Chronic neutrophilic leukemia
Encyclopedia
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative disorder that features a persistent neutrophilia
in peripheral blood, myeloid
hyperplasia
in bone marrow
, hepatosplenomegaly
, and the absence of the Philadelphia chromosome
or a BCR/ABL fusion gene.
with cases typically seen in older adults.
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 neutrophilia
is a reaction due to the neoplastic myeloma cells. The postulated cell of origin is a limited-potential, marrow-derived stem cell.
. Pruritus, gout
, and mucocutaneous bleeding are occasionally seen.
(> 25 x 109/L) with myeloid
precursors (promyelocyte
s, myelocyte
s, metamyelocyte
s) comprising less than 5% of leukocytes.
, bone marrow
, spleen
, and liver
are most common, but any organ or tissue can be infiltrated by neutrophils.
aspirate and the core biopsy, a hypercellular marrow with an increased myeloid
:erythroid ratio of 20:1 or greater. Myelocytes and neutrophils are increased, and blasts and promyelocytes are not increased. Due to the myeloproliferative nature of the disease, an increase in megakaryocytes and erythroid precursors may be observed, but dyspoiesis in not seen in any cell lineage. Also, reticulin fibrosis
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 cells.
regions, or both.
and other BCR/ABL fusion genes are not detected.
Neutrophilia
Neutrophilia is a condition where a person has a high number of neutrophil granulocytes in their blood.-Causes:...
in peripheral blood, myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
hyperplasia
Hyperplasia
Hyperplasia means increase in number of cells/proliferation of cells. It may result in the gross enlargement of an organ and the term is sometimes mixed with benign neoplasia/ benign tumor....
in bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, hepatosplenomegaly
Hepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
, and the absence of the Philadelphia chromosome
Philadelphia chromosome
Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
or a BCR/ABL fusion gene.
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.
Etiology
The etiology of CNL is currently unknown. An association between CNL and multiple myelomaMultiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
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 neutrophilia
Neutrophilia
Neutrophilia is a condition where a person has a high number of neutrophil granulocytes in their blood.-Causes:...
is a reaction due to the neoplastic myeloma cells. The postulated cell of origin is a limited-potential, marrow-derived stem cell.
Clinical Presentation
The most common clinical finding is hepatosplenomegalyHepatosplenomegaly
Hepatosplenomegaly is the simultaneous enlargement of both the liver and the spleen . Hepatosplenomegaly can occur as the result of acute viral hepatitis or infectious mononucleosis, or it can be the sign of a serious and life threatening lysosomal storage disease...
. Pruritus, gout
Gout
Gout is a medical condition usually characterized by recurrent attacks of acute inflammatory arthritis—a red, tender, hot, swollen joint. The metatarsal-phalangeal joint at the base of the big toe is the most commonly affected . However, it may also present as tophi, kidney stones, or urate...
, and mucocutaneous bleeding are occasionally seen.
Laboratory findings
Peripheral blood neutrophiliaNeutrophilia
Neutrophilia is a condition where a person has a high number of neutrophil granulocytes in their blood.-Causes:...
(> 25 x 109/L) with myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
precursors (promyelocyte
Promyelocyte
A promyelocyte is a granulocyte precursor, developing from the myeloblast and developing into the myelocyte.-External links: - "18. Bone Marrow and Hemopoiesis: bone marrow smear, promyelocyte and erythroblasts " "Bone marrow" "Bone marrow"* - "Bone marrow smear"...
s, myelocyte
Myelocyte
A myelocyte is a young cell of the granulocytic series, occurring normally in bone marrow, but not in circulating blood .-Histology:...
s, metamyelocyte
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...
s) comprising less than 5% of leukocytes.
Sites of Involvement
Peripheral bloodBlood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, spleen
Spleen
The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...
, and liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
are most common, but any organ or tissue can be infiltrated by neutrophils.
Bone Marrow Biopsy
On both the bone marrowBone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
aspirate and the core biopsy, a hypercellular marrow with an increased myeloid
Myeloid
The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
:erythroid ratio of 20:1 or greater. Myelocytes and neutrophils are increased, and blasts and promyelocytes are not increased. Due to the myeloproliferative nature of the disease, an increase in megakaryocytes and erythroid precursors may be observed, but dyspoiesis in not seen in any cell lineage. Also, reticulin fibrosis
Fibrosis
Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process. This is as opposed to formation of fibrous tissue as a normal constituent of an organ or tissue...
is rare. There is a reported association between CNL and multiple myeloma
Multiple myeloma
Multiple myeloma , also known as plasma cell myeloma or Kahler's disease , is a cancer of plasma cells, a type of white blood cell normally responsible for the production of antibodies...
, so the bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
biopsy may show evidence of a plasma cell
Plasma cell
Plasma cells, also called plasma B cells, plasmocytes, and effector B cells, are white blood cells which produce large volumes of antibodies. They are transported by the blood plasma and the lymphatic system...
dyscrasia
Dyscrasia
Dyscrasia is a concept from ancient Greek medicine with the word "dyskrasia", meaning bad mixture.The concept of dyscrasia was developed by the ancient Greek physician Galen , who elaborated a model of health and disease as a structure of elements, qualities, humors, organs, and temperaments...
with increased numbers of atypical plasma cells.
Liver
Hepatic infiltrates can be found in either the sinusoids, portal triadPortal triad
A portal triad is a distinctive arrangement in the liver. It is a component of the hepatic lobule. It consists of the following five structures:* hepatic artery* hepatic portal vein* bile duct*lymphatic vessels...
regions, or both.
Genetics
The majority (90%) of cases have not had detectable cytogenetic abnormalities. Most importantly, the Philadelphia chromosomePhiladelphia chromosome
Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia . It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t...
and other BCR/ABL fusion genes are not detected.