| Human T-lymphotropic virus |
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| HTLV-1 and HIV |
| Virus classification |
| Group: |
Group VI (ssRNA-RT) |
| Family: |
Retroviridae' |
| Subfamily: |
Orthoretrovirinae |
| Genus: |
Deltaretrovirus |
| Species: |
Simian T-lymphotropic virus |
| Serotypes |
|
Human T-lymphotropic virus
|
Human T-cell lymphotropic virus type 1 or human T-lymphotropic virus type 1 (HTLV-I), also called the adult T-cell lymphoma virus type 1, is a retrovirus of the human T-lymphotropic virus (HTLV) family that has been implicated in several kinds of diseases including very aggressive adult T-cell lymphoma (ATL), HTLV-I-associated myelopathy, uveitis, strongyloides stercoralis hyper-infection and some other diseases. However, only about 1–5% of infected persons are thought to develop cancer as a result of the infection with HTLV-I over their lifetimes.[1]
HTLV was discovered in 1977 in Japan. The virus was first isolated by Bernard Poiesz and Francis Ruscetti and their co-workers in the laboratory of Robert C. Gallo at the National Cancer Institute.[2] It was the first identified human retrovirus. Infection with HTLV-I, like infection with other retroviruses, probably occurs for life. A patient infected with HTLV can be diagnosed when antibodies against HTLV-1 are detected in the serum.[1]
Contents
- 1 Virology
- 2 Epidemiology
- 3 Transmission
- 4 Tropism
- 5 Associated diseases
- 5.1 Malignancies
- 5.1.1 Adult T cell leukemia/lymphoma
- 5.1.2 Cutaneous T-cell lymphoma
- 5.2 Inflammatory diseases
- 5.2.1 HTLV myelopathy/tropical spastic paraparesis
- 5.2.2 Arthropathy
- 5.2.3 Uveitis
- 5.3 Opportunistic infections
- 6 Treatment
- 7 References
- 8 External links
Virology
HTLV-1 is a retrovirus belonging to the family retroviridae and the genus deltaretrovirus. It has a positive-sense RNA genome that is reverse transcribed into DNA and then integrated into the cellular DNA. Once integrated, HTLV-1 continues to exist only as a provirus which can spread from cell to cell through a viral synapse. Few, if any, free virions are produced and there is usually no detectable virus in the blood plasma though the virus is present in genital secretions. Like HIV, HTLV-1 predominately infects CD4+ T cells.[1]
The viral RNA is packed into the icosahedral capsid which is contained inside the protein inner envelope. The lipid outer envelope is of host cell origin but contains viral transmembrane and surface proteins. The virion is spherical in shape with a diameter of about 100 nm.[1]
Seven HTLV-1 genotypes are recognised—HTLV-1a through HTLV-1g.[1] It is estimated that from 10 to 20 million people worldwide are infected; 3–8 million of them are in Africa.[3] The most widespread genotype is type A. Types B, D, E, F and G have only been isolated from Central Africa. Type C is only present in Asia. Simian HTLV-1 genotypes are interspersed in between the human genotypes indicating frequent animal-human and human-animal transmission.[1] The only human genotype that does not have a simian relative is A. It is thought that genotypes B, D, E, F and G originated in Africa from closely related STLV about 30,000 years ago, while the Asian genotype C is thought to have originated independently in Indonesia from the simians present there.[1] Two subtypes are found in Japan: a transcontinental subgroup and a Japanese subgroup.[4]
Epidemiology
The knowledge about HTLV-1 epidemiology is limited.
The high prevalence is detected in Japan where more than 10% of the population are infected. The reasons for this extremely high prevalence are not known. In Taiwan, in Iran, and in Fujian, a Chinese province near Taiwan the prevalence is 0.1–1%. The infection rate is about 1% in Papua New Guinea, the Solomon Islands, and Vanuatu, where the genotype C predominates. In Europe HTLV-1 is still uncommon, although it is present in some high risk populations including immigrants and intravenous drug uses. In Americas the virus is found in indigenous populations and descendants of African slaves from where it is thought to have originated. The general prevalence is from 0.1 to 1%. In Africa the prevalence is well not known but it is about 1% in some countries.[1]
HTLV-I infection in the United States appears to be about half as prevalent among IV drug users and about one-tenth as prevalent in the population at large as HIV infection. Although little serologic data exist, the prevalence of infection is thought to be highest among blacks living in the Southeast. A prevalence rate of 30% has been found among black intravenous drug users in New Jersey, and a rate of 49% has been found in a similar group in New Orleans.[5]
HTLV-I infection in Australia is very high among the indigenous peoples of central and northern Australia, with a prevalence rate of 10–30%. It is also high among the Inuit of Northern Canada, in Japan, northeastern Iran,[6] Peru, the Pacific coast of Colombia and Ecuador, the Caribbean, and in Africa.
