The Reed-Sternberg cell is a pathological landmark in the study of blood cancers, first recognized for its unusual appearance under a microscope. The cell is named after the two researchers who provided the most definitive descriptions of it in the early 20th century. Austrian pathologist Carl Sternberg published his findings in 1898, followed by American physician Dorothy Reed in 1902, whose work helped distinguish the associated disease from tuberculosis.
The Distinctive Morphology
Under high-power magnification, the Reed-Sternberg cell is immediately noticeable due to its extremely large size, often measuring up to 50 micrometers or more in diameter, making it significantly larger than most surrounding immune cells. A defining characteristic is its nuclear structure, which is often bilobed or multinucleated, giving the cell a striking, symmetrical appearance.
The classic visual presentation is referred to as the “owl-eye” appearance because of its two mirror-image nuclei. Within these nuclei are prominent, large nucleoli that stain intensely with eosin, appearing red or pink. These nucleoli are often surrounded by a clear zone of chromatin, enhancing the resemblance to the eyes of an owl.
Mononuclear variants, known as Hodgkin cells, exist alongside the classic form but possess only a single nucleus. Another morphological variant is the lacunar cell, often seen in specific subtypes of the associated disease. In lacunar cells, the cytoplasm retracts during tissue fixation, creating an empty space or “lacuna” around the hyperlobulated nucleus.
Cellular Lineage and Transformation
The Reed-Sternberg cell originates from a B-lymphocyte, a type of white blood cell that develops in the germinal center of a lymph node. These B-cells acquire mutations in their immunoglobulin genes but fail the normal cellular quality control process.
In healthy B-cells, a failure to properly rearrange antibody genes should trigger apoptosis, a controlled self-destruct mechanism. Reed-Sternberg precursor cells, however, bypass this cell death, allowing them to survive and proliferate abnormally. This survival is often driven by the continuous activation of aberrant signaling pathways within the cell.
A major mechanism for this unchecked survival is the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. This pathway usually controls cellular responses to stress and infection, but its constant activation provides strong anti-apoptotic signals. This allows the Reed-Sternberg cell to persist and grow into a malignant clone.
The transformation process results in what pathologists call a “missing B-cell phenotype.” Although the cell retains the genetic signature of a B-cell, it ceases to express most typical B-cell-specific surface markers and proteins. This loss of identity is a defining feature of the cell and a significant part of its pathogenesis.
Diagnostic Importance
The identification of Reed-Sternberg cells is necessary for the diagnosis of Classical Hodgkin Lymphoma (cHL). Pathologists primarily rely on a tissue biopsy, typically of an enlarged lymph node, to search for these distinctive cells. These malignant cells are scarce, often constituting only about one percent of the total cellular population within the affected tissue.
The majority of the surrounding cells are a mixture of reactive immune cells, such as T-cells, eosinophils, and macrophages. This dense inflammatory background is a characteristic feature of the disease, induced by signals released by the malignant cells. This interaction is known as the tumor microenvironment.
To confirm the identity of the cells beyond their classic “owl-eye” shape, pathologists use immunohistochemistry (IHC). IHC involves applying specific antibodies to the tissue sample that bind to unique proteins on the cell surface. Reed-Sternberg cells in cHL characteristically show a positive reaction for the protein markers CD30 and CD15.
Conversely, they typically lack the common B-cell marker CD20 and the leukocyte common antigen CD45. This specific immunophenotype, combined with the distinctive morphology, establishes the diagnosis. The absence of Reed-Sternberg cells, or a different profile of protein markers, directs the diagnosis toward other types of lymphomas or inflammatory conditions.