ARTICLE
Auteur(s) :, V
Vieira1,*, J Del Pozo1, W
Martínez1, JA Veiga-Barreiro2, E
Fonseca1
1Department of Dermatology CHU Juan Canalejo Paseo de
Sir John Moore s/n 15003 La Coruña, Spain
2Department of Pathology CHU Juan Canalejo Paseo de Sir
John Moore s/n 15003 La Coruña, Spain
accepté le 30 Août 2004
Necrobiotic xanthogranuloma (NXG) is a rare non-X histiocytic
disease described by Kossard and Winkelmann in 1980 [2].
Nevertheless, cases of NXG might have been previously reported as
atypical multicentric reticulohistiocytosis, unusual necrobiosis
lipoidica or atypical xanthoma disseminatum [2].NXG is clinically
characterized by two or more indurated, non-tender, yellow or
violaceous papules, nodules, or plaques, sometimes with ulceration
and scar formation. The disease mostly occurs on the periorbital
area, followed by the trunk, face, arms, thighs, legs, shoulder and
buttocks [1, 3].NXG usually has a progressive course with
involvement of internal organs, leukopenia, low serum complement or
cryoglobulinemia, association with paraproteinemia in up to 80% of
cases [4-7], and an increased risk for haematological and
lymphoproliferative malignant diseases (13% of cases), specially
multiple myeloma and lymphoma [3, 8].The treatment of these lesions
is difficult, and although several therapeutic approaches have been
performed, recurrence is frequent.We report a case of NXG on the
periorbital area and left buttock with a 4-year evolution and
associated with lymphoplasmacytic lymphoma.
Case report
A 68-year-old woman had a 4-year history of lymphoplasmacytic
lymphoma with monoclonal gammopathy IgG lambda type. Between 1998
and 1999 she received chlorambucil and prednisone treatment, with
relevant improvement. Therefore haematological ambulatory control
was instituted, without further pharmacological treatment. In April
2002, xanthomatous lesions on both upper eyelids were removed at a
Plastic Surgery Department. Histological examination of surgery
specimens revealed deep infiltrative changes involving the whole
dermis and subcutaneous tissue. Areas of necrobiosis with
cholesterol clefts, a granulomatous infiltrate with giant
multinucleated lymphocytes and foamy cells, and a necrosis area
with several foamy histiocytes in contact with the epidermis were
observed. A diagnosis of necrobiotic xanthogranuloma was
established.
Five-months later, she was referred to the Dermatology
Department for evaluation and treatment of new cutaneous lesions on
the eyelid. Physical examination demonstrated sharply demarcated,
brown and yellow infiltrated nodules and plaques, some of them with
prominent erythematous-violaceous border, located on both her lower
eyelids ( (figure
1) ) and left buttock.
Laboratory investigations demonstrated elevated sedimentation
rate 64 mm/h, (normal < 20 mm/h), low white blood cell
count 2.45 × 109/L (normal range 4.00-11.50 ×
109/L); neutropenia in blood manual count, monoclonal
gammopathy IgG lambda type in protein electrophoresis (IgG 3290
mg/dL, normal range 751-1560 mg/dL), and elevated levels of
gammaglobulin 46.10% (normal range 10.00-20.00%). β-2 microglobulin
was normal (2.19 mg/L, normal range 1.50-2.30 mg/L). Red blood cell
count, glucose, electrolytes, calcium, liver and renal function
tests, cholesterol and triglycerides levels were within normal
ranges.
The histopathological examination of a skin specimen obtained
from the buttock lesion showed a normal epidermis and the entire
dermis was infiltrated by well-formed xanthogranulomas, sheets of
histiocytic cells, foam cells, giant cells and a few lymphocytes
(figures 2 and 3). Some giant cells were of the Touton type with
interspersed necrobiotic zones.
The increase of NXG lesions altered the normal vision of
patient. The stable situation of her lymphoma at this moment did
not justify new chemotherapy treatment. In this manner, a
palliative treatment of periorbital lesions with carbon dioxide
laser was proposed.
After thorough explanation of the possible therapeutic efficacy
and consequences of CO2 laser treatment, written consent
was obtained from the patient.
Intralesional anaesthesia was performed, using mepivacaine al 2%
without epinephrine. A carbon dioxide laser (Kaplan pendulaser
system, Optomedic Medical Technologies Ltd, Or-Yehuda Israel, a
portable laser with maximal power density of 20 W/cm2,
that permits pulses of 90 ms) was used to treat the entire
surface of all eyelid lesions. Several laser passes were performed
on each lesion, using a focused mode with a power density of 5
W/cm2. After each pass, the partially desiccated tissue
was manually removed with a saline-soaked gauze. When the indurated
mass of NXG was entirely removed, a topical antibiotic ointment
(mupirocine) was applied to the wound and the area was covered with
a dressing. Three sessions of treatment were carried out over four
weeks.
