Xanthomatous Lesions Research Articles

Endometrial metastasis of cutaneous melanoma - A case-report bearing diagnostic difficulties -

To report a rare case of endometrial metastasis of cutaneous malignant melanoma, mimicked by histologically xanthomatous lesion. Only about ten other cases of endometrial metastasis of this malignancy have been reported previously. - Case report. - A 60 year old female. - Fractionated curettage and immunohistologically examination of the tissue. - Due to xanthomatous regressive changes of the metastatic tissue, difficulties in the histological confirmation as a metastasis of an unpigmented malignant melanoma occurred. But immunohistological staining showed positivity for S-100 and MART-1, as did the primary tumour. - If atypical bleeding in patients with known malignant melanoma of the skin occur endometrial metastasis should be excluded by gynaecologists.

Intramuscular injection of a plasmid vector expressing human apolipoprotein E limits progression of xanthoma and aortic atheroma in apoE-deficient mice.

Apolipoprotein-E (apoE) protects against coronary artery disease via hepatic removal of atherogenic remnant lipoproteins, sequestration of cholesterol from vessel walls and local anti-oxidant, anti-platelet and anti-inflammatory actions. ApoE gene transfer may thus ameliorate a hyperlipidaemic profile and have beneficial effects at lesion sites to prevent or regress atherosclerosis, a concept endorsed by adenoviral-mediated hepatic expression studies. Here, using plasmid vectors expressing allelic human apoE2 or apoE3 isoforms, skeletal muscle was evaluated as an effective secretory platform for apoE gene augmentation. Transfected myoblasts and myotubes were found to efficiently secrete recombinant apoE in vitro as spherical 10-16 nm lipoprotein particles with pre-beta mobility. Intramuscular plasmid injection in apoE(-/-) mice, which develop spontaneous atherosclerotic plaque and xanthoma resulted in expression and secretion of apoE. Human apoE mRNA was detected by RT-PCR in injected muscles and, although concentrations of apoE3, which is rapidly cleared from plasma, were near ELISA detection limits, levels of plasma apoE2 were measurable (17.5 +/- 4.3 ng/ml). To assess whether muscle-based expression of apoE2 could inhibit atherogenesis, long-term follow-up studies were conducted. Although hyperlipidaemia was not reduced in treated animals, end-point pathology showed clear retardation of atherosclerotic and xanthomatous lesions. Up to 9 months following a single apoE2 plasmid administration, atherosclerotic lesion coverage in proximal aorta was significantly reduced by 20-30% (P < 0.01), whereas development of gross dorsal xanthoma (>5 mm diameter) was effectively reduced to zero. We conclude that expression of apoE from ectopic muscle sites has therapeutic potential to limit progression of atherosclerosis.

Xanthoma of the Temporal Bone: Case Report

OBJECTIVE AND IMPORTANCE: Xanthomas of the cranium that are not accompanied by endocrine or metabolic abnormalities are extremely rare. It is very important to understand the pathological features of this disease, for differential diagnosis from other diseases. CLINICAL PRESENTATION: A 62-year-old woman presented to the hospital with headaches. Cranial x-rays revealed bone destruction in the right temporal bone, with osteosclerosis in the area surrounding the lesion. In computed tomographic scans, the bone cortex was intact and the diploë was dilated because of the large mass of the lesion. T1-weighted magnetic resonance imaging findings were heterogeneous, with areas of hypo- and isointensity; T2-weighted magnetic resonance imaging findings were also heterogeneous, with areas of hypo- and hyperintensity. INTERVENTION: Total removal of the tumor was performed, followed by cranioplasty using artificial bone. DIAGNOSIS: Histologically, lipid-containing foamy cells were dense and a cholesterin granuloma was observed. There was no reason to infer other diseases, and a diagnosis of xanthoma of the temporal bone was reached. CONCLUSION: Xanthomatous lesions are observed in various pathological conditions, including malignant diseases. Xanthomas are benign lesions and the prognoses for patients with these lesions are satisfactory, even after partial excision. Therefore, it is quite important to distinguish xanthomas from other diseases that produce xanthomatous lesions.

Spontaneously hyperlipidemic (SHL) mice: Japanese wild mice with apolipoprotein E deficiency.

