Xanthomatous Lesions Research Articles

Prompt Cytopathological Diagnosis of Multiple Xanthomatous Skin Nodules in an Adolescent Girl Opening the Doors to Detection of Familial Hypercholesterolemia

Background Xanthomas are papulo-nodular, yellow, soft, painless, dermal-based non-neoplastic cutaneous lesions that comprise of localized aggregates of lipid-laden histiocytes. Case report A thirteen-year-old adolescent girl presented with multiple, large, bilateral, nodules present over elbows, posterior aspect of heel, and knees for five years. Fine needle aspiration cytology was performed, and the smears showed numerous foamy histiocytes, a few benign spindle cells, and foreign-body giant cells against a lipidaceous background. Her maternal aunt and grandmother also had xanthelasma palpebrarum. Serum lipid levels were advised and were markedly deranged in all three of them. Based on the corroborative clinical, biochemical, and cytopathological findings, a final diagnosis of familial hypercholesterolemia (FH) was rendered. Conclusion The present case sheds light on the importance of prompt cytopathological diagnosis of xanthomatous lesions, especially in children and adolescents, as it can help prevent morbidity and mortality due to associated premature adverse cardiovascular and cerebrovascular events if left undiagnosed.

The significance of T-BET-positive CD8 T-cells with diminished CD5 expression in Kikuchi-Fujimoto disease.

Kikuchi-Fujimoto disease (KFD), also known as histiocytic necrotizing lymphadenitis, is a rare condition characterized by benign localized lymphadenopathy and clinical symptoms such as fever, sore throat, odynophagia, and leukopenia. Though the etiology of KFD is unknown, this condition is similar to viral infection, including increased infiltration of activated plasmacytoid dendritic cells. KFD exhibits three histological phases that reflect its progression status: proliferative, necrotic, and xanthomatous lesions. The expression loss of pan T-cell markers, such as CD2, CD5, and CD7, of infiltrating T-cells is observed in KFD cases, complicating the distinction from T-cell lymphoma. However, reports on the loss of their expression in KFD have been limited. Furthermore, the precise population of the T-cell subset in KFD is still unclear. Here, we focused on surface markers and transcription factors for T-cell differentiation and analyzed them immunohistochemically in 46 KFD cases. We observed diminished CD5 expression of CD8-positive (CD5dim CD8+) T-cells in the proliferative lesion of KFD cases. Furthermore, these CD5dim CD8+ T-cells expressed T-BET, a master regulator of type 1 helper T-cells. The upregulation of T-BET and downregulation of CD5 in CD8+ T-cells causes dysregulated activation and proliferation of CD8+ T-cells, potentially contributing to the unique histopathological features of KFD. Recognizing the frequent infiltration of T-BET-positive CD5dim CD8+ T-cells in KFD is important for distinguishing it from mature T-cell lymphoma. Our findings suggest that the immune response in KFD shares similarities with viral infections and highlight the importance of characterizing T-BET-positive CD5dim CD8+ T-cell populations for understanding KFD pathogenesis.

Features of the metabolic syndrome and subclinical atherosclerosis in patients with cerebrotendinous xanthomatosis: An augmented risk for premature cardiovascular disease.

Background: Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disease, caused by deficiency of sterol-27-hydroxylase. Xanthomatous lesions in numerous tissues, and an elevation of cholestanol levels, characterize the disease. Its natural course is progressive neurologic deterioration, leading to premature death. Chronic treatment with oral chenodeoxycholic acid (CDCA) reduces cholestanol levels. Occurrence of premature atherosclerosis has been described in CTX in an unknown mechanism. Aim: The aim of the current work was to evaluate the potential metabolic abnormalities and preclinical vascular changes in Israeli CTX patients. Methods: Ten subjects with CTX were studied. Features of the metabolic syndrome were evaluated, and carotid intima media thickness (cIMT) was measured in the common carotid arteries. Results: All patients were diagnosed with CTX, and all received treatment with CDCA, which resulted in normalization of their plasma cholestanol levels. At the conclusion of the follow up, risk factors for CVD and features of MS were present in all the patients and in three patients, cIMT was higher compared to control subjects. Conclusion: Cardiovascular risk factors and premature vascular changes exist in young CTX patients and proper assessment should be implemented with preventive measures to reduce the risk of atherosclerotic cardiovascular disease in CTX patients.

