Reed–Sternberg cells (also known as lacunar histiocytes for certain types) are distinctive,

giant cell A giant cell (also known as multinucleated giant cell, or multinucleate giant cell) is a mass formed by the union of several distinct cells (usually histiocytes), often forming a granuloma. Although there is typically a focus on the pathologica ...

s found with

light microscopy Microscopy is the technical field of using microscopes to view objects and areas of objects that cannot be seen with the naked eye (objects that are not within the resolution range of the normal eye). There are three well-known branches of micr ...

biopsies A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a disea ...

from individuals with

Hodgkin lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The conditio ...

. They are usually derived from

B lymphocytes B cells, also known as B lymphocytes, are a type of white blood cell of the lymphocyte subtype. They function in the humoral immunity component of the adaptive immune system. B cells produce antibody molecules which may be either secreted or ...

, classically considered crippled

germinal center Germinal centers or germinal centres (GCs) are transiently formed structures within B cell zone (follicles) in secondary lymphoid organs – lymph nodes, ileal Peyer's patches, and the spleen – where mature B cells are activated, prolifera ...

B cells. In the vast majority of cases, the

immunoglobulin An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of th ...

genes of Reed–Sternberg cells have undergone both

V(D)J recombination V(D)J recombination is the mechanism of somatic recombination that occurs only in developing lymphocytes during the early stages of T and B cell maturation. It results in the highly diverse repertoire of antibodies/immunoglobulins and T cell re ...

and

somatic hypermutation Somatic hypermutation (or SHM) is a cellular mechanism by which the immune system adapts to the new foreign elements that confront it (e.g. microbes), as seen during class switching. A major component of the process of affinity maturation, SHM ...

, establishing an origin from a germinal center or postgerminal center B cell. Despite having the genetic signature of a B cell, the Reed–Sternberg cells of classical Hodgkin lymphoma fail to express most B-cell–specific genes, including the immunoglobulin genes. The cause of this wholesale reprogramming of gene expression has yet to be fully explained. It presumably is the result of widespread epigenetic changes of uncertain etiology, but is partly a consequence of so-called "crippling" mutations acquired during

. 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 either multinucleated or have a bilobed

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: * Atomic nucleus, the very dense central region of an atom *Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

with prominent

eosinophilic Eosinophilic (Greek suffix -phil-, meaning ''loves eosin'') is the staining of tissues, cells, or organelles after they have been washed with eosin, a dye. Eosin is an acidic dye for staining cell cytoplasm, collagen, and muscle fibers. ''E ...

inclusion-like

nucleoli The nucleolus (, plural: nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis, which is the synthesis of ribosomes. The nucleolus also participates in the formation of s ...

(thus resembling an "owl's eye" appearance). Reed–Sternberg cells are

CD30 CD30, also known as TNFRSF8 ( TNF receptor superfamily member 8), is a cell membrane protein of the tumor necrosis factor receptor family and a tumor marker. Function This receptor is expressed by activated, but not by resting, T and B cel ...

and

CD15 Sialyl LewisX (sLeX), also known as cluster of differentiation 15s (CD15s) or stage-specific embryonic antigen 1 (SSEA-1), is a tetrasaccharide carbohydrate which is usually attached to O- glycans on the surface of cells. It is known to play a vi ...

positive except in the lymphocyte predominance type where they are negative, but are usually positive for

CD20 B-lymphocyte antigen CD20 or CD20 is expressed on the surface of all B-cells beginning at the pro-B phase ( CD45R+, CD117+) and progressively increasing in concentration until maturity. In humans CD20 is encoded by the ''MS4A1'' gene. This gene ...

and

CD45 Protein tyrosine phosphatase, receptor type, C also known as PTPRC is an enzyme that, in humans, is encoded by the ''PTPRC'' gene. PTPRC is also known as CD45 antigen (CD stands for cluster of differentiation), which was originally called leuko ...

. The presence of these cells is necessary in the diagnosis of Hodgkin lymphoma – the absence of Reed–Sternberg cells has very high

negative predictive value The positive and negative predictive values (PPV and NPV respectively) are the proportions of positive and negative results in statistics and diagnostic tests that are true positive and true negative results, respectively. The PPV and NPV des ...

. The presence of these cells is confirmed mainly by use of biomarkers in

immunohistochemistry Immunohistochemistry (IHC) is the most common application of immunostaining. It involves the process of selectively identifying antigens (proteins) in cells of a tissue section by exploiting the principle of antibodies binding specifically to ant ...

