ARTICLE
Auteur(s) : Kazuhide
Tsuji1, Daisuke Suzuki1, Youko
Naito1, Yumiko Sato2, Tadashi
Yoshino2, Keiji Iwatsuki1
1Department of Dermatology, Okayama University
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences,
Shikata-cho 2-5-1, Okayama 700-8558, Japan
2Department of Pathology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama,
Japan
accepté le 17 Août 2005
Marginal zone B-cell lymphoma (MZBL) was first recognized as a
low-grade B-cell lymphoma of mucosa-associated lymphoid tissue
(MALT) by Isaacson and Wright [1]. Extranodal MZBL was defined as a
new entity of lymphoma in the Revised European-American
classification of lymphoid neoplasms (REAL classification) [2] and
the World Health Organization (WHO) classification [3]. Although
extranodal MZBLs have been mainly described by the name
“mucosa-associated lymphoid tissue lymphoma”, they arise not only
from the stomach [4], but also from various nongastrointestinal
sites [5]. Primary cutaneous marginal zone B-cell lymphoma (PCMZL)
is also considered part of the broad group of extranodal marginal
zone B-cell lymphomas [6]. Because PCMZL has only recently been
recognized and few Asian cases have been described, we reported our
case and reviewed the cases of PCMZL in the Japanese literature.
Case report
A 46-year-old woman was referred to our hospital in March 2001
because of a subcutaneous nodule on her right forearm. The nodule
had been present for a year and gradually enlarged without
ulceration despite treatment with topical steroids. There was no
history of either acute inflammation or insect bite on the lesion.
Examination revealed a solitary, firm, subcutaneous nodule, 1-
2 cm in diameter, on the right forearm ( (figure 1) ). The nodule
was not attached to the underlying tissue. There was neither
lymphadenopathy nor hepatosplenomegaly. The results of routine
laboratory examinations were normal except for slightly increased
total cholesterol (T.Cho 227 mg/dl). Anti-Ro (SS-A) and anti-La
(SS-B) antibodies, anti-human T-cell lymphotrophic virus type 1
antibody, anti-H. pylori antibodies, and anti-and anti-Borrelia
burgdorferi antibodies of serum were negative. Although she had a
slight stomachache and a history of gastritis, both upper and lower
gastrointestinal endoscopies showed no evidence of malignancy. A
bone marrow biopsy, computed tomography, magnetic resonance
imaging, and various scintigrams did not reveal any evidence of
primary or metastatic lesions.
Hematoxylin-eosin-stained specimens revealed variously sized,
irregularly shaped nests in the dermis ( (figure 2A) ). The
overlying epidermis was not involved. The infiltrates were composed
of small lymphocytes, centrocyte-like cells, lymphoplasmacytoid
cells, plasma cells, and many reactive cells ( (figures 2B and 2C) ).
Lympho-epithelial complexes were not presented. On paraffin
immunoperoxidase stains, the atypical lymphocytes within the
nodules were positive for CD20 ( (figure 3A) ) and alkaline
phosphatase, and negative for CD5, CD10. The detection rate for
κ-light chain was much higher than λ-light chain by in situ
hybridization ( (figures
3B and 3C) ). Although clonal immunoglobulin heavy chain
gene rearrangement using JH probe by Southern blot analysis was
negative in the tumor tissue, molecular analysis by VDJ-PCR on
paraffin embedded tissue showed evidence of monoclonal B-cell
population ( (figure
4) )[7]. In this case, t(11;18)(q21;q21) involving API2 and
MALT1 genes was not detected by fluorescence in situ hybridization
(FISH) analysis on fresh tissue. With the combined morphology,
immunophenotype, and molecular analysis, we diagnosed a PCMZL of
mucosa associated lymphoid tissue (MALT) of the skin. Electron beam
irradiation (total 40 Gy) was applied after extirpation. Neither
local recurrence nor metastasis has appeared during 24 months of
follow-up.
