Review article

International Journal of STD & AIDS

2017, Vol. 28(3) 217–228
! The Author(s) 2016
Adult T-cell leukemia/lymphoma in South Reprints and permissions:
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and Central America and the Caribbean: DOI: 10.1177/0956462416684461
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systematic search and review

Pedro D Oliveira1, Rebeca F de Carvalho2 and

Achiléa L Bittencourt2

Abstract
Adult T-cell leukemia/lymphoma (ATL) is caused by the human T-cell lymphotropic virus type 1 (HTLV-1) which is
endemic in countries of Caribbean and Central and South America. We performed a systematic search and review to
identify publications on ATL in these countries to verify if this disease was getting recognition in these regions as well as
the characteristics of the observed cases. The median age of 49.4 years was lower than that referred to in Japan.
According to our findings in most Brazilian states and in some other countries, ATL is not being recognized and should be
strongly considered in the differential diagnosis of T-cell leukemias/lymphomas. Failure to identify these cases may be due
to the unsystematic realization of serology for HTLV-1 and phenotypic identification of non-Hodgkin lymphomas that
may result from lack of resources. Detection of ATL cases has been more feasible with cooperation from foreign
research centers. A huge effort should be made to improve the surveillance system for ATL diagnosis in most of the
South- and Central-American and Caribbean countries, and this attitude should be embraced by public organs to support
health professionals in this important task.

Keywords
Diagnosis, epidemiology, South America, Adult T-cell leukemia/lymphoma, HTLV-1

