Aggressive NK-cell leukemia

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Aggressive NK-cell leukemia
Other namesNK-cell large granular lymphocyte leukemia
Natural killer cell.png
NK cell
Specialty Hematology and oncology

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]

Contents

It is also called aggressive NK-cell lymphoma. [4]

Signs and symptoms

Patients usually present with constitutional symptoms (malaise, weight loss, fatigue), and hepatosplenomegaly is commonly found on physical exam. Lymphadenopathy is also found to a lesser extent. Due to the aggressive nature of the disease, patients may initially present at a more advanced stage, with coagulopathies, hemophagocytic syndrome, and multi-organ failure. [1] [2] [5] [6] [7] Rarely, individuals who have an aggressive NK cell lymphoma that is associated with latent infection with the Epstein–Barr virus (see next section) present with or develop extensive allergic reactions to mosquito bites. The symptoms of these reactions range from a greatly enlarged bite site that may be painful and involve necrosis to systemic symptoms (e.g. fever, swollen lymph nodes, abdominal pain, and diarrhea), or, in extremely rare cases, to life-threatening anaphylaxis. [8]

Cause

This disease has a strong association with the Epstein–Barr virus (EBV), [9] but the true pathogenesis of this disease has yet to be described. The cell of origin is believed to be an NK cell. [4] Blastoid NK cell lymphoma appears to be a different entity and shows no association with EBV. [1]

Sites of involvement

This disease is typically found and diagnosed in peripheral blood, and while it can involve any organ, it is usually found in the spleen, liver, and bone marrow. [4]

Diagnosis

Leukemic cells are invariably present in samples of peripheral blood to a variable extent. Pancytopenia (anemia, neutropenia, thrombocytopenia) is commonly seen as well. [4]

Peripheral blood

The leukemic cells have a diameter mildly greater than a large granular lymphocyte (LGL) and have azurophilic granules and nucleoli of varying prominence. Nuclei may be irregular and hyperchromatic. [4]

Bone marrow

Bone marrow involvement runs the spectrum between an inconspicuous infiltrate to extensive marrow replacement by leukemic cells. Reactive histiocytes displaying hemophagocytosis can be seen interspersed in the neoplastic infiltrate. [4]

Other organs

Leukemic involvement of organs is typically destructive on tissue sections with necrosis and possibly angioinvasion, and the monotonous infiltrate may be diffuse or patchy. [4]

Immunophenotype

The immunophenotype of this disease is the same as extranodal NK/T-cell lymphoma, nasal type and is shown in the table below. CD11b and CD16 show variable expression. [1] [10]

StatusAntigens
Positive CD2, CD3ε, CD56, perforin, granzyme B, TIA-1, CCR5
Negative CD57

Genetic findings

Due to the NK lineage, clonal rearrangements of lymphoid (T cell receptor; B cell receptor) genes are not seen. [4] The genome of the Epstein Barr virus (EBV) is detected in many cases, [9] along with a variety of chromosomal abnormalities. [11]

Treatment

Currently Aggressive NK-cell leukemia, being a subtype of PTCL, is treated similarly to B-cell lymphomas. However, in recent years, scientists have developed techniques to better recognize the different types of lymphomas, such as PTCL. It is now understood that PTCL behaves differently from B-cell lymphomas and therapies are being developed that specifically target these types of lymphoma. Currently, however, there are no therapies approved by the U.S. Food and Drug Administration (FDA) specifically for PTCL. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant. [12] [13] [14] [15] [16] Novel approaches to the treatment of PTCL in the relapsed or refractory setting are under investigation.

Epidemiology

This rare form of leukemia is more common among Asians in comparison to other ethnic groups. It is typically diagnosed in adolescents and young adults, with a slight predominance in males. [1] [2] [3] [5] [17] [9] [10]

Research directions

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

Related Research Articles

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<span class="mw-page-title-main">Epstein–Barr virus</span> Virus of the herpes family

The Epstein–Barr virus (EBV), formally called Human gammaherpesvirus 4, is one of the nine known human herpesvirus types in the herpes family, and is one of the most common viruses in humans. EBV is a double-stranded DNA virus. Epstein–Barr virus (EBV) is the first identified oncogenic virus, that is a virus that can cause cancer. EBV establishes permanent infection in humans. It causes infectious mononucleosis and is also tightly linked to many malignant diseases (cancers). Various vaccine formulations underwent testing in different animals or in humans. However, none of them were able to prevent EBV infection and no vaccine has been approved to date.