Transmission
Transmission of HTLV-I is believed to occur by sexual contact, from mother to child via breastfeeding, and through exposure to contaminated blood, either through blood transfusion or sharing of contaminated needles. The importance of the various routes of transmission is believed to vary geographically. The research in discordant couples showed that probability of sexual transmission is about 0.9 per 100 person-years.[1]
- In Japan, the geographic clustering of infections suggest that the virus is more dependent on mother-to-child transmission.[7]
- In the Caribbean, the geographic distribution of the virus is more uniform, and it is more common among those with many sexual partners, indicating that sexual transmission is more common.[8]
Tropism
The term viral tropism refers to which cell types HTLV-I infects. Although HTLV-1 is primarily found in CD4+ T cells, other cell types in the peripheral blood of infected individuals have been found to contain HTLV-1, including CD8+ T cells, dendritic cells and B cells. HTLV-I entry is mediated through interaction of the surface unit of the virion envelope glycoprotein (SU) with its cellular receptor GLUT1, a glucose transporter, on target cells.[9]
Associated diseases
Malignancies
Adult T cell leukemia/lymphoma
Main article: Adult T-cell leukemia/lymphoma
HTLV-1 is also associated with adult T-cell leukemia/lymphoma and has been quite well studied in Japan. The time between infection and onset of cancer also varies geographically. It is believed to be about sixty years in Japan and less than forty years in the Caribbean. The cancer is thought to be due to the pro-oncogenic effect of viral DNA incorporated into host lymphocyte DNA. Chronic stimulation of the lymphocytes at the cytokine level may play a role in the development of the malignancy. The lymphoma ranges from a very indolent and slowly progressive type to a very aggressive and nearly uniformly lethal proliferative type.
Cutaneous T-cell lymphoma
There is some evidence that HTLV-1 is a causative agent of cutaneous T-cell lymphoma.[1]
Inflammatory diseases
HTLV myelopathy/tropical spastic paraparesis
Main article: Tropical spastic paraparesis
HTLV-1 is also associated with a progressive demyelinating upper motor neuron disease known as HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP), an characterized by sensory and motor deficits, particularly of the lower extremities, incontinence and impotence.[10] Only 0.3 to 4% of infected individuals develop HAM/TSP, but this will vary from one geographic location to another.[1]
Signs and symptoms of HTLV myelopathy include:
- Motor and sensory changes in the extremities
- Spastic gait in combination with weakness of the lower limbs
- Clonus
- Bladder dysfunction(neurogenic bladder) and bladder cancer
Other neurologic findings that may be found in HTLV include:
- Mild cognitive impairment
- Erectile dysfunction[11]
Arthropathy
HTLV-1 is associated with a rheumatoid-like arthropathy, although the evidence is contradictory. In these cases patients have a negative rheumatoid factor.[1]
Uveitis
Studies from Japan demonstrated that HTLV-1 infection may be associated with an intermediate uveitis. At onset the patients present with blurred vision and floaters. The prognosis is favorable—the condition usually resolves within weeks.[1]
Opportunistic infections
Individuals infected with HTLV-1 are at risk for opportunistic infections—diseases not caused by the virus itself, but by alterations in the host's immune functions.[1]
HTLV-1, unlike the distantly related retrovirus HIV, has an immunostimulating effect which actually becomes immunosuppressive. The virus activates a subset of T-helper cells called Th1 cells. The result is a proliferation of Th1 cells and overproduction of Th1 related cytokines (mainly IFN-γ and TNF-α). Feedback mechanisms of these cytokines cause a suppression of the Th2 lymphocytes and a reduction of Th2 cytokine production (mainly IL-4, IL-5, IL-10 and IL-13). The end result is a reduction in the ability of the infected host to mount an adequate immune response to invading organisms that require a predominantly Th2 dependent response (these include parasitic infections and production of mucosal and humoral antibodies).[citation needed]
