ALK+ large B-cell lymphoma is a type of

lymphoma Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). The name typically refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph node ...

. It was first reported in 1997. It is a rare, aggressive large

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 ...

process that shows ALK expression. It is distinct from

anaplastic large cell lymphoma Anaplastic large-cell lymphoma (ALCL) refers to a group of non-Hodgkin lymphomas in which aberrant T cells proliferate uncontrollably. Considered as a single entity, ALCL is the most common type of peripheral lymphoma and represents ~10% of all per ...

, a

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 ce ...

lymphoma.

Signs and symptoms

Pathophysiology

Upregulation of ALK is mainly due to

chromosomal translocation In genetics, chromosome translocation is a phenomenon that results in unusual rearrangement of chromosomes. This includes "balanced" and "unbalanced" translocation, with three main types: "reciprocal", "nonreciprocal" and "Robertsonian" transloc ...

t(2;17), resulting in a

fusion gene In genetics, a fusion gene is a hybrid gene formed from two previously independent genes. It can occur as a result of translocation, interstitial deletion, or chromosomal inversion. Fusion genes have been found to be prevalent in all main types ...

CLTC Clathrin heavy chain 1 is a protein that in humans is encoded by the ''CLTC'' gene. Clathrin is a major protein component of the cytoplasmic face of intracellular organelles, called coated vesicles and coated pits. These specialized organelles ...

with ALK, but can rarely be due to t(2;5), fusing

NPM1 Nucleophosmin (NPM), also known as nucleolar phosphoprotein B23 or numatrin, is a protein that in humans is encoded by the ''NPM1'' gene. Gene In humans, the ''NPM1'' gene is located on the long arm of chromosome 5 (5q35). The gene spans 23 kb ...

with ALK; the later is the usual finding in

(ALCL). The t(2;17) translocation occurs in less than 1% of cases of ALK+ ALCL, but has been identified in

inflammatory myofibroblastic tumor Inflammatory myofibroblastic tumor (IMT) is a rare neoplasm of the mesodermal cells that form the connective tissues which support virtually all of the organs and tissues of the body. IMT was formerly termed inflammatory pseudotumor. Currently, h ...

s. There is no association 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 ...

or HHV8, or

immunosuppression Immunosuppression is a reduction of the activation or efficacy of the immune system. Some portions of the immune system itself have immunosuppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse react ...

. The cells are

CD20 B-lymphocyte antigen CD20 or CD20 is B lymphocyte cell-surface molecule. It is a 33-37 kDa non-glycosylated protein. CD20 is expressed on the surface of B-cells from the pre-B phase, the expression is lost in terminally differentiated plasm ...

and

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 for anaplastic large cell lymphoma. Function This receptor is expressed by activate ...

negative, showing weak focal expression in 3% and 6% respectively. They are

EMA Ema or EMA may refer to: Biology and medicine * Anti-Endomysial Antibodies test * Epithelial membrane antigen * European Medicines Agency, a European Union agency for the evaluation of medicinal products * European Medical Association, associa ...

and

CD138 Syndecan 1 is a protein which in humans is encoded by the ''SDC1'' gene. The protein is a transmembrane (type I) heparan sulfate proteoglycan and is a member of the syndecan proteoglycan family. The syndecan-1 protein functions as an integral me ...

positive, showing 100% expression respectively.

Diagnosis

The median age of diagnosis is approximately late thirties to early forties. The estimates of childhood disease vary (8%, 15%, 30%) but it can be seen at any age. The disease usually arises in

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that includ ...

s, particularly the neck, but extranodal involvement, including in the

gastrointestinal tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

, nasal cavity, ovary and brain, has been described. Morphologically, there are large immunoblast-like cells with large central

nucleoli The nucleolus (; : nucleoli ) is the largest structure in the nucleus of eukaryotic cells. It is best known as the site of ribosome biogenesis. The nucleolus also participates in the formation of signal recognition particles and plays a ro ...

, often cellular clusters, with a predilection for the lymph node sinuses in a cohesive pattern that can suggest

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesoder ...

cells.

Treatment

Multiagent chemotherapy is given, and can result in long-term success, particularly in childhood but

prognosis Prognosis ( Greek: πρόγνωσις "fore-knowing, foreseeing"; : prognoses) is a medical term for predicting the likelihood or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) ...

is generally poor, particularly in higher stage disease.

References

{{DEFAULTSORT:ALK large B-cell lymphoma Lymphoma

Signs and symptoms

Pathophysiology

Diagnosis

Treatment

See also

References