. They can also be found in reactive

lymphadenopathy Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In cl ...

(such as

infectious mononucleosis Infectious mononucleosis (IM, mono), also known as glandular fever, is an infection usually caused by the Epstein–Barr virus (EBV). Most people are infected by the virus as children, when the disease produces few or no symptoms. In young adult ...

immunoblasts which are RS like in appearance,

carbamazepine Carbamazepine (CBZ), sold under the trade name Tegretol among others, is an anticonvulsant medication used primarily in the treatment of epilepsy and neuropathic pain. It is used as an adjunctive treatment in schizophrenia along with other m ...

associated lymphadenopathy) and very rarely in other types of non-Hodgkin lymphomas. Anaplastic large cell lymphoma may show RS-like cells as well.

History

They are named after

Dorothy Reed Mendenhall Dorothy Mabel Reed Mendenhall (September 22, 1874–July 31, 1964) was a prominent pediatric physician specializing in cellular pathology. In 1901, she discovered that Hodgkin's disease was not a form of tuberculosis, by noticing the presenc ...

and

Carl Sternberg Carl Sternberg (November 20, 1872 – August 15, 1935) was an Austrian pathologist. The Reed–Sternberg cell is named after him and American physician Dorothy Reed Mendenhall. Biography Education Sternberg studied medicine at the Medical f ...

, who provided the first definitive microscopic descriptions of Hodgkin's disease.

Pathology

Hodgkin lymphoma

A special type of Reed–Sternberg cell (RSC) is the ''lacunar histiocyte'', whose cytoplasm retracts when fixed in formalin, so the nuclei give the appearance of cells that lie with empty spaces (called ''lacunae'') between them. 8th edition. These are characteristic of the

nodular sclerosis Nodular sclerosis (or "NSHL") is a form of Hodgkin's lymphoma that is the most common subtype of HL in developed countries. It affects females slightly more than males and has a median age of onset at ~28 years. It is composed of large tumor nodul ...

subtype of Hodgkin lymphoma. Mummified RSCs (compact nucleus, basophilic cytoplasm, no nucleolus) are also associated with classical

Hodgkin's lymphoma Hodgkin lymphoma (HL) is a type of lymphoma, in which cancer originates from a specific type of white blood cell called lymphocytes, where multinucleated Reed–Sternberg cells (RS cells) are present in the patient's lymph nodes. The condition w ...

while popcorn cells (small cell with hyper-lobulated nucleus and small nucleoli) are lymphohistiocytic (L-H) variant of Reed Sternberg cells and are associated with

nodular lymphocyte predominant Hodgkin lymphoma Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a slow-growing CD20 positive form of Hodgkin lymphoma, a cancer of the immune system's B cells. NLPHL is an uncommon sub-type of Hodgkin lymphoma, making up 5-10% of Hodgkin lymphomas. It ...

(NLPHL). RSCs and one RSC cell line (L1236 cells) but not other RSC cell lines express very high levels of

ALOX15 ALOX15 (also termed arachidonate 15-lipoxygenase, 15-lipoxygenase-1, 15-LO-1, 15-LOX-1) is, like other lipoxygenases, a seminal enzyme in the metabolism of polyunsaturated fatty acids to a wide range of physiologically and pathologically importa ...

(i.e., 15-lipoxygenase-1) or possibly ALOX15B (i.e. 15-lipoxygenase-2), enzymes that metabolize

arachidonic acid Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega-6 fatty acid 20:4(ω-6), or 20:4(5,8,11,14). It is structurally related to the saturated arachidic acid found in cupuaçu butter. Its name derives from the New Latin word ''ara ...

and various other

polyunsaturated fatty acids Polyunsaturated fatty acids (PUFAs) are fatty acids that contain more than one double bond in their backbone. This class includes many important compounds, such as essential fatty acids and those that give drying oils their characteristic pr ...

to a wide array of bioactive products including in particular those of the 15-Hydroperoxyeicosatetraenoic acid family of arachidonic acid metabolites. This is unusual in that lymphocytes typically express little or no ALOX15. It is suggested that ALOX15 and/or ALOX15B, perhaps operating through one of its arachidonic acid-derived products, the eoxins, contributes to the development and/or morphology of Hodgkin lymphoma.Exp Hematol. 2010 Feb;38(2):116–23.

References

{{DEFAULTSORT:Reed-Sternberg cell Histopathology Hodgkin lymphoma

History

Pathology

Hodgkin lymphoma

See also

References