Features of the metabolic syndrome and subclinical atherosclerosis in patients with cerebrotendinous xanthomatosis: An augmented risk for premature cardiovascular disease

Background and Aims : Cerebrotendinous xanthomatosis (CTX) is a rare lipid storage disease caused by mutations of the CYP27A1 gene, resulting in deficiency of sterol-27-hydroxylase, a key enzyme involved in hepatic bile acid synthesis from cholesterol. Xanthomatous lesions in numerous tissues, in conjunction with an elevation of plasma and tissue cholestanol levels. The natural course of CTX is progressive neurologic deterioration from childhood through adulthood, leading to diffuse damage of the central and peripheral nervous systems and eventually to premature death.

Three Cases of Central Xanthoma of the Jaws with Review of Literature

<h3>Background</h3> Extragnathic xanthomas are rare benign tumors associated with excess lipid production. Its gnathic counterpart was first reported in 1964. Only 45 cases of central xanthoma of jaw (CXJ) have been reported in the English literature. The etiopathogenesis of CXJ is highly suggestive of a reactive process or a metabolic condition. <h3>Materials</h3> Three cases of CXJ were identified from the UF Oral Pathology Biopsy archives. Clinical, radiographic and histopathologic features of all the cases were retrospectively analyzed. Immunohistochemical (IHC) stains for S100 and CD68 were performed. <h3>Case Series</h3> All cases of CXJ involved younger females and incidental lesions discovered during routine radiographic examination. The first patient, a 36-year-old female presented with an asymptomatic swelling and cortical expansion of the mandible adjacent to tooth #31. The second patient was a 13year-old female with an asymptomatic expansion in the left mandibular ramus. Lastly, a 15-year-old female with dull pain exhibited mild buccal and lingual bony expansion of the right mandible apical to tooth #18. Radiographically, two of the cases presented as multilocular radiolucent lesions and one demonstrated as a well-circumscribed unilocular radiolucency intermixed with radiopacities. All three lesions were treated with surgical curettage and no recurrence at one-year follow up. All cases exhibited sheets of foamy macrophages similar to other lytic xanthomatous lesions such as non-ossifying fibroma, benign fibrous histiocytoma, Rosai-Dorfman disease, Erdheim disease, Gaucher disease, etc. A diagnosis of CXJ was established by exclusion and involved careful correlation of the clinical, radiographic, histopathological and IHC features. All three cases revealed diffuse positivity for CD68 and were negative for S100. <h3>Conclusion</h3> CXJ are rare gnathic lesions of unknown etiology. We highlight three rare cases of CXJ, a lesion that may mimic other benign or reactive jaw lesions especially in young patients.

Intracranial mass lesions and skin discoloration in the armpits as unusual clues to Erdheim-Chester disease: a case report

BackgroundErdheim–Chester disease (ECD) is a non-Langerhans histiocytosis that results in multi-organ disease involving the skin, bones, lungs and kidneys. Central nervous system (CNS) involvement occurs in about 50 % of patients, and diabetes insipidus, visual disturbances, and cerebellar ataxia are the most frequent neurological signs. We report a case of Erdheim-Chester disease with central nervous system involvement in the form of enhancing intracranial mass lesions with massive edema.Case presentationThe patient presented with vertigo, ataxia, encephalopathy and pyramidal signs. Diagnosis was suggested by xanthomatous skin lesions and a biopsy was compatible with Erdheim-Chester disease demonstrating xanthogranulomas CD68 positive (clone KP1) and CD1a and S100 negative. Testing for BRAF mutation was negative, which precluded treatment with Vemurafenib. Treatment with steroids and interferon resulted in improvement of neurological signs and regression of edema on MRI.ConclusionsThe diagnosis of Erdheim-Chester disease should be considered in intracranial mass lesions. Xanthomatous skin lesions are a clue to the diagnosis.

