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Acute mast cell leukemia is a rapidly progressive disorder with leukemic mast cells in blood and in large numbers in marrow. The common signs and symptoms include fever, headache, flushing of face and trunk. The typical cutaneous mast cell infiltrates of urticaria pigmentosa are usually not present before, during, or after diagnosis in patients who have mast cell leukemia. Symptoms include abdominal pain, bone pain, and peptic ulcer which are more prevalent than in other subtypes of acute myeloid leukemia. These former symptoms are due to release of a substance called histamine from neoplastic mast cells. Enlargement of the liver and spleen, or hepatosplenomegaly is characteristic. The mast cells release also many anticoagulants like heparin which can lead to serious bleeding. Liver and splenic dysfunction also contributes to hemorrhage. Involvement of the bone can lead to osteoporosis. Abdominal ultrasound or computerized tomography (CT) scanning is used to look for hepatosplenomegaly and lymphadenopathy. Plain radiography and bone densitometry can be used to assess bone involvement and the presence of osteoporosis. Endoscopy and biopsy can be useful if gut involvement is suspected.
The most common clinical finding is hepatosplenomegaly. Pruritus, gout, and mucocutaneous bleeding are occasionally seen.
This disease is known for an indolent clinical course and incidental discovery. The most common physical finding is moderate splenomegaly. B symptoms are seen in a third of cases, and recurrent infections due to the associated neutropenia are seen in almost half of cases.
Rheumatoid arthritis is commonly observed in people with T-LGLL, leading to a clinical presentation similar to Felty's syndrome. Signs and symptoms of anemia are commonly found, due to the association between T-LGLL and erythroid hypoplasia.
In hairy cell leukemia, the "hairy cells" (malignant B lymphocytes) accumulate in the bone marrow, interfering with the production of normal white blood cells, red blood cells, and platelets. Consequently, patients may develop infections related to low white blood cell count, anemia and fatigue due to a lack of red blood cells, or easy bleeding due to a low platelet count. Leukemic cells may gather in the spleen and cause it to swell; this can have the side effect of making the person feel full even when he or she has not eaten much.
Hairy cell leukemia is commonly diagnosed after a routine blood count shows unexpectedly low numbers of one or more kinds of normal blood cells, or after unexplained bruises or recurrent infections in an otherwise apparently healthy patient.
Platelet function may be somewhat impaired in HCL patients, although this does not appear to have any significant practical effect. It may result in somewhat more mild bruises than would otherwise be expected for a given platelet count or a mildly increased bleeding time for a minor cut. It is likely the result of producing slightly abnormal platelets in the overstressed bone marrow tissue.
Patients with a high tumor burden may also have somewhat reduced levels of cholesterol, especially in patients with an enlarged spleen. Cholesterol levels return to more normal values with successful treatment of HCL.
The leukemic cells of T-LGLL can be found in peripheral blood, bone marrow, spleen, and liver. Nodal involvement is rare.
Mast cell leukemia is an extremely aggressive subtype of acute myeloid leukemia that usually occurs "de novo" but can, rarely, evolve from transformation of chronic myeloid leukemia into the more aggressive acute myeloid leukemia. In a small proportion of cases, acute mast cell leukemia may evolve from a more progressive form of systemic mastocytosis. The diagnosis of acute mast cell leukemia by the WHO criteria includes the requirement for a prevalence of 20% neoplastic mast cells in marrow and 10% in blood. If the mast cells represent less than 10% of blood cells, the tumor is called "aleukemic" mast cell leukemia.
A specific histochemical reaction, cyanide-resistant peroxidase, permits identification of leukemic blast cells with eosinophilic differentiation and diagnosis of acute eosinoblastic leukemia in some cases of AML with few identifiable eosinophils in blood or marrow.
The way CML presents depends on the stage of the disease at diagnosis as it has been known to skip stages in some cases.
