Reed-Sternberg (RS) cells are large, abnormal cells found in Hodgkin Lymphoma, a cancer affecting the lymphatic system. These distinctive cells are considered the malignant component of the disease, even though they usually constitute a very small percentage of the total tumor mass. The presence of RS cells is a definitive pathological marker that plays a central role in distinguishing Hodgkin Lymphoma from other forms of lymphoma.
Unique Characteristics and Detection
Reed-Sternberg cells are significantly larger than normal white blood cells, typically measuring 15 to 45 micrometers in diameter, and contain abundant cytoplasm. Their most recognizable feature is the nucleus, which is often bilobed or multi-lobed. This structure gives the cell a characteristic “owl’s eye” appearance, created by large, prominent nucleoli surrounded by a clear area.
Confirmation begins with a tissue biopsy, usually from an enlarged lymph node, followed by microscopic examination. To differentiate RS cells from other large cells, pathologists use specialized techniques like immunohistochemistry. This method uses antibodies to detect specific protein markers on the cell surface. Classic Reed-Sternberg cells typically test positive for the markers CD30 and CD15, confirming the diagnosis of Classical Hodgkin Lymphoma.
Biological Origin and Disease Mechanism
Reed-Sternberg cells originate from germinal center B-lymphocytes. These precursor cells undergo genetic changes during development, but in RS cells, this process goes awry. The B-cells acquire mutations that prevent them from undergoing programmed cell death (apoptosis), allowing the damaged cells to survive and proliferate. This escape from cellular control leads to the development of the malignant Reed-Sternberg cell.
Reed-Sternberg cells are scarce, often making up less than one percent of the entire tumor mass. The bulk of the tumor tissue is composed of a dense, non-cancerous inflammatory infiltrate, including T-cells, macrophages, eosinophils, and plasma cells. The malignant RS cells actively recruit these surrounding immune cells by secreting chemical signaling molecules, such as cytokines and chemokines. This intense, reactive microenvironment is a defining feature of Hodgkin Lymphoma and is manipulated by the RS cells to support their growth and survival.
Diagnostic Significance in Hodgkin Lymphoma
The identification of classic Reed-Sternberg cells is required for diagnosing Classical Hodgkin Lymphoma (CHL). Their presence is the main factor distinguishing Hodgkin Lymphoma from Non-Hodgkin Lymphoma, which requires different treatment approaches. The absence of these cells in a tissue sample carries a high negative predictive value, strongly suggesting the patient does not have CHL.
The features of the RS cells and surrounding immune cells help classify the disease into specific subtypes. Classical Hodgkin Lymphoma is divided into four main subtypes: nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. For instance, the lacunar cell, which appears to sit in an empty space due to tissue processing, is characteristic of the nodular sclerosing subtype. The mononuclear Hodgkin cell, which has only a single nucleus, is also commonly found alongside the classic binucleated RS cell.