Reed-Sternberg cells are distinctive, large cells observed under a microscope in biopsies. They serve as a significant diagnostic marker. Their unusual appearance makes them recognizable to pathologists. Dorothy Reed Mendenhall and Carl Sternberg provided their definitive microscopic descriptions, establishing their importance in pathology.
Characteristics of Reed-Sternberg Cells
Reed-Sternberg cells are notably large, ranging from 30 to 100 microns. A distinguishing feature is their bilobed or multinucleated appearance, often described as resembling an “owl’s eye” due to their large, prominent eosinophilic nucleoli and thick nuclear membranes. Their nuclei have a distinct, thick membrane and vesicular chromatin, sometimes appearing as mirror images.
The cells possess abundant cytoplasm, which can appear pale, eosinophilic, or amphophilic, and may be finely granular or homogenous. In some variations, such as lacunar cells found in nodular sclerosis Hodgkin lymphoma, the cytoplasm can retract during preparation, creating an empty space or “lacunae” around the nucleus. Other variants, like “popcorn cells” seen in nodular lymphocyte predominant Hodgkin lymphoma, are smaller with hyper-lobulated nuclei.
Role in Hodgkin Lymphoma
Reed-Sternberg cells are the defining pathological feature of classical Hodgkin lymphoma. Their presence, even if infrequent, is a strong indicator for this diagnosis and helps differentiate it from other types of lymphoma. These malignant cells, while central to the disease, often constitute a small fraction, less than 1% to 5%, of the total cellular population within affected lymph nodes or tissues.
The surrounding tissue in classical Hodgkin lymphoma is characterized by a significant inflammatory background. This environment includes a variety of reactive cells such as T-cells, B-cells, eosinophils, macrophages, plasma cells, and neutrophils, which form the bulk of the tumor mass. Reed-Sternberg cells interact with these immune cells, influencing the surrounding microenvironment and contributing to the overall pathology and clinical presentation of Hodgkin lymphoma.
Identification of Reed-Sternberg Cells
Identifying Reed-Sternberg cells begins with a biopsy, often from an enlarged lymph node. The tissue sample is prepared and examined under a microscope by pathologists, allowing for initial recognition of their characteristic “owl’s eye” appearance and large size.
To confirm their identity and differentiate them from other atypical cells, immunohistochemistry (IHC) is widely used. This technique detects specific surface markers. Reed-Sternberg cells show positive staining for CD30 and, in about 80% of classical Hodgkin lymphoma cases, for CD15. CD45 is negative, while a weak nuclear expression of PAX-5 is also characteristic. The combination of these markers helps pathologists make an accurate diagnosis.
Cellular Nature and Development
Reed-Sternberg cells originate from germinal center B lymphocytes. These B cells undergo V(D)J recombination and somatic hypermutation in germinal centers. Normally, B cells with non-functional or low-affinity antibody genes undergo programmed cell death (apoptosis). However, Reed-Sternberg cells are B lymphocytes that failed to undergo this process, becoming malignant and proliferating.
Despite their B-cell origin, classical Reed-Sternberg cells lose the typical B-cell gene expression profile, including immunoglobulin genes. This reprogramming is not fully understood but may involve widespread epigenetic changes and “crippling” mutations acquired during somatic hypermutation. Their survival is linked to the activation of specific signaling pathways, such as the NF-κB transcription factor pathway, which helps them evade immune detection and continue to grow.