All of the following are characteristic histological features of classical Hodgkin lymphoma EXCEPT:

Explanation

## Diagnostic Criteria of Classical Hodgkin Lymphoma **Key Point:** Classical Hodgkin lymphoma (cHL) is defined by the presence of Hodgkin cells and Reed-Sternberg (RS) cells within a rich inflammatory background. The neoplastic cells are typically CD30+ and CD15+, but notably they are CD45-negative (LCA-negative). ### Immunophenotypic Profile of Neoplastic Cells | Feature | Status | Significance | |---------|--------|---------------| | CD30 | **Positive** | Marker of activation; required for diagnosis | | CD15 | **Positive** | Present in ~75–85% of cHL cases | | CD45 (LCA) | **Negative** | Distinguishes neoplastic cells from background lymphocytes | | CD3, CD20 | **Negative/Weak** | Loss of pan-T or pan-B cell markers | | CD20 | Weak/Negative | Helps differentiate from B-cell lymphomas | | EBV (EBER) | **Positive** | Present in ~40% of cases (variable by subtype) | **High-Yield:** CD45 (LCA) negativity is a cardinal feature that separates cHL neoplastic cells from the surrounding reactive lymphocyte population. This is a critical diagnostic criterion. ### Morphological Features 1. **Hodgkin cells**: Large cells with prominent nucleoli, abundant cytoplasm, and moderate pleomorphism. 2. **Reed-Sternberg cells**: Multinucleated giant cells with "mirror-image" or "owl's-eye" nuclei, thick nuclear membranes, and prominent eosinophilic nucleoli. 3. **Background**: Predominantly T lymphocytes (CD8+ > CD4+), eosinophils, plasma cells, histiocytes, and fibroblasts — the neoplastic cells comprise <1% of the cellularity. **Clinical Pearl:** The scarcity of neoplastic cells in a sea of inflammation is a hallmark of cHL and explains why morphology alone can be challenging; immunohistochemistry is essential for diagnosis. ### Why CD45 Positivity is Wrong CD45 (leukocyte common antigen) is expressed on all hematopoietic cells. Hodgkin and Reed-Sternberg cells in classical Hodgkin lymphoma are **CD45-negative**, which is part of their aberrant immunophenotype and helps distinguish them from reactive lymphocytes and other lymphomas. CD45 positivity would be seen in the background inflammatory cells, not the neoplastic cells themselves. [cite:Robbins 10e Ch 13]