Post Kala-Azar Dermal Leishmaniasis: Clinical Features and Differential Diagnosis.

Post kala-azar dermal leishmaniasis (PKDL) is a mucocutaneous disease usually seen in apparently cured, inadequately treated or untreated cases of visceral leishmaniasis and is endemic to many parts of India, Nepal, Bangladesh, and eastern Africa (Sudan, Ethiopia, Kenya). The disease usually manifests as a variable combination of hypopigmented patches, erythematous succulent papulo-plaques, and nodular lesions on the face and upper body and sometimes extending on the extremities, genitalia, and tongue. Atypical morphology and presentations are not uncommon, especially in endemic areas, which include photosensitivity, verrucous, hypertrophic, xanthomatous, and ulcerative lesions. Recognition of spectrum of mucocutaneous changes helps physicians in early initiation of treatment and in reducing disease transmission in the community. The differential diagnosis depends on the pattern of manifestations, but lepromatous leprosy is the closest mimicker. Since PKDL does not cause significant morbidity, at least initially, but the affected patients continue to act as a reservoir of the disease, active case detection is required to identify cases early to control the disease transmission in the community.

INTRA-ORAL ADULT-TYPE JUVENILE XANTHOGRANULOMA, NODULAR VARIANT: A REPORT OF A CASE WITH IMMUNOHISTOCHEMICAL STUDY

Intra-oral juvenile xanthogranuloma (JXG) is a non‐Langerhans cell histiocytosis often affecting infants and children. Approximately 10% of these cases represent “adult xanthogranulomas.” To date, 33 intra-oral JXG cases have been reported. Due to its benign and self‐limiting nature, this disorder can be considered a reactive rather than a neoplastic process, although its pathogenesis remains unknown. There are 2 clinical JXG variants: papular and nodular. A 46-year-old female patient was referred presenting with a yellowish oval nodule, with circumscribed margin, measuring 1 cm in diameter, smooth-surfaced, asymptomatic, and located on the right buccal mucosa. Microscopically, it was composed mainly by numerous mononuclear macrophages containing fine cytoplasmic vacuoles in the cytoplasm, with a lipidized or xanthomatous appearance. Immunohistochemistry showed positivity for CD11c, CD68, CD163, HLA-DR, and FXIIIa. The Ki-67 labeling index was 3%. The predominant xanthomatous appearance in intra-oral JXG is uncommon, but it should be considered to exclude other xanthomatous lesions.

Eruptive xanthomas: a warning sign of future hyperlipidemia complications

&lt;p&gt;Eruptive xanthomas are localized lipid deposits in the skin or subcutaneous tissue that are associated with both primary and secondary hyperlipidemia. Typical presentation manifests as small yellow papules on the buttocks or extensor surfaces. Xanthomas can be diagnosed clinically with an extensive history and physical examination, however, can be confirmed via biopsy and histological findings. It is essential to identify the underlying cause of the skin lesions and take appropriate measures to prevent future hyperlipidemia-induced consequences. Here we report a 42-year-old female with eruptive xanthomas on her trunk and extremities. Previous visits to the primary care provider and emergency department resulted in diagnoses of viral exanthems. The consulted dermatologist ordered laboratory tests remarkable for extreme hypertriglyceridemia, hypercholesterolemia, and hyperglycemia. Lifestyle modification in conjunction with cholesterol and triglyceride lowering medications led to the resolution of abnormal laboratory findings and remission of eruptive xanthoma lesions.&lt;/p&gt;

