Xanthoma Disseminatum Research Articles

Xanthoma disseminatum. Clinical, metabolic, pathologic, and radiologic aspects

A 55-year-old man with the classical mucocutaneous lesions of xanthoma disseminatum has been followed up for a period of 13 years. The special features of this case, which make it unique, are as follows: (1) the availability of histologic data on multiple lesions for more than a ten-year period; (2) the progressive nature of the multiple osseous lesions; (3) the metabolic studies that show no evidence for accumulation of abnormal sterols in a xanthoma, the blood, or intestinal aspirate; (4) the development of hypothyroidism and symptoms or signs, or both, of an intracerebral and an intraspinal lesion; (5) the partial regression of the cutanous symptoms and lesions while receiving clofibrate, in spite of progression of the mucous membrane and osseous lesions, and (6) the failure to develop diabetes insipidus to date.

Xanthome bei Normolipämie

A short summary of normolipemic xanthomatoses is exposed. A case of xanthoma disseminatum is reported. The typical clinical picture is described and numerous investigations are recorded. No association with any systemic disorder neither diabetes insipidus nor rheumatoid arthritis could be found. Histologically the granulomas consist of many multinuclear giant cells embedded in an infiltration of histiocytic cells and lymphocytes. Fat staining demonstrates lipid accumulation as a secondary phenomenon. Systemic corticosteroid therapy was effective in preventing the regrowth of the granulomas after their surgical removal.

Xanthoma Disseminatum and Multiple Myeloma

An 87-year-old woman had xanthoma disseminatum. Laboratory studies showed underlying multiple myeloma. This association may be coincidental, but it parallels the well-known relationship of generalized plane xanthoma with myelomatosis. As occurs in the latter case, this patient's myeloma appears to be following a benign course.

Generalized Eruptive Histiocytoma

Three cases of a new syndrome of generalized eruptive histiocytoma in healthy adults are presented and compared with four others that were recognized from the literature. The lesions are generalized, symmetric, discrete, and flesh-colored to bluish-red papules with no tendency to grouping. The lesions develop in crops and often involute spontaneously. The histologic picture is monomorphous and composed of a mass of reticular and histiocytic cells without fat, mucin, iron, or changes in the connective tissue or vessels. This process seems more closely related to the first histiocytic stage of nevoxantho-endothelioma (xanthogranuloma), histiocytosis X, or xanthoma disseminatum than to the classic solitary histiocytoma (dermatofibroma) lesion and represents benign proliferation of reticular cells (reticulosis).

Tissue lipid patterns in a case of xanthoma disseminatum.

Xanthoma disseminatum is a rare disease characterized by xanthomatous lesions composed of proliferating mature histiocytes, foam cells with high cholesterol content, eosinophils, Touton cells, and fibrosis. Plaquelike skin lesions are usually seen over flexor surfaces of joint areas with multiple organ systems involved. Serum cholesterol and other serum lipid fractions are typically normal. A case of xanthoma disseminatum in a Negro female with widespread xanthomatous involvement and the finding of associated diabetes mellitus with secondary hyperlipemia is presented as the first reported case in a Negro and as an illustration of the lipid analysis of xanthomatous lesions, including fatty acid distribution by the gas chromatographic technique. Report of a Case History.— First admission: A 33-year-old Negro housewife was admitted to the Medical College of Virginia Hospitals on July 12, 1960, with the history that 10 to 12 years prior to admission she had noted raised nontender pea-sized nodules of the

Xanthomatous cutaneous lesions of histiocytosis X.

The cutaneous manifestations of histiocytosis X, particularly the Hand-Schuller-Christian type, are reviewed. Xanthomatous-appearing lesions, which are rare with histiocytosis X, can be classified according to their clinical and histologic features as (I) yellowish papular and seborrheic lesions; (2) xanthoma disseminatum; (3) juvenile xanthogranuloma; (4) plane, papular, and tuberous xanthomata secondary to complicating biliary cirrhosis; and (5) xanthelasma palpebrarum. The multiple histopathologic patterns that may be found in biopsies of such lesions are illustrated. The rare cases of histiocytosis X associated with cutaneous lesions that show features consistent with xanthoma disseminatum, juvenile xanthogranuloma, and reticulohistiocytoma suggest that these various entities are related clinicopathologic reaction patterns which form a spectrum of histiocytic proliferative disease. Although in most instances these reaction patterns are quite distinct, the occasional occurrence of cases with overlapping features should not be surprising.

