anaplastic large‐cell lymphoma; ALK, anaplastic lymphoma kinase; ATLL, adult T‐cell leukemia/lymphoma; NKTCL, natural killer/T‐cell lymphoma; NOS, not otherwise specified; PTCL, peripheral T‐cell lymphoma.
Angioimmunoblastic T‐cell Lymphoma
AITL is thought to arise from follicular helper T cells which correspond to a subset of peripheral CD4 positive T cells [22, 23]. It is the second most commonly seen subtype of PTCL. The highest incidence rates are in Europe, specially Spain, France, Norway, Germany, Italy, and the UK (28.7% of PTCLs), while lower rates are seen in North America (16% of PTCLs) and Asia (17.9% of PTCLs) [10, 24]. In the United States, the incidence is approximately 0.05 cases per 100 000 person years [25] and it is more frequently seen in Asian/Pacific Islanders and Hispanic Whites, compared with non‐Hispanic Whites and African Americans [18]. AITL is not commonly seen in American Indian/Alaskan natives.
Typically, the disease affects older adults with a median age at diagnosis of 65 years in France [26] and 69 years in the United States [27]. It is almost never seen in persons less than 20 years of age, and there is a slight male preponderance seen is some studies [28–31]. Although Epstein–Barr virus (EBV) infection is associated with pathogenesis of AITL, the exact mechanism remains a topic of debate [32]. Electrical fitters and persons with a family history of hematological malignancies appear to carry an increased risk of developing AITL [33].
Anaplastic Large‐cell Lymphoma
ALCL accounts for approximately 12% of T‐cell lymphomas and approximately 2% of all NHLs [10, 34]. It is the third most common PTCL in adults in the United States and has an estimated incidence of 0.25 cases per 100 000 people [25]. The cell of origin is thought to be mature activated cytotoxic T‐cells that are CD30+. Based on molecular characterization and clinical features, four distinct forms of ALCL are recognized: (i) primary systemic ALCL, ALK+ ALCL; (ii) primary systemic ALCL, ALK– ALCL; (iii) primary cutaneous ALCL; and (iv) BIA‐ALCL.
In the international T‐cell lymphoma project, which is the largest retrospective study conducted in the disease, approximately 6.6% and 5.5% of cases were classified as ALK+ and ALK– ALCL, respectively [10]. ALCL was the most common PTCL subtype in the United States, accounting for approximately 24% of all cases. In the United States, Asian American are known to have a lower incidence of ALCL than White Americans, American Indians, African Americans, or Asian Pacific Islanders [18, 35].
ALK+ ALCLs have a median age incidence of 33–34 years whereas ALK– ALCLs have a median age of 58 years [10, 36]. In older adults, ALCL is typically ALK–. Male predominance is generally seen, and in young patients with ALK+ ALCL, the male to female ratio may be as high as three to one [37].
People with a history of celiac disease [38], those under 30 years, those with a history of eczema, and those with a history of cigarette smoking, people 30 years and older with a history of psoriasis, occupation as electrical fitter or textile worker, all have an increased risk of the disease [20]. EBV was originally thought to be associated with the development of this disease, but this finding has been subsequently reported not to be true [39]. HIV, however, does continue to remain a risk factor particularly for ALK– ALCL [40].
BIA‐ALCL was added as a provisional entity in the new WHO classification. The exact incidence is not known. Although earlier or later presentations can be seen, most cases are known to present approximately one decade after implant placement. The median age of onset is approximately 50 years of age [41, 42]. Other implanted medical devices other than breast implants are not known to cause ALCL.
Although the absolute risk for development of BIA‐ALCL is low in women with breast implants, there is a high relative risk compared with the general population, as demonstrated in a population‐based case–control study from the Netherlands (approximately nine million women) which reported an 18‐fold higher rate of ALCL arising in the breast among women with breast implants compared with women who did not have implants [43]. The reason for implant placement (cosmetic versus reconstructive) does not seem to influence the risk of lymphoma [44].
Adult T‐cell Lymphoma/Leukemia(HTLV Associated)
ATLL is an often aggressive and relatively uncommon PTCL associated with infection by human T‐cell lymphotropic virus type 1 (HTLV1). Incidence of ATLL varies by geographical region and population according to the prevalence of HTLV‐1 infection [10]. Most affected patients live or originate from those areas where HTLV1 infection is endemic, such as several islands in the Caribbean basin (e.g. Jamaica and Trinidad), southern Japan, western Africa, northeast Iran, Peru, and the southeastern portion of the United States [45–49]. Epidemiologic studies suggest that HTLV‐1 is primarily transmitted by breastfeeding, although spread via blood transfusion, sharing of needles, and sexual intercourse also occurs.
About 2.5% of people infected with HTLV1 are estimated to be subsequently diagnosed with ATLL [50, 51]. Patients infected as adults are less likely to develop ATLL compared with those exposed as children [52]. Contrasting evidence in gender distribution was noted with one study reporting equal incidence in males and females [53], whereas a different study noted ATLL to be slightly more predominant in males [52].
In the United States, the incidence of ATLL is approximately 0.05 cases per 100 000 people [54]. It is more commonly seen in African Americans and Asian/Pacific Islanders than White Americans [18]. The median age at diagnosis overall is in the sixth decade [10, 55] but can vary with geographic location, as reported in a study from Jamaica of 126 patients with ATLL which reported a median age of 43 years [56]. Risk factors associated with development of ATLL include a family history of ATLL, advanced age, high proviral load [57].
Extranodal NK/T‐cell Lymphomas
Extranodal NK/T‐cell lymphoma (ENKTCL) is most commonly seen in Asia, Central and South America (Peru and Mexico), and Mexico, where it accounts for 5–10% of all NHLs [48, 49, 58, 59]. It is most commonly associated with EBV positivity [60]. ENKTCL is a rare disorder in the United States, Europe, South Asia, the Middle East, and Africa. In the United States, the incidence is greater in Hispanic Whites and Asian/Pacific Islanders than in African Americans, non‐Hispanic Whites, and American Indian/Alaskan natives [18]. The most common site of presentation is nasal cavity followed by skin.
The median age at presentation in Asia is 52 years (ranges from 44 to 54 years) [61] whereas median age at presentation in the United States is relatively older, around 64 years [18]. There is a male predominance with an approximately two to one male to female ratio [61, 62].
T‐cell Prolymphocytic Leukemia
T‐cell prolymphocytic leukemia (T‐PLL) is a relatively aggressive and extremely rare disease., Although the name suggests “prolymphocyte,” the cell of origin is actually a post‐thymic T cell. T‐PLL accounts for approximately 2% of peripheral T‐cell lymphomas in adults [63, 64]. It has not been definitively reported in children or young adults. Sporadic T‐PLL mainly affects older adults with a mean age at presentation of 63–65 years [65, 66], and there is a slight male predominance with a male to female ratio of 1.33 : 1 [63]. Patients with ataxia telangiectasia have a greatly increased incidence of T‐PLL with a different epidemiologic profile [67]. In contrast to patients with sporadic T‐PLL, the median age of onset of T‐PLL in patients with ataxia telangiectasia is about 30 years, with some cases appearing in adolescence [68].
Large Granular Lymphocytic Leukemia
Large granular lymphocytic leukemia (LGLL) constitutes