Plasma sublimation for the treatment of xanthelasma palpebrarum

Xanthelasma palpebrarum (XP) is a common xanthomatous lesion of the eyelid and periorbital skin. Several methods of treatment have been reported in the literature, each having its own indications and risks. We present a new treatment method for removing XP using a plasma exeresis device (Plexr®, GMV, Italy). Fifteen patients with a total of 27 treated XPs were assessed and clinically identified by the treating dermatologist. Patients were photographed and assessed by a dermatologist prior to and immediately after treatment. A patient survey was conducted 12 months after the procedure, which assessed the outcome of the procedure (redness, pigmentation disorders, and scars). After just a single treatment session using a plasma sublimation, all 27 XPs showed complete clearance. There were no reports of scars, pigmentary alteration, or recurrence of lesions up to 12 months. We present plasma sublimation as a new method for the treatment of XP. During the procedure, the method allows to control the depth of tissue destruction and the presence of xanthoma tissue, and to minimize pain and trauma, making it particularly ideal for treating areas around the eye.

Osteoarticular lesion in xanthoma disseminatum treated with total hip arthroplasty: a case report

IntroductionXanthoma disseminatum is a very rare disease classified as a benign non-Langerhans cell histiocytosis, which is rarely associated with osteoarticular lesions. There is only a report of tumor abrasion during treatment of osteoarticular lesions of this disease, artificial joint replacement has not been reported. We describe a patient in whom bilateral total joint replacement was performed for disseminated xanthoma lesions of the hip joints.Case presentationA 34-year-old Japanese woman had a chief complaint of bilateral coxalgia. She had been diagnosed as having disseminated xanthoma. Radiographs showed numerous 5-mm radiolucent bands that resembled worm-eaten tracks in the lower part of the femoral heads adjacent to the joint surface. In addition, short tau inversion recovery imaging scans showed high-intensity areas from the femoral head to the neck in both femurs, suggesting bone marrow edema. Total hip arthroplasty was performed for hip arthrosis on both hip joints caused by disseminated xanthoma. Deflection of the implants was a concern from the early stages postoperatively, but both the imaging and clinical findings have been satisfactory for 4 years of follow-up.ConclusionsA very unusual hip joint lesion of xanthoma disseminatum was replaced with a total artificial joint replacement, and the course over 4 years was good. Our patient’s course will continue to be followed carefully.

Gastric Xanthelasma: Innocent Bystander?

Introduction: Gastric xanthoma or xanthelasma are usually benign sharply demarcated yellow deposit of cholesterol underneath the skin, a rare finding during endoscopy. Their clinical significance is unknown; however they have been associated with gastric malignancy. Case Report: _A 62 year old male with a past medical history of colon cancer in 2005 treated with right hemicolectomy and chemotherapy in remission, seroconverted hepatitis C, atrial fibrillation, osteoarthritis, chronic kidney disease stage II was evaluated in the office for a screening colonoscopy. He mentioned his mother was diagnosed with gastric cancer at the age of 60, thus upper endoscopy was recommended. His physical exam was normal. His blood work showed a normal comprehensive metabolic panel with hemoglobin 15.5 and albumin of 4.4.Upper endoscopy showed two small nodular yellow areas, measuring 7-8 mm in size, on the proximal greater curvature of the body of the stomach. On microscopic examination, the lamina propria showed inclusion of foamy histiocytes with hematoxylin and eosin (H&E) staining. Immunohistochemical stain was positive for CD163, and negative for pancytokeratin and PAS stain negative for Whipple's disease. The absence of nuclear atypia and cytokeratins excluded the diagnosis of malignancy. These findings were suggestive of a gastric xanthoma. The surrounding gastric mucosa showed evidence of focal chronic inactive gastritis. Immunohistochemical stain for H. pylori was negative. The duodenum appeared normal. Discussion: Gastric xanthelasma or xanthomas (GX) are incidental relatively rare lesions found on upper endoscopy with the prevalence ranging from 0.23% to 7%. Clinically, the patient is asymptomatic, and most of the time endoscopy is performed for other reasons. Historically, GX has received little attention, maybe because clinically it has been always considered as a benign endoscopic finding. However more recent studies showed that there is a strong association between gastric xanthoma lesions and atrophic gastritis. It appears to be a close relationship between H. pylori infection, and GX. Treating H. pylori did not decrease the risk of gastric adenocarcinoma when GX was present. Some retrospective observational studies have gone as far as associating GX as a predictive marker for metachronous and synchronous gastric cancers, or even the development of gastric cancer. Previous partial gastric resection is associated with an increased incidence of GX.1857_A Figure 1 No Caption available.1857_B Figure 2 No Caption available.

