Chronic lymphoproliferative disorder of NK cells: Difference between revisions
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{{SK}} Chronic NK-cell lymphocytosis; chronic NK-Iarge granular lymphocyte (LGL) lymphoroliferative disorder; Nk-cell lineage granular lymphocyte proliferative disorder; Nk-cell LGL lymphocytosis; Indolent large granular NK-cell lymphoproliferative disorder. | {{SK}} Chronic NK-cell lymphocytosis; chronic NK-Iarge granular lymphocyte (LGL) lymphoroliferative disorder; Nk-cell lineage granular lymphocyte proliferative disorder; Nk-cell LGL lymphocytosis; Indolent large granular NK-cell lymphoproliferative disorder. | ||
== | ==Overview== | ||
The chronic Iymphoproliferative disorders of NK cells include a vast range of heterogenous diseases. These are characterized by [[NK cell]]s >2x10^9/L in peripheral blood for more than 6 months without clear cause<ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>. | The chronic Iymphoproliferative disorders of NK cells include a vast range of heterogenous diseases. These are characterized by [[NK cell]]s >2x10^9/L in peripheral blood for more than 6 months without clear cause<ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>. | ||
== | ==Historical Perspective== | ||
== | ==Classification== | ||
== | ==Pathophysiology == | ||
Chronic lymphoproliferative disorder of NK cells have been associated with other hematological tumors, [[vasculitis]], [[splenectomy]], [[neuropathy]] and [[autoimmune diseases]]. | Chronic lymphoproliferative disorder of NK cells have been associated with other hematological tumors, [[vasculitis]], [[splenectomy]], [[neuropathy]] and [[autoimmune diseases]]. | ||
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*Diminished CD161 expression. | *Diminished CD161 expression. | ||
== | ==Causes== | ||
Peripheral increased levels of [[NK cell]]s have been associated with [[autoimmune disease]]s and viral infections, although no correlation has been found between those and a chronic lymphoproliferative disorder of NK cells <ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/pubmed/10519998|title=A long-term study of patients with chronic natural killer cell lymphocytosis}}</ref> | Peripheral increased levels of [[NK cell]]s have been associated with [[autoimmune disease]]s and viral infections, although no correlation has been found between those and a chronic lymphoproliferative disorder of NK cells <ref>{{cite web|url=http://www.ncbi.nlm.nih.gov/pubmed/10519998|title=A long-term study of patients with chronic natural killer cell lymphocytosis}}</ref> | ||
However, molecular studies have shown that lymphoproliferative disease of granular lymphocytes (LDGL) express [[CD16]] and [[CD56]], but no [[CD3]]. Furthermore, LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA, but always expressed [[CD94]] and [[NKG2A]]. [[Polymerase chain reaction]] ([[PCR]]) showed that lower levels of KIR antibodies were present on LDGL patients than in healthy patients. As well as a high level of activating receptors, NK-LDGL cells have potent cytolytic function. Therefor, NK-LDGL have a higher activating-to-inhibitory KIR ratio, which might induce inappropriate lysis or cytokine production, playing a role in the disease pathogenesis <ref>{{cite web|url=http://www.bloodjournal.org/content/103/9/3431?sso-checked=true|title=Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes}}</ref>. | However, molecular studies have shown that lymphoproliferative disease of granular lymphocytes (LDGL) express [[CD16]] and [[CD56]], but no [[CD3]]. Furthermore, LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA, but always expressed [[CD94]] and [[NKG2A]]. [[Polymerase chain reaction]] ([[PCR]]) showed that lower levels of KIR antibodies were present on LDGL patients than in healthy patients. As well as a high level of activating receptors, NK-LDGL cells have potent cytolytic function. Therefor, NK-LDGL have a higher activating-to-inhibitory KIR ratio, which might induce inappropriate lysis or cytokine production, playing a role in the disease pathogenesis <ref>{{cite web|url=http://www.bloodjournal.org/content/103/9/3431?sso-checked=true|title=Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes}}</ref>. | ||
== | == Differential Diagnosis == | ||
== | == Epidemiology and Demographics== | ||
Affects predominantly adults (with an average of 60 years), with no distinguishable difference in gender and no racial or genetic predisposition<ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>. | Affects predominantly adults (with an average of 60 years), with no distinguishable difference in gender and no racial or genetic predisposition<ref>{{cite book | last = Swerdlow | first = Steven | title = WHO classification of tumours of haematopoietic and lymphoid tissues | publisher = International Agency for Research on Cancer | location = Lyon, France | year = 2008 | isbn = 9789283224310 }}</ref>. | ||
== | == Risk Factors== | ||
== | == Natural History, Complications and Prognosis== | ||
Most patients have an indolent clinical course for a long period of time. The disease might progress and develop as a cytopenia, recurrent infections and other comorbidities, in which case we'll be facing a worse prognosis. | Most patients have an indolent clinical course for a long period of time. The disease might progress and develop as a cytopenia, recurrent infections and other comorbidities, in which case we'll be facing a worse prognosis. | ||
Revision as of 16:38, 16 February 2015
Template:DiseaseDisorder infobox Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alberto Plate [2]
Synonyms and keywords: Chronic NK-cell lymphocytosis; chronic NK-Iarge granular lymphocyte (LGL) lymphoroliferative disorder; Nk-cell lineage granular lymphocyte proliferative disorder; Nk-cell LGL lymphocytosis; Indolent large granular NK-cell lymphoproliferative disorder.
