Chronic neutrophilic leukemia (CNL) is a rare

myeloproliferative neoplasm Myeloproliferative neoplasms (MPNs) are a group of rare blood cancers in which excess red blood cells, white blood cells or platelets are produced in the bone marrow. ''Myelo'' refers to the bone marrow, ''proliferative'' describes the rapid grow ...

that features a persistent

neutrophilia Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosis ...

in peripheral blood,

myeloid Myeloid tissue, in the bone marrow sense of the word '' myeloid'' ('' myelo-'' + '' -oid''), is tissue of bone marrow, of bone marrow cell lineage, or resembling bone marrow, and myelogenous tissue (''myelo-'' + '' -genous'') is any tissue ...

hyperplasia Hyperplasia (from ancient Greek ὑπέρ ''huper'' 'over' + πλάσις ''plasis'' 'formation'), or hypergenesis, is an enlargement of an organ or tissue caused by an increase in the amount of Tissue (biology), organic tissue that results from ...

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 ...

hepatosplenomegaly Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and his ...

, and the absence of the

Philadelphia chromosome The Philadelphia chromosome or Philadelphia translocation (Ph) is an abnormal version of chromosome 22 where a part of the ''ABL (gene), Abelson murine leukemia'' 1 (''ABL1'') gene on chromosome 9 breaks off and attaches to the ''BCR (gene), break ...

or a BCR/ABL fusion gene.

Signs and symptoms

The most common clinical finding is

Pruritus An itch (also known as pruritus) is a sensation that causes a strong desire or reflex to scratch. Itches have resisted many attempts to be classified as any one type of sensory experience. Itches have many similarities to pain, and while both ...

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of pain in a red, tender, hot, and Joint effusion, swollen joint, caused by the deposition of needle-like crystals of uric acid known as monosodium urate crysta ...

, and mucocutaneous bleeding are occasionally seen.

Cause

The cause of CNL is currently unknown. An association between CNL and

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 ...

has been suggested based on the observation of myeloma in 20% of CNL cases. However, a clonal genetic abnormality has not been detected in these myeloma-associated cases of CNL, raising the possibility that the

is a reaction due to the neoplastic

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 antibodies. Often, no symptoms are noticed initially. As it progresses, bone pain, a ...

cells. The postulated cell of origin is a limited-potential, marrow-derived stem cell.

Genetics

The majority (90%) of cases have not had detectable

cytogenetic Cytogenetics is essentially a branch of genetics, but is also a part of cell biology/cytology (a subdivision of human anatomy), that is concerned with how the chromosomes relate to cell behaviour, particularly to their behaviour during mitosis an ...

abnormalities. Most importantly, the

and other BCR/ABL fusion genes are not detected.

Diagnosis

Laboratory findings

Peripheral blood neutrophilia (> 25 x 10⁹/L) with

precursors (

promyelocyte A promyelocyte (or progranulocyte) is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte. Promyelocytes measure 12–20 microns in diameter. The Cell nucleus, nucleus of a promyelocyte is approximately the ...

myelocyte A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow (can be found in circulating blood when caused by certain diseases). Structure When stained with the usual dyes, the cytoplasm is distinctly basophili ...

metamyelocyte A metamyelocyte is a cell undergoing granulopoiesis, derived from a myelocyte, and leading to a band cell. It is characterized by the appearance of a bent nucleus, cytoplasmic granules, and the absence of visible nucleoli. (If the nucleus is no ...

s) comprising less than 5% of

leukocytes White blood cells (scientific name leukocytes), also called immune cells or immunocytes, are cells of the immune system that are involved in protecting the body against both infectious disease and foreign entities. White blood cells are genera ...

Sites of involvement

Peripheral

blood Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood is com ...

spleen The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ (biology), organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in reg ...

, and

liver The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

are most common, but any organ or tissue can be infiltrated by

neutrophils Neutrophils are a type of phagocytic white blood cell and part of innate immunity. More specifically, they form the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. Their functions vary in different ...

Bone marrow biopsy

On both the bone marrow aspirate and the core biopsy, a hypercellular marrow with an increased myeloid:

erythroid Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

ratio of 20:1 or greater. Myelocytes and

are increased, and blasts and promyelocytes are not increased. Due to the myeloproliferative nature of the disease, an increase in

megakaryocytes A megakaryocyte () is a large bone marrow cell with a lobated nucleus that produces blood platelets (thrombocytes), which are necessary for normal clotting. In humans, megakaryocytes usually account for 1 out of 10,000 bone marrow cells, but ca ...

and erythroid precursors may be observed, but dyspoiesis in not seen in any cell lineage. Also,

reticulin Reticular fibers, reticular fibres or reticulin is a type of fiber in connective tissue composed of type III collagen secreted by reticular cells. They are mainly composed of reticulin protein and form a network or mesh. Reticular fibers cros ...

fibrosis Fibrosis, also known as fibrotic scarring, is the development of fibrous connective tissue in response to an injury. Fibrosis can be a normal connective tissue deposition or excessive tissue deposition caused by a disease. Repeated injuries, ch ...

is rare. There is a reported association between CNL and multiple myeloma, so the bone marrow biopsy may show evidence of a plasma cell dyscrasia with increased numbers of atypical

plasma cell Plasma cells, also called plasma B cells or effector B cells, are white blood cells that originate in the lymphoid organs as B cells and secrete large quantities of proteins called antibodies in response to being presented specific substances ca ...

Spleen

Splenic The spleen (, from Ancient Greek '' σπλήν'', splḗn) is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The spleen plays important roles in regard to red blood ...

infiltrates are typically found only in the

red pulp The red pulp of the spleen is composed of connective tissue known also as the cords of Billroth and many splenic sinusoids that are engorged with blood, giving it a red color. Its primary function is to filter the blood of antigens, microorganis ...

Liver

Hepatic The liver is a major metabolic organ (anatomy), organ exclusively found in vertebrates, which performs many essential biological Function (biology), functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of var ...

infiltrates can be found in either the

sinusoids A capillary is a small blood vessel, from 5 to 10 micrometres in diameter, and is part of the microcirculation system. Capillaries are microvessels and the smallest blood vessels in the body. They are composed of only the tunica intima (the inn ...

portal triad In histology (microscopic anatomy), the lobules of liver, or hepatic lobules, are small divisions of the liver defined at the microscopic scale. The hepatic lobule is a building block of the liver tissue, consisting of portal triads, hepatocytes ...

regions, or both.

Immunophenotype

No distinct immunophenotype abnormality for CNL has been described. See OHSU 2013 findings of gene CSF3R, mutation p. T6181.

Epidemiology

This is a rare disease, with less than 100 cases reported. Of these cases, an equal male:female ratio was observed, with cases typically seen in older adults.

References

External links

{{Myeloid malignancy, us=y Chronic myeloid leukemia Rare cancers