A multisystem granulomatous disease: necrobiotic xanthogranuloma with hepatic involvement

Abstract

Necrobiotic xanthogranuloma is a rare, multisystem granulomatous disease that can have skin and visceral organ involvement. It is strongly associated with paraproteinaemia, and has rare potential for transformation to myeloma or lymphoma, warranting ongoing surveillance. We report a challenging case of necrobiotic xanthogranuloma, believed to be the fi rst reported case of hepatic involvement. Clinical recordA 51-year-old woman was referred to hospital after an incidental fi nding of abnormal liver function test results . She was otherwise well and asymptomatic. Her past medical history included resistant hypertension with renal denervation 8 months earlier, and chronic macrocytic anaemia secondary to alcohol. Physical examination was largely unremarkable apart from several skin nodules and hepatomegaly (4 cm below the costal margin). She underwent an abdominal ultrasound, which showed multiple hypoechoic liver lesions suspicious for metastasis. An abdominal computed tomography (CT) scan (Box 1) confi rmed the presence of hypovascular liver lesions suggestive of metastasis. Malignancy screening, including mammography, colonoscopy and CT of the chest, abdomen and pelvis, was negative. A subsequent liver biopsy specimen showed necrotising granulomas with no evidence of malignancy. The initial histopathological impression was of mycobacterial infection, despite negative Ziehl-Neelsen and Gram stains and the absence of infective organisms.Further assessment found no risk factors for tuberculosis exposure and no symptoms of underlying infection. Dermatology consultation was requested and the skin nodules were closely examined. These included a 1 2 cm violaceous nodule on the left side of the woman's neck, a 2 5 cm yellowish plaque on her left fl ank, and a large violaceous-yellow plaque exhibiting Koebner phenomenon along the scar from her left total knee replacement surgery (Box 2). The patient reported that they had been present for 8-12 months and were asymptomatic. Biopsy specimens from the lesions on her neck and fl ank showed identical histological features to the liver specimen, again negative for Mycobacterium tuberculosis on Ziehl-Neelsen stain, culture and polymerase chain reaction (PCR) testing. A previous biopsy sample of the plaque overlying her kneereplacement scar had been taken by a dermatologist and showed non-discrete granulomatous infl ammation and necrobiosis (Box 3, A). In retrospect, this was consistent with her current skin sample.Thorough investigations were performed for causes of systemic granulomatous diseases. Infective causes that were investigated included histoplasmosis, brucellosis and mycobacterial infections. However, results from extensive serological testing, cultures, tuberculosis PCR testing of the skin and liver biopsy samples, and an interferon-γ release assay were negative. Non-infective differential diagnoses included sarcoidosis or vasculitis. However, angiotensin-converting enzyme concentration was low and no hilar lymphadenopathy was found on CT of the chest. Results of au...

A Multicenter Cross-Sectional Study and Systematic Review of Necrobiotic Xanthogranuloma With Proposed Diagnostic Criteria

“…In the systematic review, the initial search yielded 1199 records, 151 of which were included (Figure). These reports described 201 patients with NXG, with demographics, comorbidities, and clinical features (detailed in the eTable in the Supplement).…”

An unusual case of necrobiotic xanthogranuloma with IgG-λ monoclonal gammopathy presenting as cerebral manifestations

“…The clinical signs often affect the periorbital skin, with light yellow or orange pimple-like lesions. Multiple organs may be involved, such as the gastrointestinal tract, heart, liver, spleen, lung, and bone (5,12). Involvement of the nervous system is very rare, and was only reported in 2004 by Shah et al, who described a case of bilateral frontal lobe parenchymal NXG but not involving the meninges or frontal scalp (13).…”

A 55‐Year‐Old Man With Periorbital and Inguinal Masses, Pericarditis, and Pleuritis

“…Periorbital skin involvement is observed in the majority of patients and can lead to complications including ptosis, restricted ocular mobility, and proptosis . Visceral organ involvement with nodular NXG lesions, including the myocardium, lungs, and liver, has also been reported . Histology in NXG is characterized by collagen necrobiosis, Touton giant cells, cholesterol clefts, lymphoid aggregates, and foamy histiocytes that extend from the dermis into the subcutaneous tissue .…”

“…Histology in NXG is characterized by collagen necrobiosis, Touton giant cells, cholesterol clefts, lymphoid aggregates, and foamy histiocytes that extend from the dermis into the subcutaneous tissue . Many patients have an associated monoclonal gammopathy, most often of the IgG‐kappa type . Other disease associations include multiple myeloma, lymphoma, and chronic lymphocytic leukemia .…”