Date received: 6 July 2016; accepted: 17 November 2016

in approximately 70% of their genome sequences and,

Introduction
Adult T-cell leukemia/lymphoma (ATL) is a malig-
nancy of peripheral T-cells caused by the human T-
cell lymphotropic virus type-1 (HTLV-1).1 HTLV-1 is
highly endemic in southwestern Japan, the Caribbean,
sub-Saharan Africa, South America and foci in the
Middle East and Australo-Melanesia. The number of
individuals infected worldwide is estimated between five
and ten million, with variable distribution in the world.
There are differences in the prevalence of HTLV-1
infection in adult populations in different countries of
Latin America, and even in one single country there are
vast variations in different areas and populational
groups.2 It has been shown that HTLV-1 prevalence
increases with age and is higher in women than in men.3
The most commonly used serologic test for detec-
tion of HTLV-1 infection is an enzyme-linked
immunoassay. The HTLV-1 and HTLV-2 are similar
because of this, there are serologic cross-reactions
between them. Thus, it is necessary to distinguish
between each one when performing a confirmatory
test, and the most commonly used is Western
blotting.1
Although the majority of HTLV-1-infected people
remain asymptomatic carriers, the virus may cause vari-
ous diseases, among them, adult-cell leukemia/
1
Department of Dermatology, Federal University of Bahia, Salvador,
Brazil
2
Department of Pathology, Complexo Hospitalar Universitário Prof
Edgard Santos, Federal University of Bahia, Salvador, Brazil
Corresponding author:
Achilea L Bittencourt, Department of Pathology, Complexo Hospitalar
Universitário Professor Edgard Santos, Avenida Augusto Viana, SN,
Canela, Salvador, Bahia 40110410, Brazil.
Email: achilea@uol.com.br
218
lymphoma (ATL), HTLV-1-associated myelopathy/
tropical spastic paraparesis (HAM/TSP), infective
dermatitis associated with HTLV-1 (IDH) and
HTLV-1-associated uveitis (HAU).4,5
HTLV-1 acts slowly within the organism; hence, the
diseases caused by the virus are considered to be of late-
onset, emerging in adulthood even when the infection
occurred early in life.6 HTLV-1 infection causes dysre-
gulation of the immune system with spontaneous lym-
phoproliferation and increased T-cell activation,
making the carriers more prone to develop other infec-
tious diseases.7
ATL is generally classified into four types, namely
acute, chronic, lymphoma and smoldering based on the
presence or absence of lymphocytosis and hypercalce-
mia, the percentage of atypical lymphocytes, levels of
lactate dehydrogenase and sites of involvement. They
differ in their presentation, progression and response to
treatment.8 Bittencourt et al.9 proposed the inclusion in
this classification of another clinical type, the primary
cutaneous tumoral (PCT) which is generally included
among the smoldering ATL.10,11 The PCT differs from
the smoldering type in the morphology of the skin
lesions and prognosis.
The criteria for the diagnosis of ATL are (1) positive
HTLV-1 serology; (2) cytologic or histopathological
findings of leukemia or T-cell lymphoma CD4þ/
CD25þ; (3) presence of atypical T lymphocytes in
blood smears and (4) demonstration of monoclonal
HTLV-1 proviral integration whenever possible.12 For
some authors, the confirmation of HTLV-1 monoclo-
nal viral integration is not always necessary for diagno-
sis in clinically and morphologically typical cases.13
In Jamaica, Trinidad and Tobago and Martinique,
endemic areas for HTLV-1, ATL has been frequently
identified among T-cell non-Hodgkin lymphomas
(NHL) at times representing 50% or more of these
malignancies.14,15 In two Brazilian states, a high fre-
quency of ATL among leukemias/lymphomas T was
observed.16,17 Considering these data, we decided to
identify, through publications between 1982 and
December 2015, the number of ATL cases diagnosed
and published in South and Central America, the
Caribbean and in other Brazilian states, to verify if
this disease was getting recognition in other Latin-
American countries. We also intended to verify the
characteristics of the ATL cases in these countries.
Methods
Search strategy
Boolean methods were applied to research information
in the databanks Medline, SciELO, Lilacs, Medcarib,
CUMED and Coleciona SUS through searching
International Journal of STD & AIDS 28(3)
Pubmed, Bireme and SciELO for the terms ‘case’ or
‘cases’ combined with ‘adult T-cell leukemia lymph-
oma’ or ‘adult T-cell lymphoma leukemia’ and the
name of each South- and Central American and
Caribbean country, according to the United Nations
Statistics Division.18 In the searches carried out in the
Scielo and Bireme, the country names were not used,
because they are Latin American platforms.
To evaluate the prevalence of HTLV-1 in these
countries, a second search was carried out with the fol-
lowing Boolean expressions: ‘screening’, ‘blood donors’
or ‘pregnancy’ combined with ‘prevalence’ or ‘epidemi-
ology’ and ‘HTLV’ or ‘lymphotropic virus’.
The searches were limited to articles published in
English, Spanish, Portuguese or French from 1982 to
December 2015. Citations from identified articles were
also scrutinized to get references of interest.
Inclusion and exclusion criteria
We carefully checked the publications including the
same authors in order to avoid case repetition. Case
reports, series of cases, clinical trials or research includ-
ing case reports were included. We only considered
cases with enough data for analysis and diagnosed in
these countries even when foreign specialists had colla-
borated. Cases without confirmation of serology were
also included. All cases without serology or with nega-
tive HTLV-1 serology without confirmation of infec-
tion by molecular biology have been excluded.
Data extraction
Two independent reviewers extracted the following
data: number of cases, period of diagnosis, gender,
age or average age, age range, country and city where
the diagnosis was performed, clinical type of ATL and
HTLV-1-associated diseases. Only the ATL clinical
types referred to by the authors were included, even if
the clinical data were apparently enough for clinical
classification. In the prevalence evaluation, studies per-
formed in the general population and pregnant women
were preferentially included. In the absence of these
studies, we have included data obtained from blood
donors. In order to estimate the number of HTLV-1-
infected people in the different countries, we used data
obtained in Gessain and Cassar.2 From these data, we
estimate the number of cases of ATL in each country
considering a lifetime risk of 2.5%.19
Results
For the purpose of evaluation of HTLV-1 infection
prevalence 624 papers from databases were found, of
which 574 were discarded. From the selected 50 articles,
Oliveira et al. 219

Table 1. Prevalence of HTLV-1 infection in South- and Central American and Caribbean countries, number of papers and ATL cases
published and estimates of number of HTLV-1 carriers and ATL cases.