<span class="mw-page-title-main">Burkitt lymphoma</span> Cancer of the lymphatic system

Burkitt lymphoma is a cancer of the lymphatic system, particularly B lymphocytes found in the germinal center. It is named after Denis Parsons Burkitt, the Irish surgeon who first described the disease in 1958 while working in equatorial Africa. It is a highly aggressive form of cancer which often, but not always, manifests after a person develops acquired immunodeficiency from infection with Epstein-Barr Virus or Human Immunodeficiency Virus (HIV).

Lymphoid leukemias are a group of leukemias affecting circulating lymphocytes, a type of white blood cell. The lymphocytic leukemias are closely related to lymphomas of the lymphocytes, to the point that some of them are unitary disease entities that can be called by either name. Such diseases are all lymphoproliferative disorders. Most lymphoid leukemias involve a particular subtype of lymphocytes, the B cells.

<span class="mw-page-title-main">T-cell lymphoma</span> Cancerous overproduction of T cells

T cell lymphoma is a rare form of cancerous lymphoma affecting T cells. Lymphoma arises mainly from the uncontrolled proliferation of T cells and can become cancerous.

<span class="mw-page-title-main">Intravascular lymphomas</span> Medical condition

Intravascular lymphomas (IVL) are rare cancers in which malignant lymphocytes proliferate and accumulate within blood vessels. Almost all other types of lymphoma involve the proliferation and accumulation of malignant lymphocytes in lymph nodes, other parts of the lymphatic system, and various non-lymphatic organs but not in blood vessels.

<span class="mw-page-title-main">Diffuse large B-cell lymphoma</span> Type of blood cancer

Diffuse large B-cell lymphoma (DLBCL) is a cancer of B cells, a type of lymphocyte that is responsible for producing antibodies. It is the most common form of non-Hodgkin lymphoma among adults, with an annual incidence of 7–8 cases per 100,000 people per year in the US and UK. This cancer occurs primarily in older individuals, with a median age of diagnosis at ~70 years, although it can occur in young adults and, in rare cases, children. DLBCL can arise in virtually any part of the body and, depending on various factors, is often a very aggressive malignancy. The first sign of this illness is typically the observation of a rapidly growing mass or tissue infiltration that is sometimes associated with systemic B symptoms, e.g. fever, weight loss, and night sweats.

Angioimmunoblastic T-cell lymphoma is a mature T-cell lymphoma of blood or lymph vessel immunoblasts characterized by a polymorphous lymph node infiltrate showing a marked increase in follicular dendritic cells (FDCs) and high endothelial venules (HEVs) and systemic involvement.

Richter's transformation (RT), also known as Richter's syndrome, is the conversion of chronic lymphocytic leukemia (CLL) or its variant, small lymphocytic lymphoma (SLL), into a new and more aggressively malignant disease. CLL is the circulation of malignant B lymphocytes with or without the infiltration of these cells into lymphatic or other tissues while SLL is the infiltration of these malignant B lymphocytes into lymphatic and/or other tissues with little or no circulation of these cells in the blood. CLL along with its SLL variant are grouped together in the term CLL/SLL.

X-linked lymphoproliferative disease is a lymphoproliferative disorder, usually caused by SH2DIA gene mutations in males. XLP-positive individuals experience immune system deficiencies that render them unable to effectively respond to the Epstein-Barr virus (EBV), a common virus in humans that typically induces mild symptoms or infectious mononucleosis (IM) in patients. There are two currently known variations of the disorder, known as XLP1 and XLP2. XLP1 is estimated to occur in approximately one in every million males, while XLP2 is rarer, estimated to occur in one of every five million males. Due to therapies such as chemotherapy and stem cell transplants, the survival rate of XLP1 has increased dramatically since its discovery in the 1970s.

