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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Lymphoma is a group of blood and lymph tumors that develop from lymphocytes. In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlarged lymph nodes, fever, drenching sweats, unintended weight loss, itching, and constantly feeling tired. The enlarged lymph nodes are usually painless. The sweats are most common at night.

<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.

<span class="mw-page-title-main">Burkitt lymphoma</span> Medical condition

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. The overall cure rate for Burkitt lymphoma in developed countries is about 90%, and it is worse in low-income countries. Burkitt lymphoma is uncommon in adults, in whom it has a worse prognosis.

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> Medical condition

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 tyes 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.

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.

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.

There are several forms of Epstein–Barr virus (EBV) infection. These include asymptomatic infections, the primary infection, infectious mononucleosis, and the progression of asymptomatic or primary infections to: 1) any one of various Epstein–Barr virus-associated lymphoproliferative diseases such as chronic active EBV infection, EBV+ hemophagocytic lymphohistiocytosis, Burkitt's lymphoma, and Epstein–Barr virus positive diffuse large B-cell lymphoma, not otherwise specified); 2) non-lymphoid cancers such as Epstein–Barr virus associated gastric cancer, soft tissue sarcomas, leiomyosarcoma, and nasopharyngeal cancers; and 3) Epstein–Barr virus-associated non-lymphoproliferative diseases such as some cases of the immune disorders of multiple sclerosis and systemic lupus erythematosis and the childhood disorders of Alice in Wonderland Syndrome and acute cerebellar ataxia.

Epstein–Barr virus latent membrane protein 1 (LMP1) is an Epstein–Barr virus (EBV) protein that regulates its own expression and the expression of human genes. It has a molecular weight of approximately 63 kDa, and its expression induces many of the changes associated with EBV infections and activation of primary B cells. LMP1 is the best-documented oncoprotein of the EBV latent gene products, as it is expressed in most EBV-related human cancers such as the various malignant Epstein-Barr virus-associated lymphoproliferative diseases.

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

Hydroa vacciniforme (HV) is a very rare, chronic photodermatitis-type skin condition with usual onset in childhood. It was first described in 1862 by Bazin. It is sometimes called "Bazin's hydroa vacciniforme". A study published in Scotland in 2000 reviewed the cases of 17 patients and estimated a prevalence of 0.34 cases per 100,000 population. In this study they reported an average age of onset of 7.9 years. Frequently the rash first appeared in the spring or summer months and involved sun-exposed skin. The rash starts as a vesicular eruption, later becoming umbilicated, and resulted in vacciniform scarring. It is most frequently found on the nose, cheeks, ears, dorsum of the hand, and arms.

Subcutaneous T-cell lymphoma is a cutaneous condition that most commonly presents in young adults, and is characterized by subcutaneous nodules. Common symptoms include fever, fatigue, and pancytopenia.

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 Karposi'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.

Chronic active EBV infection or in its expanded form, chronic active Epstein–Barr virus infection is a very rare and often fatal complication of Epstein–Barr virus (EBV) infection that most often occurs in children or adolescents of Asian or South American lineage, although cases in Hispanics, Europeans and Africans have been reported. It is classified as one of the Epstein-Barr virus-associated lymphoproliferative diseases.

Epstein–Barr virus–associated lymphoproliferative diseases are a group of disorders in which one or more types of lymphoid cells, i.e. B cells, T cells, NK cells, and histiocytic-dendritic cells, are infected with the Epstein–Barr virus (EBV). This causes the infected cells to divide excessively, and is associated with the development of various non-cancerous, pre-cancerous, and cancerous lymphoproliferative disorders (LPDs). These LPDs include the well-known disorder occurring during the initial infection with the EBV, infectious mononucleosis, and the large number of subsequent disorders that may occur thereafter. The virus is usually involved in the development and/or progression of these LPDs although in some cases it may be an "innocent" bystander, i.e. present in, but not contributing to, the disease.

<span class="mw-page-title-main">Mosquito bite allergy</span>

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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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