During inbreeding of Japanese wild mice (Mus musculus molossinus), we established a strain of mice with severe cutaneous xanthomatous lesions. Since those mice showed high plasma cholesterol values, we named them spontaneously hyperlipidemic (SHL) mice; total cholesterol values of these mice (even when fed on conventional low-fat diet) are unusually high throughout the life span. The xanthomatous lesions appear in palms and distal extremities of forelimbs as early as 4 weeks after birth, and continue to expand to chest, abdomen, and face until the mice die before 14 months of age. Histological examination of these lesions revealed cholesterol crystal deposits, an infiltration of foam cells or macrophages, while that of the vascular system revealed atherosclerosis in the aortic sinus. Immunoblot and Northern blot analyses failed to detect apolipoprotein E (APOE) expression in these animals. Consistent with these findings, Southern blot analysis found disruption of the Apoe gene in SHL mice. Phenotypes of SHL mice, however, were distinct from those of Apoetm1Unc (hereafter Apoe-/-) mice, whose Apoe gene was disrupted by homologous recombination; hypercholesterolemia and xanthoma were more severe in SHL mice than in Apoe-/- mice, while atherosclerosis was milder in SHL mice. These distinctions suggest that there are modifier genes for the phenotypes. Alternatively, other gene(s), besides the Apoe gene, may be mutated in SHL mice. In either case, comparative genetic and molecular dissection of SHL mice will provide a good opportunity to understand the genetic basis for hyperlipidemia and atherosclerosis.

Xanthomatous Lesion of the Gingiva: A possible cause of delayed tooth eruption.

The authors report the rare case of a granular cell lesion of the gingiva overlying a maxillary incisor tooth that was delayed in eruption in a 9-year-old Japanese boy. The lesion was composed of a nodular aggregation of ovoid-shaped cells with eosinophilic and granular cytoplasm, which was immunohistochemically positive for LDL, CD68, HLA-DR, cathepsin D and heparanase. These cells were neither positive for S-100 protein, vimentin, desmin nor myosin. The results suggested that this lesion is a sort of xanthoma, but neither granular cell tumor nor congenital epulis. The etiology of this lesion is unknown, but it seems to be associated with tissue remodeling processes of the pericoronal mesenchymal tissue during tooth eruption. Such an unusual pericoronal tissue containing a xanthomatous lesion may be one of the causes for delay in tooth eruption.

Dietary cholesterol-induced xanthomatosis in atherosclerosis-susceptible Japanese quail ( Cotunix japonica)

Japanese quail of a strain (SUS) susceptible to dietary cholesterol-induced atherosclerosis were fed a diet supplemented with cholesterol (0.5% w/w) for 4, 8 or 12 weeks. Plasma cholesterol increased significantly from 240-1550 mg/dl at 4 weeks and remained at that concentration for 8 and 12 weeks on the same diet. Plasma triglycerides (TGs) increased from 112-384 mg/dl after 4 weeks but showed no significant increases thereafter. Striking eruptive xanthomatous lesions were noticed on the feet of 50% of these birds at 4 weeks, and the percentage of birds affected increased to 85 after 12 weeks on the cholesterol-supplemented diet. This is the first report of xanthomatosis in birds. These birds had also developed atherosclerotic plaques in the aorta and brachiocephalic arteries by 4 weeks. There was no significant correlation between xanthoma scores and plasma cholesterol and TG concentrations at any of the three sampling periods (4, 8 and 12 weeks of cholesterol feeding). There was, however, a significant negative correlation (r = -0.61) between xanthoma scores and atherosclerotic plaque scores at 4 weeks. The correlation became non-significant at later stages of cholesterol exposure. Similarities between mammalian and SUS Japanese quail xanthomatosis may make the SUS quail a useful model for the study of this disorder.

Helicobacter pylori infection in gastric xanthomas: immunohistochemical analysis of 145 lesions.

A total of 145 paraffin-embedded biopsy samples of gastric xanthoma were analyzed for the localization of Helicobacter pylori (HP) antigens. By the indirect immunoperoxidase method using a polyclonal antibody, HP infection was identified on the surface of foveolar cells in 69 (48%) samples. In 38 (55%) of the 69 lesions, the HP antigens were demonstrated in the cytoplasm of xanthoma cells clustered in the actively inflamed lamina propria mucosae. Among the remaining 76 xanthoma lesions negative for HP infection on the epithelial surface, only eight (11%) showed the existence of HP antigens in the foamy histiocytes, and 39 (51%) revealed mild inflammatory change. Monoclonal antibody study using 75 specimens also gave a comparable result. Pre-embedding immuno-electron microscopy using paraffin sections revealed positively labeled rod-shaped bacteria both on the epithelial surface and in the phagosome of the xanthoma cells. These findings strongly suggest that some of the xanthoma lesions are provoked by lamina proprial invasion of surface-infected HP.

Cutaneous xanthomatous tumours as an expression of chronic myelomonocytic leukaemia?

Nonspecific cutaneous xanthomas have been reported in a variety of lymphocytic neoplastic processes, but to date only three cases of xanthomatous lesions associated with monocytic leukaemias have been described. We now report a patient with a chronic myelomonocytic leukaemia (CMML) associated with these lesions. The clinical and immunohistochemical features do not correspond to any entity previously described and suggest that xanthomas is are a cutaneous expression of the CMML.