<span class="mw-page-title-main">Hydroa vacciniforme</span> Medical condition

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<span class="mw-page-title-main">Extranodal NK/T-cell lymphoma, nasal type</span> Medical condition

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL-NT) is a rare type of lymphoma that commonly involves midline areas of the nasal cavity, oral cavity, and/or pharynx At these sites, the disease often takes the form of massive, necrotic, and extremely disfiguring lesions. However, ENKTCL-NT can also involve the eye, larynx, lung, gastrointestinal tract, skin, and various other tissues. ENKTCL-NT mainly affects adults; it is relatively common in Asia and to lesser extents Mexico, Central America, and South America but is rare in Europe and North America. In Korea, ENKTCL-NT often involves the skin and is reported to be the most common form of cutaneous lymphoma after mycosis fungoides.

<span class="mw-page-title-main">Peripheral T-cell lymphoma not otherwise specified</span> Medical condition

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), is a subtype of peripheral T-cell lymphoma. Peripheral T-cell lymphoma (PTCL) is defined as a diverse group of aggressive lymphomas that develop from mature-stage white blood cells called T-cells and natural killer cells. PTCL is a type of non-Hodgkin's lymphoma (NHL). PTCL specifically affects T-cells rather than B-cells, and results when T-cells develop and grow abnormally.

<span class="mw-page-title-main">Plasmablastic lymphoma</span> Type of large B-cell lymphoma

Plasmablastic lymphoma (PBL) is a type of large B-cell lymphoma recognized by the World Health Organization (WHO) in 2017 as belonging to a subgroup of lymphomas termed lymphoid neoplasms with plasmablastic differentiation. The other lymphoid neoplasms within this subgroup are: plasmablastic plasma cell lymphoma ; primary effusion lymphoma that is Kaposi's sarcoma-associated herpesvirus positive or Kaposi's sarcoma-associated Herpesvirus negative; anaplastic lymphoma kinase-positive large B-cell lymphoma; and human herpesvirus 8-positive diffuse large B-cell lymphoma, not otherwise specified. All of these lymphomas are malignancies of plasmablasts, i.e. B-cells that have differentiated into plasmablasts but because of their malignant nature: fail to differentiate further into mature plasma cells; proliferate excessively; and accumulate in and injure various tissues and organs.

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<span class="mw-page-title-main">Mosquito bite allergy</span> Excessive reactions to mosquito bites

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Mature T-cell lymphoma, also called peripheral T-cell lymphoma, is a group of rare, aggressive lymphomas that develop from mature white blood cells and originate from lymphoid tissues outside of the bone marrow. Mature T-cell lymphoma is under the category of non-Hodgkin lymphoma. Mature T-cell lymphomas account for 10% to 15% of all lymphomas and is more common in Asia than in Europe and America. Its common subtypes include angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma and peripheral T-cell lymphoma not otherwise specified. While different subtypes have variable symptoms, common symptoms include enlarged painless lymph nodes, fever, weight loss, rash and night sweats.

