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 growt ...

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 granulocytosi ...

in peripheral blood, myeloid hyperplasia in bone marrow,

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 a specific genetic abnormality in chromosome 22 of leukemia cancer cells (particularly chronic myeloid leukemia (CML) cells). This chromosome is defective and unusually short becaus ...

or a BCR/ABL fusion gene.

Signs and symptoms

The most common clinical finding is

Pruritus Itch (also known as pruritus) is a sensation that causes the desire or reflex to scratch. Itch has resisted many attempts to be classified as any one type of sensory experience. Itch has many similarities to pain, and while both are unpleasant ...

gout Gout ( ) is a form of inflammatory arthritis characterized by recurrent attacks of a red, tender, hot and swollen joint, caused by deposition of monosodium urate monohydrate crystals. Pain typically comes on rapidly, reaching maximal intens ...

, and mucocutaneous bleeding are occasionally seen.

Cause

The cause of CNL is currently unknown. An association between CNL and multiple myeloma 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, anemi ...

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

(> 25 x 10⁹/L) with myeloid 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 nucleus of a promyelocyte is approximately the same size as a mye ...

s, myelocytes,

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 n ...

s) comprising less than 5% of

leukocytes White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

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 in the cir ...

, bone marrow,

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, and

liver The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...

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

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), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...

ratio of 20:1 or greater.

Myelocytes 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 basophilic ...

and neutrophils are increased, and blasts and

promyelocytes 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 nucleus of a promyelocyte is approximately the same size as a ...

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

megakaryocytes A megakaryocyte (''mega-'' + '' karyo-'' + '' -cyte'', "large-nucleus cell") is a large bone marrow cell with a lobated nucleus responsible for the production of blood thrombocytes (platelets), which are necessary for normal blood clotting. In hum ...

and

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. Reticular fibers crosslink to form a fine meshwork (reticulin). This network acts as a support ...

fibrosis Fibrosis, also known as fibrotic scarring, is a pathological wound healing in which connective tissue replaces normal parenchymal tissue to the extent that it goes unchecked, leading to considerable tissue remodelling and the formation of perma ...

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 In medicine, both ancient and modern, a dyscrasia is any of various disorders. The word has ancient Greek roots meaning "bad mixture". The concept of dyscrasia was developed by the Greek physician Galen (129–216 AD), who elaborated a model of h ...

with increased numbers of atypical

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

Spleen

Splenic The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

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, microorgani ...

Liver

Hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it is ...

infiltrates can be found in either the

sinusoids A capillary is a small blood vessel from 5 to 10 micrometres (μm) in diameter. Capillaries are composed of only the tunica intima, consisting of a thin wall of simple squamous endothelial cells. They are the smallest blood vessels in the body: ...

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 a portal triad, hepatocyte ...

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