ARTICLE
Waldenström’s Macroglobulinemia (WM) is a rare low grade B-cell
lymphoproliferative disorder. It is characterized by the monoclonal proliferation
of lymphoplasmocytes in the bone marrow and/or lymph nodes and/or spleen
associated with a monoclonal peak of immunoglobulin M on serum protein
electrophoresis [1]. Cutaneous manifestations are rare. We describe a
woman who presented specific cutaneous lesions.
Case report
A 73 year old Caucasian woman presented at hospital in December
1997 for oedema and erythema of the face with burning sensation. The cutaneous
lesions had been present for 4 months. Her medical history revealed
a rosacea for 30 years, treated by electrocoagulation; a colic diverticulosis;
a thyroidectomy for toxic nodule. Her familial medical history was remarkable
for multiple cancers of the larynx, kidney, breast, liver and melanoma.
On clinical examination, we noticed violaceous oedema of the cheeks and
the nose. Her general condition was good. The rest of the examination
was normal, especially the orthorhino and stomatological examination.
Peripheral lymphadenopathy and splenomegaly were absent. Biological data,
including blood cell count, erythrocyte sediment rate (ESR), C reactive
protein, antinuclear factors (ANF), were normal or negative, except a
decrease of C4 complement level 0.04 g/L (normal > 0.16 g/L).
Chest Xray was normal. The deep skin biopsy showed a non specific pattern:
an atrophic epidermis with an actinic elastosis and few lymphocytes in
the dermis, without any lymphoproliferative disorder. Diagnosis of rosacea
was made and topical treatment was used.
In July 2000, she presented with extensive violaceous infiltrated plaques
on the cheeks (Fig. 1).
The lesions were variable with the ambiant temperature. Physical examination
revealed voluminous cervical and axillary adenopathies. The rest of the
examination was normal. The following data were normal or negative: blood
cell count, ANF, anti DNA and antineutrophil cytoplasmic antibodies, hemostatic
studies. C4 complement rate was subnormal 0.12 g/L (normal > 0.16 g/L).
ESR was increased to 62 mm at first hour (normal < 20).
The serum protein immunoelectrophoresis showed a monoclonal peak of IgM
kappa 22 g/L (normal < 1.53 g/L) with decrease
of IgA rate, 4.9 g/L (normal > 7 g/L) and normal
IgG rate. Cryoglobulinemia type II was strongly positive with the same
IgM as monoclonal component found in the serum (quantification was not
made). Cerebral and thoracic computed tomographic scans were normal, such
as abdominal echotomography.
Node biopsy was performed. Histological examination
revealed that the nodal architecture was completely effaced by a proliferation
of small round lymphocytes with little cytoplasm, associated with plasmacytoid
lymphocytes with slightly excentric nuclei and well-developed plasma cells.
The immunohistochemical study showed the following pattern: CD20+, CD79a+,
CD10—, CD5— and CD23—.
The diagnosis of low grade non Hodgkin B cell lymphoma was made and according
to the Revised European-American Classification of Lymphoid Neoplasms,
we considered it as lymphoplasmacytoid lymphoma (immunocytoma). There
was no argument for follicle center cell lymphoma, mantle cell lymphoma
or B cell small lymphocytic lymphoma. We excluded the diagnosis of marginal
zone lymphoma because the first skin biopsy did not show any lymphoma
at all.
Histological examination of the bone marrow biopsy showed a widespread
lymphoid infiltrate with identical pattern of the node. The skin biopsy
revealed a prominent lymphoid infiltrate of the dermo-hypodermal junction
and of the deep dermis (Fig.
2a and 2b). The epidermis and the papillary dermis were normal. The
immunohistochemical studies of bone marrow and skin biopsies were exactly
the same as the node.
These histological findings were consistent with Waldenström’s
Macroglobulinemia. Oral treatment with Chlorambucil (4 mg a day)
was started. Two months after the initiation of the therapy, a decrease
of the IgM rate (15 g/L) was noted as well as the skin infiltration
of the face.
Discussion
Initially described in 1944 [1], WM is a rare chronic lymphoproliferative
disorder of unknown etiology. It is observed with a little predominance
in males and usually occurs in the elderly, especially in the sixth or
seventh decade [2]. The biological characteristic is a monoclonal IgM
peak produced by a neoplasic proliferation of lymphocytes and plasmocytes
in the bone marrow. Excessive production of IgM leads to hyperviscosity
of the blood and the interaction of IgM with coagulation factors is responsible
for a bleeding syndrome. Weakness and weight loss are usually the early
symptoms, but our patient was in excellent condition. Later, lymphadenopathies
and hepatosplenomegaly may develop. Some symptoms such as headache or
ocular disturbance are secondary to hyperviscosity or bleeding syndrome.
Others result from the involvement by the lymphoproliferative infiltration
of several organs including the lung, gastrointestinal tract and central
nervous system. Peripheral neuropathy has been reported in WM resulting
from cryoglobulinemia. Cutaneous manifestations are rare and occur in
only 5 % of WM [3]. They include non specific and specific lesions.
