Therapy of necrobiotic xanthogranuloma - case series and review of the literature.

Necrobiotic xanthogranuloma is a rare disease that is part of the non-Langerhans cell histiocytoses. It is characterized by yellowish skin lesions, which are typically periorbitally localized. Extracutaneous manifestations of all organs are possible and can cause potentially life-threatening complications. The disease also belongs to the facultative paraneoplasias and is often associated with paraproteinemia. These aspects should be considered regarding further diagnostics. Due to the rarity of the disease, there are no standardized guidelines for therapy so far. The combination of prednisolone and chlorambucil as well as intravenous immunoglobulins seem to be effective therapeutic options. We present four cases from our clinic as well as the current results of the literature in this mini-review and would like to highlight the therapeutic challenge as well as the need for the development of guidelines.

Non-dermatologic isolated intracranial necrobiotic xanthogranuloma.

Necrobiotic xanthogranuloma is a condition that was first identified in 1980 based on its characteristic histological identity, and it has been known since then as a dermatologic manifestation of an underlying systemic dysproteinemia. Intracranial manifestation is a rare presentation of this condition and has been reported only once in its more than 40 years of existence. Herein and to our knowledge, we report the second observation of an intracranial manifestation and, surprisingly, the first case without the expected dermatologic and systemic dysproteinemia associations. This case identifies an existing knowledge gap in our understanding of necrobiotic xanthogranuloma and emphasises the need for further research into understanding the presentation, comorbidities and management of this condition.

Necrobiotic Xanthogranuloma With Associated Monoclonal Gammopathy Presenting as an Eyelid Nodule.

Necrobiotic xanthogranuloma (NXG) is a progressive non-Langerhans cell histiocytosis with a predilection for the periorbital area. NXG is most commonly associated with monoclonal gammopathy and ophthalmic complications. The authors present a 69-year-old man who was evaluated for a left upper eyelid nodule and plaques on the lower extremities, trunk, abdomen, and right upper extremity. Biopsy of the eyelid was supportive for NXG. Serum protein electrophoresis was positive for a monoclonal gammopathy, IgG light chain kappa. MRI showed preseptal involvement. The periocular nodules cleared with a high dose of prednisone; however, the other skin lesions persisted. Bone marrow biopsy showed kappa-restricted 6% plasma cells and he was treated with intravenous immunoglobulin. This case illustrates the importance of clinicopathologic correlations to render an NXG diagnosis.

[The clinicopathological features of adult orbital xanthogranulomatous disease with lacrimal gland reactive lymphoid hyperplasia].

Objective: To investigate the clinicopathological features of adult orbital xanthogranulomatous disease (AOXGD) with lacrimal gland reactive lymphoid hyperplasia. Methods: Retrospective case series study. The clinical and pathological data of AOXGD cases diagnosed and treated in Tianjin Eye Hospital from January 2002 to December 2021 was reviewed, and the clinical characteristics, radiologic findings and pathological characteristics of periocular and lacrimal gland lesions of 5 cases were retrospectively analyzed. The expression of IgG4 and IgG protein in periocular and lacrimal gland lesions was detected by immunohistochemical staining, and the role of IgG4 in AOXGD was preliminarily studied. Results: There were four females and one male with an average age of 53.8 years (39 to 77 years). Among the five AOXGD cases, there were three cases of adult-onset xanthogranuloma, one case of adult-onset asthma and periocular xanthogranuloma, and one case of necrobiotic xanthogranuloma. All cases involved both eyes. The swelling of eyelids was observed in five cases, and the yellow or pale yellow eyelid skin was found in two cases. Imaging examinations showed the tumor mainly involved the eyelids, subcutaneous tissues, anterior orbit and lacrimal gland. A large number of foam cells and typical Touton giant cells were found in the periorbital lesions, accompanied by different degrees of fibrosis. The fibrinoid necrosis was detected in one case of necrobiotic xanthogranuloma. The lacrimal gland lesions showed different types of reactive lymphoid hyperplasia, including IgG4-related disease in two cases, follicular lymphoid hyperplasia in two cases and focal lymphoid hyperplasia in one case. IgG4 levels of periorbital and lacrimal gland lesions were elevated in four cases. Asthma and elevated serum IgG4 were found in one case of adult-onset periocular xanthogranuloma. Three patients underwent surgical resection and adjuvant hormone or immunosuppressive therapy, and two patients underwent simple surgical resection. The patients were followed up for 1.5 to 10.0 years, one patient was lost, and four patients had no recurrence. Conclusions: AOXGD with lacrimal gland reactive lymphoid hyperplasia is a group of rare diseases. The periorbital lesions of that are characterized by proliferation of foamy histiocytes and Touton giant cells, and the lacrimal gland lesions of that manifest as IgG4-related disease in some cases.

Slow increase of bilirubin concentration during administration of lenalidomide, bortezomib and dexamethasone for multiple myeloma (unmasking previously undiagnosed Gilbert syndrome) and disappearance of necrobiotic xanthogranuloma after complete remission of multiple myeloma.