References

  1. 1 2 3 4 5 Chan JK, Sin VC, Wong KF, et al. (June 1997). "Nonnasal lymphoma expressing the natural killer cell marker CD56: a clinicopathologic study of 49 cases of an uncommon aggressive neoplasm". Blood. 89 (12): 4501–13. doi: 10.1182/blood.V89.12.4501 . PMID   9192774.
  2. 1 2 3 Imamura N, Kusunoki Y, Kawa-Ha K, et al. (May 1990). "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. 75 (1): 49–59. doi:10.1111/j.1365-2141.1990.tb02615.x. PMID   2375924. S2CID   45676891.
  3. 1 2 Chan JK (1998). "Natural killer cell neoplasms". Anat Pathol. 3: 77–145. PMID   10389582.
  4. 1 2 3 4 5 6 7 8 Elaine Sarkin Jaffe; Nancy Lee Harris; World Health Organization, International Agency for Research on Cancer; Harald Stein; J.W. Vardiman (2001). Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization Classification of Tumors. Vol. 3. Lyon: IARC Press. ISBN   978-92-832-2411-2.
  5. 1 2 Kwong YL, Wong KF, Chan LC, et al. (January 1995). "Large granular lymphocyte leukemia. A study of nine cases in a Chinese population". Am. J. Clin. Pathol. 103 (1): 76–81. doi:10.1093/ajcp/103.1.76. PMID   7817949.
  6. ↑ Kobayashi Y, Uehara S, Inamori K, et al. (August 1996). "Hemophagocytosis as a para-neoplastic syndrome in NK cell leukemia". Int. J. Hematol. 64 (2): 135–42. doi:10.1016/0925-5710(96)00477-X. PMID   8854571.
  7. ↑ Okuda T, Sakamoto S, Deguchi T, et al. (December 1991). "Hemophagocytic syndrome associated with aggressive natural killer cell leukemia". Am. J. Hematol. 38 (4): 321–3. doi:10.1002/ajh.2830380412. PMID   1746541. S2CID   6708698.
  8. ↑ Park S, Ko YH (January 2014). "Epstein–Barr virus-associated T/natural killer-cell lymphoproliferative disorders". The Journal of Dermatology. 41 (1): 29–39. doi:10.1111/1346-8138.12322. PMID   24438142. S2CID   42534926.
  9. 1 2 3 Gelb AB, van de Rijn M, Regula DP, et al. (September 1994). "Epstein–Barr virus-associated natural killer-large granular lymphocyte leukemia". Hum. Pathol. 25 (9): 953–60. doi: 10.1016/0046-8177(94)90018-3 . PMID   8088773.
  10. 1 2 Oshimi K (June 1996). "Lymphoproliferative disorders of natural killer cells". Int. J. Hematol. 63 (4): 279–90. doi:10.1016/0925-5710(96)00450-1. PMID   8762811.
  11. ↑ Wong KF, Zhang YM, Chan JK (July 1999). "Cytogenetic abnormalities in natural killer cell lymphoma/leukaemia—is there a consistent pattern?". Leuk. Lymphoma. 34 (3–4): 241–50. doi:10.3109/10428199909050949. PMID   10439361.
  12. ↑ Reimer P, Rüdiger T, Geissinger E, et al. (January 2009). "Autologous stem-cell transplantation as first-line therapy in peripheral T-cell lymphomas: results of a prospective multicenter study". J. Clin. Oncol. 27 (1): 106–13. doi:10.1200/JCO.2008.17.4870. PMID   19029417. Archived from the original on 2012-08-03.
  13. ↑ Mercadal S, Briones J, Xicoy B, et al. (May 2008). "Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma". Ann. Oncol. 19 (5): 958–63. doi: 10.1093/annonc/mdn022 . PMID   18303032.
  14. ↑ Rodríguez J, Conde E, Gutiérrez A, et al. (July 2007). "Frontline autologous stem cell transplantation in high-risk peripheral T-cell lymphoma: a prospective study from The Gel-Tamo Study Group". Eur. J. Haematol. 79 (1): 32–8. doi:10.1111/j.1600-0609.2007.00856.x. PMID   17598836. S2CID   32509254.
  15. ↑ Corradini P, Tarella C, Zallio F, et al. (September 2006). "Long-term follow-up of patients with peripheral T-cell lymphomas treated up-front with high-dose chemotherapy followed by autologous stem cell transplantation". Leukemia. 20 (9): 1533–8. doi:10.1038/sj.leu.2404306. PMID   16871285.
  16. ↑ d'Amore F, et al. Blood. 2006;108:A401
  17. ↑ Kwong YL, Chan AC, Liang RH (May 1997). "Natural killer cell lymphoma/leukemia: pathology and treatment". Hematol Oncol. 15 (2): 71–9. doi:10.1002/(SICI)1099-1069(199705)15:2<71::AID-HON601>3.0.CO;2-U. PMID   9375032. S2CID   43307154.
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