Necrobiotic Xanthogranuloma in a Patient with Multiple Myeloma.

An 82-year-old woman presented with a 9-month history of multiple, well-defined skin lesions on her neck and upper chest, progressively increasing in size. Histological examination of a skin biopsy showed a regular epidermis. In the dermis, granulomatous changes with central necrobiosis were found which extended focally into the subcutaneous fat. The necrobiotic areas were surrounded by Touton cells and foreign-body giant cells. Laboratory analysis revealed leucopenia. Serum electrophoresis and immunofixation disclosed the presence of an IgG-λ paraprotein. Bone marrow aspiration cytology showed 20% plasmatic cells. The skeletal X-ray revealed frontal and occipital osteolytic skull lesions as well as pubic osteolysis. Urinalysis was unremarkable without proteinuria. Based on the clinical, laboratory, and histological findings, necrobiotic xanthogranuloma in association with multiple myeloma was diagnosed. The patient was treated with bortezomib combined with oral dexamethasone. Follow-up at week 13 revealed the complete disappearance of the IgG paraproteinemia. However, the skin lesions remained unchanged. Therefore, bortezomib treatment was discontinued, and systemic corticosteroids were continued at a higher dosage. After the steroid treatment, the lesions markedly flattened.

Case Report

An 82-year-old woman presented with a 9-month history of multiple, well-defined skin lesions on her neck and upper chest, progressively increasing in size. They presented as asymptomatic, reddish-yellowish, indurated nonscaly plaques measuring up to 10 cm in diameter (Fig 1a). In the center of some lesions, atrophic areas were observed. The patient had no remarkable illness and did not regularly take medication.

Fig. 1

a Extensive indurated plaques with central atrophy and yellowish discoloration. b Granulomatous infiltrate with necrobiotic areas in the dermis (hematoxylin and eosin, original magnification ×40). c Immunocytochemistry: staining positive for CD68.

Histological examination of a skin biopsy taken from an indurated plaque on the right chest showed a regular epidermis. In the dermis, granulomatous changes with central necrobiosis were found which extended focally into the subcutaneous fat. The necrobiotic areas were surrounded by Touton cells and foreign-body giant cells (Fig 1b). Immunocytochemistry showed the infiltrate to be largely composed of CD-68-positive macrophages and monocytes (Fig 1c). Laboratory analysis revealed leucopenia (2.92 g/L) as well as an elevated erythrocyte sedimentation rate (88 mm after 1 h, 100 mm after 2 h). Serum electrophoresis and immunofixation disclosed the presence of an IgG-λ paraprotein (IgG 25.31 g/L; normal range 5.52–16.31 g/L). Lyme disease serology was negative. Bone marrow aspiration cytology showed 20% plasma cells. The skeletal X-ray disclosed frontal and occipital osteolytic skull lesions as well as pubic osteolysis. Urinalysis was unremarkable without proteinuria.

Based on the clinical, laboratory, and histological findings, necrobiotic xanthogranuloma (NXG) in association with multiple myeloma was diagnosed. The patient was treated with bortezomib (1.3 mg/m2 body surface s.c. once a week) for 12 weeks combined with oral dexamethasone (initially 20 mg/day). The dosage of the corticosteroid was progressively reduced during the following weeks.

Follow-up at week 13 revealed the complete disappearance of the IgG paraproteinemia. However, the skin lesions remained unchanged. Therefore, bortezomib treatment was discontinued, and systemic corticosteroids were continued at a higher dosage. The patient received oral dexamethasone (40 mg/day) for 2 weeks, followed by maintenance therapy (4 mg/every other day) during 2 months. After the steroid treatment, the lesions markedly flattened.

Discussion

We report here a patient whose primarily dermatological concern led us to the diagnosis of multiple myeloma. NXG is very rare and was first described by Kossard and Winkelmann in 1980 [1]. NXG is a disease of adults; the average age of onset is in the sixth decade. In 85% of cases, NXG is located in the periorbital area, and the lesions tend to progress towards the face. The trunk and proximal extremities are other affected sites. Lesions have a red-orange or yellow color and may present telangiectasia, atrophy, and ulceration. Ocular involvement occurs in approximately 50% of cases, including orbital masses, conjunctivitis, keratitis, scleritis, and uveitis. Extracutaneous involvement includes the heart, lungs, kidneys, liver, spleen, intestine, skeletal muscles, and central nervous system. NXG is categorized as non-Langerhans cell histiocytosis, often associated with monoclonal gammopathy (up to 90%). Some patients were reported to have multiple myeloma (10%), lymphoproliferative disorders, and/or atypical plasma cells in bone marrow examination [2, 3].

The link between NXG and paraproteinemia remains unclear. A deposition of immunoglobulins and lipid complexes with monocyte activation and foreign-body giant-cell reaction is suspected [4]. Recently, no treatment modality has been shown consistently effective. Treatment includes systemic or intralesional corticosteroids, chlorambucil, melphalan, topical mechlorethamine, dapsone, intravenous immunoglobulins, and lenalidomide [5, 6, 7]. Extracorporeal photopheresis has been used as well as autologous stem cell transplantation [8].

Bortezomib is a proteasome inhibitor and is considered as a major milestone in the treatment of multiple myeloma. In 2008, the US FDA approved bortezomib as a first-line therapy of multiple myeloma [9]. To the best of our knowledge, this is one of the first treatment trials of NXG and multiple myeloma with bortezomib reported in the literature [9]. In our patient, bortezomib combined with low-dose systemic corticosteroids normalized the paraproteinemia but had no effect on the skin lesions. The latter improved after high-dose dexamethasone therapy, as previously reported in the literature [10, 11, 12]. This may underline that NXG is a reactive rather than a neoplastic skin disease.

Statement of Ethics

The patient has signed an informed consent for the publication of this case report.

The authors have no conflicts of interest to declare.