No. published Estimates of

HTLV-1 infection papers no. of HTLV-1 Estimates of no.
Countries frequency (%) Studied groups (No. ATL cases) carriers2 of ATL cases

Brazil4,20 0.08–1.35 Blood donors 34 (286) 300,000–800,000 7500–20,000

1.8 Population study
Martinique2 2 Pregnant women 8 (183) 3000–6000 75–150
Jamaica2 6.1 Health persons 7 (173) 100,000–140,000 2500–3500
Peru2 1.3–3.8 Pregnant women 5 (118) 150,000–450,000 3750–11,250
Columbia (Tumaco)2 2.8–5.3 Population study 9 (45) 1000–1500 25–37
Chile2 0.7–1.9 Blood donors 9 (42) 90,000–250,000 2250–6250
Barbados21 4 Health persons 1 (23)
F. Guyana22 4.4 Pregnant women 2 (19) 2000–5000 50–125
Trinidad and Tobago15 6 Health persons 4 (17) 9000–18,000 225–450
Argentina23 0.03–0.16 Blood donors 4 (15)
Dominica24 2.6 Blood donors 2 (6)
Cuba25 0.037 Different risk groups 2 (5)
Panama2 0.2–2 Population study 2 (4) 3500–25,000 87–625
Venezuela2 0.2 Blood donors 1 (4) 14,000–70,000 350–1750
Guadelupe21 0.33 Blood donors 0 3000–6000 75–150
Haiti2 3.8–4.3 Pregnant women 0 150,000–350,000 3750–8750
Guyana26 1.3 Blood donors 0 2000–5000 50–125
Suriname27 1.2 Blood donors 0 3000–7000 75–175
ATL: adult-cell leukemia/lymphoma.

only 11 were finally included.2,4,15,20–27 The paper by
Gessain and Cassar2 was repeatedly used because it
includes many references on the epidemiology of
HTLV-1 infection in Latin America and thus allowed
a decrease in the number of references (Table 1).
When searching publications with ATL cases, 360
were identified in databases, 282 were discarded
because of irrelevant content or duplicated data. To
the remaining 78 articles, we added 12 obtained in
ATL references in books and papers. Finally, 90 art-
icles were chosen including 940 ATL reported cases; 24
papers were found in the Caribbean,15,24,25,28–48 two in
from 1.8 to 95 years, and the mean age was 49.5, but at
least 18 occurred in children and adoles-
cents.9,35,37,39,41,42,59,60,69,78,101 The male/female ratio
was 394/396. In relation to the clinical forms of ATL,
307 were acute, 160 lymphoma, 116 chronic, 46 smolder-
ing and six PCT. Two of the articles did not present infor-
mation on the gender of the patients, and 26 did not
mention the ATL clinical form. There was an association
with HAM/TSP in 26 cases, with IDH in five and with
HAU in one. Search for proviral integration has been
performed in 22 publications.9,16,31,32,35,51,53,60,62,67–69,
73–75,77–80,91,103,106

Central America (Table 2)49,50 and 64 in South America

(Table 3).9,16,51–112 In order of frequency, by country,
286 cases have been reported in Brazil, 183 in
Martinique, 173 in Jamaica, 118 in Peru, 42 in Chile,
45 in Colombia, 23 in Barbados, 19 in French Guiana,
17 in Trinidad and Tobago, 15 in Argentina, six in
Dominica, five in Cuba, four in Panama and four in
Venezuela. In Peru, 31 ATL cases were reported
throughout nine years, but only 18 had serology for
HTLV-1. This study was not included in Table 2
because it was not possible to obtain the data of the
seropositive cases.113 With few exceptions, the number
of reported cases was very small in relation to the pre-
sumed number of ATL cases. The patients’ age ranged
Comments
The first cases of NHL with HTLV-1 positive serology
were reported in Martinique, Jamaica and Trinidad and
Tobago after 1984, most of them with foreign research-
ers’ cooperation, especially from USA and
France.28,36,43,97 Blattner et al.114 observed that from
16 consecutive patients presenting with NHL in
Jamaica, 69% had HTLV antibodies. Subsequently,
many other ATL case reports were published in this
country. According to the cases found in the literature,
183 have been described in Martinique and 173 in
Jamaica. However, in 2007, Wang et al.14 refer to 195
220 International Journal of STD & AIDS 28(3)

