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Case: A 47-year-old Japanese woman with a medical history of xanthoma disseminatum (XD) presented with posterior neck pain and abnormal gait without a history of trauma. Imaging studies revealed odontoid process thinning resulting in its fracture due to XD involvement in the atlantoaxial joint and subsequent cervical myelopathy. Posterior C1-C2 fusion surgery improved the patient's symptoms. An XD lesion around the odontoid process was confirmed intraoperatively., Conclusion: We report cervical myelopathy caused by XD involvement in the C1-C2 joint, showing that early fusion surgery is critical for treating pathological fractures in patients with XD., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B885)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Abstract: Xanthoma disseminatum (XD) is a rare non-Langerhans cell histiocytosis characterized by xanthomatous lesions in the absence of hyperlipidemia. XD usually develops in young adults, and there are rare cases among children. BRAF mutations are frequent in Langerhans cell histiocytosis and Erdheim-Chester disease but absent or only rarely detected in other histiocytosis. Herein, we described a 6-year-old Chinese girl presented with generalized skin lesions and diabetes insipidus for 5 months. There were multiple periorbital xanthelasma with histopathological features of foamy histiocytes infiltration with Touton cells. Pituitary magnetic resonance imaging showed pituitary enlargement and pituitary stalk thickening. The presence of BRAF p.V600E mutation makes this case distinctive and also offers a potential therapeutic target. According to our review of the literature, this is the first pediatric XD with diabetes insipidus and BRAF mutation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: We report the case of a 60-year-old woman who underwent 18F-FDG PET/CT to evaluate a metastatic breast carcinoma. Follow-up 18F-FDG PET/CT showed progressive disease with 18F-FDG increased in primary tumor, axillary lymph nodes, and pleural and bone diffuse metastases but also a concomitant uptake in multiples joints. The anatomopathological analysis from skin biopsy revealed a multicentric reticulohistiocytosis, considered paraneoplastic in the context. Second follow-up PET/CT after treatment showed a decrease of 18F-FDG uptake in previously affected joints, consistent with the symptoms evolution. 18F-FDG PET/CT could be helpful in the detection and the evaluation of such rare systemic disorder., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Cutaneous disease can present with lesions of all colors of the visible spectrum. Lesions of the skin, nail, and mucous membranes with an orange color can be due to a variety of etiologies. The conditions may appear as purely orange, yellow-orange, red-orange, tan, or brown with an orange hue. The orange color may also present as a transient phase of a disease process. As with all dermatologic pathology, a key way to distinguish orange-colored lesions is by distribution and morphology. The sclera, palate, lips, gingiva, and nails may also be involved. A literature review using PubMed with keywords, including orange, skin, mucosa, cutaneous, xanthoderma, and granuloma, was conducted to gather all dermatologic conditions that can present with an orange color. The relevant diseases were categorized by etiology and include inflammatory, infectious, neoplastic, and exogenous causes., (Copyright © 2019. Published by Elsevier Inc.)

A 9-year-old boy presented with multiple hyperpigmented papules over flexors with polyuria, polydipsia and progressive loss of vision. Histopathology of papule suggested a diagnosis of non-Langerhans cell histiocytosis and systemic evaluation showed central diabetes insipidus and optic atrophy. With a diagnosis of xanthoma disseminatum with significant neurological involvement, he received cladribine therapy and showed significant improvement in both cutaneous and nervous system lesions., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: The prevalence of concomitant myeloid neoplasms was recently reported to be unexpectedly high among adults without non-Langerhans cell histiocytosis (non-LCH); however, the coexistence of non-LCH with RUNX1 genetic aberration has not been reported previously., Methods: Herein, we report a 23-year-old woman with severe pancytopenia diagnosed with non-LCH following presentation with pancytopenia and marrow examination showing histiocytosis positive for CD45, CD68, CD136, and lysozyme but negative for CD1a, langerin, and S100., Results: Whole-exome sequencing showed RUNX1 mutation and NF1 mutation. In the ensuing 6 months, she developed hepatosplenomegaly, and repeat bone marrow evaluation was diagnostic of acute myeloid leukemia (AML). Repeat mutational analysis showed again presence of RUNX1 mutation. She underwent induction therapy but died of septic shock., Conclusions: The demonstration of RUNX1 mutation in both non-LCH and AML bone marrow specimens at differing time points is suggestive of a biologic association of both distinct disease entities., (© American Society for Clinical Pathology, 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Competing interests: None declared.

Competing Interests: Competing interests: None declared.

