Lymphoproliferative disorders (LPDs) refer to a specific class of diagnoses, comprising a group of several conditions, in which

lymphocytes A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), and ...

are produced in excessive quantities. These disorders primarily present in patients who have a compromised

immune system The immune system is a network of biological systems that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to bacteria, as well as Tumor immunology, cancer cells, Parasitic worm, parasitic ...

. Due to this factor, there are instances of these conditions being equated with " immunoproliferative disorders"; although, in terms of

nomenclature Nomenclature (, ) is a system of names or terms, or the rules for forming these terms in a particular field of arts or sciences. (The theoretical field studying nomenclature is sometimes referred to as ''onymology'' or ''taxonymy'' ). The principl ...

, lymphoproliferative disorders are a subclass of immunoproliferative disorders—along with hypergammaglobulinemia and paraproteinemias.

Lymphoproliferative disorders (examples)

Follicular lymphoma Follicular lymphoma (FL) is a cancer that involves certain types of white blood cells known as lymphocytes. This cancer is a form of Non-Hodgkin Lymphoma and it originates from the uncontrolled division of specific types of B-cells ( centrocytes ...

Chronic lymphocytic leukemia Chronic lymphocytic leukemia (CLL) is a type of cancer that affects the blood and bone marrow. In CLL, the bone marrow makes too many lymphocytes, which are a type of white blood cell. In patients with CLL, B cell lymphocytes can begin to colle ...

Acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

Hairy cell leukemia Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. The incidence of hairy cell leukemia (HCL) is 0.28-0.30 cases per 100,000 people in Europe and the United States and the pre ...

Hemophagocytic lymphohistiocytosis In hematology, hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis ( British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than ...

(HLH) *

B-cell lymphoma The B-cell lymphomas are types of lymphoma affecting B cells. Lymphomas are Tumors of the hematopoietic and lymphoid tissues, "blood cancers" in the lymph nodes. They develop more frequently in older adults and in immunocompromised individuals. ...

s *

T-cell lymphoma T-cell lymphoma is a rare form of cancerous lymphoma affecting T cell, T-cells. Lymphoma arises mainly from the uncontrolled proliferation of lymphocytes, such as T-cells, and can become cancerous. T-cell lymphoma is categorized under Non-Hodgkin ...

s *

Multiple myeloma Multiple myeloma (MM), also known as plasma cell myeloma and simply myeloma, is a cancer of plasma cells, a type of white blood cell that normally produces antibody, antibodies. Often, no symptoms are noticed initially. As it progresses, bone ...

* Waldenström's macroglobulinemia *

Wiskott–Aldrich syndrome Wiskott–Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet count), immune deficiency, and bloody diarrhea (secondary to the thrombocytopenia). It is also sometimes called the e ...

Langerhans cell histiocytosis Langerhans cell histiocytosis (LCH) is an abnormal clonal proliferation of Langerhans cells, abnormal cells deriving from bone marrow and capable of migrating from skin to lymph nodes. Symptoms range from isolated bone lesions to multisystem d ...

(LCH) * Lymphocyte-variant hypereosinophilia * Pityriasis lichenoides (PL, PLC, PLVA) * Post-transplant lymphoproliferative disorder * Autoimmune lymphoproliferative syndrome (ALPS) *

Lymphoid interstitial pneumonia Lymphocytic interstitial pneumonia (LIP) is a syndrome secondary to autoimmune and other lymphoproliferative disorders. Symptoms include fever, cough, and shortness of breath. Lymphocytic interstitial pneumonia applies to disorders associated w ...

