ARTICLE
Auteur(s) : Sei-ichiro Motegi, Etsuko
Okada, Yayoi Nagai, Atsushi Tamura, Osamu Ishikawa
Department of Dermatology, Gunma University Graduate School of
Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan
accepté le 9 Mars 2006
Mantle cell lymphoma (MCL) is an uncommon but aggressive form of
non-Hodgkin’s lymphoma that typically involves lymph nodes. The
extranodal involvement is frequent, especially in bone marrow,
spleen, gastrointestinal tract and Waldeyer’s ring [1, 2], however,
skin is rarely affected. MCL was listed in the new World Health
Organization (WHO)- European Organization for Research and
Treatment for Cancer (EORTC) classification of cutaneous lymphomas
as an extracutaneous lymphoma involving the skin secondarily [3-5].
We herein report a case of MCL with cutaneous involvement and
review skin manifestations of previously reported cases of MCL.
Case report
A 62-year-old Japanese man was referred to our hospital with a
one-year history of multiple reddish nodules on the back and upper
extremities. Painful ulcers had developed on his oral mucosa for
the last 3 months. The family and past history were not
contributory.
Physical examination revealed several dome-shaped small red
nodules scattered on the back and upper extremities ( (figure 1A) ). In addition,
pale-reddish ulcerated erythemas were seen on the chest and penis
shaft ( (figure
1B) ). Aphthoid lesions were noted on the buccal and hard
palate mucosa. Non-tender lymph nodes measuring 2-3cm in diameter
were palpated on the left neck.
Abnormal laboratory results included slight anemia with a
hemoglobin of 11.4 g/dL (normal 13.2-17.3), elevated serum total
protein (9.3 g/dL: normal 6.3-7.9) and high levels of
gamma-globulin (3.4 g/dL: normal 1.0-1.9). Elevated serum soluble
IL-2 receptor was noted (1241 U/mL: normal 135-483). Serum lactate
dehydrogenase level was normal. Anti human T-cell leukemia virus-1
antibody was negative. Computed tomographic scans of the whole body
disclosed multiple lymphadenopathy in the cervical,
supraclavicular, para-aortic, axillary and inguinal regions and
enlargement of the bilateral tonsillae. 67Ga
scintigraphy showed unremarkable uptake of the whole body.
Fluorodeoxyglucose-positron emission tomography (FDG-PET) scan
showed areas of abnormal uptake in bilateral cervical, axillary and
inguinal lymph nodes, as well as tonsillae and spleen. The
gastrointestinal fiberscopic examination revealed erosive lesions
in gastric mucosa.
Histopathological examination of a nodule on the back showed a
massive proliferation of small- to medium-sized atypical lymphoid
cells throughout the dermis and subcutis ( (figure 2A) ). There was a
grenz zone with sparing the epidermis. The neoplastic cells had
irregular nuclear contours, coarse chromatin, inconspicuous
nucleoli and scant cytoplasm ( (figure 2B) ). On
immunohistochemical analyses, tumor cells were positive for CD20
(L26) ( (figure
2C) ), CD5, CD43 and cyclin D1 ( (figure 2D) ), but negative
for CD45RO (UCHL-1), CD3, CD10 and CD23. The additional biopsied
specimens from the oral and stomach lesions showed the same
histopathological and immunohistochemical findings.
Based on the clinico-pathological and immunohistochemical
findings, the diagnosis of mantle cell lymphoma was established. He
received the fractionated Hyper-CVAD/MTX-AraC chemotherapy regimen
(cyclophosphamide/ vincristine/ doxorubicin/ dexamethasone
alternated with methotrexate/ cytarabine) combined with rituximab.
With two cycles of the chemotherapy, he achieved partial response
with complete remission of skin lesions and improvement of
lymphadenopathy. Increasing lactate dehydrogenase level was not
shown. During a 4-month follow-up period, he has been in complete
remission of skin lesions.
Discussion
Mantle cell lymphoma (MCL) is a malignant tumor derived from B
cells in the mantle zone of lymphoid follicles characterized by
specific pathologic, immunophenotypic and molecular genetic
features, and usually takes an aggressive clinical course, defined
in the World Health Organization (WHO) classification [3-5].
Histologically, it shows a diffuse or nodular monotonous
proliferation of small lymphoid cells with scant cytoplasm and
irregular nuclear contours in lymph nodes. Immunophenotypically,
the tumor cells are positive for B-cell markers CD79a, CD19, CD20
and CD22 as well as CD5, and are usually negative for CD10 and CD23
[6, 7]. The majority of MCL carries a cytogenetic abnormality with
t(11, 14) (q13; q32) translocation, which results in the
juxtaposition of the CCND-1 gene on chromosome 11 with the
immunoglobulin heavy chain gene on chromosome 14, and causes
overexpression of cyclin D1 protein, which acts as a positive
signal for the transition from the G1 to S phase [8-10]. Cyclin D1
overexpression is considered to be important as a diagnostic marker
[11]. The result of our immunohistochemical analyses completes the
different diagnosis from other small B-cell lymphomas (marginal
zone lymphoma; negative for CD5, CD10, CD23 and cyclin D1, B-cell
lymphocytic lymphoma; positive for CD5, CD23 and negative for CD10,
cyclin D1, follicular lymphoma; positive for CD10 and negative for
CD5, cyclin D1).