Most patients (~90%) are diagnosed during the chronic stage which is most often asymptomatic. In these cases it may be diagnosed incidentally with an elevated white blood cell count on a routine laboratory test. It can also present with symptoms indicative of hepatosplenomegaly and the resulting upper quadrant pain this causes. The enlarged spleen may put pressure on the stomach causing a loss of appetite and resulting weight loss. It may also present with mild fever and night sweats due to an elevated basal level of metabolism.
Some (<10%) are diagnosed during the accelerated stage which most often presents bleeding, petechiae and ecchymosis. In these patients fevers are most commonly the result of opportunistic infections.
Some patients are initially diagnosed in the blast phase in which the symptoms are most likely fever, bone pain and an increase in bone marrow fibrosis.
Patients treated with imatinib, dasatinib, and nilotinib have shown meaningful rates of hematologic and cytogenetic response.
People affected by T-cell prolymphocytic leukemia typically have systemic disease at presentation, including enlargement of the liver and spleen, widespread enlargement of the lymph nodes, and skin infiltrates.
Due to the systemic nature of this disease, leukemic cells can be found in peripheral blood, lymph nodes, bone marrow, spleen, liver, and skin. A high lymphocyte count (> 100 x 10/L) along with low amounts of red blood cells and platelets in the blood are common findings. HTLV-1 serologies are negative, and serum immunoglobins are within normal limits with no paraproteins present.
Hairy cell leukemia is an uncommon hematological malignancy characterized by an accumulation of abnormal B lymphocytes. It is usually classified as a sub-type of chronic lymphoid leukemia. Hairy cell leukemia makes up approximately 2% of all leukemias, with fewer than 2,000 new cases diagnosed annually in North America and Western Europe combined.
Hairy cell leukemia was originally described as histiocytic leukemia, malignant reticulosis, or lymphoid myelofibrosis in publications dating back to the 1920s. The disease was formally named leukemic reticuloendotheliosis and its characterization significantly advanced by Bertha Bouroncle and colleagues at The Ohio State University College of Medicine in 1958. Its common name, which was coined in 1966, is derived from the "hairy" appearance of the malignant B cells under a microscope.
Most initial symptoms of leukemia are similar to symptoms for irregular bone-marrow function. Typically, most symptoms do not occur during the early stages of leukemia, and children may experience different symptoms. The following are symptoms of leukemia that lead doctors to look for different types of juvenile leukemia:
Chronic neutrophilic leukemia (CNL) is a rare myeloproliferative neoplasm 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.
The most common symptoms in children are easy bruising, pale skin, fever, and an enlarged spleen or liver.
Damage to the bone marrow, by way of displacing the normal bone marrow cells with higher numbers of immature white blood cells, results in a lack of blood platelets, which are important in the blood clotting process. This means people with leukemia may easily become bruised, bleed excessively, or develop pinprick bleeds (petechiae).
White blood cells, which are involved in fighting pathogens, may be suppressed or dysfunctional. This could cause the patient's immune system to be unable to fight off a simple infection or to start attacking other body cells. Because leukemia prevents the immune system from working normally, some patients experience frequent infection, ranging from infected tonsils, sores in the mouth, or diarrhea to life-threatening pneumonia or opportunistic infections.
Finally, the red blood cell deficiency leads to anemia, which may cause dyspnea and .
Some patients experience other symptoms, such as feeling sick, having fevers, chills, night sweats, feeling fatigued and other flu-like symptoms. Some patients experience nausea or a feeling of fullness due to an enlarged liver and spleen; this can result in unintentional weight loss. Blasts affected by the disease may come together and become swollen in the liver or in the lymph nodes causing pain and leading to nausea.
If the leukemic cells invade the central nervous system, then neurological symptoms (notably headaches) can occur. Uncommon neurological symptoms like migraines, seizures, or coma can occur as a result of brain stem pressure. All symptoms associated with leukemia can be attributed to other diseases. Consequently, leukemia is always diagnosed through medical tests.