* Epstein–Barr virus-associated lymphoproliferative diseases * Castleman disease * X-linked lymphoproliferative disease * Primary cutaneous acral CD8 positive T cell lymphoproliferative disorder

Types

Lymphoproliferative disorders are a set of disorders characterized by the abnormal proliferation of

lymphocyte A lymphocyte is a type of white blood cell (leukocyte) in the immune system of most vertebrates. Lymphocytes include T cells (for cell-mediated and cytotoxic adaptive immunity), B cells (for humoral, antibody-driven adaptive immunity), an ...

s into a monoclonal lymphocytosis. The two major types of lymphocytes are

B cell B cells, also known as B lymphocytes, are a type 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 inserted into the plasm ...

s and

T cell T cells (also known as T lymphocytes) are an important part of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell receptor (TCR) on their cell ...

s, which are derived from

pluripotent Cell potency is a cell's ability to differentiate into other cell types. The more cell types a cell can differentiate into, the greater its potency. Potency is also described as the gene activation potential within a cell, which like a continuum ...

hematopoietic stem cells Hematopoietic stem cells (HSCs) are the stem cells that give rise to other blood cells. This process is called haematopoiesis. In vertebrates, the first definitive HSCs arise from the ventral endothelial wall of the embryonic aorta within the ...

in the

bone marrow Bone marrow is a semi-solid biological tissue, tissue found within the Spongy bone, spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It i ...

. Individuals who have some sort of dysfunction with their immune system are susceptible to develop a lymphoproliferative disorder because when any of the numerous control points of the immune system become dysfunctional,

immunodeficiency Immunodeficiency, also known as immunocompromise, is a state in which the immune system's ability to fight infectious diseases and cancer is compromised or entirely absent. Most cases are acquired ("secondary") due to extrinsic factors that aff ...

or deregulation of lymphocytes is more likely to occur. There are several inherited gene mutations that have been identified to cause lymphoproliferative disorders; however, there are also acquired and

iatrogenic Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence." Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 27 ...

causes.Winter, S.S. Lymphoproliferative disorders. Emedicine. December 20, 2006. http://www.emedicine.com/ped/topic1345.htm. Accessed March 2007.

X-linked Lymphoproliferative disorder

A mutation on the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

is associated with a T cell and

natural killer cell Natural killer cells, also known as NK cells, are a type of cytotoxic lymphocyte critical to the innate immune system. They are a kind of large granular lymphocytes (LGL), and belong to the rapidly expanding family of known innate lymphoid cells ...

lymphoproliferative disorder.

Autoimmune lymphoproliferative disorder

Some children with autoimmune lymphoproliferative disorders are heterozygous for a mutation in the gene that codes for the

Fas receptor The Fas receptor, also known as Fas, FasR, apoptosis antigen 1 (APO-1 or APT), cluster of differentiation 95 (CD95) or tumor necrosis factor receptor superfamily member 6 (TNFRSF6), is a protein that in humans is encoded by the ''FAS'' gene. Fas ...

, which is located on the long arm of

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 134 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tota ...

at position 24.1, denoted 10q24.1.Entrez Gene. FAS Fas (TNF receptor superfamily, member 6). https://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=gene&dopt=full_report&list_uids=355. Accessed March 2007. This gene is member 6 of the TNF-receptor superfamily (TNFRSF6). The Fas receptor contains a death domain and has been shown to play a central role in the physiological regulation of programmed cell death. Normally, stimulation of recently activated T cells by antigen leads to coexpression of Fas and Fas receptor on the T cell surface. The engagement of Fas by Fas receptor results in

apoptosis Apoptosis (from ) is a form of programmed cell death that occurs in multicellular organisms and in some eukaryotic, single-celled microorganisms such as yeast. Biochemistry, Biochemical events lead to characteristic cell changes (Morphology (biol ...

of the cell and is important for eliminating T cells that are repeatedly stimulated by antigens.Abbas, A.K and Lichtman, A.H. Cellular and Molecular Immunology. Fifth Edition. Elsevier Saunders. Philadelphia. 2005 As a result of the mutation in the Fas receptor gene, there is no recognition of Fas by

, leading to a primitive population of T cells that proliferates in an uncontrolled manner.

