Reed Sternberg Cell

• A Reed Sternberg Cell is a large, abnormal cell primarily associated with Hodgkin lymphoma.
• These cells are characterized by their distinctive bilobed or multinucleated appearance, often resembling “owl’s eyes.”
• They originate from germinal center B-cells that have undergone malignant transformation.
• Despite being the diagnostic feature, Reed Sternberg cells constitute a small fraction of the tumor mass, surrounded by reactive inflammatory cells.
• Their presence is essential for the diagnosis of classical Hodgkin lymphoma.

What is a Reed Sternberg Cell?

A Reed Sternberg Cell is a giant, malignant cell identified by pathologists as the diagnostic hallmark of classical Hodgkin lymphoma. These cells are typically large, ranging from 15 to 45 micrometers in diameter, and possess a distinctive morphology that sets them apart from other cancerous or inflammatory cells. Their identification under a microscope is a critical step in confirming a diagnosis of Hodgkin lymphoma, differentiating it from other lymphomas and reactive conditions.

While these cells are central to the diagnosis, they are often sparsely distributed within the affected tissue. The bulk of the tumor mass in Hodgkin lymphoma is composed of a diverse infiltrate of reactive inflammatory cells, such as lymphocytes, plasma cells, eosinophils, and histiocytes, which are recruited and sustained by cytokines secreted by the Reed Sternberg cells themselves. This unique microenvironment is crucial for the survival and proliferation of the malignant cells.

Characteristics of Reed Sternberg Cells

The defining features of Reed Sternberg cells are primarily morphological, observed through microscopic examination of biopsy samples. These characteristics are essential for their identification and differentiation from other cell types. The most classic presentation involves a bilobed or multinucleated appearance with prominent nucleoli, often described as having an “owl’s eye” appearance due to the large, eosinophilic nucleoli surrounded by a clear halo.

Key characteristics include:

• Size: Unusually large, typically 15-45 µm in diameter.
• Nuclei: Often bilobed (mirror-image nuclei) or multinucleated, giving a characteristic appearance.
• Nucleoli: Large, prominent, eosinophilic (red-staining) nucleoli, often surrounded by a clear halo.
• Cytoplasm: Abundant and amphophilic (stains with both acidic and basic dyes).
• Immunophenotype: Typically express CD30 and CD15 markers, while lacking most B-cell and T-cell markers (e.g., CD20, CD3), which helps distinguish them from other lymphomas.

Variants of the classic Reed Sternberg cell also exist, such as lacunar cells (found in nodular sclerosis Hodgkin lymphoma) and L&H cells (lymphocytic and histiocytic, or “popcorn” cells, found in nodular lymphocyte-predominant Hodgkin lymphoma). These variants share some features but have distinct morphological differences and are associated with specific subtypes of Hodgkin lymphoma.

Reed Sternberg Cell Origin and Association with Hodgkin Lymphoma

The Reed Sternberg cell origin is now well-established, primarily tracing back to germinal center B-lymphocytes. These cells undergo an aberrant transformation, failing to complete their normal differentiation program and acquiring mutations that prevent apoptosis (programmed cell death). Despite their B-cell lineage, Reed Sternberg cells often lose many characteristic B-cell markers, which was a source of confusion in earlier research regarding their true cellular origin.

The strong association between the Reed Sternberg cell Hodgkin lymphoma is fundamental to its diagnosis. Classical Hodgkin lymphoma is defined by the presence of these cells within a reactive inflammatory background. The malignant Reed Sternberg cells secrete various cytokines and chemokines, which recruit and sustain the surrounding non-malignant cells. This intricate interaction creates a supportive microenvironment that promotes the survival and proliferation of the malignant cells, while simultaneously suppressing an effective anti-tumor immune response.

Understanding the origin and the complex interplay between Reed Sternberg cells and their microenvironment is crucial for developing targeted therapies for Hodgkin lymphoma. Advances in molecular pathology continue to refine our understanding of these unique cells, leading to improved diagnostic accuracy and treatment strategies for patients.