A 32-year-old man is diagnosed with classical Hodgkin lymphoma on lymph node biopsy. Which is the most common diagnostic cell type seen on histopathology?

Question

Accepted Answer

D. Reed-Sternberg cells. ## Diagnostic Cells in Classical Hodgkin Lymphoma

**Key Point:** **Reed-Sternberg (RS) cells** are the pathognomonic and most characteristic diagnostic cells in classical Hodgkin lymphoma. They are large, multinucleated cells with prominent eosinophilic nucleoli ("owl's eye" appearance).

### Morphology and Diagnostic Criteria

| Cell Type | Origin | Morphology | Diagnostic Role | Frequency |
|-----------|--------|-----------|-----------------|----------|
| **Reed-Sternberg (RS) cells** | Clonal B cells | Large, multinucleated, "owl's eye" nucleoli, abundant cytoplasm | **Pathognomonic** for cHL | Required for diagnosis |
| **Hodgkin cells** | Clonal B cells | Mononuclear variants of RS cells; similar morphology | Diagnostic equivalent | Present in all cases |
| **Lacunar cells** | RS cells in formalin-fixed tissue | RS cells in clear spaces (lacunae) in nodular sclerosis | Subtype-specific | Nodular sclerosis only |
| **Immunoblasts** | Non-neoplastic T cells | Large activated lymphocytes | Background inflammatory cells | Non-diagnostic |

**High-Yield:** RS cells are **required for the diagnosis of classical Hodgkin lymphoma**. The WHO diagnostic criteria mandate the presence of RS cells or Hodgkin cells in a background of small lymphocytes, histiocytes, and eosinophils.

### Morphological Features of Reed-Sternberg Cells

**Mnemonic:** **"OWL'S EYE"** = Obvious, Widely-separated, Large nucleoli; Eosinophilic, Abundant cytoplasm; Multinucleated, Enlarged cell.

**Clinical Pearl:** The classic RS cell has:
- **Multiple nuclei** (usually 2–4, but can be more)
- **Prominent, eosinophilic nucleoli** that resemble owl eyes
- **Abundant, basophilic cytoplasm**
- **Thick nuclear membranes**
- **Frequent mitotic figures**

### Immunophenotype

RS and Hodgkin cells characteristically express:
- **CD30** (strong, membrane/Golgi pattern) — most sensitive marker
- **CD15** (75–85% of cases)
- **CD45 negative** (loss of pan-B-cell antigen)
- **CD20 negative or weak** (loss of B-cell marker)
- **CD3 negative** (not T cells)
- **EBV positive** (in many cases, detected by EBER in situ hybridization)

**Warning:** Do not confuse RS cells with:
- ~~Immunoblasts~~ (which are non-neoplastic activated T cells in the background)
- ~~Atypical lymphocytes~~ (which are smaller and have different morphology)
- ~~Carcinoma cells~~ (which are epithelial and have different immunophenotype)

### Why Lacunar Cells Are NOT the Answer

Lacunar cells are **RS cell variants** seen specifically in **nodular sclerosis Hodgkin lymphoma** when tissue is fixed in formalin. They are the same neoplastic cell as RS cells but appear in clear spaces (lacunae) due to tissue retraction. They are **subtype-specific**, not universally present in all HL cases.

Answer

A. Lacunar cells

Answer

B. Hodgkin cells

Answer

C. Immunoblasts

A 32-year-old man is diagnosed with classical Hodgkin lymphoma on lymph node biopsy. Which is the most common diagnostic cell type seen on histopathology?

Explanation

Diagnostic Cells in Classical Hodgkin Lymphoma

Morphology and Diagnostic Criteria

Morphological Features of Reed-Sternberg Cells

Immunophenotype

Why Lacunar Cells Are NOT the Answer

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Cell Type	Origin	Morphology	Diagnostic Role	Frequency
Reed-Sternberg (RS) cells	Clonal B cells	Large, multinucleated, "owl's eye" nucleoli, abundant cytoplasm	Pathognomonic for cHL	Required for diagnosis
Hodgkin cells	Clonal B cells	Mononuclear variants of RS cells; similar morphology	Diagnostic equivalent	Present in all cases
Lacunar cells	RS cells in formalin-fixed tissue	RS cells in clear spaces (lacunae) in nodular sclerosis	Subtype-specific	Nodular sclerosis only
Immunoblasts	Non-neoplastic T cells	Large activated lymphocytes	Background inflammatory cells	Non-diagnostic