The word "leukemia", which means 'white blood', is derived from the characteristic high white blood cell count that presents in most afflicted patients before treatment. The high number of white blood cells are apparent when a blood sample is viewed under a microscope, with the extra white blood cells frequently being immature or dysfunctional. The excessive number of cells can also interfere with the level of other cells, causing further harmful imbalance in the blood count.
Some leukemia patients do not have high white blood cell counts visible during a regular blood count. This less-common condition is called "aleukemia". The bone marrow still contains cancerous white blood cells which disrupt the normal production of blood cells, but they remain in the marrow instead of entering the bloodstream, where they would be visible in a blood test. For an aleukemic patient, the white blood cell counts in the bloodstream can be normal or low. Aleukemia can occur in any of the four major types of leukemia, and is particularly common in hairy cell leukemia.
Prognosis is very poor once chronic myelogenous leukemia reaches the accelerated phase; it behaves similarly to acute myeloid leukemia.
Chronic eosinophilic leukemia (CEL) is a disease in which too many eosinophils (a type of white blood cell) are found in the bone marrow, blood, and other tissues. CEL may stay the same for many years, or it may progress quickly to acute leukemia. It is generally caused by overactivation of the oncogene, e.g. PDGFRA through a chromosome translocation or fusion between two genes on the same chromosome, e.g. "FIP1L1-PDGFRA" gene fusion-induced eosinophilic leukemia. Though a highly rare disease, CEL is extremely manageable with the use of Gleevec, which suppresses the oncogenic effects of PDGFRA.
The following symptoms are typical ones which lead to testing for JMML, though children with JMML may exhibit any combination of them: pallor, fever, infection, bleeding, cough, poor weight gain, a maculopapular rash (discolored but not raised, or small and raised but not containing pus), lymphadenopathy (enlarged lymph nodes), moderate hepatomegaly (enlarged liver), marked splenomegaly (enlarged spleen), leukocytosis (high white blood cell count in blood), absolute monocytosis (high monocyte count in blood), anemia (low red blood cell count in blood), and thrombocytopenia (low platelet count in blood). Most of these conditions are common, nonspecific signs and symptoms.
Children with JMML and neurofibromatosis 1 (NF1) (about 14% of children with JMML are also clinically diagnosed with NF1, though up to 30% carry the NF1 gene mutation) may also exhibit any of the following symptoms associated with NF1 (in general, only young children with NF1 are at an increased risk of developing JMML):
- 6 or more café-au-lait (flat, coffee-colored) spots on the skin
- 2 or more neurofibromas (pea-size bumps that are noncancerous tumors) on or under the skin
- Plexiform neurofibromas (larger areas on skin that appear swollen)
- Optic glioma (a tumor on the optic nerve that affects vision)
- Freckles under the arms or in the groin
- 2 or more Lisch nodules (tiny tan or brown-colored spots on the iris of the eye)
- Various bone deformations including bowing of the legs below the knee, scoliosis, or thinning of the shin bone
Noonan syndrome (NS) may predispose to the development of JMML or a myeloproliferative disorder (MPD) associated with NS (MPD/NS) which resembles JMML in the first weeks of life. However, MPD/NS may resolve without treatment. Children with JMML and Noonan's syndrome may also exhibit any of the following most-common symptoms associated with Noonan's syndrome:
- Congenital heart defects, in particular, pulmonic stenosis (a narrowing of the valve from the heart to the lungs)
- Undescended testicles in males
- Excess skin and low hair line on back of neck
- Widely set eyes
- Diamond-shaped eyebrows
- Ears that are low-set, backward-rotated, thick outer rim
- Deeply grooved philtrum (upper lip line)
- Learning delays
Acute eosinophilic leukemia (AEL) is a rare subtype of acute myeloid leukemia with 50 to 80 percent of eosinophilic cells in the blood and marrow. It can arise de novo or may develop in patients having the chronic form of a hypereosinophilic syndrome. Patients with acute eosinophilic leukemia have a propensity for developing bronchospasm and heart failure from endomyocardial fibrosis. Hepatomegaly and splenomegaly are more common than in other variants of AML.
