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)?

Explanation

## 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]