Spectacular skin nodules: cutaneous necrobiotic xanthogranuloma without paraproteinemia.

Necrobiotic xanthogranuloma (NXG) is a very rare, progressive variant of non-Langerhans cell histiocytosis. It is known to be associated with multisystem involvement and paraproteinemias. A 65-year-old female presented with chronic, slowly growing, asymptomatic periorbital nodules. The lesions had recurred after local excision elsewhere. No systemic involvement or paraproteinemias were detected. A provisional diagnosis of isolated cutaneous NXG was made which was confirmed by histopathology and immunohistochemistry staining. The lesions were surgically excised with excellent cosmetic and functional results. There was no recurrence over a period of 9 months. To our knowledge, this is the second case of NXG reported from India and the first without any systemic manifestations.

Introduction

Necrobiotic xanthogranuloma (NXG) was first described as a separate entity by Kossard and Winkelmann in 1980. It belongs to Class II b of non-Langerhans cell histiocytosis.[1] The disease is characterized by multiple, plaque- like, yellow-brown lesions, with a predilection for the periorbital area (spectacle-like distribution). The lesions are sometimes associated with atrophy, telangiectasias and ulceration. Majority of the cases reported have an associated paraproteinemia of the IgG-κ type.

About 100 cases have been reported in world literature.[2] To our knowledge, this is the first case of isolated cutaneous NXG being reported from India.

Case Report

A 65-year-old female presented with a 3-year history of gradually enlarging, periorbital, asymptomatic lesions. One of the lesions had been excised surgically 2 years ago in another hospital. However, it recurred in a few months and was accompanied by new larger nodules. There was no history of ulceration or any involvement of other sites. There was no history of any eye complaints or any significant systemic symptoms. The patient's medical history was not pertinent.On examination, there were multiple, yellowish brown, firm nodules distributed symmetrically in the periorbital area. The size of the nodules varied from 3 to 7 cm in their widest dimensions. The surface showed a few telangiectasias and mild atrophy [Figures 1 and 2]. There was mild right-sided ectropion.

Figure 1

Yellow brown firm periorbital nodules

Figure 2

Superficial telangiectasias and mild atrophy

With this history and clinical findings, a provisional diagnosis of a xanthomatous disorder was made.

Histopathological examination of a surgical wedge biopsy showed ill-defined large foci of dense granulomatous infiltrate of large histiocytes and histiocytic foamy cells with lymphocytes and few plasma cells. Several histiocytic giant cells resembling Touton giant cells were present [Figures 3 and 4]. However, typical findings of necrobiosis were not seen.

Figure 3

Dense granulomatous infiltrate of histiocytes

Figure 4

Touton giant cell

Laboratory investigations were normal for blood counts, electrolytes, glucose levels, LFTs, except for S.triglycerides and S.cholesterol levels which were mildly elevated.

Serum protein electrophoresis was within normal limits. Immunohistochemistry was positive for CD 68 [Figure 5] and negative for CD 1a and S100.

Figure 5

CD 68 positive

Thus, a final diagnosis of isolated cutaneous NXG without paraproteinemia or associated disorders was made.

Surgical excision of the xanthogranuloma was done with primary closure.

The patient was maintained on a regular follow-up of every 15 days for the first 2 months and then once a month for 9 months. No evidence of any recurrence was seen [Figure 6].

Figure 6

Post treatment (after 9 months)

Discussion

NXG is a rare, progressive, histiocytic disease that features destructive cutaneous lesions, a close association with paraproteinemia, and multisystem extracutaneous manifestations. NXG is a disease of adults with an average age of onset in the sixth decade. NXG begins as papules and nodules that slowly enlarge into indurated plaques ranging from 0.5 to 25 cm. Characteristic lesions have a red-orange or yellow color as well as telangiectasias, atrophy, scarsand ulcers.[34] The most common site of involvement is the face, particularly the periorbital region (85% of cases); the trunk and proximal extremities are other affected sites.[3] Ophthalmological complications affect approximately 50% of cases and include orbital masses, conjunctival involvement, keratitis, scleritis, ectropion, uveitis and blindness.[34]

NXG may involve other extracutaneous sites, including the heart, lungs, kidneys, liver, spleen, intestines, skeletal muscle and central nervous system.[56] Paraproteinemia is closely associated with NXG, with approximately 80% of patients demonstrating a monoclonal gammopathy of IgG-κ on serum protein electrophoresis; furthermore, 10% of these patients develop multiple myeloma.[3] Other lymphoproliferative disorders such as Hodgkin's lymphoma have been associated with NXG.[7] Hepatosplenomegaly, lymphadenopathy, an increased erythrocyte sedimentation rate, leukopenia, hypocomplementemia, thrombocytopenia and cryoglobulinemia are other common findings.[34] Bone marrow biopsy can show plasmacytosis, myeloma or myelodysplastic syndromes.

The link between paraproteinemia and NXG remains unclear. Theories regarding pathogenesis include deposition of immunoglobulins and lipid complexes with a foreign body giant-cell reaction and monocyte activation with intracellular lipid accumulation.[8] Histopathological examination shows a palisading xanthogranuloma with areas of necrobiotic, degenerated collagen that infiltrates the mid-dermis with extension into the subcutaneous fat. Multiple xanthomatized histiocytes, touton giant cells, other bizarre giant cells, cholesterol clefts and lymphoid follicles are often present within granulomas.[9]

Only anecdotal reports are available to support treatment options for NXG. Improvement in skin lesions has been seen with low-dose chlorambucil,[9] melphalan with or without prednisolone, methotrexate, localized radiotherapy,[10] systemic glucocorticoids,[11] interferon α-2a,[12] and plasmapheresis with hydroxychloroquine.[13] Topically nitrogen mustard, BNCU, intralesional corticosteroids and intravenous immunoglobulin[2] have also been tried. Surgical excision has also been advocated.[14]

In our patient, we decided to surgically excise the lesions in view of absence of systemic involvement. We are gratified to observe no recurrence of any lesion over 9 months. Thus this could be considered as a viable therapeutic option in isolated cutaneous NXG.