In the central Australian Aboriginal population, HTLV-1 is thought to be related to their extremely high rate of death from sepsis. It is also particularly associated with bronchiectasis, a chronic lung condition predisposing to recurrent pneumonia. It is also associated with chronic infected dermatitis, often superinfected with Staphylococcus aureus and a severe form of Strongyloides stercoralis infection called hyper-infestation which may lead to death from polymicrobial sepsis. HTLV-1 infection has also been associated with tuberculosis.[1]
Treatment
|
This section requires expansion. (January 2010) |
Treatment of opportunistic infections varies depending on the type of disease and ranges from careful observation to aggressive chemotherapy and antiretroviral agents.[citation needed] Adult T cell lymphoma is a common complication of HLTV infection and requires aggressive chemotherapy, typically R-CHOP. Other treatments for ATL in HLTV infected patients include interferon alpha, zidovudine with interferon alpha and CHOP with arsenic trioxide. Treatments for HLTV myelopathy are even more limited and focus mainly on symptomatic therapy. Therapies studied include corticosteroids, plasmapheresis, cyclophosphamide, and interferon, which may produce a temporary symptomatic improvement in myelopathy symptoms.[12]
Valproic acid has been studied to determine if it might slow the progression of HLTV disease by reducing viral load. Although in one human study it was effective in reducing viral load, there did not appear to be a clinical benefit. Recently however, a study of valproic acid combined with zidovudine showed a major decrease in the viral load of baboons infected with HLTV-1. It is important to monitor HLTV patients for opportunistic infections such as cytomegalovirus, histoplasmosis, scabies, pneumocystis pneumonia, and staphylococcal infections. HIV testing should also be performed, as some patients may be co-infected with both viruses.[13]
Allogenic bone marrow transplantation has been investigated in the treatment of HLTV-1 disease with varied results. One case report describes an HLTV-1 infected woman who developed chronic refractory eczema, corneal injury and adult T cell leukemia. She was subsequently treated with allogenic stem cell transplantation and had complete resolution of symptoms. One year post-transplant, she has had no recurrence of any symptoms, and furthermore has had a decrease in her proviral load.[14]
References
- ^ a b c d e f g h i j k l m n o Verdonck, K.; González, E.; Van Dooren, S.; Vandamme, A. M.; Vanham, G.; Gotuzzo, E. (2007). "Human T-lymphotropic virus 1: Recent knowledge about an ancient infection". The Lancet Infectious Diseases 7 (4): 266. doi:10.1016/S1473-3099(07)70081-6. edit
- ^ Poiesz BJ, Ruscetti FW, Reitz MS, Kalyanaraman VS, Gallo RC (1981). "Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sézary T-cell leukaemia". Nature 294 (5838): 268–71. doi:10.1038/294268a0. PMID 6272125.
- ^ Zanella L, Otsuki K, Marin MA, Bendet I, Vicente AC (2012) Complete genome sequence of central Africa human T-cell lymphotropic virus subtype 1b. J Virol 86(22):12451. doi: 10.1128/JVI.02258-12
- ^ Otani M, Honda N, Xia PC, Eguchi K, Ichikawa T, Watanabe T, Yamaguchi K, Nakao K, Yamamoto T (2012) Distribution of Two Subgroups of Human T-Lymphotropic Virus Type 1 (HTLV-1) in Endemic Japan. Trop Med Health 40(2):55–8. doi: 10.2149/tmh.2012-02
- ^ Cantor KP, Weiss SH, Goedert JJ, Battjes RJ (1991). "HTLV-I/II seroprevalence and HIV/HTLV coinfection among U.S. intravenous drug users". J. Acquir. Immune Defic. Syndr. 4 (5): 460–7. PMID 2016683.
- ^ Sabouri, AH.; Saito, M; Usuku, K; Bajestan, SN; Mahmoudi, M; Forughipour, M; Sabouri, Z; Abbaspour, Z et al. (2005). "Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals". J Gen Virol 86 (3): 773–81. doi:10.1099/vir.0.80509-0. PMID 15722539.