The clinical spectrum of xanthomatous lesions of the eyelids.

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.

Review of xanthomatous lesions of the sella.

Xanthomatous lesions of the sellar region have traditionally been divided into two separate categories, xanthomatous hypophysitis (XH) and xanthogranuloma (XG) of the sellar region. The seminal article on XH, a condition typified by foamy histiocytes and lymphoplasmacytic infiltrates in the pituitary gland/sellar region, but usually little or no hemosiderin pigment, detailed three patients. However, most reports since that time have been single cases, making understanding of the entity difficult. In contrast, the seminal report on XG, characterized by sellar region cholesterol clefts, lymphoplasmacytic infiltrates, marked hemosiderin deposits, fibrosis, multinucleated giant cells around cholesterol clefts, eosinophilic granular necrotic debris, and accumulation of macrophages, included 37 patients, allowing more insights into etiology. Few examples could be linked to adamantinomatous craniopharyngioma, and although ciliated epithelium similar to that of Rathke cleft cyst (RCC) was identified up to 35% of the 37 cases, it could not be proven that XG was related to hemorrhage into RCC. Case reports since that time, however, occasionally linked XG to RCC when an etiology could be identified at all, and a few recognized that a spectrum exists in xanthomatous lesions of the sella. They review literature, adding 23 cases from our own experience, to confirm that overlap occurs between XH and XG, and that the majority-but not all-can be linked to RCC leakage/rupture/hemorrhage. It was suggested that progressive accumulation of hemosiderin pigment in the lesion, possibly caused by the multiple episodes of bleeding, could account for the transition of at least some cases of XH to XG.

Los xantomas gástricos están asociados con lesiones malignas y premalignas

Los xantomas gástricos son lesiones encontradas incidentalmente en la endoscopia digestiva alta. Consisten en la acumulación de lípidos en la mucosa gástrica. Estas lesiones se han reportado en serie de casos asociadas con metaplasia o atrofia y en reportes de casos vinculados con cáncer gástrico; sin embargo, no se han realizado estudios comparativos que busquen comprobar esta asociación. El objetivo de este trabajo es evaluar si los pacientes con xantomas tienen más lesiones malignas (displasia o cáncer) o condiciones premalignas (atrofia o metaplasia). Materiales y métodos: se trata de un estudio retrospectivo de casos y controles realizado en el Hospital El Tunal, en pacientes que fueron sometidos a endoscopia de vías digestivas altas (EVDA) para evaluación de dispepsia. A cada caso de xantoma se le asignó un control de endoscopia realizado el mismo día por el síntoma de dispepsia y escogido de manera aleatoria. Todos los pacientes fueron sometidos a biopsias para evaluación histológica y por infección de Helicobacter pylori. Resultados: en total se reclutaron 186 pacientes que cumplieron los criterios de inclusión, ya que tenían indicación de EVDA porque cursaban con dispepsia no investigada. Fueron comparados dos grupos de pa- cientes: el primero, con hallazgo de xantomas gástricos en la endoscopia (n = 90) y el segundo, sin estos hallazgos (n = 96). El promedio de edad de los pacientes con xantomas fue de 57, 4 versus 38,3 del grupo control, 35% sexo masculino versus 35,6%, respectivamente. Los xantomas fueron únicos en el 72%. La mayoría se ubicó en el antro (53%), cuerpo (32%), antro o cuerpo (10%) y fondo (5%). En los pacientes sin xantomas no se presentaron casos de displasia (0%), mientras que en el grupo con xantomas, 5,5% de los pacientes lo presentó (5 casos), de los cuales 2 fueron de bajo grado y 3, de alto grado. El 66% del grupo xantoma versus el 85% del control tenía infección por H. pylori. Tres pacientes presentaron cáncer gástrico temprano (3,3%) en el grupo de los xantomas versus 0% en el control. Conclusión: nuestro trabajo muestra que los xantomas gástricos son un factor de riesgo para la presencia de condiciones premalignas: atrofia o metaplasia intestinal. Lo más importante es que están asociados con displasia y cáncer gástrico, lo cual nos obliga a ser aún más cuidadosos en la evaluación endoscópica, cuan- do nos encontremos incidentalmente un xantoma, y probablemente a realizarles un mapeo gástrico, ya que por lo general es posible observar una condición premaligna. Sin embargo, se deben llevar a cabo estudios más grandes y multicéntricos para comprobar estas asociaciones.