After the three sessions of treatment, residual lesions of NXG
were present, nevertheless the improvement of the cutaneous lesions
was very relevant, achieving good functional results. After 12
months of follow-up, no relapse of the cutaneous lesions was
observed.
Discussion
Approximately 70 cases of NXG have been described in the literature
[9-11], with no sex predilection and an average age of appearance
of 56 years (range 17 to 85 years) [3]. As with 90% of described
cases [9, 12], our patient had monoclonal gammopathy IgG lambda
type.
Skin lesions frequently involve the periorbital region, trunk
and extremities. Several reports have documented the association
with extracutaneous involvement, including upper respiratory tract,
granulomatous infiltration of the lung, skeletal muscle, kidney,
hepatic and splenic granulomas, necrobiotic lesions of the
intestine, pelvic and retroperitoneal xanthogranuloma lesions [3,
10], and myocardial infiltration evidenced at autopsy [5, 13]. In
our case, the clinical appearance of the lesions was very
characteristic, with involvement of the periorbital area and left
buttock, and no evidence of extracutaneous involvement.
NXG may be a paraneoplastic feature. In 13% of cases NXG is
associated with carcinoma or lymphoproliferative diseases [3, 6].
Patients with benign monoclonal gammopathy have a 10% risk of
further development of multiple myeloma, macroglobulinemia,
amyloidosis or malignant lymphoproliferative diseases [14]. Our
patient had lymphoplasmacytic lymphoma diagnosed 4 years before.
The association of NXG and lymphomas is well described in the
literature [15-17]. However, to our knowledge, the specific
relationship of lymphoplasmacytic lymphoma to NXG has not been
reported.
The histopathological picture of NXG is characterized by a
confluent granulomatous infiltrate involving the whole dermis and
extending into subcutaneous tissues, comprising a mixture of
lymphocytes, epithelioid cells, foamy cells, and Touton giant
cells. Cholesterol clefts, lymphoid nodules, some of which develop
germinal centres, and perivascular aggregates of plasma cells are
frequent features. Numerous, atypical, bizarrely angulated,
multinucleated giant cells may be seen adjacent to the areas of
necrobiosis. Less common, but characteristic when occurring, are
palisading cholesterol cleft granulomas and xanthogranulomatous
panniculitis [4, 18, 19]. Our case presented typical
histopathological features.
Laboratory findings include: paraproteinemia (IgG kappa or
lambda), cryoglobulinemia, found in about 40% of cases, elevated
sedimentation rate, neutropenia, leukopenia, and
hypocomplementemia. Lipids may be elevated, normal or reduced [4,
9, 18, 20]. Many of these abnormalities were seen in our case.
Although there is no specific therapy for NXG, various
treatments have been used with variable outcome, such as alkylating
agents (chlorambucil or melphalan), associated or not with
corticosteroids, methotrexate, cyclophosphamide, azathioprine,
nitrogen mustard, plasmapheresis, local radiation therapy, and
combination treatment with interferon alpha 2b [6, 18, 21]. The
treatment of cutaneous lesions through surgical interventions is
controversial, because the lesions have a tendency to recur after
these interventions [8]. Jakobiec et al. [22] reported recurrence
of xanthogranulomas similar to NXG within 6 months to 1 year after
surgical procedure. In this study, recurrence of the lesions after
excision was noted in 11 patients (42%), and development of lesions
on previously disease-free incision sites occurred in 3 patients
(12%). Cutaneous lesions in 2 patients worsened after trauma and
intralesional corticosteroid injection. Problems with healing
occurred in 2 patients after incisional surgery. Thus, more than a
half of the patients experienced both rapid recurrence and lesions
ultimately become larger than their original surgical scars. It may
be prudent to delay the surgical treatment as long as possible
[23].
In contrast with other reports [7, 22, 24], in our case we
decided to perform a palliative treatment of the cutaneous lesions
with carbon dioxide laser, because a new treatment with alkylating
agents, associated or not with corticosteroids, was not justified
because of the stable situation of her lymphoplasmacytic lymphoma.
The CO2 laser, especially when the principles of
selective photothermolysis are adhered to, offers the laser surgeon
multiple opportunities to enhance the care of patients with
selected cutaneous conditions ( (figure 4) )[24]. Adequate
surgical technique and postoperative care minimize the possible
secondary effects of CO2 laser treatment, such as
scarring or pigmentary changes. In our case, the improvement of the
lower eyelid lesions after CO2 laser treatment was very
relevant, and a new increase of cutaneous lesions after a 12-month
follow-up was not observed.
Therefore, we believe that CO2 laser surgery may be
an additional palliative therapeutic option for selected cases of
NXG.
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