Overview
The chronic Iymphoproliferative disorders of NK cells include a vast range of heterogenous diseases. These are characterized by NK cells >2x10^9/L in peripheral blood for more than 6 months without clear cause[1].
Historical Perspective
Classification
Pathophysiology
Chronic lymphoproliferative disorder of NK cells have been associated with other hematological tumors, vasculitis, splenectomy, neuropathy and autoimmune diseases.
Morphology
Circulating NK cells tend to be intermediate size with a round nucleus and condensed chromatin, with basofilix cytoplasm and azurophilic granules. The bone marrow biopsy, instead, show intrasinusoidal and interstitial infiltration of small cells with small and irregular nucleus and pale cytoplasm[2].
Immunophenotype
- Surface CD3 is negative, while cytoplasmic CD3 tends to be positive.
- CD16 positive
- Weak expression of CD56
- Cytotoxic markers: TIA-1, granzyme B and granzyme M positive.
- Diminished expression of CD2, CD7 and CD57.
- Aberrant expression of CD5 and CD8.
- Diminished CD161 expression.
Causes
Peripheral increased levels of NK cells have been associated with autoimmune diseases and viral infections, although no correlation has been found between those and a chronic lymphoproliferative disorder of NK cells [3]
However, molecular studies have shown that lymphoproliferative disease of granular lymphocytes (LDGL) express CD16 and CD56, but no CD3. Furthermore, LDGL patients variably expressed NKp30, NKp44, and NKp46 RNA, but always expressed CD94 and NKG2A. Polymerase chain reaction (PCR) showed that lower levels of KIR antibodies were present on LDGL patients than in healthy patients. As well as a high level of activating receptors, NK-LDGL cells have potent cytolytic function. Therefor, NK-LDGL have a higher activating-to-inhibitory KIR ratio, which might induce inappropriate lysis or cytokine production, playing a role in the disease pathogenesis [4].
Differential Diagnosis
Epidemiology and Demographics
Affects predominantly adults (with an average of 60 years), with no distinguishable difference in gender and no racial or genetic predisposition[5].
Risk Factors
Natural History, Complications and Prognosis
Most patients have an indolent clinical course for a long period of time. The disease might progress and develop as a cytopenia, recurrent infections and other comorbidities, in which case we'll be facing a worse prognosis.
In some cases, spontaneous and complete remission happens[6] , although, some cases, might transform into anaggresive NK-cell disorder. Some factors have been associated with the malignant transformation, such as
- Morphologic factors: mature, medium-sized lymphocytes with sparse azurophil granules
- Surface receptors: CD2+, CD11+, CD16+ and CD3-.
- Karyotipic abnormalities: Trisomy 8.
Diagnosis
History and Symptoms
Generally patients are asymptomatic, although some present with diverse cytopenias, mainly anemia and neutropenia. Less frequently, patients may present with hepatomegaly, splenomegaly and cutaneous lessions.
Treatment
References
- ↑ Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ "A long-term study of patients with chronic natural killer cell lymphocytosis".
- ↑ "Dysregulated NK receptor expression in patients with lymphoproliferative disease of granular lymphocytes".
- ↑ Swerdlow, Steven (2008). WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon, France: International Agency for Research on Cancer. ISBN 9789283224310.
- ↑ "Laboratory findings and clinical courses of 33 patients with granular lymphocyte-proliferative disorders".