DERMATOLOGY PRACTICAL & CONCEPTUAL
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Observation  |  Dermatol Pract Concept 2012;2(2):3 9

Background: Adult T-cell leukemia/lymphoma (ATLL) is a distinctive peripheral T- lymphocytic ma-
lignancy associated with human T-cell lymphotropic virus type 1 (HTLV-1). It may closely resemble 
other skin lymphomas, particularly mycosis fungoides (MF).
Case report: A 38-year-old woman presented some ellipsoid scaling patches lasting 18 months and 
developed a large tumoral lesion in the abdomen, which were previously diagnosed as MF. Although 
histopathologic and immunohistochemistry findings were in consonance with this diagnosis, the fast 
progression of the disease raised the suspicion that it could represent another type of T-cell lym-
phoma. The work-up revealed a positive anti-HTLV-1 serology and molecular studies confirmed the 
monoclonal integration of HTLV-1 provirus into neoplastic cells of the skin, but not into circulating 
lymphocytes. Extensive investigations were unable to demonstrate any systemic involvement. The 
final diagnosis was of primary cutaneous type of ATLL. The patient was submitted to a chemotherapy 
regimen with cyclophosphamide, doxorubicin, vincristine and prednisone, later to conjugated dexa-
methasone and surgical cytoreduction and then to a second line treatment with gemcitabine, resulting 
in partial response. A bone marrow heterologous transplantation was performed, but failed to achieve 
a sustained remission.
Discussion: ATLL is a rare lymphoid malignancy in non-endemic HTLV-1 areas, the diagnosis of 
which could be missed if not highly suspected. In addition to the four subtypes of Shimoyama clas-
sification (acute, lymphomatous, chronic and smoldering), a fifth one denominated primary cutaneous 
and characterized by presence of lesions only in the skin had been proposed and is herein exemplified.

ABSTRACT

Adult T-cell leukemia/lymphoma: 
a case report of primary cutaneous tumoral type

Julia Ocampo Lyra-da-Silva, M.D.1, Yung Bruno de Mello Gonzaga, M.D.2, Otávio de Melo 
Espíndola, M.D.3, Maria José de Andrada-Serpa, M.D.3, Cassio Dib, M.D.3, Thiago Jeunon, M.D.1,4

1 Department of Dermatology, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil
2 Department of Hematology, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil
3 Laboratório de Pesquisa em Patogenia Viral do Instituto de Pesquisa Clínica Evandro Chagas, Fundação Oswaldo Cruz, Rio de Janeiro, Brazil
4 Department of Anatomical Pathology, Hospital Federal de Bonsucesso, Rio de Janeiro, Brazil

Key words: T-cell leukemia/lymphoma, ATLL, lymphoma

Citation: Lyra-da-Silva JO, Gonzaga YBM, Espíndola OM, Andrada-Serpa MJ, Dib, Cassio, Jeunon T. Adult T-cell leukemia/lymphoma: a 
case report of primary cutaneous tumoral type. Dermatol Pract Conc. 2012;2(2):3. http://dx.doi.org/10.5826/dpc.0202a03.

Received: November 21, 2011; Accepted: February 25, 2012; Published: April 30, 2012

Copyright: ©2012 Lyra-da-Silva et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are 
credited.

Funding sources: None.

Conflict of interest: None.

Corresponding author: Thiago Jeunon, M.D., Rua General Roca 778/1005 Saens Peña, Rio de Janeiro, Brasil, CEP 20521-070. Tel. +55 21 
97377993; Fax. 22340722. E-mail: thiago.jeunon@gmail.com.

http://www.google.com/search?hl=pt-br&biw=1280&bih=673&&sa=X&ei=AgljTaGNHoG0lQee69j7Cw&ved=0CCkQBSgA&q=cyclophosfamide&spell=1
mailto:thiago.jeunon@gmail.com


10 Observation  |  Dermatol Pract Concept 2012;2(2):3

Introduction

Lymphomas may involve the skin primarily, when there is no 

extracutaneous disease by the time of the diagnosis, or sec-

ondarily, as an infiltration of a lymphoma from another site, 

most often lymph nodes [1,2]. Mycosis fungoides (MF) is the 

most common primary cutaneous lymphoma, accounting for 

almost 50% of cases of lymphoma restricted to the skin. It is 

characterized by an indolent course, evolving from patches 

to plaques and rarely eventuating in tumors over the course 

of years or even decades [3,4].

