Aggressive NK-cell leukemia
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [4] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [5]
Synonyms and keywords: ANKL
Overview
Aggressive NK-cell leukemia is a disease with an aggressive, systemic proliferation of natural killer cells (NK cells) and a rapidly declining clinical course.[1][2][3] There is no classification system for aggressive NK-cell leukemia. The pathogenesis of aggressive NK-cell leukemia is characterized by the proliferation of natural killer cells. Aggressive NK-cell leukemia is very uncommon, and is most commonly seen among middle aged adults. The most common risk factors in the development of aggressive NK-cell leukemia is the Epstein-Barr virus (EBV) infection. The majority of patients with aggressive NK-cell leukemia are symptomatic at diagnosis. Early clinical features include fatigue, night sweats, and fever. Physical examination among patients with aggressive NK-cell leukemia may be remarkable for hepatosplenomegaly. Aggressive NK-cell leukemia may also be diagnosed using bone marrow biopsy, findings include: extensive marrow replacement by leukemic cells and reactive histiocytes displaying hemophagocytosis. The mainstay of therapy for aggressive NK-cell leukemia is anthracycline-containing chemotherapy.[4]
Classification
- There is no classification system for aggressive NK-cell leukemia.[3]
Pathophysiology
- The pathogenesis of aggressive NK-cell leukemia is characterized by the aggressive, systemic proliferation of natural killer cells.
- The mutation in oncogene p53 has been associated with the development of aggressive NK-cell leukemia.
- On gross pathology, characteristic findings of aggressive NK-cell leukemia, include:
- No remarkable findings
- On microscopic histopathological analysis, characteristic findings of aggressive NK-cell leukemia, include:[3]
- Large cells with abundant blue cytoplasm
- Azurophilic granules
- Irregular nuclei
- Open chromatin
- Distinct nucleoli
- CD11b and CD16 show variable expression
- The table below demonstrates the immunophenotype for patients with aggressive NK-cell leukemia.[3]
Causes
- There are no established causes for aggressive NK-cell leukemia.
Differentiating Aggressive NK-cell Leukemia from Other Diseases
- Aggressive NK-cell leukemia must be differentiated from other diseases that cause fever, fatigue, and lymphadenopathy such as:
- Human immunodeficiency virus
- Chronic neutrophilic leukemia
- Juvenile myelomonocytic leukemia
Epidemiology and Demographics
- Aggressive NK-cell leukemia is very uncommon.[4]
Age
- Aggressive NK-cell leukemia is more commonly observed among middle aged adults.
Gender
- Aggressive NK-cell leukemia affects men and women equally.
Race
- Aggressive NK-cell leukemia usually affects individuals of the Asians race.
Risk Factors
- Common risk factors in the development of aggressive NK-cell leukemia, include:
- Epstein-Barr virus (EBV) infection
Natural History, Complications and Prognosis
- The majority of patients with aggressive NK-cell leukemia are symptomatic at diagnosis.[4]
- Early clinical features include fatigue, night sweats, and fever.
- If left untreated, patients with aggressive NK-cell leukemia may progress to develop recurrent infections.
- Common complications of aggressive NK-cell leukemia, include:
- Coagulopathies
- Hemophagocytic syndrome
- Multiple organ failure
- Myelofibrosis
- Prognosis is generally poor, and the median survival rate of patients with aggressive NK-cell leukemia is approximately 12 months.[4]
Diagnosis
Symptoms
- Aggressive NK-cell leukemia is usually asymptomatic.
- Symptoms of aggressive NK-cell leukemia may include the following:[3]
- Fever
- Swelling in the lymph nodes in the neck
- Night sweats
- Persistent fatigue
- Loss of appetite
- Nausea
- Vomiting
Physical Examination
- Patients with aggressive NK-cell leukemia usually appear pale and malnourished.
- Physical examination may be remarkable for:[4]
- Hepatoesplenomegaly
Laboratory Findings
- Laboratory findings consistent with the diagnosis of aggressive NK-cell leukemia, include:[4]
Peripheral Blood Smear
- Large granular lymphocyte (LGL)
- Azurophilic granules and nucleoli of varying prominence
- Nuclei may be irregular and hyperchromatic
Imaging Findings
- There are no imaging findings associated with aggressive NK-cell leukemia.