Eruptive Xanthoma with Acute Pancreatitis in a Patient with Hypertriglyceridemia and Diabetes.

Dear Editor: A 41-year-old Japanese man presented in October 2013 with a 2-week history of pruritic, erythematous papules. He had diabetes mellitus, hyperlipidemia, and hypertriglyceridemia, but had stopped treatment 5 years prior to this visit. He also suffered from acute pancreatitis, and was admitted to the Department of Medicine, Japan Community Healthcare Organization Osaka Hospital, 1 day prior. Topical steroid ointment prescribed during a previous visit to another clinic was ineffective for the treatment of the papules. At the time of consultation, he presented with multiple, approximately 5-mm, pruritic, yellowish, erythematous papules on the trunk and extensor surfaces of the extremities (Fig. 1A). Dermoscopic examination of the papules clearly revealed granular yellowish characteristics (Fig. 1B). The laboratory findings (normal values are in parentheses) were: white blood cell count, 13.3×103 (4.0×103~8.5×103)/µl; neutrophils, 83.5% (38%~58%); alkaline phosphatase, 369 (115~359) U/L; C reactive protein, 5.91 (<0.3) mg/dl; hemoglobin A1c, 9.2% (4.6%~6.2%); amylase, 340 (40~130) IU/L; lipase, 960 (11~53) U/L; triglyceride, 6,784 (30~150) mg/dl; total cholesterol, 803 (130/219) mg/dl; high density lipoprotein cholesterol, 12 (42~74) mg/dl; low density lipoprotein cholesterol, 23 (70~140) mg/dl; remnant-like lipoprotein particle cholesterol, 84.4 (<7.5) mg/dl; apolipoprotein (Apo) A-I, 89 (119~155) mg/dl; Apo A-II, 12.6 (25.9~35.7) mg/dl; Apo B, 135 (73~109) mg/dl; Apo E, 11.0 (2.7~4.3) mg/dl; Apo C-II, 16.5 (1.8~4.6) mg/dl; Apo C-III, 28.3 (5.8~10.0) mg/dl. A skin biopsy sample obtained from papules on the waist revealed foamy cells that infiltrated the dermis. At higher magnification, foamy cells and extracellular lipids were present (Fig. 2). Therefore, we diagnosed the patient as having eruptive xanthoma with type V hyperlipoproteinemia according to Fredrickson's classification of hyperlipoproteinemias. We treated the acute pancreatitis with fasting, nafamostat mesilate, and ulinastatin, and the hypercholesterolemia with bezafibrate. The acute pancreatitis improved 16 days after admission. Serum triglyceride and total cholesterol values decreased to within normal range 1.5 months after the initiation of treatment. The eruptive xanthoma lesions rapidly resolved as the hyperlipidemia improved. Fig. 1 (A) Clinical appearance and (B) dermoscopic appearance of multiple yellowish erythematous papules on the patient's back in October 2013. Fig. 2 Skin biopsy from the erythematous papules present on the patient's waist. (A) At lower magnification, numerous pale areas containing foamy cells infiltrate the dermis, especially the upper dermis and perivascular areas (H&E, ×40). (B) ... Hyperlipidemia is divided into six subgroups. Cutaneous xanthomatous lesions can occur in all six types of hyperlipidemia1. Cutaneous xanthomas can be divided into subgroups, including eruptive xanthomas, tuberous xanthomas, tendon xanthomas, xanthelasmata, and plane xanthomas2. Eruptive xanthomas can be associated with hypertriglyceridemia (Type I, IV, or V hypercholesterolemia), particularly when diabetes is poorly controlled2,3. Eruptive xanthomas contain more triglycerides and fewer cholesteryl esters than other types of xanthomas, and lipids present in xanthomas are derived from circulating plasma lipoproteins. Triglyceride is mobilized more rapidly than cholesterol, so resolving eruptive xanthomas are rich in cholesterol4. Hypertriglyceridemia also increases the risk of acute pancreatitis, and the risk of eruptive xanthoma and pancreatitis increases when the serum triglyceride concentration reaches the thousands5. Eruptive xanthomas manifested in this patient 2 weeks before his visit, followed by acute pancreatitis. Dermatologists should carefully consider the possibility of acute pancreatitis with hypertriglyceridemia in eruptive xanthoma patients.

