Acta Derm Venereol 90
Letters to the Editor
© 2010 The Authors. doi: 10.2340/00015555-0854
Journal Compilation © 2010 Acta Dermato-Venereologica. ISSN 0001-5555
Primary cutaneous CD8+ aggressive epidermotropic cy-
totoxic T-cell lymphoma is rare, accounting for less than
1% of all cutaneous T-cell lymphoma (CTCL) (1). We
report here a case of this type of lymphoma in a human
T-cell leukaemia virus type-1 (HTLV-1) carrier.
A 58-year-old Japanese woman visited our hospital in
2006. She first noticed a red plaque on her left thigh
approximately ten years previously. The number and
the size of the plaques gradually increased despite
treatment with topical steroid. At the initial visit, der-
matological examination revealed irregularly shaped
elevated erythematous plaques and ulcers with pus
and crusts on her right breast (Fig. 1a). She also had
multiple infiltrated red plaques with scales and crusts
on her trunk and thigh (Fig. 1b). No superficial lymph
nodes were swollen. Her general condition was good.
She was from Kyushu, Japan, an area endemic for
HTLV-1, and she was seropositive for the virus. The
peripheral white cell count was normal without any
atypical lymphocytes. Laboratory values were within
normal limits except for a slightly increased level of se-
rum soluble IL-2 receptor (965 U/ml, normal: 167–497
U/ml). Systemic examination revealed
no visceral involvement. A skin biopsy
specimen from the ulcer on the right
chest showed diffuse infiltration of
leukocytes in the dermis and subcuta-
neous tissues. In the upper and middle
part of the dermis, there was dense
infiltrate of neutrophils, histiocytes
and lymphocytes. Approximately half
of infiltrating cells were CD3+. These
T cells were mainly CD4+CD25+, and
the rest were CD8+. Many CD8+ cells
and some CD4+CD25+ cells infiltrated
the lower dermis and adipose tissues.
By Southern blotting analyses, neither
rearranged bands for T-cell receptor
beta chain nor clonal integration of
HTLV-1 were detected using DNA
from the skin lesion. Considering
her skin manifestation characteristic
for CTCL, seropositivity of HTLV-1,
and infiltration of CD4+CD25+ cells in
the skin, she was first diagnosed with
smouldering type of adult T-cell leu-
kaemia (ATL). Topical corticosteroid,
psoralen plus ultraviolet A (PUVA)
and oral retinoid were applied. These
were partially effective, and the skin
lesions disappeared 3 months after ini-
tiation of oral retinoid therapy except
for the ulcers on the patient’s right
breast (Fig. 1c) and left thigh. She
was subsequently treated with metho
trexate instead of retinoid, but the
Primary Cutaneous CD8+ Aggressive Epidermotropic Cytotoxic T-cell Lymphoma in a Human
T-cell Leukaemia Virus Type-1 Carrier
Hanako Ohmatsu1, Makoto Sugaya1, Hideki Fujita1, Tomomitsu Miyagaki1, Takafumi Kadono1, Daichi Maeda2, Yutaka Taka-
zawa2, Masashi Fukayama2, Kunihiko Tamaki1 and Shinichi Sato1
Departments of 1Dermatology and 2Pathology, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail;
Accepted January 21, 2010.
Fig. 1. (a) Multiple elevated erythematous plaques and ulcers with pus and crusts on the right
chest. (b) A red plaque on the left thigh. (c) A deep ulcer in the right breast that appeared 8 months
after the patient’s first visit. (d) Multiple purplered macules with central necrosis that appeared
14 months after her initial visit.
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Letters to the Editor
ulcers remained. The ulcers responded well to radiation
therapy. one month after the end of radiation therapy,
however, she began to develop new macules (Fig. 1d).
A biopsy specimen from the purple-red macule showed
infiltration of atypical lymphocytes in the epidermis
and upper dermis. Intraepidermal pagetoid spreading
of atypical lymphocytes, with clear cytoplasm, and
scattered necrotic keratinocytes were noted (Fig. 2a, b).
Atypical cells were positive for CD3, CD7, CD8 (Fig.
2c) and granzyme B (Fig. 2d), but negative for CD4
(Fig. 2e), CD5, CD20, CD25 (Fig. 2f) and perforin. She
was diagnosed with primary cutaneous CD8+ aggres-
sive epidermotropic cytotoxic T-cell lymphoma based
on typical clinical and pathological findings. Systemic
examination revealed invasion to the pancreas and the
thyroid gland. The patient refused multidrug chemo-
therapy. She was treated with oral corticosteroid only,
and died at the age of 60 years, 16 months after her
first visit. An autopsy revealed tumour cell infiltration
into the heart, lung, pancreas, bone marrow, thyroid
gland, abdominal para-aortic lymph nodes and peri-
pancreatic lymph nodes. Tumour cells observed in
these organs were positive for CD8, but negative for
CD4 and CD25.
Primary cutaneous CD8+ aggressive epidermotropic
cytotoxic T-cell lymphoma is characterized by a proli-
feration of CD8+ cytotoxic T cells and has an aggressive
clinical course with a median survival of 32 months (2).
Clinically, this lymphoma is characterized by localized
or disseminated eruptive papules and nodules showing
central ulceration and necrosis, or hyperkeratotic pat-
ches and plaques. Prominent epidermotropism, forming
pagetoid clusters of tumour cells, epidermal necrosis,
and cell positivity for CD8 and cytotoxic molecules
are pathological characteristics. Differentiation from
other types of CTCL expressing a CD8+ cytotoxic T-cell
phenotype is based on clinical presentation and clinical
behaviour. The patient showed variable eruptions during
the course of the disease and an aggressive clinical be-
haviour consistent with the diagnosis. It was, however,
not easy to reach a diagnosis because of seropositivity
of HTLV1 and mixed cell infiltration in the first biopsy
specimen. This case emphasizes the importance of exa-
mining repeated biopsies from the skin lesions.
The pathogenesis of this lymphoma remains un-
known. Specific genetic abnormalities and association
with a specific virus, including HTLV1, have not been
described. In fact, this is the first report of a primary
cutaneous CD8+ aggressive epidermotropic cytotoxic T-
cell lymphoma in a HTLV-1 carrier. HTLV-1 is associa-
ted with various inflammatory diseases, such as HTLV1
associated myelopathy/tropical spastic paraparesis (3)
and HTLV-1 uveitis (4). HTLV-1 may not directly in-
duce proliferation of tumour cells in our case because
no HTLV-1 DNA was detected from the skin lesion,
but an immunomodulatory effect of HTLV-1 might be
involved in the pathogenesis. This case shows that an
HTLV-1 carrier can develop CTCL other than ATL.
The authors declare no conflict of interest.
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Fig. 2. Histology of the purple-red macule. Atypical lymphoid cells
infiltrating in the epidermis, forming pagetoid clusters. Sparse perivascular
lymphoid cell infiltration is also observed (a: ×200; b: ×400). Tumour cells
are positive for CD8 (c) and granzyme B (d), but negative for CD4 (e) and
CD25 (f) (×400).
Acta Derm Venereol 90