Table 2. Data of adult T-cell leukemia/lymphoma cases referred in countries of Caribbean and Central America, in order of fre-
quency by country.
Age or Age
Country City Authors Period No. M/F mean age variation Ac Chr Lym Sm Ass
28
Martinique Fort de France Gessain et al. 1981–1983 8 4/4 59.4 46–81 ... ... ... ... ...
Martinique Fort de France Gessain et al.,29 1983–2013 175 88/87 56 16–95 110 51 14 – –
Panelatti et al.,30
Agapé et al.,31,a
Besson et al.,32,a
Merle et al.33 and
Plumelle et al.34,35,a
Jamaica Kingston Gibbs et al.36 1982–1985 24 ... ... ... ... ... ... ... –
Jamaica Kingston Wilks et al.37 ... 2 1/1 20 16–24 ... ... ... ... –
Jamaica Kingston Williams et al.38 – 1 1/0 42 – ... ... ... ... –
Jamaica Kingston Mann et al.,15 1985–1995 126 65/61 43 17–85 59 26 34 7 3 HAM
Hanchard39 and 1 IDH
Giusti et al.40
Jamaica Kingston Berkowitz et al.41,b 1999–2009 20 9/11 45 14–79 4 3 4 9 –
Barbados Bridgetown Deardren et al.42 1988–1993 23 9/14 38 14–84 12 – 10 1 2 HAM
Trinidad Port of Spain Bartholomew et al.43,a 1982–1984 12 8/4 49 22–84 ... ... ... ... –
and Tobago
Trinidad St. Augustine Daisley and Charles44 1991 1 1/0 42 – ... ... ... ... –
and Tobago
Trinidad St. Augustine Daisley and Charles45 – 3 2/1 30.6 19–38 ... ... ... ... –
and Tobago
Trinidad St. Augustine Charles et al.46 – 1 1/0 45 – ... ... ... ... –
and Tobago
Dominica Roseau Adedayo et al.47 and 1991–2001 6 3/3 46 ... 6 – – – –
Adedayo and Shehu24,c
Cuba Havana Perurena et al.48 1990 1 0/1 38 – 1d – – – –
25
Cuba Havana Diaz Torres et al. 1996–2007 4 4/0 51.7 32–60 4 – – – –
Panama Ciudad de Levine et al.49,e 1984–1986 3 2/1 63.3 61–67 ... ... ... ... –
Panama
Panama Colon León et al.50 – 1 1/0 73 – 1 – – – –

No.: number of ATL reported cases; M/F: male/female; Ac: acute; Chr: chronic; Lym: lymphoma; Sm: smoldering; Ass: associations with other HTLV-1-
related diseases; HAM: HTLV-1-associated myelopathy; IDH: infective dermatitis associated with HTLV-1.
a
With confirmed mono or oligoclonal proviral integration, at least in some cases.
b
From a total of 34 ATL patients.
c
Besides the six ATL cases, 44% of the NHL were HTLV-1 positive.
d
Referred in reference 25.
e
Among 88 cases of lymphoproliferative diseases.

ATL cases identified from the nationwide lymphoma
registry of the University of the West Indies Jamaica,
which corresponded to 50% of the NHL registered. In
Martinique, ATL corresponds to 61% of the NHL
cases.32
In Trinidad and Tobago, few cases have been pub-
lished compared to the high prevalence of HTLV-1
infection. In this country, 79% of the T-cell lymphomas
are HTLV-1 seropositive.15 It was shown that patients
with T-cell NHL in Trinidad are far more frequently
HTLV-1 seropositive than in Jamaica.115 Few publica-
tions about ATL have been found in Barbados,
Dominica and Cuba,24,25,42,47,48 the first two also
highly endemic countries. Nevertheless, there is a
great difference in HTLV-1 seroprevalence in Cuba
cities. In Matanzas, 6.1% of lymphoproliferative dis-
eases were associated with HTLV-1 while in Havana
only 2% were.25 From the other Caribbean countries,
only in Haiti and Guadeloupe, we found HTLV-1
prevalence studies, with rates of 3.8%–4.3% in the
former and 0.33% in the latter but no ATL case
reports.2,26 A lymphoma prevalence evaluation in
Guadeloupe did not mention HTLV-1 infection.116
In South America, Brazil, Peru, Chile, Colombia
and French Guyana are the countries where HTLV-1
is most prevalent. In Brazil, infection rate varies con-
siderably across states. The highest prevalence is
observed in Bahia, Maranhão and Pará;4 however,
the majority of publications are from Rio de Janeiro,
Bahia and São Paulo. The first cases, in Brazil, were
Oliveira et al. 221