Adult T-cell leukemia/lymphoma (ATLL) is a lymphoid 

malignancy etiologically related to human T-cell lympho-

tropic virus type 1 (HTLV-1) infection. It is frequently a 

multi- systemic disease and has been classically classified 

by Shimoyama et al. into four subtypes, namely acute, lym-

phomatous, chronic and smoldering [5]. Later, the concept 

of primary cutaneous ATLL has been set forth, with further 

subdivision into primary cutaneous erythematopapular (also 

called primary cutaneous smoldering) and primary cutane-

ous tumoral (PCT) [6,7,8].

Although not included in the 2005 WHO-EORTC and 

2008 WHO classifications, primary cutaneous forms of 

ATLL seem to have clinical, virological and prognostic par-

ticularities and deserve attention of the medical community. 

Table 1 summarizes the features of clinical forms of ATLL.

Case report

In October 2009, a 38-year-old woman from Macapá/AP 

was referred to our hospital in Rio de Janeiro/RJ with the 

diagnosis of MF. For about eight months, she had noted 

some asymptomatic round and ovoid reddish brown scaling 

patches on the abdomen and axilla and a large dome-shaped 

tumoral lesion on right flank, measuring approximately 15 

TABLE 1. Clinical forms of ATLL

 Cutaneous

Acute lymphoma chronic smoldering
Erythemato-

papular
Tumoral

Prevalence 60% 20% 15% 5% unknown unknown

MST* Months 
to a year

Months to 
a year

years >5 years 60 months 19 
months

LDH** elevated elevated > 2x the 
normal 

upper limit

>1,5 x the 
normal upper 

limit

<1,5x the up-
per limit

<1,5x 
the upper 

limit

Hypercalcemia + + or- - - - -

PB + <1% >5% >5% or 
<5% with a 

histologically-
proven skin

and/or pulmo-
nary lesions 
should be 
present

<5% <5%

Lymphocytosis + - + - - -

BM**** 35% of 
cases

- - -

Lymphadenopathy + + + - - -

Skin lesions +/- +/- +/- +/- + +

*Median survival time **Lactate dehydrogenase ***Peripheral blood circulating lymphocytes with highly abnormal convo-
luted nuclei ****Bone marrow involvement



Observation  |  Dermatol Pract Concept 2012;2(2):3 11

cm at greatest diameter (Figures 1 and 2). It should be high-

lighted that the woman had three blood transfusions eight 

years prior as consequence of a polytrauma.

The patient brought a pathology report dated April 2009 

suggesting MF, but the original slides and paraffin blocks 

were not available. Therefore, we decided to collect new 

samples. Sections of tissue from a flat lesion showed a super-

ficial perivascular infiltration of small atypical cerebriform 

lymphocytes that tended to be arranged in band-like array 

in the dermis and that formed formidable collections in the 

epidermis (Figure 3). In the tumoral lesion, in addition to 

the epidermotropism, there was a sheet of medium and large 

sized cerebriform lymphocytes in the dermis, with many typi-

cal and atypical mitotic figures and destruction of adnexal 

structures (Figure 4).

Immunohistochemistry revealed positivity of neoplastic 

cells to vimentin, CD3, CD4, CD5, CD7 and negativity to 

CD20, CD8, CD30, ALK, S-100, Melan-A and AE1-AE3 

(Figure 5). Although these findings were in consonance with 

the diagnosis of MF, the unexpected clinical course raised the 

suspicion that we could be dealing with another type of T-cell 

lymphoma.

A work-up, including complete physical exam, blood 

count, complete biochemistry encompassing serum calcium 

and lactate dehydrogenase (LDH), chest X-ray, and thorax 

and abdominal computed tomography scans were unable to 

demonstrate any systemic involvement. No abnormal lym-

phocytes were detected on blood smears. Serological tests 

were negative for HIV and for hepatitis B and C viruses, but 

positive for HTLV-1. These findings strongly suggested the 

possibility of ATLL and motivated molecular studies using 

real-time quantitative polymerase chain reaction (qPCR) 

to determine the HTLV-1 proviral load in skin lesion and 

in peripheral blood (PB) [9]. Inverse-long PCR (IL-PCR) 

[10] was also done to demonstrate monoclonal integration 

of HTLV-1 proviral DNA into neoplastic cells in skin and 

blood samples. In addition, multiplex PCR for detection of 

monoclonal recombination in the gamma chain of T cell 

receptor (TCR) [11] was performed to confirm transforma-

tion of T-lymphocytes. The proviral load was of 20.65% in 

cells from the skin and less than one infected cell for 10,000 

leukocytes in PB. The monoclonal integration was present in 

the skin sample and absent in the blood sample (Figure 6).