Other inherited causes

Boys with X-linked immunodeficiency syndrome are at a higher risk of mortality associated with

Epstein–Barr virus The Epstein–Barr virus (EBV), also known as human herpesvirus 4 (HHV-4), is one of the nine known Herpesviridae#Human herpesvirus types, human herpesvirus types in the Herpesviridae, herpes family, and is one of the most common viruses in ...

infections, and are predisposed to develop a lymphoproliferative disorder or lymphoma. Children with

common variable immunodeficiency Common variable immunodeficiency (CVID) is an inborn immune disorder characterized by recurrent infections and low antibody levels, specifically in immunoglobulin (Ig) types IgG, IgM, and IgA. Symptoms generally include high susceptibility to ...

(CVID) are also at a higher risk of developing a lymphoproliferative disorder. Some disorders that predispose a person to lymphoproliferative disorders are

severe combined immunodeficiency Severe combined immunodeficiency (SCID), also known as Swiss-type agammaglobulinemia, is a rare genetic disorder characterized by the disturbed development of functional T cells and B cells caused by numerous genetic mutations that result in diff ...

(SCID),

Chédiak–Higashi syndrome Chédiak–Higashi syndrome (CHS) is a rare autosomal recessive disorder that arises from a mutation of a lysosomal trafficking regulator protein, which leads to a decrease in phagocytosis. The decrease in phagocytosis results in recurrent pyogenic ...

(an X-linked recessive disorder), and

ataxia–telangiectasia Ataxia–telangiectasia (AT or A–T), also referred to as ataxia–telangiectasia syndrome or Louis–Bar syndrome, is a rare, neurodegenerative disease causing severe disability. Ataxia refers to poor coordination and telangiectasia to small dil ...

. Even though ataxia telangiectasia is an autosomal recessive disorder, people who are

heterozygote Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

s for this still have an increased risk of developing a lymphoproliferative disorder.

Acquired causes

Viral infection A viral disease (or viral infection) occurs when an organism's body is invaded by pathogenic viruses, and infectious virus particles (virions) attach to and enter susceptible cells. Examples include the common cold, gastroenteritis, COVID-19, t ...

is a very common cause of lymphoproliferative disorders. In children, the most common is believed to be congenital

HIV The human immunodeficiency viruses (HIV) are two species of '' Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the im ...

infection because it is highly associated with acquired immunodeficiency, which often leads to lymphoproliferative disorders.

Iatrogenic causes

There are many lymphoproliferative disorders that are associated with

organ transplantation Organ transplantation is a medical procedure in which an organ is removed from one body and placed in the body of a recipient, to replace a damaged or missing organ. The donor and recipient may be at the same location, or organs may be trans ...

and

immunosuppressant Immunosuppressive drugs, also known as immunosuppressive agents, immunosuppressants and antirejection medications, are drugs that inhibit or prevent the activity of the immune system. Classification Immunosuppressive drugs can be classified ...

therapies. In most reported cases, these cause B cell lymphoproliferative disorders; however, some T cell variations have been described. The T cell variations are usually caused by the prolonged use of T cell suppressant drugs, such as

sirolimus Sirolimus, also known as rapamycin and sold under the brand name Rapamune among others, is a macrolide compound that is used to coat coronary stents, prevent organ transplant rejection, treat a rare lung disease called lymphangioleiomyomatosis ...

tacrolimus Tacrolimus, sold under the brand name Prograf among others, is an immunosuppressive drug. After Allotransplantation, allogenic organ transplant, the risk of organ Transplant rejection, rejection is moderate. To lower the risk of organ rejectio ...

, or

ciclosporin Ciclosporin, also spelled cyclosporine and cyclosporin, is a calcineurin inhibitor, used as an immunosuppressant medication. It is taken Oral administration, orally or intravenously for rheumatoid arthritis, psoriasis, Crohn's disease, nephr ...

. The Epstein-Barr virus, which infects >90% of the world population, is also a common cause of these disorders, being responsible for a wide range of non-malignant, pre-malignant, and malignant Epstein-Barr virus-associated lymphoproliferative diseases.

References

External links

{{Lymphoid malignancy Lymphocytic immune system disorders Infectious causes of cancer