Non specific cutaneous lesions are polymorphic with urticaria, purpura,
ulcers or purple discoloration of toes, fingers and ear lobes. They are
sometimes the result of a cryoglobulinemia [4]. Several specific manifestations
are
also described. Violaceous skin induration is the most common cutaneous
lesion [5, 6]. When symetrical and located on the face, it is very suggestive
of WM as it was in our patient. However, it may appear on the trunk or
the proximal extremities. Violaceous firm nodules, sometimes ulcerated,
may grow on the same areas [7, 8]. Histologically, violaceous infiltration
and nodules result from the direct lympho-plasmacytoid infiltrate of the
reticular dermis and the hypodermis. The epidermis and usually the papillary
dermis are not involved. Sometimes, cells contain intranuclear periodic
acid-schiff (PAS) positive inclusions which correspond to IgM deposits.
Clinical variants include IgM storage papules which are flesh colored
papules located on the face, the extensor surfaces of extremities, the
trunk and the buttocks [9, 10]. They are usually asymptomatic, sometimes
pruritic. Histologically, storage papules reveal homogeneous eosinophilic
material in the dermis which is PAS positive and result from direct depositions
of IgM in the dermis [11]. More recently, vesiculobullous eruptions have
been described [12, 13]. The skin biopsies of blisters revealed subepidermal
separation and immunofluorescent techniques demonstrated deposits of IgM
along the basement membrane zone which could be responsible for the blister
formation.
Cutaneous manifestations may appear at the beginning
of the disease [14] as described in this case report or later, when WM
diagnosis is confirmed and the disease treated. There is no correlation
between the onset of skin manifestations and the blood level of IgM or
the disease activity. Cutaneous lesions are not correlated with a poor
prognosis [7]. Our patient was treated with chlorambucil which is the
the drug of choice for WM in the literature. Chlorambucil may be associated
or not with corticosteroids. Melphalan, cyclophosphamide may be alternative
therapies. These treatments have variable efficacity on cutaneous lesions.
Some isolated skin lesions have been treated successfully with radiotherapy
[4, 15].
This report may be interesting for the prominent specific cutaneous
involvement as the initial manifestation of a WM.
Article accepted on 8/10/2002REFERENCES
1
Waldenstrom J. Incipient myelomatosis or essential hyperglobulinemia
with fibrinogenopenia: a new syndrome ? Acta Med Scand 1944;
117: 216-47.
2
Herrinton LJ, Weis NS. Incidence of Waldenstrom’ macroglobulinemia.
Blood 1993; 82: 3148-50.
3
Lorette G, Guilmot JL, Binet C, Carli-Basset C. Les manifestations
cutanées des dysglobu-linémies. Sem. Hôp. Paris
1981; 57: 163-7.
4
Daoud MS, Lust JA, Kyle RA, Pittelkow MR. Monoclonal gammapathies
and associated skin disorders. J Am Acad Dermatol 1999; 40: 507-35.
5
Bureau Y, Barriere H, Bureau B. Les localisations cutanées
de la macroglobulinémie de Waldenström. Ann Derm Syph
1968; 95: 125-37.
6
Fayol J, Bernard P, Bordessoule D, Vire O, Malinvaud G, Bonnetblanc
JM. Localisations cutanées spécifiques au cours du myelome
multiple et de la macroglobulinémie de Waldenström. Ann
Dermatol Venereol 1985; 112: 509-16.
7
Mascaro JM, Montserrat E, Estrach T, Feliu E, Ferrando J, Castel T,
Mallolas J, Rozman C. Specific cutaneous manifestations of Waldenstrom’s
macroglobulinemia. A report of two cases. Br J Dermatol 1982; 106:
217-22.
8
Dupré A, Bonafé JL, Fontan B, Touron P, Oksman F, Pieraggi
MT. Nodules cutanés spécifiques d’une macroglobulinémie
de Waldenström. Ann Dermatol Veneorol 1981; 108: 961-7.
9
Hanke CW, Steck WD, Bergfeld WF, Valenzuela R, Weick JK, Young JR,
Gross EG. Cutaneous macroglobulinosis. Arch Dermatol 1980; 116:
575-7.
10
Lowe L, Fitzpatrick JE, Huff JC, Shanley PF, Golitz LE. Cutaneous
Macroglobulinosis: a case report with unique ultrastructural findings.
Arch dermatol 1992; 128: 377-80.
11
Lipsker D, Cribier B, Spehner D, Boehm N, Heid E, Grosshans E. Examination
of cutaneous macroglobulinosis by immunoelectron microscopy. Br J Dermatol
1996; 135: 287-91.
12
Whittaker SJ, Bhogal BS, Black MM. Acquired immunobullous disease:
a cutaneous manifestation of IgM macroglobulinaemia. Br J Dermatol
1996; 135: 283-6.
13
West NY, Fitzpatrick JE, David-Bajar KM, Bennion SD. Waldenstrom macroglobulinemia
induced-bullous dermatosis. Arch Dermatol 1998; 134: 1127-31.
14
Sigal M, Foldès C, Grossin M, Pocidalo MA, Basset F, Belaïch
S. Localisations cutanées spécifiques d’une maladie
de Waldenström. Ann Dermatol Venereol 1985; 112: 763-4.
15
Orengo IF, Kettler AH, Bruce S, Levy ML, Rosen T, Tschen J. Cutaneous
waldenström’s macroglobulinemia. A report of a case successfully
treated with radiotherapy. Cancer 1987; 60: 1341-5.
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