Article

Necrobiotic Xanthogranuloma Without a Monoclonal Gammopathy

Cutis. 2014 December;94(6):293-296

Necrobiotic xanthogranuloma (NXG) is an indolent non–Langerhans cell histiocytosis characterized by yellow xanthomatous plaques that tend to ulcerate. Necrobiotic xanthogranulomas have a predilection for the bilateral periorbital region and often present with consequential ophthalmic findings. Histopathology usually reveals a distinctive pattern of histiocytic xanthogranuloma with hyaline necrobiosis. Necrobiotic xanthogranuloma has been documented to have a close association with paraproteinemia. We report the case of a 76-year-old man with periorbital NXG without development of a monoclonal gammopathy. Clinically, the patient presented with dry eyes and substantial periorbital edema with multiple yellow indurated plaques. He developed the condition 30 years prior to presentation at which time it was initially diagnosed as xanthelasma. He underwent surgical excision of the lesions 10 years prior to the current presentation and biopsy results revealed a diagnosis of NXG. The periorbital lesions recurred several years prior to presentation, prompting annual computed tomography scans to rule out ocular invasion. Periorbital edema and plaques improved during a 6-month regimen of acitretin but returned to baseline just months after discontinuation.

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Practice Points

Necrobiotic xanthogranuloma is a rare histiocytic disease that is strongly associated with monoclonal gammopathy.
Due to the rarity and uncertain etiology, there are no definitive first-line therapies.

References

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Necrobiotic xanthogranuloma (NXG) was first described in 1980 by Kossard and Winkelmann¹ as a xanthomatosis associated with paraproteinemia. It is an indolent disorder characterized by indurated, yellow to violaceous red papules, plaques, or nodules often presenting with telangiectases and ulceration.² The lesions have a predilection for the bilateral periorbital region in the majority of documented cases, consequently producing ocular findings such as periocular skin lesions, blepharoptosis, restricted ocular motility, and proptosis.³

Necrobiotic xanthogranuloma is a systemic disease that may involve extracutaneous sites such as the heart, respiratory tract, spleen, kidneys, ovaries, liver, skeletal muscle, and central nervous system.^4-6 The most common sites include the respiratory tract and heart, with documented cases of pulmonary and myocardial giant cell granulomas.⁴ In a 2009 review, Spicknall and Mehregan⁷ reported an increased frequency of systemic involvement.

The distinctive histopathologic features of NXG consist of large bands of necrobiosis and a pattern of palisading histiocytic granulomas comprised of Touton giant cells, bizarre foreign body giant cells, foam cells, and cholesterol clefts.⁸ These histopathologic findings differentiate NXG from other clinical differential diagnoses such as necrobiosis lipoidica.

Necrobiotic xanthogranuloma is associated with paraproteinemia in 80% of documented cases, most commonly as an IgG monoclonal gammopathy.² The etiology of this indolent disorder remains unclear despite proposed theories of its pathogenesis. Consequently, treatment proves difficult with no recommended first-line therapy and a tendency for recurrent cutaneous lesions. We report an unusual case of periorbital NXG without development of a monoclonal gammopathy.

Case Report

A 76-year-old man presented with a long-standing history (30 years) of bilateral periorbital NXG. Approximately 30 years prior to the current presentation, the patient presented to a dermatologist with dry eyes and periorbital cutaneous lesions that were originally diagnosed as xanthelasma. He later developed edema of the right periorbital region that progressed to involve the left periorbital region. He underwent surgical excision of the lesions 10 years prior to the current presentation, which showed the lesions were infiltrating into the muscle. At that time, a diagnosis of NXG was made. The department of plastic surgery at an outside institution evaluated the patient and identified no further treatment options; however, annual computed tomography scans were performed to detect disease progression.

The patient presented for increasing periorbital manifestations of NXG. He denied any other remarkable medical history or any family history of NXG, malignancy, or hematologic disorders. His surgical history was exclusive to the excisional surgery of the periorbital lesions. At the time of presentation he was not taking medications and had no known drug allergies. He denied tobacco use but occasionally consumed alcohol.

On systemic inquiry the patient’s only concerns were ocular in nature and included dry, sensitive, and painful eyes. Dermatologic examination revealed substantial periorbital edema with multiple yellow indurated plaques (Figure). There were no additional findings on physical examination.

^{^{Bilateral periorbital edema with yellow indurated plaques (A). A lateral view showed substantial right periorbital edema with multiple yellow plaques (B).}}

Extensive hematologic and oncologic investigations revealed the absence of a monoclonal gammopathy. Serum protein electrophoresis was negative for paraproteinemia and quantitative serum immunoglobulin testing was normal. A complete blood cell count, lipid panel, CD4 count, CD8 count, C3, C4, and computed tomography scan did not reveal any abnormalities. A complete metabolic panel identified elevated serum glucose levels (162 mg/dL [reference range, 74–118 mg/dL]), low serum albumin levels (3.3 g/dL [reference range, 3.5–4.8 g/dL]), and low serum calcium levels (8.8 mg/dL [reference range, 8.9–10.3 mg/dL]). IgG subclass (SC) proteins were mildly increasedwith an IgG SC1 of 950 mg/dL (reference range, 382–929 mg/dL), IgG SC3 of 211 mg/dL (reference range, 22–178 mg/dL), and IgG SC4 of 292 mg/dL (reference range, 4–86 mg/dL), and the plasma IgG was in the upper limit of the reference range with a value of 1591 mg/dL (reference range, 791–1643 mg/dL).

After the hematologic and oncologic workup was completed, intravenous immunoglobulin and acitretin were recommended to the patient as viable treatment options to reduce the cutaneous sequelae of NXG. A 6-month regimen of acitretin markedly improved cutaneous edema and plaque size. However, these sequelae returned to baseline just months after acitretin was discontinued.

Comment

Necrobiotic xanthogranuloma is a distinct granulomatous disorder with no predilection for sex and the average age of onset is 54 years.² Consistent with prior reports, our patient presented with bilateral periorbital lesions and ophthalmic concerns of dryness, burning, and sensitivity. Reddy et al⁹ demonstrated that aggressive forms of periorbital NXG may involve ocular tissues and result in vision loss and corneal perforation. On follow-up, our patient underwent annual computed tomography scans to rule out further progression.