The final diagnosis was of primary cutaneous type of 

ATLL. Initially, the patient was treated with cyclophospha-

mide, doxorubicin, vincristine and prednisone (CHOP) che-

motherapy regimen. At the end of the sixth cycle, there was 

a poor response, with relapses between each cycle. Thus, 

cytoreduction with dexamethasone and partial excision of 

the tumor followed by a second-line treatment with gem-

citabine was tried, but also failed to induce disease remis-

sion. Remarkably, in spite of the poor response to all thera-

peutic regimens, the patient did not experience fever, signs 

of infection, lymphadenopathy, visceromegaly or increase 

in serum calcium or LDH levels. Considering the unfavor-

able prognosis and the lack of response to previous thera-

pies, heterologous peripheral blood stem cell transplantation 

from an HLA compatible brother was successfully done on 

April 2011, after conditioning chemotherapy with reduced 

intensity using cyclophosphamide and fludarabine. After the 

transplant the patient was monitored for three months, but 

the lesions progressed and showed no response to therapy, 

even after three additional donor lymphocyte infusions. 

Thus, the patient will require another hospitalization for 

salvage chemotherapy (DHAP scheme) and to evaluate if 

another donor lymphocyte infusion or a bone marrow trans-

plantation should be performed, or if  we have arrived at the 

end of curative efforts.

Figure 1. Two reddish-brown, slightly scaling patches on the left 

flank. The scar in the lesion on the right indicates a biopsy site. 

[Copyright: ©2012 Lyra-da-Silva et al.]

Figure 2. A large dome-shaped tumoral lesion on right flank. The 

surface is convoluted and focally eroded. [Copyright: ©2012 Lyra-

da-Silva et al.]



12 Observation  |  Dermatol Pract Concept 2012;2(2):3

Discussion

ATLL is a rare T-lymphocytic malignancy, which occurs 

mainly in adults. It has a poor prognosis and is remarkably 

resistant to several therapies. ATLL is related to HTLV-1 

infection and the expression of provirus integrated into 

T-lymphocytes plays a major role in transformation of those 

cells. The mechanisms through which HTLV-1 infection 

induces the development of ATLL are complex and involve 

the interaction of viral protein Tax with cellular factors and 

activation of transcription pathways controlled by NF-kb, 

AP-1 and SRF for example. Tax protein also interferes with 

function of p53, p16 and MAD1, preventing infected T-cells 

to undergo cell cycle arrest by DNA damage checkpoints or 

induction of apoptosis, thus inducing genetic instability. The 

activity of cytotoxic T-cell lymphocytes is crucial for con-

Figure 3. Photomicrograph of a patch: there is a superficial perivascular infiltrate of small atypical cerebriform lymphocytes tending to a 

band-like array in the dermis and forming collections into the epidermis. There is no spongiosis. Hematoxylin & eosin (HE), (A) 20x, (B) 40x, 

(C) 100x, (D) 200x, (E) 400x, and (F) 400x. [Copyright: ©2012 Lyra-da-Silva et al.]

A B

C D

E F



Observation  |  Dermatol Pract Concept 2012;2(2):3 13

trolling viral replication and proliferation of infected cells 

in vivo. Therefore, inefficiency of the immune host control 

is an important step in the development of ATLL [12]. The 

inflammatory response elicited by host immune system is 

responsible for other manifestations of HTLV-1 infection, 

such as infective dermatitis, uveitis and tropical spastic 

paraparesis/HTLV-1 associated myelopathy. HTLV-1 infec-

tion is endemic in southwestern Japan, the Caribbean basin 

and parts of Central Africa and South America. In Brazil, 

the highest HTLV-1 seroprevalence is seen in Bahia and Rio 

de Janeiro states [1]. HTLV-1 may be transmitted vertically 

through placental circulation, during the delivery and breast-

feeding period, or horizontally by sexual intercourse, syringe 

sharing and contaminated blood derivatives. The cumula-

tive risk for development of ATLL among HTLV-1 carri-

ers in Japan is estimated to be around 6.6% for males and 

2.1% for females, indicating that most infected persons do 

not develop disease and the transformation of infected cells 

occurs after a period of latency of up to 60 years [13].