- ^ Tajima, K. (1988). "The third nation-wide study on adult T-cell leukaemia/lymphoma (ATL) in Japan: characteristic patterns of HLA antigen and HTLV-I infection in ATL patients and their relatives. The T- and B-cell Malignancy Study Group". Int J Cancer 41 (4): 505–12. doi:10.1002/ijc.2910410406. PMID 2895748.
- ^ Clark J, Saxinger C, Gibbs W, Lofters W, Lagranade L, Deceulaer K, Ensroth A, Robert-Guroff M, Gallo R, Blattner W (1985). "Seroepidemiologic studies of human T-cell leukemia/lymphoma virus type I in Jamaica". Int J Cancer 36 (1): 37–41. doi:10.1002/ijc.2910360107. PMID 2862109.
- ^ Manel N, Kim FJ, Kinet S, Taylor N, Sitbon M, Battini JL (November 2003). "The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV". Cell 115 (4): 449–59. doi:10.1016/S0092-8674(03)00881-X. PMID 14622599.
- ^ Osame, M.; Usuku, K; Izumo, S; Ijichi, N; Amitani, H; Igata, A; Matsumoto, M; Tara, M (1986). "HTLV-I associated myelopathy, a new clinical entity". Lancet 3 (1): 1031–2. doi:10.1016/S0140-6736(86)91298-5. PMID 2871307.
- ^ http://www.emedicine.net[dead link]
- ^ Goncalves, D. U.; Proietti, F. A.; Ribas, J. G. R.; Araujo, M. G.; Pinheiro, S. R.; Guedes, A. C.; Carneiro-Proietti, A. B. F. (2010). "Epidemiology, Treatment, and Prevention of Human T-Cell Leukemia Virus Type 1-Associated Diseases". Clinical Microbiology Reviews 23 (3): 577–589. doi:10.1128/CMR.00063-09. PMC 2901658. PMID 20610824. edit
- ^ http://www.emedicine.net
- ^ http://emedicine.medscape.com
External links
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Wikimedia Commons has media related to Human T-lymphotropic virus 1. |
- International Retrovirology Association
- Human T-lymphotropic virus 1 at the US National Library of Medicine Medical Subject Headings (MeSH)
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Virus: Retroviruses
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| ssRNA-RT virus |
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Retroviridae
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Alpharetrovirus
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- Avian sarcoma leukosis virus
- Rous sarcoma virus
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Betaretrovirus
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- Mouse mammary tumor virus
- Jaagsiekte sheep retrovirus
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Deltaretrovirus
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- Human T-lymphotropic virus (HTLV-1
- HTLV-2, 3, 4)
- Simian-T-lymphotropic virus (types 1-4)
- Bovine leukemia virus
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Epsilonretrovirus
|
- Walleye epidermal hyperplasia virus
|
|
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Gammaretrovirus
|
- Murine leukemia virus
- Abelson murine leukemia virus
- Friend virus
- Feline leukemia virus
- Koala retrovirus
- Xenotropic murine leukemia virus-related virus
|
|
|
Lentivirus
|
- HIV
- Simian immunodeficiency virus
- Feline immunodeficiency virus
- Puma lentivirus
- Equine infectious anemia
- Bovine immunodeficiency virus
- Caprine arthritis encephalitis virus
- Visna virus
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|
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Spumavirus
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- Simian foamy virus
- Human foamy virus
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Other
|
- Metaviridae
- Pseudoviridae
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|
|
| dsDNA-RT virus |
- Hepadnaviridae (Hepatitis B virus)
- Caulimoviridae
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| Endogenous |
- ERVWE1
- HCP5
- Human teratocarcinoma-derived virus
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|
|
Infectious diseases – viral systemic diseases (A80–B34, 042–079)
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|
| Oncovirus |
- DNA virus
- HBV
- Hepatocellular carcinoma
- HPV
- Cervical cancer
- Anal cancer
- Penile cancer
- Vulvar cancer
- Vaginal cancer
- Oropharyngeal cancer
- KSHV
- Kaposi's sarcoma
- EBV
- Nasopharynx cancer
- Burkitt's lymphoma
- Hodgkin's lymphoma
- Follicular dendritic cell sarcoma
- Nasal type NK/T-cell lymphoma
- MCPyV
- Merkel cell carcinoma
- RNA virus
- HCV
- Hepatocellular carcinoma
- Splenic marginal zone lymphoma
- HTLV-I
- Adult T-cell leukemia/lymphoma
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| Immune disorders |
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|
Central
nervous system |
Encephalitis/
meningitis |
- DNA virus
- JCV
- Progressive multifocal leukoencephalopathy
- RNA virus
- MeV
- Subacute sclerosing panencephalitis
- LCV
- Lymphocytic choriomeningitis
- Arbovirus encephalitis
- Orthomyxoviridae (probable)
- Encephalitis lethargica
- RV
- Rabies
- Chandipura virus