Yellowish papules, nodules, or plaques, namely "xanthomatous" lesions, may be seen on the eyelids in the course of various disorders. The prototype is "xanthelasma palpebrarum" (XP) that is localized only to the eyelids and may be associated with hyperlipidemia. On the other hand, different types of normolipemic disorders may also cause xanthomatous eyelid lesions. Among these, Langerhans cell histiocytosis, diffuse normolipemic xanthoma, and non-Langerhans cell histiocytoses (papular xanthoma, juvenile xanthogranuloma, xanthoma disseminatum, adult-onset xanthogranuloma, adult-onset asthma and periocular xanthogranuloma, necrobiotic xanthogranuloma, Erdheim-Chester disease, Rosai-Dorfman disease, and reticulohistiocytosis) can be listed. The eyelid findings of this heterogeneous group of disorders are challenging to differentiate from each other due to common clinical aspects that may even sometimes mimic XP. Nodularity, induration, ulceration, diffuse eyelid involvement, and extension from eyelids to the neighboring skin may represent the clinical features of xanthomatous lesions other than XP. It is necessary to obtain a thorough history and exclude XP and then perform detailed dermatological and systemic examination, biopsy for histopathologic confirmation, and appropriate specific imaging screens. As some of the conditions may be associated with other systemic disorders, especially malignancies, the differentiation of xanthomatous eyelid lesions has a critical importance, and clinical signs can be guiding., (© 2017 The International Society of Dermatology.)

Erdheim-Chester disease (ECD) is a rare non-Langerhans cell histiocytosis that most commonly affects adults and is driven by a high frequency of mutations in BRAF , MAP2K1 , and kinases promoting MAPK signaling. Because of the relative rarity of ECD, key clinical features of the disease may not be well defined. Across a multi-institutional cohort of 189 patients with ECD and ECD overlapping with Langerhans cell histiocytosis (so-called mixed histiocytosis [MH]), we identified an unexpected and heretofore undescribed frequent occurrence of myeloid neoplasms among patients with ECD and MH. Some 10.1% (19/189) of patients with ECD have an overlapping myeloid neoplasm, most commonly occurring as a myeloproliferative neoplasm (MPN), myelodysplastic syndrome (MDS), or mixed MDS/MPN overlap syndrome (including chronic myelomonocytic leukemia). Consistent with this, molecular analysis frequently detected hallmark driver mutations of myeloid neoplasms (such as JAK2 V617F and CALR mutations) coexisting with those characteristic of histiocytosis (such as BRAF V600E and MAP2K1 mutations). Histiocytosis patients diagnosed with a concomitant myeloid malignancy were significantly older at diagnosis and more commonly presented with MH than those without a myeloid malignancy. In some cases, the presence of distinct kinase mutations in the histiocytosis and myeloid neoplasm resulted in discordant and adverse responses to kinase-directed targeted therapies. These data highlight the clinical importance of evaluating adults with histiocytosis for a concomitant myeloid neoplasm., (© 2017 by The American Society of Hematology.)

Xanthoma disseminatum (XD) is a nonfamilial type of normolipidemic mucocutaneous xanthomatosis that belongs to the group of non-Langerhans cell histiocytoses. More than 100 cases of XD have been reported. In this study we report a case of XD in a 4-year-old boy with diabetes insipidus (DI). This boy is one of the youngest patients ever to present with XD combined with DI., (© 2017 Wiley Periodicals, Inc.)

A 68-year-old man presented with polyarthritis, proximal muscle weakness, and erythema of the face, arms, neck, and anterior chest that resembled the V-neck sign. Initially, dermatomyositis (DM) was considered because of the erythema, polyarthritis, and muscle weakness. He also had mediastinal and hilar lymphadenopathy on contrast-enhanced computed tomography. Unexpectedly, a biopsy of the forehead skin revealed numerous multinucleated giant cells. A biopsy of a solitary nodule on the dorsum of his right middle finger revealed similar multinucleated giant cells with ground-glass cytoplasm, leading to the diagnosis of multicentric reticulohistiocytosis (MRH). Although MRH is rare, it should be remembered that MRH can mimic DM.

A young male presented with panhypopituitarism (including diabetes insipidus) and temporal lobe epilepsy. A histology specimen of cutaneous papules was diagnostic of non-Langerhans histiocytosis. The diagnosis of xanthoma granulomata was considered based on the clinical and brain MRI findings. Brain lesions significantly worsened over time despite radiotherapy until anakinra induced a complete clinical and radiological remission of all active lesions. Although a single case, the outcome of this patient with xanthoma disseminatum treated with an interleukin-1 receptor antagonist opens and strengthens new and recent physiopathogenic and treatment perspectives for the otherwise difficult-to-treat non-Langerhans cell histiocytosis. Similar results with anakinra have been observed in patients with Erdheim-Chester disease and in multicentric reticulohistiocytosis., (© 2016 S. Karger AG, Basel.)

