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Specific cutaneous manifestations in adult T-cell

Cutaneous manifestations
Pezeshkpoor,
Report Yazdanpanah,in and
adult
Shirdel
T-cell leukemia/lymphoma

leukemia/lymphoma
Fakhralzaman Pezeshkpoor, MD, Mohammad Javad Yazdanpanah, MD, and Abbas Shirdel, MD

From the Departments of Dermatology and Abstract

Internal Medicine, Mashhad University of Background Adult T-cell leukemia/lymphoma (ATLL) is an aggressive malignancy which may
Medical Sciences, Mashhad, Iran occur in individuals infected with human T-cell lymphotropic virus type-I (HTLV-I). HTLV-I is
endemic in Khorasan, with a frequency of 2.3% in the general population. As specific cutaneous
Correspondence
Fakhrozaman Pezeshkpoor, MD
manifestations of lymphoma may occur in a significant number of patients, we studied these
Department of Dermatology manifestations in ATLL patients admitted to the Hematology and Dermatology Departments of
Ghaem Hospital Ghaem Hospital, Mashhad, Iran, during 1995–2004.
Mashhad University of Medical Sciences Methods In this descriptive study, demographic and clinical information was obtained from
Mashhad
23 patients suffering from ATLL with specific cutaneous lesions (atypical lymphocytes on
Iran
E-mail: fn-pezeshkpoor@mums.ac.ir
histopathology of cutaneous lesions), and was analyzed statistically.
Results Of the 23 patients, 11 were male and 12 were female. The mean age was
48.17 ± 14.1 years. The birth place in over 85% of cases was the north of Khorasan. The most
common type of specific skin lesion was a maculopapular eruption (11 cases; 47.8%); papular
lesions were seen in four cases (17.4%). Other lesions included plaques, ichthyosis-like lesions,
erythroderma, tumors, papules, and nodular lesions. In most patients (56.5%), the skin lesions
were generalized.
Conclusion The most common type of specific skin lesion in ATLL was maculopapular
eruption, especially with a generalized distribution. Other types of specific skin lesion,
in order of frequency, were papules, plaques, ichthyosis-like skin lesions, nodules, tumors,
and erythroderma.

admitted to the Hematology and Dermatology Departments of

Introduction
In the Middle East, a focus of human T-cell lymphotropic
virus type I (HTLV-I) has been found in Iranian Jews who
reside in Mashhad.1 Mashhad is the center of Khorasan
province. Khorasan is an endemic region of HTLV-I in Iran,
with 2.3% of the population infected with the virus.2
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive
lymphoma that occurs in 2–5% of infected persons after
several decades. Specific cutaneous manifestations (presence
of lymphomatous cells on histopathology of skin biopsy) can
be used to identify ATLL patients.3
We studied the cutaneous manifestations in ATLL patients
admitted to the Hematology and Dermatology Departments
of Ghaem Hospital, Mashhad, Iran, during 1995–2004.
Methods
In this descriptive study, information was obtained from the files of
patients with ATLL and specific cutaneous lesions (atypical
lymphocytes on histopathology of cutaneous lesions) who were
Ghaem Hospital, Mashhad, Iran, during 1995–2004. The
diagnosis of ATLL was based on HTLV-I contamination confirmed
by serology and polymerase chain reaction and histologic
confirmation of T-cell lymphoproliferative malignancy by skin
biopsy, immunohistochemistry, and flow cytometry.
The age, gender, city of birth, clinical features of the skin lesions,
and localization of the lesions were studied.
Results
In the 10-year period between 1995 and 2004, 23 cases of
ATLL with cutaneous lymphoma involvement were admitted
to the Hematology and Dermatology Departments of Ghaem
Hospital, Mashhad, Iran. Eleven (47.8%) were male and 12
(52.2%) were female. The mean age ± standard deviation was
48.17 ± 14.1 years (minimum, 17 years; maximum, 70 years).
Twenty patients (86.96%) were born in the north of Khorasan.
The most common form of cutaneous lesion was maculo-
papular eruption (11 cases; 47.8%); papular lesions were seen
in four cases (17.4%) and plaques (with or without papules) 359

© 2008 The International Society of Dermatology International Journal of Dermatology 2008, 47, 359– 362
360 Report Cutaneous manifestations in adult T-cell leukemia/lymphoma Pezeshkpoor, Yazdanpanah, and Shirdel

Table 1 Frequency of skin lesions in patients with adult T-cell

leukemia/lymphoma

Skin lesion Frequency %

Maculopapular 11 47.8
Papule 4 17.4
Plaque 2 8.7
Plaque and papule 1 4.3
Papule and nodule 1 4.3
Tumor 1 4.3
Erythroderma 1 4.3
Ichthyosis-like 2 8.7
Total 23 100

Table 2 Distribution of skin lesions in patients with adult T-cell

leukemia/lymphoma

Distribution % Frequency

Generalized 56.5 13
Trunk 8.7 2
Trunk and limbs 26.1 6
Lower leg 4.3 1
Head, neck, and limbs 4.3 1
Figure 2 Papules and nodules on the back
Total 100 23

Figure 1 Ulcerated tumor on the forearm

in three cases (13.04%). Other clinical features, such as eryth-

roderma, tumors, and nodules, were seen in one case each,
and two cases (8.7%) had ichthyosiform features (Table 1;
Figs 1–4).
Thirteen patients (56.5%) presented with a generalized
eruption, with a maculopapular morphology in nine (69.2%).
Isolated trunk involvement was observed in two patients
(8.7%), the trunk and limbs were involved in six patients
(26.1%), and isolated involvement of the head, neck, limbs,
or shin was observed in one patient each (4.3%) (Table 2).
Figure 3 Maculopapular eruption on the left side of the
abdomen
The most common anatomic site involved alone or in com-
bination with other areas was the trunk (21 cases; 91.3%).
Involvement of the palm with papules and plaques or a
maculopapular eruption was seen in three cases (13.04%).