Table 3. Data of adult T-cell leukemia/lymphoma cases referred in countries of South America.
Age or
mean Age
Country City Authors Period No. M/F age variations Ac Chr Lym Sm PCT Ass

Brazil Rio de Janeiro Pombo de ... 48 23/25 40.2 1.8–65 ... ... ... ... – –
Oliveira et al.16,a,b;51,a,b
Brazil Campinas Lorand-Metze and – 1 1/0 52 – 1 – – – – –
Pombo de Oliveira52,c
Brazil Recife Pombo de 1994–1998 23 – – – ... ... ... ... ... –
Brazil São Paulo Oliveira et al.53,b,d 29 – – – ... ... ... ... ... –
Brazil Rio de Janeiro 70 – – – ... ... ... ... ... –
Brazil Belo Horizonte Gonçalves et al.54 – 1 0/1 27 – ... ... ... ... ... HAM,
HAU
Brazil Belo Horizonte Gonçalves et al.55 – 1 0/1 28 – – – – 1 – IDH
Brazil Recife Loureiro et al.56 – 1 1/0 46 – – 1 – – – –
Brazil São Paulo Jhayya et al.57 – 1 0/1 32 – ... ... ... ... ... –
Brazil Rio de Janeiro Milito et al.58,c 1989–1997 10 5/5 38.5 23–59 6 1 3 – – –
Brazil Rio de Janeiro do Valle et al.59 – 1 1/0 15 – 1 – – – – –
Brazil Rio de Janeiro Pombo de – 1 1/0 7 – ... ... ... ... ... –
Oliveira et al.60,b,e
Brazil São Paulo Albuquerque et al.61 – 1 0/1 30 – – – 1 – – –
Brazil São Paulo Sakamoto et al.62,b – 1 1/0 32 – – 1 – – – –
Brazil Salvador Bittencourt et al.,63,d 1991–2006 70 36/34 48.6 9–84 19 10 17 19 5 10 HAM,
Freitas et al.,64,d 1 IDH
Barbosa et al.,65,f
Bittencourt et al.9,b;66,d;67,b,d;68b,d
and Farre et al.69,b,d
Brazil Uberaba Olivo et al.70 ... 2 1/1 36.5 35–38 1 – 1 – – 1 IDH
Brazil Belo Horizonte Gonçalves et al.71 – 1 1/0 21 – ... ... ... ... ... HAM
Brazil São Paulo Gualco et al.72,g 1997–2007 4 1/3 34 29–37 ... ... ... ... ... –
Brazil Salvador Bittencourt et al.,73,b;74,b 1991–2008 10 5/5 54.1 35–86 3 3 1 3 – 1 HAM
Santos et al.75,b and
Oliveira et al.76,d
Brazil Rio de Janeiro Lyra-da-Silva et al.77,b – 1 0/1 38 – – – – – 1 –
Brazil São Paulo Lage et al.78,b – 1 0/1 17 – 1 – – – – –
Brazil Salvador Oliveira et al.79,b – 1 0/1 19 – 1 – – – – IDH
Brazil Salvador Bittencourt et al.80,b – 1 0/1 48 – – 1 – – – HAM
Brazil Belém Brito Junior et al.81 – 1 0/1 53 – ... ... ... ... ... –
Brazil São Paulo Chang et al.82 1989–2006 5 4/1 57 45–76 ... ... ... ... ... ...
Peru Bellavista Rengifo-Pinedo et al.83 – 1 1/0 54 – ... ... ... ... ... –
Peru Lima Gárate et al.84 1997–2004 21 7/14 58.5 33–86 ... ... ... ... ... –
Peru Lima Beltran et al.85,86 1987–2008 95 49/46 61 23–92 40 14 41 – – –
Peru Ica Remón-Torres and – 1 1/0 51 – ... ... ... ... ... –
Remón-Torres87,c
Chile Santiago Cabrera et al.88–90,91,b and 1989–1998 26 13/13 50 24–78 12 4 6 4 – 7 HAM
Cartier et al.92,d
Chile Santiago Cabrera et al.93,h – 1 1/0 25 – ... ... ... ... ... –
Chile Santiago Cabrera et al.94,i 1999–2001 11 4/7 54 36–62 ... ... ... ... ... –
Chile Santiago Cabrera et al.95 2004–2006 1 1/0 45 – ... ... ... ... ... –
Chile Santiago Benedetto et al.96,j – 3 2/1 74.6 68–78 ... ... ... ... ... –
Columbia Cali Duque et al.97 1981–1982 4 2/2 34.5 21–50 ... ... ... ... ... –
Columbia Cali and Ramirez et al.98 – 2 1/1 41 37–45 ... ... ... ... ... –
Barbados
Columbia Cali Blank et al.99–101 1985–1995 24 12/12 39 17–69 6 – 18 – – –
Columbia Cali Carrascal et al.102 1997–1998 5 1/4 43.6 29–61 ... ... ... ... ... –
(continued)
222 International Journal of STD & AIDS 28(3)

