Male predominance; tends to be seen in older adults |
| Prognosis | Very good to excellent |
Distinguished from Nodular Lymphocyte Predominant by the presence of mononuclear/classic RS cells with the "classic" CD15+/CD30+ immunophenotype
4. Lymphocyte-Depleted (LD-HL)
Least common classic subtype - <5% of cases
| Feature | Detail |
|---|---|
| RS cell variant | Abundant RS cells and pleomorphic variants |
| Background | Paucity of lymphocytes (hence the name) |
| Key histology | Reticular variant: sheets of RS cells with few reactive cells |
| Immunophenotype | CD15+, CD30+; EBV+ in >90% |
| Demographics | Older adults, HIV-positive individuals, people in developing countries |
| Stage at presentation | Advanced stage; systemic symptoms frequent |
| Prognosis | Least favorable among HL subtypes |
Key exam point: Most tumors suspected clinically to be LD-HL turn out to be NHL on immunophenotyping - so immunophenotyping is essential for diagnosis.
5. Nodular Lymphocyte Predominant (NLP-HL)
Non-classic - ~5% of cases
| Feature | Detail |
|---|---|
| RS cell variant | L&H (lymphohistiocytic) variants = "Popcorn cells" - multilobed, crumpled, delicate nucleus resembling popped corn |
| Background | Large nodules of reactive small B cells + follicular dendritic cells; eosinophils and plasma cells scanty/absent |
| Key histology | Nodular growth pattern; classic RS cells absent or very rare |
| Immunophenotype | CD20+, BCL6+; CD15-, CD30- (opposite of classic!) |
| EBV | Rarely associated |
| Demographics | Predominantly males <35 years; cervical or axillary lymphadenopathy |
| Special note | In 3-5% of cases, transforms to diffuse large B-cell lymphoma |
| Prognosis | Excellent, but more prone to late relapses |
The ICC (International Consensus Classification) has renamed this entity "Nodular Lymphocyte-Predominant B-cell Lymphoma", dropping the Hodgkin moniker entirely, because the immunophenotype is closer to a B-cell lymphoma than to classic HL.
Quick Comparison Table
| Subtype | Frequency | RS Cell Variant | EBV | CD15 | CD30 | CD20 | Prognosis |
|---|---|---|---|---|---|---|---|
| Nodular Sclerosis | 65-70% | Lacunar cell | Rare | + | + | - | Excellent |
| Mixed Cellularity | 20-25% | Classic RS | ~70% | + | + | - | Very good |
| Lymphocyte-Rich | Uncommon | Classic/mononuclear | ~40% | + | + | - | Excellent |
| Lymphocyte-Depleted | <5% | Pleomorphic/abundant | >90% | + | + | - | Poor (relative) |
| NLP (non-classic) | ~5% | L&H / Popcorn | Rare | - | - | + | Excellent |
Key Pathogenesis Points (Exam Favorites)
- All RS cells originate from germinal center B cells (proven by clonal Ig gene rearrangements)
- In classic HL, RS cells lose all B-cell gene expression due to epigenetic changes
- NF-κB activation is the central survival mechanism in classic HL
- RS cells express PD-L1 and PD-L2 (chromosome 9p amplification) - explains response to anti-PD-1 (pembrolizumab/nivolumab) therapy
- RS cells constitute only a small minority of the tumor mass - most is reactive inflammatory infiltrate
- The reactive cells are recruited by RS cell-secreted cytokines (IL-5 for eosinophils, TGF-β for fibrosis, IL-10 for immune suppression)
Sources: Robbins, Cotran & Kumar - Pathologic Basis of Disease (10th ed.), p. 573-575; Robbins & Kumar Basic Pathology, p. 417-420
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