T-cell-prolymphocytic leukemia (T-PLL) is a mature T-cell leukemia with aggressive behavior and predilection for blood, bone marrow, lymph nodes, liver, spleen, and skin involvement. T-PLL is a very rare leukemia, primarily affecting adults over the age of 30. It represents 2% of all small lymphocytic leukemias in adults. Other names include "T-cell chronic lymphocytic leukemia", ""knobby" type of T-cell leukemia", and "T-prolymphocytic leukemia/T-cell lymphocytic leukemia."
Aggressive NK-cell leukemia (ANKL) is a lymphoid leukemia that is a deficiency NK cells. Not very much is known about this disease due to its rarity, but it is highly aggressive. Most patients will die within 2 years.
As noted above, a leukemoid reaction is typically a response to an underlying medical issue. Causes of leukemoid reactions include:
- Severe hemorrhage (retroperitoneal hemorrhage)
- Drugs
- Use of sulfa drugs
- Use of dapsone
- Use of glucocorticoids
- Use of G-CSF or related growth factors
- All-trans retinoic acid (ATRA)
- Ethylene glycol intoxication
- Infections
- Clostridium difficile
- Tuberculosis
- Pertussis
- Infectious mononucleosis (lymphocyte predominant)
- Visceral larva migrans (eosinophil predominant)
- Asplenia
- Diabetic ketoacidosis
- Organ necrosis
- Hepatic necrosis
- Ischemic colitis
- As a feature of trisomy 21 in infancy (incidence of ~10%)
- As a paraneoplastic phenomenon (rare)
Childhood leukemia is a type of leukemia, usually acute lymphocytic leukemia (ALL), and a type of childhood cancer. The cure rate of childhood leukemia is generally higher than adult leukemia, approaching 90%, although some side effects of treatment last into adulthood. The older aggressive treatments of cranial irradiation and anthracyclines (such as doxorubicin) caused increased risk of solid tumors, heart failure, growth retardation, and cognitive defects.
Leukemia is a hematological malignancy or a cancer of the blood. It develops in the bone marrow, the soft inner part of bones where new blood cells are made. When a child has leukemia, the bone marrow produces white blood cells that do not mature correctly. Normal healthy cells only reproduce when there is enough space for them. The body will regulate the production of cells by sending signals of when to stop production. When a child has leukemia, the cells do not respond to the signals telling them when to stop and when to produce cells, regardless of the available space.
Although not a malignant neoplasm like other cancers, MPNs are classified within the hematological neoplasms. There are four main myeloproliferative diseases, which can be further categorized by the presence of the Philadelphia chromosome:
In 2008, the World Health Organization listed these diagnoses as types of MPD:
- Chronic myelogenous leukemia (BCR-ABL1–positive)
- Chronic neutrophilic leukemia
- Polycythemia vera
- Primary myelofibrosis
- Essential thrombocythemia
- Chronic eosinophilic leukemia (not otherwise specified)
- Mastocytosis
M2 is a subtype of AML (Acute Myeloid Leukemia).
It is also known as "Acute Myeloblastic Leukemia with Maturation".
"T-cell leukemia" describes several different types of lymphoid leukemias which affect T cells.
The most common T-cell leukemia is precursor T-cell lymphoblastic leukemia. It causes 15% of acute leukemias in childhood, and also 40% of lymphomas in childhood. It is most common in adolescent males. Its morphology is identical to that of "precursor B-cell lymphoblastic leukemia". Cell markers include TdT, CD2, CD7. It often presents as a mediastinal mass because of involvement of the thymus. It is highly associated with NOTCH1 mutations.
Other types include:
- Large granular lymphocytic leukemia
- Adult T-cell leukemia/lymphoma
- T-cell prolymphocytic leukemia
In practice, it can be hard to distinguish T-cell leukemia from T-cell lymphoma, and they are often grouped together.