The Reed-Sternberg (RS) cell is an abnormal, often giant cell observed by pathologists when examining tissue from a patient with lymphoma. Its presence is central to the diagnosis of Hodgkin Lymphoma, a specific type of cancer originating in the lymphatic system. This cell, along with its variants, represents the malignant component of the disease, though it is usually surrounded by a much larger number of non-cancerous immune cells.
Defining the Reed-Sternberg Cell
The classic Reed-Sternberg cell is a large, distinctive cell, measuring up to 100 microns in size, which is significantly larger than a typical lymphocyte. It possesses abundant cytoplasm and is most recognizable by its unique nuclear structure. The nucleus is frequently bilobed or multinucleated, creating a mirror-image effect.
Within each nuclear lobe is a prominent, large nucleolus surrounded by a clear space, or halo. This morphology, featuring two such nuclei with prominent nucleoli, often causes the cell to resemble an “owl’s eye” when viewed under a microscope. The Reed-Sternberg cell originates from a B-lymphocyte, a type of white blood cell responsible for producing antibodies.
Genetic evidence confirms this lineage, showing the cell has undergone the immunoglobulin gene rearrangement typical of B-cells. However, during transformation, the cell loses the expression of most B-cell-specific genes, a characteristic of classical Hodgkin Lymphoma. The resulting malignant cell expresses markers like CD30 and CD15, which are used for identification, instead of the B-cell markers it originated from.
Association with Hodgkin Lymphoma
The presence of classic Reed-Sternberg cells and their variants is mandatory for a diagnosis of Classical Hodgkin Lymphoma (CHL). However, the RS cell itself is a relatively rare component of the tumor mass, typically constituting less than one percent of the total cells in the affected lymph node. This low concentration is unusual for a cancer and is a defining feature of the disease.
The vast majority of the tissue mass consists of a reactive inflammatory background, including healthy T-cells, B-cells, plasma cells, eosinophils, and histiocytes. This inflammatory environment is not accidental; the RS cells actively recruit and organize these non-cancerous cells by secreting various chemical messengers, such as cytokines and chemokines. This communication helps the malignant cells evade the immune system and promotes their survival by creating a supportive tumor microenvironment.
This interplay between the scarce malignant RS cells and the abundant reactive immune cells defines the unique pathological features of Classical Hodgkin Lymphoma. The RS cell effectively manipulates its surroundings, establishing a self-protective niche that contributes to the disease’s progression. This characteristic microenvironment differentiates Hodgkin Lymphoma from other types of lymphoma, where the malignant cells usually make up the bulk of the tumor.
Diagnostic Subtyping and Cell Variants
The identification of Reed-Sternberg cells through a tissue biopsy is foundational for classifying Hodgkin Lymphoma, and the specific variants present dictate the disease subtype. The simplest variant is the Hodgkin cell, which is a mononuclear version of the RS cell, possessing only a single, large nucleus with the characteristic prominent nucleolus. Hodgkin cells are often more numerous than the classic multinucleated RS cells and are thought to be the primary proliferating malignant cell.
Another variation is the lacunar cell, characteristic of the Nodular Sclerosis subtype of Classical Hodgkin Lymphoma, the most common form. These cells appear to sit in an empty space, or lacuna, which is an artifact created when the abundant cytoplasm shrinks during tissue preparation. The nucleus of the lacunar cell is often multilobulated and contains multiple small nucleoli.
A distinct variant is the L&H cell, also known as the lymphocyte-predominant or “popcorn” cell, which defines Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL). This cell has a hyperlobulated, folded nucleus that resembles a piece of popcorn, distinguishing it morphologically from the classic RS cell. Crucially, L&H cells have a different immunophenotype, expressing B-cell markers like CD20 and CD45, while lacking the CD15 and CD30 expression seen in Classical Hodgkin Lymphoma RS cells.
Because of these differences in cell markers and overall behavior, NLPHL is considered a different clinical entity from Classical Hodgkin Lymphoma subtypes. The presence of L&H cells instead of classic RS cells signals a different disease course and approach to treatment. Analysis of these specific cell variants and their associated protein markers allows pathologists to precisely subtype the disease for guiding patient management.