Other Diagnostic Studies
- Aggressive NK-cell leukemia may also be diagnosed using bone marrow biopsy.
- Findings on bone marrow biopsy, include:[4]
- Extensive marrow replacement by leukemic cells
- Reactive histiocytes displaying hemophagocytosis
Treatment
Medical Therapy
- The mainstay of therapy for aggressive NK-cell leukemia is anthracycline-containing chemotherapy.[4]
- Other novel treatments may include pralatrexate.[4]
Surgery
- Surgery is not recommended among patients with aggressive NK-cell leukemia.
Prevention
- There are no primary preventive measures available for aggressive NK-cell leukemia.
Overview
Historical Perspective
- [Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
- In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
- In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
Classification
- [Disease name] may be classified according to [classification method] into [number] subtypes/groups:
- [group1]
- [group2]
- [group3]
- Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].
Pathophysiology
- The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
- The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
- On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
- On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
Clinical Features
Differentiating [disease name] from other Diseases
- [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
- [Differential dx1]
- [Differential dx2]
- [Differential dx3]
Epidemiology and Demographics
- The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
- In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
Age
- Patients of all age groups may develop [disease name].
- [Disease name] is more commonly observed among patients aged [age range] years old.
- [Disease name] is more commonly observed among [elderly patients/young patients/children].
Gender
- [Disease name] affects men and women equally.
- [Gender 1] are more commonly affected with [disease name] than [gender 2].
- The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
Race
- There is no racial predilection for [disease name].
- [Disease name] usually affects individuals of the [race 1] race.
- [Race 2] individuals are less likely to develop [disease name].
Risk Factors
- Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
Natural History, Complications and Prognosis
- The majority of patients with [disease name] remain asymptomatic for [duration/years].
- Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
- If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
- Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
- Prognosis is generally [excellent/good/poor], and the [1/5/10year mortality/survival rate] of patients with [disease name] is approximately [#%].
Diagnosis
Diagnostic Criteria
- The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
- [criterion 1]
- [criterion 2]
- [criterion 3]
- [criterion 4]
Symptoms
- [Disease name] is usually asymptomatic.
- Symptoms of [disease name] may include the following:
- [symptom 1]
- [symptom 2]
- [symptom 3]
- [symptom 4]
- [symptom 5]
- [symptom 6]
Physical Examination
- Patients with [disease name] usually appear [general appearance].
- Physical examination may be remarkable for:
- [finding 1]
- [finding 2]
- [finding 3]
- [finding 4]
- [finding 5]
- [finding 6]
Laboratory Findings
- There are no specific laboratory findings associated with [disease name].
- A [positive/negative] [test name] is diagnostic of [disease name].
- An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
- Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
Imaging Findings
- There are no [imaging study] findings associated with [disease name].
- [Imaging study 1] is the imaging modality of choice for [disease name].
- On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
- [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
- [Disease name] may also be diagnosed using [diagnostic study name].
- Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
- There is no treatment for [disease name]; the mainstay of therapy is supportive care.
- The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
- [Medical therapy 1] acts by [mechanism of action 1].
- Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
Surgery
- Surgery is the mainstay of therapy for [disease name].
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
- [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
Prevention
- There are no primary preventive measures available for [disease name].
- Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
- Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].
References
- ↑ [1] Chan JK, Sin VC, Wong KF, Ng CS, Tsang WY, Chan CH, Cheung MM, Lau WH. "Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm." Blood. 1997 Jun 15;89(12):4501-13. PMID 9192774
- ↑ [2] Imamura N, Kusunoki Y, Kawa-Ha K, Yumura K, Hara J, Oda K, Abe K, Dohy H, Inada T, Kajihara H, et al. "Aggressive natural killer cell leukaemia/lymphoma: report of four cases and review of the literature. Possible existence of a new clinical entity originating from the third lineage of lymphoid cells." Br J Haematol. 1990 May;75(1):49-59. PMID 2375924
- ↑ 3.0 3.1 3.2 3.3 3.4 [3] Chan JK. "Natural killer cell neoplasms." Anat Pathol. 1998;3:77-145. PMID 10389582
- ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 4.8 Aggressive NK-cell leukemia. https://en.wikipedia.org/wiki/Aggressive_NK-cell_leukemia Accessed on May 5, 2016