We could not determine exactly the route of HTLV-1 

transmission to our patient, since we were unable to test the 

mother. However, her brothers were seronegative. Since the 

patient received blood transfusions in 2003, we suspect that 

infection was horizontally transmitted. This relatively short 

latency is in consonance with the epidemiological data about 

Figure 4. Photomicrograph of a tumor: there is a sheet of medium 

and large irregular atypical convoluted lymphocytes in the dermis 

and tiny collections in the epidermis without any spongiosis. HE, 

(A) 20x, (B) 400x, and (C) 200x. [Copyright: ©2012 Lyra-da-Silva 

et al.]

A B

C

ATLL in Brazil, indicating a shorter latency and younger age 

of onset for ATLL (median 40 years old, ranging from 2 to 

94 years old) in contrast to the worldwide experience [14].

HTLV-1 serology is an excellent screening test for ATLL 

and must be part of the investigative work in any patient 

under initial evaluation for a T-cell lymphoma. Considering 

that infection by HTLV-1 is a prerequisite for development 

of ATLL, seronegativity excludes this disease [15]. However, 

it is conceivable that an asymptomatic carrier of HTLV-1 

could present a T-cell lymphoma of other types, particularly 

in endemic areas. This concern is reinforced by the fact that 

a minority of HTLV carriers develops ATLL during their 

lives and that ATLL may closely resemble others lympho-

mas and vice versa. In this context, we strongly recommend 

that, whenever it is possible, a definitive diagnosis of ATLL 

must be sustained by demonstration of monoclonal integra-

tion of HTLV-1 provirus into neoplastic cells by IL-PCR or 

Southern blot. Monoclonal integration of HTLV-1 is found 

in most of the cases of ATLL.

Specific cutaneous lesions occur in 43-72% of cases of 

ATLL [7] and might be observed in any subtype of the dis-

ease. The primary cutaneous ATLL is defined by the pres-

ence of skin lesions of ATLL in the absence of lymphadeno-

megaly, lymphocytosis, hypercalcemia or any involvement of 

internal organs. Further stratification into primary cutane-



14 Observation  |  Dermatol Pract Concept 2012;2(2):3

A B

C D

E F

G H



Observation  |  Dermatol Pract Concept 2012;2(2):3 15

ous erythematous-papular and primary cutaneous tumoral 

forms is supported by differences in median survival time (60 

versus 19 months) [7]. In 2009, Bittencourt et al found very 

similar results in Bahia [6].

In summary, ATLL is a T-cell lymphoma with variable 

clinical presentation, which frequently involves the skin. It 

may be misdiagnosed as other primary cutaneous T-cell lym-

phomas, especially in the absence of any systemic involve-

ment. In this context, it is crucial to be aware of the primary 

cutaneous forms of ATLL, which are still not contemplated 

in the 2008 WHO classification of lymphomas. Proper sero-

logical and molecular studies for HTLV-1 are essential to 

confirm or exclude this possibility. ATLL has a poor progno-

sis and a remarkable refractoriness for several chemothera-

pies and even bone marrow transplantation, requiring multi-

disciplinary attention for optimal management.

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Figure 5 (previous page). Immunohistochemistry. (A) CD3, (B) CD 

5, (C) CD7, (D) CD4, (E) CD8, (F) CD20, (G) CD30, and (H) ALK. 

[Copyright: ©2012 Lyra-da-Silva et al.]

Figure 6. Molecular diagnosis of ATLL. (A) Agarose gel eletrophore-

sis of amplicons from inverse long PCR (IL-PCR). The IL-PCR was 

performed in triplicates according to Etoh et al with DNA from: 1, 

peripheral blood leukocytes; 2, skin lesion. The arrow indicates a 

monoclonal band for the site of HTLV-1 integration into cellular 

DNA, which was present only in cells from the skin lesion. P, 500bp 

DNA ladder. (B) Multiplex PCR for detection of T-cell receptor 

(TCR) gamma chain gene rearrangements. The assay was performed 

as described by Fodinger et al with DNA extracted from: 1, periph-

eral blood leukocytes from the patient; 2, skin lesion; 3, leukocytes 

from a healthy donor, as a negative control; 4, HTLV-1-infected cell 

lineage MT2, as a positive control. Healthy individuals show a poly-

clonal pattern, which is seen as a smear. In line 2, the arrow indicates 

a band that represents a predominant clonal population of T-cells 

with a unique rearrangement of TCR-gamma chain, which suggests 

a malignant process of T- cells. Line 5, no template control and P, 

100bp DNA ladder. [Copyright: ©2012 Lyra-da-Silva et al.]

A B

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