- Herpesviral meningitis
- Ramsay Hunt syndrome type II
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|
| Myelitis |
- Poliovirus
- Poliomyelitis
- Post-polio syndrome
- HTLV-I
- Tropical spastic paraparesis
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| Eye |
- Cytomegalovirus
- Cytomegalovirus retinitis
- HSV
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|
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| Cardiovascular |
|
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Respiratory system/
acute viral nasopharyngitis/
viral pneumonia |
| DNA virus |
- Epstein–Barr virus
- EBV infection/Infectious mononucleosis
- Cytomegalovirus
|
|
| RNA virus |
- IV: SARS coronavirus
- Severe acute respiratory syndrome
- V: Orthomyxoviridae: Influenzavirus A/B/C
- Influenza/Avian influenza
- V, Paramyxoviridae: Human parainfluenza viruses
- RSV
- hMPV
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|
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| Human digestive system |
| Pharynx/Esophagus |
- MuV
- Cytomegalovirus
- Cytomegalovirus esophagitis
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Gastroenteritis/
diarrhea |
- DNA virus
- Adenovirus
- Adenovirus infection
- RNA virus
- Rotavirus
- Norovirus
- Astrovirus
- Coronavirus
|
|
| Hepatitis |
- DNA virus
- HBV (B)
- RNA virus
- CBV
- HAV (A)
- HCV (C)
- HDV (D)
- HEV (E)
- HGV (G)
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| Pancreatitis |
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| Urogenital |
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cutn/syst (hppv/hiva, infl/zost/zoon)/epon
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drug (dnaa, rnaa, rtva, vacc)
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Zoonotic viral diseases (A80–B34, 042–079)
|
|
| Arthropod-borne |
| Mosquito-borne |
| Bunyaviridae |
- Arbovirus encephalitides: La Crosse encephalitis
- California encephalitis
- Viral hemorrhagic fevers: Rift Valley fever
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|
| Flaviviridae |
- Arbovirus encephalitides: Japanese encephalitis
- Australian encephalitis
- Saint Louis encephalitis
- West Nile fever
- Viral hemorrhagic fevers: Dengue fever
- Yellow fever
- ZIKV
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| Togaviridae |
- Arbovirus encephalitides: Eastern equine encephalomyelitis
- Western equine encephalomyelitis
- Venezuelan equine encephalomyelitis
- Chikungunya
- O'Nyong-nyong fever
- Ross River fever
- Semliki Forest virus
- Sindbis fever
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| Reoviridae |
|
|
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| Tick-borne |
| Bunyaviridae |
- Viral hemorrhagic fevers: Crimean–Congo hemorrhagic fever
|
|
| Flaviviridae |
- Arbovirus encephalitides: Tick-borne encephalitis
- Powassan encephalitis
- Viral hemorrhagic fevers: Omsk hemorrhagic fever
- Kyasanur forest disease
- Langat virus (LGTV)
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| Reoviridae |
- Colorado tick fever
- Kemerovo tickborne viral fever
|
|
|
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| Mammal-borne |
| Rodent-borne |
| Arenaviridae |
- Viral hemorrhagic fevers: Lassa fever
- Venezuelan hemorrhagic fever
- Argentine hemorrhagic fever
- Brazilian hemorrhagic fever
- Bolivian hemorrhagic fever
- LUJV
- CHPV
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| Bunyaviridae |
- Hemorrhagic fever with renal syndrome
- Hantavirus pulmonary syndrome
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|
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| Bat-borne |
| Filoviridae |
- Viral hemorrhagic fevers: Ebola virus disease
- Marburg virus disease
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| Rhabdoviridae |
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| Paramyxoviridae |
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| Primate-borne |
| Herpesviridae |
|
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| Retroviridae |
- Simian foamy virus
- HTLV-1
- HTLV-2
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| Poxviridae |
- Tanapox
- Yaba monkey tumor virus
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| Multiple vectors |
| Rhabdoviridae |
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| Poxviridae |
Monkeypox
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cutn/syst (hppv/hiva, infl/zost/zoon)/epon
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drug (dnaa, rnaa, rtva, vacc)
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Hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
Lymphoid/Lymphoproliferative, Lymphomas/Lymphoid leukemias (9590–9739, 9800–9839)
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B cell
(lymphoma,
leukemia)
(most CD19