Discussion
Table 1( Table 1 ) summarizes
clinicopathological findings of the 16 cases of PCMZL described in
the Japanese literature during last ten years. The age of the
patients at the time of diagnosis ranged from 26 to 75 years (mean
55.7 years old) with a slight female predilection (male/female
ratio 7:9). The regions involved were the face and neck in eight
cases, the trunk in six and the arms in five. Clinically, most of
the skin lesions were erythematous nodular lesions. Three cases
were recognized as plaques, 1 as papules and 12 as nodules. The
lesions were solitary in nine cases and multiple in seven. In three
of seven multiple cases, more than one anatomic site was involved.
None of the 16 patients had B.burgdorferi and H. pylori infection.
In the Japanese, involvement of B. burgdorferi and H. pylori seems
extremely rare and plays a limited role in the development or
pathogenesis of PCMZL, as described in Taiwanese cases [9]. Two
patients had a history of Sjögren’s syndrome (cases 2, 13). No
patients had suffered from thyroiditis. Histopathologically, the
dermis was the major site of tumor infiltration, and the upper
subcutis was frequently involved (seven cases). In contrast, the
epidermis was never involved. Lymphoepithelial lesions were found
in nine cases in which neoplastic cells invaded the skin adnexa
with lymphoepithelial complex formation. As Servitje et al. [10]
reported that adnexal involvement was seen in about 90% of cases
(20/22), lymphoepithelial lesions might be common in PCMZL.
Recently, a number of recurring chromosomal translocations have
been described in MALT lymphoma. Although neither t(11;18)(q21;q21)
nor t(1;14)(q22;q32) has been identified in PCMZL, including
Japanese cases, t(14;18)(q32;q21) involving IGH and MALT1 and
t(3;14)(p14.1;q32) involving IGH and FOXP1 have been detected in
some PCMZL cases [11, 12]. The clinicopathological significances of
these two novel gene alterations are important translocations in a
site-dependent subset of MALT lymphomas [13].
Of the Japanese cases investigated for cytoplasmic or surface
light chain expression, monotypic expression of light chains was
observed in 12 cases (seven κ; five λ). With the light chain
immunoglobulin expression, Southern blot analysis of the
immunoglobulin gene is the established method for molecular genetic
demonstration of monoclonality but it is complex and requires fresh
frozen tissue samples. PCR-based clonality analysis is sufficiently
sensitive and reliable for use as a routine diagnostic adjunct
[14]. The combination with immunohistochemical and PCR-based
clonality analysis can be useful in differentiating PCMZL from a
reactive process, especially for small specimens.
Local treatment results in remission in most cases. 11 cases
were treated by surgery and 12 by radiation. Two patients developed
skin-limited recurrences affecting the initially treated site or
distant skin sites after radiation therapy (cases 2, 8), however,
none of the 16 cases died of PCMZL (the median follow-up period was
18.3 months after treatment (range: 4-36 months)). There is a
significant risk of relapse, however, only a small minority of
these patients will die of their disease.
Table 1 Clinical characteristics of 16 patients with
primary cutaneous marginal zone B-cell lymphoma
|
Case No.
|
Age
|
Sex
|
Primary site
|
Gross appearance
|
Solitary or multiple
|
Sjogren’s syndrome
|
subcutis involvement
|
- Lympho-
- epithelial lesion
|
Method of detecting Ig rearrangementa
|
Light chains
|
Therapyb
|
Coursec
|
Ref.