Table 3. Continued.
Age or
mean Age
Country City Authors Period No. M/F age variations Ac Chr Lym Sm PCT Ass

Columbia Cali Salcedo-Cifuentes et al.103,b 1998–2003 7 2/5 48.2 29–61 ... ... ... ... ... –
Columbia Orito/Cali Medina et al.104 – 2 2/0 64.5 58–71 1 – 1 – – –
Columbia Medellı́n Arango and Echeverri105 – 1 0/1 53 – ... ... ... ... ... –
F. Guyana Cayenne Gerard et al.106,b 1990–1993 18 6/12 41 21–71 8 – 8 2 – –
F. Guyana Cayenne Del Giudice et al.107,k 1 1/0 28 – 1 – – – – –
Argentina Buenos Aires Gioseffi et al.108,c 2/1993–10/1994 5 4/1 48.2 38–59 5 – – – – –
Argentina La Plata Prates et al.109 1994 2 0/2 61 59–63 1 – 1 – – –
Argentina Jujuy Marin et al.110 1980–1992 5 1/4 52 24–70 ... ... ... ... ... –
Argentina San Juan Arias et al.111 1999–2001 3 3/0 41.3 38–46 ... ... ... ... ... –
Venezuela Caracas Ball de Picón et al.112 1998–2003 4 2/2 52 50–54 3 1 – – – –

M/F: male/female; Ac: acute; Chr: chronic; Lym: lymphoma; Sm: smoldering; PCT: primary cutaneous tumoral; Ass: associations with other HTLV-1-
related diseases; HAM: HTLV-1-associated myelopathy; HAU: HTLV-1-associated uveitis; IDH: infective dermatitis associated with HTLV-1.
a
Does not include the cases with negative serology and/or PCR.
b
With confirmed mono or oligoclonal proviral integration, at least in some cases.
c
Cases without serologic confirmation.
d
Cases from Bahia included in reference 9.
e
Other cases included previously.53
f
Included in reference 9, except one case with HIV infection.
g
Four ATL cases observed among 11 breast T-cell lymphomas.
h
Primary intestinal presentation.
i
Among 23 cases of T-cell leukemias, but HTLV-1 serology was only performed in indicated cases.
j
Among 25 cases of T-cell lymphomas.
k
The other three cases are included in reference 106.