Importance: Generalized eruptive histiocytosis (GEH) is a rare non-Langerhans cell histiocytosis with a benign, self-healing course. Neoplastic hematologic disorders of the myeloid lineage have been reported in association with GEH in 4 patients. A clonal association between GEH and the underlying leukemia was suspected in these patients but could only be confirmed in one patient., Observations: A male patient in his 20s presented with asymptomatic red to brown macules and papules. A skin biopsy confirmed a diagnosis of GEH. His blood cell count revealed hypereosinophilia. Morphologic and molecular analyses from bone marrow and blood samples revealed FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. The patient was treated with imatinib and achieved complete clinical remission of his leukemia and the GEH., Conclusions and Relevance: To our knowledge, this is the first report of a patient with GEH associated with FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Generalized eruptive histiocytosis in association with a myeloid neoplasm may occur in 2 variants: a reactive condition or a clonal derivative of the underlying leukemia. In this case, both diseases responded well after initiation of treatment with imatinib.

Xanthoma disseminatum (XD) is a rare, benign, non-Langerhans cell histiocytosis characterized by disseminated xanthomatous lesions with a predilection for the face, flexures, and mucosae. Approximately 100 cases have been reported in the literature. We report XD in an 8-year-old boy with symmetric synovitis and arthritis involving the wrists and knees. This case is interesting in view of the association between arthritis and synovitis and XD, which to our knowledge has not been reported in the literature. This case has to be differentiated from multicentric histiocytosis, another non-Langerhans cell histiocytosis, in which joint involvement is common., (© 2014 Wiley Periodicals, Inc.)

Multicentric reticulohistiocytosis (MR) is a rare debilitating disease that involves the skin and joints. It most commonly affects white individuals but has been reported in other ethnic groups including black individuals, Native Americans, and Asians. The Hispanic population is largely underrepresented in the epidemiology of MR. We describe 2 Hispanic patients with contrasting presentations of MR. Prompt recognition of MR is essential to expedite treatment and prevent potentially disabling sequelae of undiagnosed disease; however, diagnosis can be challenging due to the wide range of clinical presentations of MR as well as variable laboratory findings, especially in patients with skin of color. Our case reports underscore this phenomenon and demonstrate the importance of considering MR in all ethnic groups, including Hispanic patients.

Xanthoma disseminatum (XD) is a rare, benign, non-Langerhans cell histiocytic disorder. The pathogenesis is not clear. It manifests with multiple, grouped, red-brown to yellow papules and nodules involving the skin, mucous membranes, and internal organs. We present a case of progressive XD in a 10-year-old male child. The patient presented with progressive, bilateral and symmetrical, reddish-brown, coalescent papules on the neck, around both eyes and all over his trunk and extremities. Skin lesions were accompanied by blurred vision and hoarseness of voice. Examination revealed xanthomatous infiltration of cornea, oral, pharyngeal, and laryngeal mucosae. The patient had diabetes insipidus that was diagnosed 2 years before the appearance of skin lesions. Medical treatment with corticosteroids (20 mg/day) and azathioprine (2 mg/kg/day) did not stop the disease progression.

We report a patient with the extremely rare familial multiple lipomatosis syndrome, who developed the uncommon autoimmune disease cytophagic histiocytic panniculitis, manifested as inflammation of preexisting lipomas. Despite his initial critical condition and unsuccessful treatment with steroids, he responded to cyclosporin and remains well 15 years after diagnosis. In contrast with most previous reports, our patient stays dependent on cyclosporin; repeated attempts of discontinuing or substituting treatment were quickly followed by relapse. Haemophagocytic panniculitis is considered as a T-cell disorder, but its exact pathophysiological mechanism has not been clarified. Differential diagnosis of cytophagic histiocytic panniculitis mainly includes malignant histiocytosis, subcutaneous panniculitis-like T-cell lymphoma (SPTCL) and lupus erythematosus panniculitis (lupus profundus). We discuss the main clinical features, diagnostic challenges and treatment issues of this usually benign, but at times life-threatening autoimmune condition.

Multicentric reticulohistiocytosis (MRH), a rare histiocytic systemic condition characterized by mutilating arthritis and multiple cutaneous nodules, has been associated with malignancy including that of the breast, thyroid and colon. An unsubstantiated link with infectious agents such as mycobacterium tuberculosis has been described. Many treatments have been used with varying success. We describe the case of a 60-year-old man with MRH and no underlying malignancy who initially responded well to azathioprine and whose disease recurred upon cessation. A second course of azathioprine administered in conjunction with antituberculous treatment resulted in disease control. Broader associations and features of this rare disease are discussed., (© 2011 The Authors. Australasian Journal of Dermatology © 2011 The Australasian College of Dermatologists.)

