Excellent! I now have the key textbook figure (Fig. 13.25 from Robbins) and all the information needed. Let me now compile a comprehensive, exam-ready answer for a 2nd year MBBS student in the style of Harsh Mohan's Textbook of Pathology.
Reed-Sternberg (RS) Cells — Types and Descriptions
(Reference: Harsh Mohan, Textbook of Pathology, 8th ed.; Robbins & Cotran Pathologic Basis of Disease)
What is a Reed-Sternberg Cell?
Reed-Sternberg (RS) cells are the pathognomonic neoplastic cells of Hodgkin Lymphoma (HL). They are derived from germinal centre B lymphocytes (confirmed by clonal IGH gene rearrangements and somatic hypermutation).
Basic features of classic RS cells:
- Large cells (~45 μm in diameter)
- Binucleated or bilobed nucleus, with mirror-image appearance
- Each nucleus contains a large, eosinophilic, inclusion-like nucleolus (5–7 μm — size of a small lymphocyte)
- Surrounded by a clear halo → "Owl-eye appearance" (the hallmark)
- Abundant pale cytoplasm
- Set against a background of lymphocytes, eosinophils, plasma cells, and macrophages
Immunophenotype (classic HL): CD30⁺, CD15⁺, PAX5 (weak)+, CD45⁻, CD20⁻
Types / Variants of Reed-Sternberg Cells
Fig. 13.25 (Robbins) — RS cells and variants. (A) Diagnostic RS cell (owl-eye, binucleate). (B) Mononuclear variant. (C) Lacunar variant (cell sitting in empty space/lacuna). (D) Lymphohistiocytic (L&H / popcorn) variants with multilobated nuclei and small nucleoli.
1. Classic (Diagnostic) RS Cell
| Feature | Detail |
|---|
| Nucleus | Binucleate or bilobed; mirror-image |
| Nucleolus | Large, prominent, eosinophilic — "inclusion-like" (5–7 μm); one per lobe → "Owl-eye" appearance |
| Cytoplasm | Abundant, pale eosinophilic |
| Size | ~45 μm |
| Background | Lymphocytes, eosinophils, plasma cells, macrophages |
| Subtype | Required for diagnosis in all classic HL subtypes |
| IHC | CD15⁺, CD30⁺, PAX5 weak+, CD45⁻ |
Key fact (Harsh Mohan): The classic RS cell is the sine qua non for diagnosing Hodgkin lymphoma. Its identification in an appropriate cellular background is mandatory for diagnosis.
2. Mononuclear Variant (Hodgkin Cell)
| Feature | Detail |
|---|
| Nucleus | Single nucleus (instead of two) |
| Nucleolus | One large, prominent, eosinophilic, inclusion-like nucleolus |
| Cytoplasm | Abundant |
| Morphology | Essentially half of a classic RS cell |
| Subtype | Common in Mixed Cellularity and Lymphocyte-Rich subtypes |
| Note | Also called "Hodgkin cell" |
3. Lacunar Variant
| Feature | Detail |
|---|
| Nucleus | Multilobated/folded; delicate nuclear membranes |
| Nucleolus | Small to inconspicuous (multiple small ones) |
| Cytoplasm | Abundant pale cytoplasm that retracts during formalin fixation, leaving the nucleus in an empty clear space = lacuna |
| Artifact | The "lacuna" (empty space) is a fixation artifact — NOT seen in B5-fixed specimens |
| Subtype | Characteristic of Nodular Sclerosis HL (most common subtype, 65–70%) |
| IHC | CD15⁺, CD30⁺ |
Mnemnonic tip: "Lacunar = Nodular Sclerosis" — the lacunar cell + collagen bands = nodular sclerosis pattern.
Lacunar variant RS cells in Nodular Sclerosis HL — note clear "lacunae" around the folded nuclei (H&E)
4. Lymphohistiocytic (L&H) Variant — "Popcorn Cell"
| Feature | Detail |
|---|
| Nucleus | Multilobated, polypoid/folded — resembles popcorn |
| Nucleolus | Multiple, small, basophilic (not the large eosinophilic nucleolus of classic RS) |
| Chromatin | Fine, vesicular |
| Cytoplasm | Moderately abundant, pale |
| Subtype | Characteristic of Nodular Lymphocyte-Predominant HL (NLPHL) |
| IHC | CD20⁺, CD45⁺, CD15⁻, CD30⁻ (opposite to classic HL!) |
| Background | B-cell rich nodules with follicular dendritic cells; T cells form rosettes around LP cells |
Key distinction: L&H cells express B-cell markers (CD20+) and are CD15⁻/CD30⁻, unlike all other RS variants. NLPHL has an indolent course and excellent prognosis.
L&H (popcorn) cells in Nodular Lymphocyte-Predominant HL — irregular lobulated nuclei with small nucleoli, dense lymphocytic background (H&E)
5. "Mummified" (Pyknotic) RS Cell
| Feature | Detail |
|---|
| Nucleus | Pyknotic, shrunken, condensed chromatin |
| Cytoplasm | Deeply eosinophilic |
| Mechanism | A peculiar form of cell death seen in classic HL subtypes |
| Significance | Seen especially in Lymphocyte-Depleted HL |
Summary Table
| RS Cell Variant | Also Called | Nucleus | Nucleolus | Associated HL Subtype | CD15 | CD30 | CD20 |
|---|
| Classic RS cell | Diagnostic RS cell | Binucleate, owl-eye | Large, eosinophilic (×2) | All classic HL subtypes | ⊕ | ⊕ | ⊖ |
| Mononuclear | Hodgkin cell | Single nucleus | Large, eosinophilic (×1) | Mixed Cellularity, Lymphocyte-Rich | ⊕ | ⊕ | ⊖ |
| Lacunar | — | Multilobated, folded | Small/multiple | Nodular Sclerosis | ⊕ | ⊕ | ⊖ |
| L&H / Popcorn | Lymphohistiocytic | Polypoid, multifolded | Small, basophilic | Nodular Lymphocyte-Predominant | ⊖ | ⊖ | ⊕ |
| Mummified | Pyknotic RS cell | Pyknotic, condensed | Absent | Lymphocyte-Depleted | ⊕ | ⊕ | ⊖ |
Diagnostic Rule (Harsh Mohan)
Classic RS cells are necessary but NOT sufficient for diagnosis. They must be found in an appropriate reactive cellular background (lymphocytes, eosinophils, plasma cells). RS-like cells occur in:
- Infectious mononucleosis
- Non-Hodgkin lymphomas (especially ALCL)
- Solid tissue carcinomas (mimics)
Immunohistochemistry (CD15, CD30, CD20, CD45, PAX5) is used to confirm when morphology is uncertain.
Classic Reed-Sternberg cell — binucleate "owl-eye" cell at center, surrounded by mixed inflammatory background (H&E)
Sources: Robbins, Cotran & Kumar — Pathologic Basis of Disease, Fig. 13.25 & Table 13.8 (corresponds to Harsh Mohan's classification of RS cell types in the Lymph Nodes chapter).