MCL frequently involves extranodal organs, particularly such as
bone marrow, gastrointestinal tract and Waldeyer’s ring, and was
fundamentally considered as the extracutaneous lymphoma, which
rarely affects the skin. In two large series of 121 and 59 cases of
MCL, only 3 and 2 patients had skin lesions, respectively [5, 12].
To the best of our knowledge, there have been only 17 patients
reported who exhibited skin lesions described in detail in English
literature [10, 13-18]. We summarized the clinical features of 17
patients in table 1( Table 1 ). The age
ranged from 22 to 89 years old, with a mean age of 62.5. The ratio
of male to female was 13: 4. The most common site of skin
involvement was trunk in 11 of 17 patients, followed by face in 4
cases, arms in 3 cases and thighs, legs, scalp in each one case,
respectively. Skin lesions manifested as nodular lesions in 6
patients (35%), macular or maculopapular lesions in 5 (29%),
tumoral or infiltrated plaques in 4 (24%), and subcutaneous nodules
in 2 (12%). Fourteen patients (82%; excluding No. 1, 12, 17)
exhibited skin lesions at the time of the initial diagnosis of MCL.
Most of the patients (82%) also had extracutaneous lesions such as
lymph node, bone marrow or gastrointestinal tract, and were
classified as stage IV. Aggressive combination chemotherapy was
given to 16 patients. Four patients (No. 4, 6, 12, 15) achieved a
complete remission of the skin lesions and no recurrence had been
observed during a follow-up period (1-17 years).
A cutaneous eruption simulating insect bites has been
incidentally described in association with MCL. It seems to be
reactive rather than neoplastic because of no evidence of MCL
involvement in the skin lesions [19-21]. The lesions of our case
clinically resembled insect bite like eruptions associated with
MCL. However, our case was not considered to exhibit exaggerated
reactions to insect bites, because of the presence of tumor cells
in the skin lesions.
Skin involvement is rare in MCL. Once developed, however, it
usually suggests a disseminated stage. Although the prognosis of
MCL is poor, aggressive chemotherapy may improve the survival rate.
Since cutaneous lesions can be the first manifestation of MCL,
awareness of MCL is important for dermatologists to establish an
early diagnosis and perform an appropriate treatment.
Table 1 Reported cases of mantle cell lymphoma with
skin lesions
|
No
|
Author
|
Age/Sex
|
Location
|
Clinical presentation
|
Extracutaneous Involvement
|
Stage
|
Prognosis
|
|
1
|
Ellison
|
66M
|
Temple
|
Macular skin lesions
|
LN, liver, spleen, lung, pleural cavity, CNS
|
IV
|
D (55d; after initial hospitalization)
|
|
2
|
Geerts
|
65F
|
Forehead
|
Nodules
|
LN, BM
|
IVA
|
D (1.5y; after diagnosis)
|
|
3
|
Geerts
|
77F
|
Back, breast, arm
|
Tumoral plaques
|
Bronchus wall
|
IVA
|
|
|
4
|
Bertero
|
51M
|
Breast
|
Subcutaneous nodule
|
LN, liver, spleen
|
IVA
|
A (17y; after onset)
|
|
5
|
Bertero
|
78F
|
Breast, back
|
Nodules
|
none
|
I E
|
D (3y; after diagnosis)
|
|
6
|
Bertero
|
43M
|
Back, face, arm
|
Infiltrated plaques
|
LN, liver, spleen
|
IVA
|
A
|
|
7
|
Bertero
|
22M
|
Breast
|
Nodules
|
none
|
I E
|
A
|
|
8
|
Marti
|
61F
|
Abdomen
|
Tumoral plaque
|
LN, BM, tonsils
|
IVA
|
D (15m; after diagnosis)
|
|
9
|
Moody
|
47M
|
Ear
|
Nodules
|
LN, BM
|
IVA
|
A (3y; after onset)
|
|
10
|
Dubus
|
56M
|
Breast, back
|
Erythematous papules
|
LN, BM, PB
|
IVA
|
D (1y; after treatment)
|
|
11
|
Dubus
|
89M
|
Breast, back, abdomen
|
Infiltrated purpuric papules
|
LN, BM, PB
|
IVA
|
D (5d; after diagnosis)
|
|
12
|
Dubus
|
72M
|
Face,breast, arm, axilla
|
Subcutaneous nodules
|
LN, BM
|
IVA
|
A (1y; after treatment)
|
|
13
|
Sen
|
85M
|
Leg
|
Macular rash
|
LN. BM, buccal mucosa
|
IVB
|
D (20m; after onset)
|
|
14
|
Sen
|
76M
|
Thigh
|
Nodule
|
none
|
I E
|
A (30m; after onset)
|
|
15
|
Sen
|
56M
|
Chest
|
Nodules
|
BM, GI
|
IVA
|
A (21m; after onset)
|
|
16
|
Sen
|
57M
|
Legs
|
Maculopapular rash
|
LN, BM, PB
|
IVB
|
D (9m; after onset)
|
|
17
|
Sen
|
61M
|
Flank back, thigh
|
Plaques
|
LN, BM, PB leptomeninges
|
IVB
|
D (15m; after onset)
|
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