Multicentric reticulohistiocytosis is a rare, systemic, reactive histiocytic disease of unknown aetiology. Autoimmune diseases have previously been reported in association with multicentric reticulohistiocytosis, but whether this is a true association or mere coincidence is not known. Here, we report the case of a 50-year-old woman who had been diagnosed as suffering from rheumatoid arthritis (RA), four years ago with positive rheumatoid serology was evaluated for multiple asymptotic papulonodules eruption. Histopathologic examination was suggestive of multicentric reticulohistiocytosis. She developed concomitantly Sjogren syndrome with systemic manifestations. Multicentric reticulohistiocytosis may be misdiagnosed as RA, but evaluation of the time course of specific symptoms can greatly help in the correct diagnosis. The possibility of commune etiopathogeny of these affections is discussed., (Copyright 2010 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

We report a case of multicentric reticulohistiocytosis (MRH) demonstrating classic clinical and histologic findings. This rare idiopathic disease is manifested by severe destructive polyarthritis and papulonodular mucocutaneous lesions. The characteristic clinical and histologic findings are discussed as well as the workup and treatment of the disease.

Histiocytoses are a heterogeneous group of disorders which are difficult to categorize because of overlapping clinical and microscopic features, and incompletely understood mechanisms of cellular origin and triggers of proliferation. Progressive nodular histiocytosis (PNH) is a rare non-Langerhans cell histiocytic (NLH) disorder. We present the case of a 34-year-old woman with PNH, who has involvement of the back, head and neck, face, and uniquely, extensive involvement of the posterior pharynx and larynx, which has shown progressive worsening and deformity over a 7-year course. Clinically it is best classified as PNH, although it microscopically closely resembles juvenile and adult xanthogranulomatosis. This study reinforces the concept that the NLH is a closely related group of disorders, possibly representing a spectrum of a single underlying process.

Multicentric reticulohistiocytosis (MRH) is a rare multisystem disease characterized by skin nodules and a destructive polyarthritis. We describe cardiac disease in a 42-year-old African American female with a history of MRH for 29 years and dilated cardiomyopathy for 5 years. During a congestive heart failure flare, the patient was slow to respond to standard treatment. A left/right heart catheterization and endomyocardial biopsy were performed, and the patient was found to have evidence of myocardial MRH infiltration.

Background: Multicentric reticulohistiocytosis (MR) is a rare multisystem granulomatous disease that frequently results in disfiguring cutaneous deposition, destructive arthritis, and debilitating constitutional symptoms. No consistently effective treatment has been identified. Recently, studies characterizing the cytokine expression profile in MR have prompted therapeutic attempts with tumor necrosis factor (TNF) inhibition. Owing to the rarity of the condition, few such cases have been reported, and controlled studies are unlikely to be performed., Observations: A 63-year-old man developed MR refractory to traditional therapies and etanercept therapy. The addition of infliximab to his current regimen of methotrexate sodium and prednisone resulted in a rapid and sustained improvement in his cutaneous, articular, and constitutional manifestations of disease throughout 12 months of follow-up., Conclusions: We present this case to highlight the growing body of evidence characterizing the cytokine involvement in MR that has led to successful therapy via TNF inhibition. Our patient responded dramatically to infliximab in combination with methotrexate and prednisone despite previously failing to benefit from etanercept therapy. An analysis of our case combined with those previously reported in the literature suggests that despite some disparity in the response of cutaneous and articular manifestations of MR, TNF blockade is emerging as a promising therapeutic option.

Multicentric reticulohistiocytosis (MRH) is a rare disease of unknown etiology characterized by cutaneous nodules and destructive, sometimes crippling, polyarthritis. The diagnosis is confirmed by histopathologic features of the cutaneous nodules or synovial tissue, including an infiltrate composed of histiocytes, many of them multinucleate, with a ground glass appearance. Multicentric reticulohistiocytosis has been associated with a number of chronic conditions and various malignancies. We report a case of MRH in a patient with Burkitt lymphoma and metastatic adenocarcinoma of the gastrointestinal tract.

Xanthoma disseminatum is a normolipemic xanthomatosis classified in the group of non-Langerhans cell histiocytic disorders. Classic clinical findings are cutaneous and mucosal xanthomas and diabetes insipidus. Ocular, liver, bone marrow, respiratory, skeletal, and central nervous system involvement may accompany the classic findings of the disease. Skeletal involvement is a rare manifestation of the disease in children. We report on a 5-year-old boy with cranial bone involvement, proptosis and xanthomatous cutaneous lesions, treated successfully with systemic corticosteroids.