Diffuse plane xanthomatosis associated with a monoclonal band displaying anti-smooth muscle antibody activity

We report a patient with diffuse planar xanthomatous lesions associated with a benign monoclonal gammopathy. This patient has a very high titre of anti-smooth muscle antibody (1:10,240), but normal liver function tests and a normal liver biopsy. The paraprotein band displays anti-smooth muscle antibody activity. There is no evidence of any other underlying disease process. The findings are consistent with a diagnosis of diffuse plane xanthomatosis, but the mechanism of xanthoma formation remains unclear.

Atypical xanthomatosis in apolipoprotein E-deficient mice after cholesterol feeding

Apolipoprotein (apo) E-deficient mice were fed a hypercholesterolemic diet for 14 weeks. Mean serum cholesterol levels rose to 37.5 mM. Upon complete necroscopy, massive xanthomatous lesions were noticed in various tissues, with a predilection for subcutaneous and peritendinous tissues, while control animals on the same diet (3.4 mM serum cholesterol) and apo E-deficient mice on a regular chow diet (20 mM serum cholesterol) did not show such lesions. Also, apo E3-Leiden transgenic mice fed a high fat diet, with 60 mM of serum cholesterol, did not exhibit any xanthomatosis. The xanthomatous lesions found in the Apoe knock-out mouse clearly differed in location from xanthomas previously found in low density lipoprotein receptor-deficient mice. We conclude that the lack of apo E results in atypical disseminated xanthomatosis, suggesting that apo E has an important role in determining the tissue distribution of cholesterol deposition.

Xanthomatous lesion of the mandible: Report of a case

Xanthomatous lesions of the jawbone are rare and ill-defined. In the case presented, infiltration of the mandibular bone marrow by abundant foam cells was combined with extensive reactive bone formation.

Symptomatic xanthogranuloma of choroid plexus with unilateral hydrocephalus

Xanthogranulomas involving the choroid plexus of the lateral ventricles are generally asymptomatic lesions. The case is reported of a 50-year-old man in whom a xanthogranuloma of the choroid plexus had occluded the left trigone, causing unilateral hydrocephalus of the left temporal horn and neurological symptoms. A review of the literature shows that xanthogranulomas of the glomus of the lateral ventricles differ from the xanthomatous cystic lesions of the third ventricle, which are probably akin to colloid cysts.

Diffuse-plane normolipaemic xanthoma with aortic-valve xanthoma

A patient with diffuse-plane normolipaemic xanthomatosis had mucous-membrane, conjunctival, and aortic-valve xanthomatosis. The presence of a monoclonal protein and hypocomplementaemia suggests that the xanthomatous lesions were probably not metabolic in origin but developed as secondary events in a histiocytosis of involved tissues. No heart-valve xanthomatization in like circumstances has previously been reported.

Extraordinary Case Reports

Numerous nodular xanthomatous lesions arose, gradually increasing in number on the back, chest, lips, tongue, and exposed “V” area of the chest on a 78-year-old man. Painful oral nodules and hoarseness developed subsequently. Histologic examination of the skin revealed a suppurative and granulomatous inflammation with an accumulation of acute polymorphonuclear neutrophils, nuclear dust, and xanthomatous histiocytes. Giant cells were rare and cholesterol clefts were absent. Biopsy of the oral mucosa and the larynx showed a similar process. Direct immunofluorescenee was positive for vascular immune reactants at the basement membrane and fibrin in between collagen bundles. The patient had a serum IgA level of 432 mg/dl (normal level, up to 380), with normal Igü and IgM serum concentrations. A Raji cell assay was 240 $mUg/AHGEQ/ml (normal < 5). CH-50 was decreased and C2, C4, and C3 were within normal limits. The dermatopathology was initially thought to be consistent with erythema elevatum diutinum, and the patient was treated with dapsone and prednisone, with a marginal response. There were no dermatopathologic findings of vasculitis. On review, the patient's dermatopathology was more consistent with necrobiotic xanthogranuloma (NXG). To our knowledge, this is the first report of an association of NXG with an IgA gammopathy and the second reported case of extracutaneous involvement with NXG.

Another CHILD Syndrome with Xanthomatous Pattern

We report on a patient with verruciform xanthoma lesions in an epithelial nevus and developmental anomalies since birth that may be classified as CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). Histological analyses of the lesion revealed verrucous features with acanthosis, hyperkeratosis, parakeratosis and the typical infiltrate of xanthomatous cells in dermal papillae. To our knowledge only 5 cases of verruciform xanthoma on epidermal nevus have been reported to date. In our view, the present case of CHILD syndrome is the first reported in which xanthomatous transformation has been revealed in biopsies taken when the girl was a baby.