diagnosed in Rio de Janeiro by Pombo de Oliveira
et al.,51 and four more papers were subsequently pub-
lished in this state up till 2002.16,53,58–60 Thereafter, only
one case was referred.77 Nevertheless, Pombo de
Oliveira et al.16 identified 32.4% of ATL cases among
mature T-cell leukemias/lymphomas in this state. In
Bahia, Brazil, among cases of primary cutaneous T-
cell lymphoma, 26.4% correspond to primary and
66.7% to secondary ATL.17 In a retrospective study
in Botucatu, São Paulo, in a center of histopathological
diagnosis, 4 ATL cases among 11 breast T-cell lymph-
omas were shown, indicating a high frequency of
ATL.72 Besides, in the same center, in 2010, two cases
of ATL (2.1%) were found among 93 T-cell lymphomas
diagnosed in children and adolescents between 1999
and 2009.117 This finding is important because as
ATL occurs generally in adulthood; the pediatricians
need to be aware of this disease in cases of mature T-
cell leukemia/lymphomas in this age group. Pombo de
Oliveira et al.53 published 195 cases of ATL bringing
together patients of different groups in Brazil, Rio de
Janeiro, Bahia, Pernambuco, São Paulo and a smaller
number of cases in other states. In this study, the ana-
lysis of cases was taken by birthplace, and there were
patients from various other states, mainly from Minas
Gerais, Paraı́ba, Ceará and Pará. However, only one
ATL case report was found in Pará81 and no published
case in Maranhão, highly endemic HTLV-1 Brazilian
states.4
In Lima, Peru, from 300 new cases of NHL detected
each year at the National Institute of Cancer at least
10% are associated with HTLV-1.118 In a review of
primary skin lymphomas, in 2008, 13 cases of ATL
were observed among 55 T/NK primary skin lymph-
omas (23.6%) and 78% of the secondary cutaneous
lymphomas corresponded to systemic ATL.84 In 2011,
in order to evaluate prognostic factors, another study
was published which included 95 ATL cases.86
In Chile, up till 2003, seven articles were pub-
lished.88–94 In one of them, ATL was shown as the
most frequent disease (48%) among 23 T-cell mature
leukemias/lymphomas. In this study, serology for
HTLV-1 was only performed in indicated cases.94 In
2012, the same group studying consecutive cases of
NHL found among 20 mature T-cell neoplasms only
one ATL case (5%).95 In this evaluation, there was
no information about the performance of HTLV-1 ser-
ology in all T-cell lymphomas. After that, three ATL
cases have been observed in Chile, in a retrospective
study.96
In Colombia, the majority of cases were from the
Southwest region diagnosed at the University
Hospital of Valle in Cali. In 1994, it was admitted
that, even in Cali, patients with ATL were not being
Oliveira et al.
diagnosed due to lack of serology test for HTLV-1 and
due to no recognition of this condition.102
In French Guiana, few cases have been described up
until 1997,106,107 in spite of the fact that the HTLV-1
seroprevalence is 4.4% among pregnant women, being
more prevalent among ethnic groups of African
origin.22
In Argentina, Jujuy, Marin et al.,110 found 22.7% of
ATL among 22 cases of T/NK-cell lymphomas. In
Argentina, the overall prevalence of HTLV-1 infection
among blood donors is 0.9% but Jujuy province, in
Northwest Argentina, has the highest rate of infection
(3.5%).110
From Central America, we found ATL reports only
in Panama49,50 where the frequency of infection varies
from 0.2% to 2%.2 There, among 88 lymphoprolifera-
tive diseases, 3.4% of ATL cases were identified.49 In
two studies about NHL in Guatemala and
Mexico,119,120 no reference was made to HTLV-1 ser-
ology or to ATL. No HTLV-1 record about the preva-
lence of HTLV-1 infection has been found in
Guatemala2 and in Mexico, one evaluation among
potentially high-risk populations have not found cases
of this infection.121 In Uruguay, Honduras, Costa Rica
and Nicaragua, countries with <0.7% of HTLV-1
infection rates, no case reports were found.2
The estimated lifetime risk of developing ATL in
HTLV-1 carriers was 2.5% in Japan, 3%–5% in
males and 1%–2% in females.19 Another estimate
showed a slight increase in these percentages, 6%–
7% for men and 2%–3% for women.122 We preferred
to employ the value of 2.5% to obtain the presumed
number of ATL cases in each country. In Table 1, we
see that with few exceptions the number of reported
cases was very small in relation to the presumed num-
bers of ATL cases. Besides, in some endemic places
with many referred cases in the past, only rare cases
have been published recently. We should ask if the
cases are really being diagnosed and not published
or if they are not being identified or if there was a
decrease in ATL occurrence. It is possible that ATL is
underestimated due to confusion with other NHL
such as mycosis fungoides, Sezary syndrome or
other types of T-cell NHL. It is well known that
there are marked similarities between the clinical and
histopathological features of ATL and other types of
cutaneous T-cell lymphomas9,62,123; thus it is necessary
to perform serology for HTLV-1 in order to obtain a
differential diagnosis. Decrease in ATL occurrence is
not probable because vertical transmission, mainly
through breastfeeding, is the transmission route in
ATL patients and, at least, in Brazil, and probably
