ARTICLE
Auteur(s) : Naho
Yoshizawa1, Hiroaki Yagi2, Takahiro
Horibe2, Masahiro Takigawa2, Makoto
Sugiura1
1Department of Dermatology, Shizuoka Municipal
Shimizu Hospital, 1231 Miyakami Shimizu, Shizuoka 424-8636,
Japan
2Department of Dermatology, Hamamatsu University School
of Medicine, 1-20-1 Handayama, Hamamatsu 431-3192, Japan
accepté le 25 Avril 2007
Clinicopathological features of primary cutaneous aggressive
epidermotropic CD8+ T-cell lymphoma (CD8+TCL)
are homogeneous and distinctive [1], presenting with generalized
skin lesions and aggressive dissemination of tumor cells not only
to internal organs such as the spleen, lungs, liver and CNS but
also to unusual sites such as the oral cavity and testis. On the
other hand, lymph nodes are rarely involved. Prognosis is generally
poor since the tumor is unresponsive or even worsening during
specific cutaneous T-cell lymphoma (CTCL) treatment, including
photochemotherapy, interferon-α and polychemotherapy. CD15 (Leu-M1)
designates the cluster of antibodies that recognize a carbohydrate
antigen referred to as X hapten, Lex or stage-specific
embryonic antigen [2]. The CD15 antigen is present on more than 95%
of mature peripheral blood eosinophils and neutrophils. While this
molecule is typically associated with classic Hodgkin’s lymphoma,
peripheral T-cell lymphomas including CTCLs may, rarely, express
this molecule [2-4]. Here, we report the first case of a Japanese
patient with primary cutaneous aggressive epidermotropic
CD8+TCL, in which lymphoma cells are
CD15+CD30– with a medium-to-large pleomorphic
phenotype.
Case report
A 68-year-old man noticed an erythematous lesion on the left side
of his back five months before his first visit to our hospital. The
skin lesions had progressed very rapidly thereafter; the patient’s
physical examination revealed widespread annular erythemato-scaling
patches, papillomatous plaques, and nodules (figure 1A). Results of
laboratory tests including hemograms, liver and renal functions,
were normal. No abnormal lymphocytes were detected in peripheral
blood by blood smear examination and flow cytometry analysis.
Plasma soluble IL-2 receptor level was 1370 U/mL (normal, less than
530). Serological tests for anti-HTLV-1 and anti-HIV-1 antibodies
were negative. Persistent EBV infection was not found. Biopsy
specimens showed a band-like infiltrate of atypical medium-to-large
pleomorphic lymphocytes at the dermoepidermal junction zone with
marked epidermotropism (figure 1B). Both
immunohistochemical staining (figures 2A-C) and flow
cytometric analysis (figure 2D) of the lesional
skin biopsies revealed that the neoplastic cells were positive for
CD2, CD3, CD7, CD8 (figure 2B), CD15
(membranous positivity, figures 2C and D), CD45RO,
CXC chemokine receptor 3, T-cell receptor (TCR) Vβ7, TIA-1 and
granzyme B, and negative for CD4 (figure 2A), CD5, CD20,
CD30 (figure
2D), CD45RA, CD56, CC chemokine receptor 4 and cutaneous
lymphocyte-associated antigen. Southern blotting analysis of DNA
from lesional skin revealed rearranged, non-germline bands with a
DNA probe for TCRCβ1. No lymphoma involvement was
apparent in any organ other than the skin by repeated bone marrow
aspirations, whole body computed tomography and 67Ga
scintigraphy. The response to CHOP therapy, administered in
parallel with local and total skin electron beam irradiation (total
45 Gy per 30 days), was partial if any, as new skin lesions
appeared quickly after each regimen. In addition, after 6 courses
of CHOP therapy, the patient developed multiple pulmonary nodules.
No bacteria, fungi, or mycobacteria were grown in cultures of both
sputum and pleural effusion. By flow cytometric analysis of pleural
effusion, more than 65% of the CD45+ cells had a
CD8+TCRVβ7+ phenotype, suggestive of lung
invasion of cutaneous lymphoma cells. Lymphoma cells were not
detected in the peripheral blood, and surface and visceral lymph
nodes involvement was not apparent. The patient died of respiratory
dysfunction 7 months after the diagnosis.
Discussion
On the basis of typical clinical and pathological findings, the
present case was diagnosed as primary cutaneous aggressive
epidermotropic CD8+TCL. In a review of 17 patients with
CD8-positive cutaneous lymphomas, Berti et al. [1] noted
distinctive clinical and pathological features in eight cases and,
thus, defined these unique lymphomas as primary cutaneous
aggressive epidermotropic CD8+TCL. Because the clinical
features of primary cutaneous aggressive epidermotropic
CD8+TCL mimic Mycosis Fungoides (MF), the similar cases
were formerly described as a rare, fulminant MF-like cases with the
CD8+ neoplastic T lymphocytes [5]. Recently, the
WHO-European Organization for Research and Treatment of Cancer
classification [6] has separated these cases as a provisional
entity forming a category of primary cutaneous peripheral T-cell
lymphoma, unspecified.
Both immunohistochemical and flow cytometric analyses clearly
revealed that the skin infiltrating lymphoma cells of the present
case were CD15+CD30–. The expression of CD15
has not been described in the previously reported primary cutaneous
aggressive epidermotropic CD8+TCL cases. Although the
functional characteristics of CD15 expression in cutaneous
lymphomas are not fully understood, it was suggested in an earlier
study that CD15 is expressed in aggressive peripheral T-cell
lymphomas such as advanced stage CTCLs [7]. A recent study revealed
that the expression of CD15 in unspecified peripheral T-cell
lymphomas, correlates to low survival rates as well as known
unfavourable prognostic factors such as CD2 negativity, the MIB-1
(Ki-67) index, EBV-encoded small RNA expression [3],
angiocentricity/angionecrosis and pagetoid epidermotropism. Poor
prognosis of primary cutaneous aggressive epidermotropic
CD8+TCL might be associated with the presence of this
molecule in our case. Although the evaluation of more cases is
necessary, we suggest that CD15 can be an important marker for the
diagnosis of rare and aggressive types of cutaneous T-cell
lymphoma, including epidermotropic CD8+TCL.
Acknowledgements
Financial support: none. Conflict of interest: none.
References
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