Neutral lipid accumulation in macrophages during lipid-induced macrophage growth.

We previously reported that lipids such as cholesterol esters, triglycerides, and some phospholipids that are components of cell membranes or serum lipoproteins induced the growth of mouse peritoneal macrophages in vitro. Here, we report that macrophage growth was directly induced by lipids without any soluble factors and that the continuous presence of lipids was required for their growth during culture. When macrophages were cultured with several phospholipids that stimulated macrophage growth, their triglyceride content was dramatically increased during culture, whereas their contents of phospholipids, cholesterol, and esterified cholesterols were scarcely changed. On the other hand, phosphatidylcholine and sphingomyelin, which did not stimulate macrophage growth, caused less accumulation of triglycerides in the cells. Macrophages in which triglycerides accumulated resembled foam cells, since they contained many particles that stained with oil red O. Macrophages that cultured with cholesteryl linoleate also contained many oil red O-stainable particles. These data suggest that accumulation of lipid droplets is correlated with macrophage growth induced by lipids and that foam cells in pathological states such as those in atherosclerotic or xanthoma lesions might proliferate in situ.

Xanthomatous lesions of the mandible: Osseous expression of non-X histiocytosis and benign fibrous histiocytoma

Seven cases of xanthomatous lesions of the manidble, followed from 1 to 18 years, are documented. All lesions were benign and painless; radiographic appearances varied from single and well-demarcated to diffuse and multilocular. Microscopic examination showed sheets of histiocytes with xanthoma or foam cells, fibroblasts and fibrous tissue, and inflammatory cells as well as cells in transition, with characteristics of both histiocytes and fibroblasts. Immunohistochemical staining and electron microscopic observation provided further evidence of the biphasic nature of this cell population. Twelve similar cases were found in the literature under a variety of diagnostic or descriptive labels. Our findings show that these lesions are histiocytic in nature and that they range from small, innocuous lesions, which we regard as the osseous counterpart of non-X histiocytosis, to larger, more destructive lesions diagnosed as benign fibrous histiocytoma (fibrous xanthoma) of bone.

History

More than a century has passed since the first case of PXE was described in the medical literature. In 1884, a French physician and director of the laboratory at the Hôpital Saint Louis in Paris, Felix Balzer, 1 reported the case of a 49-year-old bricklayer who suffered and died from tuberculosis. Balzer's clinical description of the patient noted pale yellow xanthomatous skin lesions present from childhood only in flexural sites; Balzer performed histologic studies on all organs and recounted in detail his observations of “elastic grains” composed of hypertrophied and broken elastic fibers in the skin and heart. Because his patient fit no currently known entity, he thought that he had observed a very rare and unusual variant of xanthelasma. ∗ ∗ Xanthelasma is an obselete term for xanthoma. In current usage xanthelasma is a type of xanthoma and refers only to xanthomas found about the eyes.

Immunohistochemical Study on Cutaneous Histioproliferative Lesions

Immunohistochemical examinations were performed using five kinds of histiocytic markers [S100 protein, lysozyme, non-specific cross reacting antigen with carcinoembryonic antigen (NCA), alpha 1-antichymotrypsin (alpha 1-ACT) and alpha 1-antitrypsin (alpha 1-AT)] in biopsied tissues from histiocytosis X, juvenile xanthogranuloma, xanthoma tuberosum, xanthoma disseminatum, reticulohistiocytic granuloma and multicentric reticulohistiocytoma, all of which have been classified as histiocytic proliferative disorders. Our results suggested that xanthomatous lesions of the skin to be composed of the histiocytic proliferation of two different cell lineages, i.e. S100+lyso-NCA- T-zone histiocytes and S100-lyso+NCA+ tissue macrophages. Only lesions of histiocytosis X were composed of the former cells. It is suggested that these markers will be useful in determining the delineation of the histiocytic system on the basis of functional heterogeneity.

Juvenile xanthogranuloma with central nervous system lesions

We describe two boys in whom extensive normolipemic cutaneous papulonodular xanthomatous lesions developed and disabling central nervous system disease later developed. Histologically, lesional skin from each patient was consistent with juvenile xanthogranuloma. Electron microscopic studies in each case failed to reveal Langerhans (Birbeck) granules. Results of S-100 protein studies done with the peroxidase-immunoperoxidase technic were negative in each case. Radiation therapy and systemic corticosteroids have been partially successful in controlling the cerebellar ataxia experienced by one of the patients. The other patient had progressive central nervous system disease and died 8 years after the onset of his skin lesions despite radiation therapy and systemic chemotherapy. We believe that these cases are examples of normolipemic, xanthomatous, non-X histiocytosis with features of juvenile xanthogranuloma and aggressive central nervous system disease.