A 32-year-old man from Delhi presents with progressive cervical lymphadenopathy and constitutional symptoms (fever, night sweats, weight loss) over 3 months. Lymph node biopsy shows Hodgkin and Reed-Sternberg cells with a rich inflammatory background. Immunophenotyping reveals CD30+ and CD15+ neoplastic cells. Which single feature most reliably distinguishes this classical Hodgkin lymphoma from primary mediastinal B-cell lymphoma (PMBL)?

Question

Accepted Answer

B. CD20 negativity of neoplastic cells. ## Classical Hodgkin Lymphoma vs. Primary Mediastinal B-Cell Lymphoma

### Clinical Overlap and Diagnostic Challenge

Both cHL and PMBL present with mediastinal masses, constitutional symptoms, and can have overlapping morphology. However, their immunophenotypes are distinctly different and allow reliable separation.

### Immunophenotypic Distinction

| Feature | Classical HL | PMBL |
|---------|-------------|------|
| **CD20** | **Negative** | **Positive** |
| **CD45** | Negative | Positive (weak) |
| **CD30** | Positive | Positive |
| **CD15** | Positive | Negative |
| **CD19** | Negative | Positive |
| **CD79a** | Negative | Positive |
| **B-cell lineage markers** | Absent | Present |

### Why CD20 is the Gold Standard Discriminator

**Key Point:** CD20 negativity in cHL versus CD20 positivity in PMBL is the most reliable single immunophenotypic feature distinguishing these two entities. This reflects the fundamental difference: cHL cells are derived from B cells that have lost B-cell markers, while PMBL is a true B-cell lymphoma that retains B-cell markers.

**High-Yield:** CD20 status is routinely used in diagnostic algorithms and is the first-line immunophenotypic discriminator in practice. It has direct therapeutic implications:
- cHL: typically treated with chemotherapy (ABVD) ± radiation
- PMBL: may benefit from rituximab (anti-CD20 monoclonal antibody) in addition to chemotherapy

### Why Other Features Are Not Discriminatory

**Clinical Pearl:** CD15 positivity is characteristic of cHL but is not present in PMBL. However, CD15 is a myeloid antigen and is not a B-cell marker; its absence in PMBL does not define PMBL's B-cell nature. CD20 positivity, on the other hand, directly confirms B-cell lineage in PMBL.

**Mnemonic:** **B-CELL PMBL vs. NON-B-CELL cHL**
- **B**-cell markers (CD20, CD19, CD79a) = PMBL
- **C**D15 and CD30 = cHL (but CD30 is shared)
- **E**BV = variable in both
- **L**arge cells (RS-like) = both
- **L**ymphocyte background = both

### Mediastinal Involvement: Not Discriminatory

**Warning:** Both cHL (especially nodular sclerosis subtype) and PMBL commonly present with mediastinal masses. Mediastinal involvement is not a discriminating feature.

### Hodgkin and Reed-Sternberg Cells: Morphological Overlap

**Tip:** While Hodgkin and Reed-Sternberg cells are characteristic of cHL, PMBL can show large atypical cells that mimic RS cells morphologically. Morphology alone is insufficient; immunophenotype is essential.

### Diagnostic Algorithm

```mermaid
flowchart TD
  A[Large cell lymphoma with mediastinal mass]:::outcome --> B{CD20 positive?}:::decision
  B -->|Yes| C[B-cell marker panel]:::action
  C --> D{CD19, CD79a positive?}:::decision
  D -->|Yes| E[Primary Mediastinal B-Cell Lymphoma]:::outcome
  B -->|No| F{CD15 and CD30 positive?}:::decision
  F -->|Yes| G[Classical Hodgkin Lymphoma]:::outcome
  F -->|No| H[Other diagnosis]:::outcome
```

[cite:Robbins 10e Ch 13]

Answer

A. Mediastinal involvement

Answer

C. Presence of Hodgkin and Reed-Sternberg cells

Answer

D. CD15 positivity of neoplastic cells

Explanation

Classical Hodgkin Lymphoma vs. Primary Mediastinal B-Cell Lymphoma

Clinical Overlap and Diagnostic Challenge

Immunophenotypic Distinction

Why CD20 is the Gold Standard Discriminator

Why Other Features Are Not Discriminatory

Mediastinal Involvement: Not Discriminatory

Hodgkin and Reed-Sternberg Cells: Morphological Overlap

Diagnostic Algorithm

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Feature	Classical HL	PMBL
CD20	Negative	Positive
CD45	Negative	Positive (weak)
CD30	Positive	Positive
CD15	Positive	Negative
CD19	Negative	Positive
CD79a	Negative	Positive
B-cell lineage markers	Absent	Present