Uncommon histiocytic disorders: Rosai–Dorfman, juvenile xanthogranuloma, and Erdheim–Chester disease

Abstract Rosai–Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim–Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. In most cases, RDD is self-limited and observation is the standard approach. Treatment is restricted to patients with life-threatening, multiple-relapsing, or autoimmune-associated disease. JXG is a pediatric histiocytosis characterized by xanthomatous skin lesions that usually resolve spontaneously. In a minority of cases, systemic disease can occur and can be life threatening. Juvenile myelomonocytic leukemia (JMML), as well as germline mutations in NF1 and NF2, have been reported in children with JXG. Recent whole-exome sequencing of JXG cases did not show the BRAF-V600E mutation, although 1 patient had PI3KCD mutation. ECD is an adult histiocytosis characterized by symmetrical long bone involvement, cardiovascular infiltration, a hairy kidney, and retroperitoneal fibrosis. Central nervous system involvement is a poor prognostic factor. Interferon-α is the standard as front-line therapy, although cladribine and anakinra can be effective in a few refractory cases. More than one-half of ECD patients carry the BRAF-V600E mutation. Currently, &gt;40 patients worldwide with multisystemic, refractory BRAF-V600E+ ECD have been treated with vemurafenib, a BRAF inhibitor, which was found to be highly effective. Other recurrent mutations of the MAP kinase and PI3K pathways have been described in ECD. These discoveries may redefine ECD, JXG, and LCH as inflammatory myeloid neoplasms, which may lead to new targeted therapies.

Uncommon histiocytic disorders: Rosai-Dorfman, juvenile xanthogranuloma, and Erdheim-Chester disease.

Rosai-Dorfman disease (RDD), juvenile xanthogranuloma (JXG), and Erdheim-Chester disease (ECD) are non-Langerhans cell (non-LCH) disorders arising from either a dendritic or a macrophage cell. RDD is a benign disorder that presents with massive lymphadenopathy, but can have extranodal involvement. In most cases, RDD is self-limited and observation is the standard approach. Treatment is restricted to patients with life-threatening, multiple-relapsing, or autoimmune-associated disease. JXG is a pediatric histiocytosis characterized by xanthomatous skin lesions that usually resolve spontaneously. In a minority of cases, systemic disease can occur and can be life threatening. Juvenile myelomonocytic leukemia (JMML), as well as germline mutations in NF1 and NF2, have been reported in children with JXG. Recent whole-exome sequencing of JXG cases did not show the BRAF-V600E mutation, although 1 patient had PI3KCD mutation. ECD is an adult histiocytosis characterized by symmetrical long bone involvement, cardiovascular infiltration, a hairy kidney, and retroperitoneal fibrosis. Central nervous system involvement is a poor prognostic factor. Interferon-α is the standard as front-line therapy, although cladribine and anakinra can be effective in a few refractory cases. More than one-half of ECD patients carry the BRAF-V600E mutation. Currently, >40 patients worldwide with multisystemic, refractory BRAF-V600E(+) ECD have been treated with vemurafenib, a BRAF inhibitor, which was found to be highly effective. Other recurrent mutations of the MAP kinase and PI3K pathways have been described in ECD. These discoveries may redefine ECD, JXG, and LCH as inflammatory myeloid neoplasms, which may lead to new targeted therapies.