in the majority of the studied countries, there is no
health policy to control this way of HTLV-1
transmission.124
223
In South and Central America and the Caribbean,
the major problem for performing serology for HTLV-
1 is the cost and the lack of resources for researchers.
Serologic inquiries and active search for detecting ATL
cases are more feasible with the cooperation of foreign
research centers. On the other hand, confirmatory tests
are performed in few labs due to high cost. The search
for monoclonal or oligoclonal proviral integration of
the HTLV-1 is only possible in rare laboratories.
Nevertheless, it is important to consider that in most
cases HTLV-1 proviral integration analysis is not essen-
tial for the diagnosis of ATL.13 As scientific evidence, it
is more important in patients with atypical features,
such as very long evolution or very early appearance.9
On the other hand, we know that in endemic areas only
rare cases of T-cell lymphomas other than ATL have
been observed developing in HTLV-1 carriers.12
In spite of having various endemic countries in
South America, in a recent publication on peripheral
T-cell lymphomas including cases in South America,
Europe, USA and Middle East, serology for HTLV-1
was not performed, and there was no reference to
ATL.125 On the other hand, in another project on
NHL including 22 cases of T-cell lymphomas from
Argentina, 18 from Brazil, 22 from Chile, 25 from
Guatemala and 31 from Peru, the authors found only
one case of ATL in Chile (4.5%) and nine in Peru
(29%). In this project, HTLV-1 serology was per-
formed only in indicated cases.126 In an International
Peripheral T-Cell NHL Study, including the United
States and European countries not endemic for
HTLV-1 and Asia, serology for HTLV-1 was added
to the cases evaluated. As expected, they diagnosed
ATL in 25% of cases in Asia, 2% in the USA and
1% in Europe.127
We know that the ideal way to have trustable epi-
demiological data would be through official health sys-
tem’s registries, as many of diagnosed cases are not
published, especially in countries with low investments
on research. The biggest issue is that in most of the
countries there is no such registry available, with a
few exceptions such as in Martinique and
Jamaica,35,39 so the best possible way to infer ATL
burden was through reported cases. We made an
effort towards finding the great majority of published
ATL cases, but we are aware that some cases published
in nonindexed journals may not be found. Besides,
some patients after the initial diagnosis of ATL in
their own country may have traveled abroad in order
to receive a better treatment, and it is difficult to appre-
ciate the number of such cases. We were very careful to
avoid duplicated cases.
The median age of ATL patients is lower than that
referred in Japan,8 and at least 18 cases corresponded
to children or adolescents indicating that ATL can
224
present at an earlier age in South and Central America
and the Caribbean. These age differences probably may
be due to genetic or environment factors; 14 from the
22 ATL cases associated with HAM/TSP were
observed in Brazil54 but, in Chile, this association hap-
pened in 27% of the ATL cases.93 According to
Cabrera et al.,93 the reason for this association is not
known but may be due to genetic and/or environment
factors or the result of a careful examination of their
patients. This is an exceptional association in other
countries.128 The association with IDH is rare, and
except for one all cases were diagnosed in
Brazil.39,55,69,70,79
The clinical classification of ATL was not reported
in some papers, in spite of the fact that it is of prime
importance in order to determine the prognosis and the
adequate therapeutic approach.12 Acute ATL was
much more frequent than other types, possibly because
it is generally easier to diagnose due to marked lympho-
cytosis, hypercalcemia and presence of many ‘flower’
cells in peripheral blood.8,12 The reduced number of
the PCT form is because it is usually included in smol-
dering ATL.10
According to our findings, we would like to empha-
size that in most Brazilian states and in some other
Latin American countries, ATL is probably not being
recognized and should be strongly considered in the
differential diagnosis of T-cell leukemias/lymphomas
due to the expected higher prevalence of ATL. It is
mandatory in endemic areas to search for HTLV-1
infection in all cases diagnosed as mature T-cell leuke-
mia/lymphomas and not only in indicated cases. A
huge effort should be made to have a better surveillance
system for ATL diagnosis in most of the South- and
Central American and Caribbean countries, and this
attitude should be embraced by public organs to sup-
port health professionals in this important task.
Acknowledgment
We would like to acknowledge Dr Yves Plumelle for the
information from his published papers.
Declaration of conflicting interests
The authors declared no potential conflicts of interest with
respect to the research, authorship, and/or publication of this
article.
Funding
The authors received no financial support for the research,
authorship, and/or publication of this article.
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