BACKGROUND: Lenalidomid ranks among immunomodulatory drugs. There are a few of the more common side effects, like a higher risk of venous trombembolism or diarrhea. Other side effects are rare. The hyperbilirubinemia described in this article can be assigned to them. In our case, the increase of bilirubin was associated with unrecognized Gilbert syndrome. CASE DESCRIPTION: We report a patient with multiple myeloma and necrobio-tic xanthogranuloma (NXG) of the skin and liver. After the treatment with bortezomib, lenalidomid and dexamethasone, complete remission was attained after 4 cycles with decrease of monoclonal immunoglobulin to an unmeasurable concentration. At the same time, the dis-appearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT was evident. The administration of bortezomib was stopped after 8 cycles and only continued with lenalidomide as a maintenance therapy. However, after four cycles of this therapy, bilirubin increased above the upper limit and the increase continued till the 11th month of lenadomide administration, when bilirubin reached the highest concentration of 75 μmol/l (more than the three-fold of the upper limit, grade III toxicity). The patient had asymptomatic hyperbilirubinemia with no underlying liver disease or renal impairment while being on lenalidomide therapy. Genetic studies proved mutation; insertion in the promotor gene UGT1A1 typical for Gilbert syndrome. Hyperbilirubinemia may be attributed to the unmasking of previously undia-gnosed Gilbert syndrome. Therefore, the therapy with lenalidomide was interrupted after 11 months. The bilirubin level decreased after the discontinuation of the drug. CONCLUSION: NXG disappeared after fulfilling complete remission of multiple myeloma with disappearance of monoclonal immunoglobulin. This observation supports the hypothesis that monoclonal immunoglobulin has a crucial role in the ethiopathogenesis of NXG and suggests the treatment of monoclonal gammopathy if present in a patient with NXG, hoping that this will result in xantogranuloma disappearance.

Tratamiento quirúrgico del xantogranuloma palpebral. Caso clínico / Surgical treatment of eyelid xanthogranulomas. Case report

El xantogranuloma es una lesión poco frecuente que caracteriza al amplio grupo de las histiocitosis de células no Langerhans (NLCH). Se describen diferentes variantes de NLCH: xantoma, xantogranuloma juvenil, xantoma disseminatum, xantogranuloma necrobiótico, retículohistiocitosis, enfermedad de Rosai Dorfman y un conjunto heterogéneo de enfermedades infrecuentes que comparten manifestaciones cutáneas e histopatológicas comunes y que se describen como enfermedad xantogranulomatosa orbitaria del adulto (EXOA). La enfermedad de Erdheim Chester (EEC) está incluida en este último grupo. Nuestro objetivo es describir un caso clínico con gran compromiso sistémico y lesiones cutáneas en ambos párpados superiores e inferiores que invalidaban a la paciente física y psicológicamente. Presentamos su resolución quirúrgica con resección amplia de lesiones y reconstrucción con injertos de piel total con un muy buen resultado estético y funcional. (AU)

Xanthogranuloma is a rare lesion that characterizes the large group of non-Langerhans cell histiocytosis (NLCH). Different variants of NLCH: xanthoma, juvenile xanthogranuloma, xanthoma disseminatum, necrobiotic xanthogranuloma, reticulum histiocytosis, Rosai Dorfman disease, and a heterogeneous set of rare diseases that share common cutaneous and histopathological manifestations are described as orbital xanthogranulomatous disease of the adult (EXOA). Erdheim Chester disease (ECD) is included in this last group. Our objective is to describe a clinical case with great systemic involvement and skin lesions in both upper and lower eyelids that invalidate the patient physically and psychologically. We present its surgical resolution with wide resection of lesions and reconstruction with total skin grafts with a very good aesthetic and functional result. (AU)

First case report of pre-mortem biopsy-proven kidney involvement by necrobiotic xanthogranuloma with monoclonal gammopathy.

Necrobiotic xanthogranuloma (NXG) is a rare non-Langerhans cell histiocytosis with characteristic cutaneous features and rare visceral involvement. More than 80% of individuals with this disease have a detectable paraprotein but the precise pathogenesis remains obscure. A 68-year-old man with known cutaneous necrobiotic xanthogranuloma presented with acute kidney injury and imaging suggestive of bilateral perinephric infiltration. Renal biopsy showed a prominent histiocytic infiltration of renal capsule and cortex with necrobiosis and characteristic 'Touton-type' giant cells suggestive of necrobiotic xanthogranuloma involvement. Kidney function returned to normal and cutaneous lesions improved with a combination of corticosteroid, chlorambucil and rituximab. This case represents only the second reported incidence of kidney involvement by necrobiotic xanthogranuloma and the first with acute kidney injury and pre-mortem histopathology. This report adds to a small body of literature on the diagnosis and management of visceral involvement by this rare disease.

Complete remission of necrobiotic xanthogranuloma after disappearance of monoclonal immunoglobulin induced by bortezomib, lenalidomid and dexamethasone.

Necrobiotic xanthogranuloma (NXG) is a rare chronic condition, belonging to the group non-Langerhans cell histiocytoses, which is relevant due to the possibility of extracutaneous involvement and association with systemic diseases, particularly monoclonal gammopathy, MGUS and multiple myeloma. The case reported here NXG was diagnosed after 1 years of evolution in patient with asymptomatic multiple myeloma. After treatment with bortezomib, lenalidomid and dexamethasone, there was evident abrupt decrease of monoclonal immunoglobulin to not measurable level (complete remission of multiple myeloma) and in the same time was evident disappearance of cutaneous and hepatic lesions of NXG on FDG-PET/CT. The etiopathogenetic association of monoclonal immunoglobulin with NXG is documented in this case report with disappearance of NXG in the time of disappearance of monoclonal immunoglobulin.