High-density lipoprotein deficiency in genetically modified mice deeply affects skin morphology: A structural and ultrastructural study

Cutaneous lipids, endogenously synthetized and transported by lipoproteins, play a pivotal role in maintaining skin barrier. An impairment of extracutaneous lipid trafficking leads to the development of xanthomas, mostly arising in hyperlipidemic patients, but also in subjects with high-density lipoprotein (HDL) deficiency.The aim of this work was to evaluate, in a genetically modified mouse model, lacking two protein components of HDL particles, apolipoprotein(apo)E and apoA-I, the effect of HDL deficiency on skin morphology.Control mice (C57BL/6), apoE deficient mice (EKO), apoA-I deficient mice (A-IKO) and apoA-I/apoE double knockout mice (A-IKO/EKO) were maintained on a low-fat/low-cholesterol diet up to 30 weeks of age. At sacrifice, skin biopsies were processed for light (LM) and transmission electron microscopy (TEM).Whereas the skin of EKO, A-IKO, and C57BL/6 mice was comparable, LM analysis in A-IKO/EKO mice showed an increase in dermal thickness and the presence of foam cells and T lymphocytes in reticular dermis. TEM analysis revealed the accumulation of cholesterol clefts in the papillary dermis and of cholesterol crystals within foam cells.In conclusion, A-IKO/EKO mice represent an experimental model for investigating the cutaneous phenotype of human HDL deficiency, thus mimicking a condition in which human xanthomatous lesions can develop.

Xanthoma disseminatum avec atteinte viscérale multifocale asymptomatique

Xanthogranulomas belong to non-Langerhans histiocytosis of the second group in the Histiocyte Society classification. They comprise a heterogeneous group of rare entities frequently involving cutaneous tropism. Xanthoma disseminatum belongs to this group of non-Langerhans histiocytosis. We report a case of xanthoma disseminatum (XD) in which localized skin and mucous impairment revealed multisystem involvement. A 28-year-old man presented with a two-year history of progressive yellow-orange and infiltrated xanthomatous papulonodular lesions of the face. Lesions of the oral mucosa and genital region were seen, with no functional repercussions. No ophthalmic or other complications were found. Histopathology showed a dense histiocytic infiltrate within the dermis with Touton giant cells, foamy multinucleated giant cells and inflammatory cells, without necrobiosis. Histiocytes were positive for CD68 but negative for CD1a. Gastric and lung involvement was seen and was confirmed at histology. Bone scintigraphy showed suspicious left ulnar hyperfixation suggesting bone involvement. No monoclonal gammopathy or diabetes insipidus was seen. Our patient was treated with corticosteroids 1mg/kg/day and thalidomide 100mg/day. The outcome was marked by regression and exfiltration of the cutaneous lesions from the second week of treatment, with subsidence continuing at 3 months. This case involves a very rare form of xanthoma disseminatum. The localized facial skin lesions revealed multifocal non-Langerhans histiocytosis that was in fact asymptomatic. The diagnosis of XD was based on clinical, histological and immunohistochemical criteria. Xanthoma disseminatum is a non-Langerhans histiocytic proliferation first described by Montgomery in 1938. This rare entity is characterized by skin and mucous membrane xanthomatosis in which the facial involvement is common, together with diabetes insipidus and normal lipid metabolism. The prognosis is determined by the presence of mucosal xanthomas and visceral involvement. Thus, all xanthogranulomas involving multiple lesions warrant screening for visceral involvement. Diagnosis of this entity can be difficult and is usually based on clinical and histopathological findings. In addition, treatment is complex and non-consensual.