International Journal of Dermatology 2008, 47, 359– 362 © 2008 The International Society of Dermatology
Pezeshkpoor, Yazdanpanah, and Shirdel
Figure 4 Papular eruptions on the back
Discussion
The Retroviridae family consists of large and variable viruses,
isolated from virtually all vertebrate species. These viruses are
RNA genome viruses. After entering the host cell, RNA is
translated to DNA by reverse transcriptase, and DNA is then
integrated into the host genome.
This family is divided into seven genera: (i) Alpharetrovirus
(which contains avian leukosis and sarcoma viruses); (ii)
Betaretrovirus (most mammary tumor viruses); (iii) Gamma-
retrovirus (mammalian leukemia and sarcoma viruses); (iv)
Deltaretrovirus (HTLV); (v) Epsilonretrovirus (fish viruses);
(vi) Spumavirus (which contains viruses able to cause foamy
degeneration of inoculated cells, but which are not associated
which any known disease process); (vii) Lentivirus [which
encompasses agents able to cause chronic infections with
slowly progressive neurologic impairment, including human
immunodeficiency virus (HIV)].
A few retroviruses are linked to human tumors. HTLV-I
has been established as the causative agent of ATLL, as well
© 2008 The International Society of Dermatology
Cutaneous manifestations in adult T-cell leukemia/lymphoma Report 361
as a nervous system degenerative disorder called tropical
spastic paraparesis. A related human virus, HTLV-II, has
been isolated, but has not been conclusively associated with
a specific disease. The lentiviruses are nontransforming, cyto-
lytic viruses that include the HIV virus and viruses that cause
neurologic disease. Moreover, patients with acquired immuno-
deficiency syndrome (AIDS) are at elevated risk of several types
of cancer because of the immune suppression associated with
HIV infection; these cancers include lymphoma and cervical
cancer.4
An estimated 10–20 million individuals are infected with
HTLV-I worldwide.5 More than 90% of infected individuals
remain as asymptomatic carriers, and fewer than approxi-
mately 5% become symptomatic. HTLV-I is associated with
ATLL, which occurs in 2–4% of infected persons, HTLV-I-
associated myelopathy (spastic paraparesis), and several
inflammatory diseases, such as infective dermatitis, uvetitis,
arthritis, polymyositis, and peripheral neuropathy.5–7 In
carriers, the virus is mainly found in CD4+ T lymphocytes.8
The incubation period from infection with HTLV-I to the
development of ATLL has been estimated to be 15–20 years
or more.3
The major route of transmission of HTLV-I is from an
infected mother to her child via breast milk, with a 25% risk
of infection of the child. Other routes of infection include
sexual transmission (mainly from male to female) and blood
transfusion (leukocyte transfer is necessary).3 Transfusion of
plasma is not associated with transmission, showing that
viable infected cells are necessary for transmission.9 The average
age of onset of ATLL in patients from Japan is 56 years and
in those from the Caribbean is 43 years.7
ATLL is a uniformly fatal adult malignancy that appears to
confer an identical clinical presentation in all endemic areas.
It is characterized by the variable combination of multisystem
involvement, including hepatosplenomegaly, systemic lym-
phadenopathy, central nervous system involvement, and skin
lesions, with the presence of multilobated leukemic cells in
peripheral blood. Leukemic infiltrates of different organs may
determine the clinical presentation and morbidity.7
Skin lesions are variable and are seen in up to two-thirds of
patients. Specific cutaneous lesions in which leukemic infil-
trates are seen include papules, plaques, nodules, tumors,
erythematous nonspecific patches, and erythroderma.10 Pur-
puric skin lesions because of infiltration and distraction of
blood vessels of skin with malignant cell may occur.11 Rare
lesions, such as pompholyx-like lesions of the hand and foot,
and ulcerated nodules, can be observed.12 Keloid-like lesions,
hyperpigmented lesions, and granuloma-like lesions with
nodular dermal lymphoid aggregates have been reported.11 A
case of vesicular and bullous lesions has been reported.13 In
our study, the most common form of skin lesion was a gener-
alized maculopapular eruption. In Jamaica, however, tumors,
nodules, plaques, and ulcers were more common than
International Journal of Dermatology 2008, 47, 359– 362
362 Report Cutaneous manifestations in adult T-cell leukemia/lymphoma
maculopapular eruptions, and other reported lesions included
eczematous-like, sclerodermatous-like, and ichthyosiform-
like lesions.14 On histopathology, small papules of ATLL dis-
play a dense dermal infiltrate of lymphocytes with medium-sized
convoluted nuclei. A band-like array of lymphocytes in the
papillary dermis, with some convoluted lymphocytes within
the epidermis, can also be seen, similar to the changes of
mycosis fungoides. Nodules and tumors of ATLL contain
lymphocytes similar to those of anaplastic large-cell lymphoma.
Angiocentricity can be seen in nodules or tumors. The peri-
pheral blood commonly contains lymphocytes with multilobated
nuclei. Peripheral eosinophilia is also frequently observed.15
Conclusions
In our study, the most common specific cutaneous lesion in
ATLL was a maculopapular eruption (47.8%), followed by
papular lesions (17.4%). Patients frequently showed a general-
ized eruption at presentation (91.3%). Over 85% of our
patients were born in the north of Khorasan.
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© 2008 The International Society of Dermatology