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By development/
marker
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TdT+
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- ALL (Precursor B acute lymphoblastic leukemia/lymphoma)
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CD5+
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mantle zone (Mantle cell)
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CD22+
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- Prolymphocytic
- CD11c+ (Hairy cell leukemia)
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CD79a+
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- germinal center/follicular B cell (Follicular
- Burkitt's
- GCB DLBCL
- Primary cutaneous follicular lymphoma)
marginal zone/marginal-zone B cell (Splenic marginal zone
- MALT
- Nodal marginal zone
- Primary cutaneous marginal zone lymphoma)
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RS (CD15+, CD30+)
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- Classic Hodgkin's lymphoma (Nodular sclerosis)
- CD20+ (Nodular lymphocyte predominant Hodgkin's lymphoma)
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PCDs/PP
(CD38+/CD138+)
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- see immunoproliferative immunoglobulin disorders
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By infection
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- KSHV (Primary effusion)
- EBV (Lymphomatoid granulomatosis
- Post-transplant lymphoproliferative disorder)
- HIV (AIDS-related lymphoma)
- Helicobacter pylori (MALT lymphoma)
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Cutaneous
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- Diffuse large B-cell lymphoma
- Intravascular large B-cell lymphoma
- Primary cutaneous marginal zone lymphoma
- Primary cutaneous immunocytoma
- Plasmacytoma
- Plasmacytosis
- Primary cutaneous follicular lymphoma
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T/NK
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T cell
(lymphoma,
leukemia)
(most CD3
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By development/
marker
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- TdT+: ALL (Precursor T acute lymphoblastic leukemia/lymphoma)
- prolymphocyte (Prolymphocytic)
- CD30+ (Anaplastic large-cell lymphoma
- Lymphomatoid papulosis type A)
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Cutaneous
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MF+variants
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- indolent: Mycosis fungoides
- Pagetoid reticulosis
- Granulomatous slack skin
aggressive: Sézary's disease
- Adult T-cell leukemia/lymphoma
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Non-MF
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- CD30-: Non-mycosis fungoides CD30− cutaneous large T-cell lymphoma
- Pleomorphic T-cell lymphoma
- Lymphomatoid papulosis type B
CD30+: CD30+ cutaneous T-cell lymphoma
- Secondary cutaneous CD30+ large cell lymphoma
- Lymphomatoid papulosis type A
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Other peripheral
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- Hepatosplenic
- Angioimmunoblastic
- Enteropathy-associated T-cell lymphoma
- Peripheral T-cell lymphoma-Not-Otherwise-Specified (Lennert lymphoma)
- Subcutaneous T-cell lymphoma
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By infection
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- HTLV-1 (Adult T-cell leukemia/lymphoma)
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NK cell/
(most CD56)
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- Aggressive NK-cell leukemia
- Blastic NK cell lymphoma
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T or NK
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- EBV (Extranodal NK-T-cell lymphoma/Angiocentric lymphoma)
- Large granular lymphocytic leukemia
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Lymphoid+myeloid
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- Acute biphenotypic leukaemia
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Lymphocytosis
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- Lymphoproliferative disorders (X-linked lymphoproliferative disease
- Autoimmune lymphoproliferative syndrome)
- Leukemoid reaction
- Diffuse infiltrative lymphocytosis syndrome
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|
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| Cutaneous lymphoid hyperplasia |
- Cutaneous lymphoid hyperplasia
- with bandlike and perivascular patterns
- with nodular pattern
- Jessner lymphocytic infiltrate of the skin
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cell/phys/auag/auab/comp, igrc
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