Micrography showing a “popcorn cell”, the variant of the Reed-Sternberg cell seen in predominantly nodular lymphocytic Hodgkin’s lymphoma. H&E coloring
Reed-Sternberg cells (also known as lacunar histiocytes for certain types) are distinctive, giant cells found with microscope light at the biopsies of individuals with Hodgkin’s lymphoma. They are usually derived from B lymphocytesclassically considered crippled germinal center B cells. In the vast majority of cases, the immunoglobulin Reed-Sternberg cell genes passed through both V(D)J recombination and somatic hypermutation, establishing an origin from a B cell of the germinal center or the postgerminal center. Despite having the genetic signature of a B cell, the Reed-Sternberg cells of classic Hodgkin’s lymphoma fail to express most B cell-specific genes, including immunoglobulin genes. The cause of this total reprogramming of gene expression has yet to be fully explained. Presumably it is the result of generalized epigenetic changes of uncertain etiology, but is in part a consequence of so-called “paralyzing” mutations acquired during somatic hypermutation. Seen against a sea of B cells, they give the tissue a moth-eaten appearance.
Reed-Sternberg cells are large (30-50 microns) and are multinucleated or bilobed. core with prominent eosinophilic inclusion type nucleolus (thus resembling an “owl’s eye” appearance). Reed-Sternberg cells are CD30 and CD15 positive, except in the lymphocyte predominant type, where they are negative, but are usually positive for CD20 and CD45. The presence of these cells is required in the diagnosis of Hodgkin’s lymphoma – the absence of Reed-Sternberg cells is of high value negative predictive value. The presence of these cells is mainly confirmed by the use of biomarkers in immunohistochemistry. They can also be found in reagents lymphadenopathy (such as infectious mononucleosis immunoblasts that are like RS in appearance, carbamazepine associated lymphadenopathy) and very rarely in other types of non-Hodgkin’s lymphomas. Anaplastic large cell lymphoma may also have RS-like cells.
A special type of Reed-Sternberg cell (RSC) is the lacunar histiocytewhose cytoplasm shrinks when fixed in formalin, so that the nuclei give the appearance of cells lying down with empty spaces (called gaps) between them. These are features of nodular sclerosis subtype of Hodgkin’s lymphoma.
Mummified CSRs (compact nucleus, basophilic cytoplasm, no nucleolus) are also associated with classical Hodgkin’s Lymphoma while popcorn cells (small cells with hyperlobulated nuclei and small nucleoli) are lymphohistiocytic (LH) variants of Reed Sternberg cells and are associated with predominantly nodular lymphocytic Hodgkin’s lymphoma (PLNL).
RSCs and one RSC cell line (L1236 cells), but not other RSC cell lines, express very high levels of ALOX15 (i.e. 15-lipoxygenase-1) or possibly ALOX15B (i.e. 15-lipoxygenase-2), enzymes that metabolize arachidonic acid and several others polyunsaturated fatty acids to a wide range of bioactive products, including in particular those from 15-Hydroperoxyeicosatetraenoic acid family of arachidonic acid metabolites. This is unusual because lymphocytes normally express little or no ALOX15. It is suggested that ALOX15 and/or ALOX15B, perhaps operating through one of its products derived from arachidonic acid, the eoxins, contribute to the development and/or morphology of Hodgkin’s lymphoma.
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