Case 11 -

Necrobiotic Xanthogranuloma with Paraproteinemia Carlo Tomasini, MD

A 61-year-old woman presented with a 6 months-history of slowly enlarging red-yellowish nodules on the lower extremities. The remainder of the skin including the face and mucous membranes was spared. Past medical history was unremarkable. A biopsy of a cutaneous nodule was performed and material was submitted for routine histopathologic examination. Specimens showed a diffuse, predominantly granulomatous infiltrate through the dermis and panniculus consisting of sheets of histiocytes as well as giant cells of both the Touton and foreign-body types, and fewer lymphocytes. The granulomatous masses were associated with areas of degenerated hyalinized collagen ("necrobiosis") containing cholesterol clefts. Case 11 - Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Hematocrit and platelet count were within normal limits. Protein electrophoresis showed a spike in the gamma region, which reflected an elevated gamma-globulin level of 23 g/l. The erythrocyte sedimentation rate was elevated (96 mm/h). Iliac crest bone marrow cytology showed a normal cytology with an excess of interstitial plasmacells (17%), some of them with cytologic atypia, consonant with a diagnosis of monoclonal gammopathy of uncertain significance or early smouldering myeloma. Comment Necrobiotic xanthogranuloma (NXG) is a rare, progressive histiocytosis that features destructive cutaneous lesions, a close association with paraproteinemia, and multisystem extracutaneous manifestations. NXG occurs in adults most often in the sixth decade with papules and nodules that slowly enlarge into indurated plaques with tendency to ulcerate [1, 2]. Characteristic lesions have a red-orange or yellow color as well as teleangectasia, athrophy, scars, and ulcers. The periorbital region is the most common site of involvement. Other frequent sites include the trunk, face, arms, thighs, and lower extremities. Usually the number of lesions ranges from one-two to several. Approximately 50% of the patients have ophtalmic complaints, including burning, itching, or painful eyes and occasionally periorbital swelling reflecting histiocytic infiltration. Extracutaneous manifestations may involve the hearth, lungs, kidneys, liver, spleen, intestines, skeletal muscle, and central nervous system [1, 2]. Laboratory investigations should be performed in order to detect extracutaneous, potentially life-threatening localizations. Conversely, NXG without dermatologic involvement has been reported [3]. A monoclonal paraproteinemia, most commonly of IgG kappa light chain, is demonstrated in approximately 80 percent of patients with NXG by immunoelectrophoresis; furthermore, 10 percent of these patients develop multiple myeloma [1, 2]. A solitary variant of NXG without paraproteinemia has been reported [4], although it should be remembered that paraproteinemia may post-date the appearance of skin lesions by up to 10 years [5]. The link between paraproteinemia and NXG remains unknown. Recent theories suggest that deposition of immunoglobulin/lipid complexes could lead to a foreign body giant-cell reaction and monocytic activation resulting in a proliferation of a specific population of macrophages with surface receptors for the Fc fragment of Ig G [6]. Histopathologic findings Histopathology is characteristic in most cases showing huge zones of degenerated collagen accompanied by large number of necrotic inflammatory cells within the reticular dermis and subcutaneous fat. Cholesterol clefts, lymphoid nodules (with or without germinal center fromation), and foci of plasma cells complete the histologic picture, although they are inconsistently seen. Touton cell panniculitis and palisading cholesterol cleft granulomas are unique and may be diagnostic of this entity. Histopathologic differential diagnosis Histopathologic differential diagnosis mainly includes necrobiosis lipoidica that, however, displays much less degeneration of collagen, no necrosis en masses of inflammatory cells, no foam cells, adipocytes, or cholesterol clefts. Furthermore the panniculitis in necrobiosis lipoidica is mostly confined to the septa, whereas that of NXG involves both septa and lobules extensively. At a lesser extent, lupus panniculitis may be suggested in cases of NXG with prominent lymphoid nodules and panniculitis; however, granulomatous inflammation is a rare finding in lupus panniculitis, whereas is is quite extensive in NXG. Conclusion The early diagnosis of NXG in the skin is of great importance because it signals a patient who has or will have paraproteinemia. Period examinations for the rest of the patient's life are mandatory to detect the development of associated malignancies, especially multiple myeloma. References Kossard S, Winkelmann RK. Necrobiotic xanthogranuloma with paraproteinemia. J Am Acad Dermatol 1980;3: 257-70. Meheregan DA, Winkelmann RK. Necrobiotic xanthogranuloma. Arch Dermatol 1992;128:94-100 Tucker NA, Discepola MJ, Blanco G, Burnier MN Jr. Necrobiotic xanthogranuloma without dermatologic involvement. Can J Ophthalmol 1997;32:396-9. Chang SE, Lee WS, Lee W, Choi JH, Sung KJ, Moon KC, Koh JK. A case of necrobiotic xanthogranuloma withou paraproteinemia presenting as a solitary tumor on the thigh. Int J Dermatol 2003;42:470-2. Johnason KA, Grimwood RE, Meffert JJ, Deering KC. Necrobiotic xanthogranuloma with paraproteinemia: an evolving presentation. Cutis 1997; 59:333-6. Collet E, Dalac S, Guy H, Tavernier C, Lorcerie B, Besancenot JF, Escallier F, Lambert D. Manifestations cutanees au cours du myelome multiple. Ann Dermatol Venereol 1991;118:35-44.