|
|
1
|
36
|
M
|
lt. shoulder
|
Nodule
|
Solitary
|
n/r
|
Yes
|
n/rd
|
SB
|
λ
|
EB 40Gy
|
CR(34)e
|
[8]
|
|
2f
|
57
|
F
|
abdomen
|
Plaque
|
Solitary
|
Yes
|
Yes
|
Yes
|
SB
|
κ
|
Ext+EB40-Gy CHOP
|
rec(4)
|
|
|
3g
|
49
|
M
|
lt. eye lid
|
Papule
|
Solitary
|
No
|
No
|
Yes
|
PCR
|
λ
|
Ext + EB 30Gy
|
CR(15)
|
|
|
4h
|
70
|
M
|
lt. arm
|
Plaque Nodules
|
Multiple
|
No
|
Yes
|
No
|
PCR
|
κ
|
Ext
|
CR(12)
|
|
|
5i
|
52
|
F
|
lt. cheek
|
Nodule
|
Solitary
|
n/r
|
Yes
|
Yes
|
SB
|
κ
|
Ext + EB 40Gy
|
CR(24)
|
|
|
6j
|
26
|
M
|
rt. shoulder and neck
|
Nodules
|
Multiple
|
No
|
No
|
Yes
|
SB
|
κ
|
EB 30Gy
|
CR(24)
|
|
|
7k
|
34
|
F
|
rt. upper arm
|
Nodule
|
Solitary
|
No
|
No
|
Yes
|
n/r
|
λ
|
Ext
|
n/r
|
|
|
8l
|
75
|
F
|
rt. cheek and eyelids
|
Grouped Nodules
|
Multiple
|
n/r
|
No
|
Yes
|
SB
|
n/r
|
Ext + EB 40Gy + 30Gy
|
rec
|
|
|
9m
|
73
|
F
|
lt. upper arm
|
Plaque
|
Solitary
|
No
|
No
|
No
|
SB
|
n/r
|
Ext
|
CR(12)
|
|
|
10n
|
51
|
F
|
lt. cheek
|
Nodule
|
Solitary
|
No
|
Yes
|
n/r
|
n/r
|
κ
|
Ext + EB 34Gy
|
CR(12)
|
|
|
11o
|
75
|
M
|
back
|
Plaques
|
Multiple
|
n/r
|
Yes
|
Yes
|
n/r
|
λ
|
Ext + RT
|
n/r
|
|
|
12p
|
59
|
M
|
lt. lower eyelid
|
Nodule
|
Solitary
|
No
|
Yes
|
No
|
PCR
|
n/r
|
|
CR(36)
|
|
|
13q
|
61
|
F
|
back, shoulder, arms
|
Nodules
|
Multiple
|
Yes
|
n/r
|
Yes
|
SB
|
κ
|
EB
|
CR(12)
|
|
|
14r
|
68
|
F
|
retroauricular forehead
|
Nodules
|
Multiple
|
n/r
|
Yes
|
Yes
|
SB
|
n/r
|
PSL 15mg
|
SD(5)
|
|
|
15s
|
59
|
M
|
forehead, cheek, chest
|
Nodules
|
Multiple
|
No
|
No
|
n/r
|
SB
|
λ
|
RT+CHOP
|
CR(24)
|
|
|
16
|
46
|
F
|
rt. arm
|
Nodule
|
Solitary
|
No
|
Yes
|
No
|
PCR
|
κ
|
Ext + EB 40Gy
|
CR(24)
|
Our case
|
aSB, Southern blot analysis; PCR, PCR-based
clonality analysis.
bRT, radiotherapy; EB, electron-beam; Ext,
extirpation.
cCR, complete response; rec, recurrence;
SD, stable disease.
dn/r, not referred.
eMonths of follow-up.
fFurutani K et al. Jpn J Dermatol 2001;
111: 843.
gHayashi M et al. Rinsho Derma 2004; 46:
1381.
hTakatsuka S et al. Rinsho Hifuka 2001;
55: 175.
iFuruta M et al. Rinsho Hifuka 2003; 57:
1210.
jNamba Y et al. Hifu no lymphoma 1997; 16:
98.
kHarada M et al. Nihon Hifubyorisoshiki
Gakkaishi 1999; 15: 10.
lSaito M et al. Rinsho Derma 2003; 57:
193.
mKimura T et al. Jpn J Dermatol 2000; 110:
1602.
nKakeda N et al. Jpn J Dermatol 2003; 113:
315-6.
oKodanagi M et al. Jpn J Dermatol 2004;
114: 592.
pIyoda E et al. Jpn J Dermatol 2003; 113:
1026.
qOnoda N et al. Nippon Byori Gakkai Kaishi
Transactiones Societatis Pathologicae Japonicae 1995; 84: 206.
rKoiso H et al. Rinsho Ketsueki 1999; 40:
910.
sWatanabe I et al. Hifu no kagaku 2002; 1:
149.
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