Disseminated Xanthosiderohistiocytosis (Xanthoma Disseminatum)

Introduction During the 1930's a group of patients without elevated serum lipids or cholesterol and exhibiting the symptom triad of diabetes insipidus, widespread plaque-like xanthomatous lesions of the skin, and xanthomatous involvement of the mucous membrane of the upper respiratory tract were reported by Finney, Montgomery, and Osterberg. 1-3 These cases were originally presented as xanthoma multiplex with unusual findings, but subsequently were called xanthoma disseminatum. Although exceedingly rare, this entity is quite distinct from either the hypercholesteremic or hyperlipemic xanthomatoses and from reticuloendothelioses such as Hand-Schuller-Christian disease. As implied by the title chosen for this paper, we believe that the term xanthoma disseminatum by connoting a disturbance of lipid metabolism does not properly designate the disorder, because the accumulation of lipid in the lesions most likely is secondary to the proliferation of histiocytic elements rather than to a metabolic disturbance. Instead of being related to the other xanthomas, a

Flat cutaneous xanthomatosis. A review and case report including quantitative fractionation of skin lipid.

Xanthomas were divided into hypercholesterolemic and normocholesterolemic forms by Thannhauser and Magendantz. 1 This subdivision, founded on serum biochemical determinations, has remained for 21 years the standard classification of xanthomatous lesions. By contrast, chemical analysis of the affected tissue, particularly in the normocholesterolemic group, has been curiously neglected. In xanthoma disseminatum, Hand-Schuller-Christian disease, Letterer-Siwe disease, and eosinophilic granuloma of bone, the serum-lipid levels are normal. The last three are now generally accepted as variants of a single pathological process which Lichtenstein 2 referred to as Histiocytosis X. A variety of other all-embracing names for this entity has been suggested, including eosinophilic granuloma syndrome, 3 Letterer-Christian disease, 4 histiocytic type of reticuloendotheliosis, 5 and granulomatous reticuloendotheliosis. 6 Other possibly related conditions are juvenile xanthoma and McDonagh's 7 naevoxanthoendothelioma which Polano 8 and Nomland 9 regard as separate entities. On the other hand, Thannhauser, 3 Crocker 10 and Calnan 11 consider them to be similar to

Cutaneous xanthomas; a reappraisal of their significance.

Xanthomas have been known to man for centuries and their clinical description was recorded by Thomas Addison in 1848, 1 long before modern medical diagnostic techniques were evolved. Accordingly, our understanding of xanthomas resulted chiefly through observation of minute morphological differences in lesions, the recording of various distributional patterns, and the occasional detection of some associated state such as jaundice, diabetes, or a familial tendency. A relatively complex terminology resulted, i. e. xanthoma disseminatum, xanthoma diabeticorum, biliary xanthomatosis, etc. This nomenclature frequently did not reflect distinguishing morphological characteristics among various xanthomatous lesions but merely reflected differences of associated conditions in individual patients and histories. The growth of physiological chemistry and the development of modern serum analytic techniques has largely replaced the need for such a complex morphological approach and has rendered much of this traditional terminology obsolescent. Morphology Xanthomas are circumscribed dermal infiltrations of cholesterol

Xanthoma disseminatum; an unusual form with extension of xanthomatous changes into muscle.

XANTHOMA disseminatum is an entity that is infrequently encountered. It represents a systemic disorder involving the reticuloendothelial system, particularly the reticulum cells and the histiocytes. It differs in the main from xanthoma tuberosum in that the blood serum cholesterol is normal or low 1 and the lesions are more commonly found on the flexural surfaces of the skin. In addition to skin involvement, many other organs and tissues have been found with xanthomatous changes. Lesions have been demonstrated on the mucosal surface of the mouth, epiglottis, and larynx, on the cornea and sclera, 2 in the pleura, lungs, pituitary gland, and the tuber cinereum, 3 in bones, spinal cord, lymph glands, and spleen, 4 in the brain, 5 in the liver, 6 and on the serous surfaces of the pericardium and peritoneum, the walls of the esophagus, stomach, and intestinal mucosa, as well as in glands (thymus, pancreas, and

SPECIAL REVIEWS

It is suggested that the term "xanthoma" be limited to lesions containing a high percentage of lipid as cholesterol and, since these are small yellow tumors, this seems appropriate. The patient with these lesions deserves careful clinical study, and an estimation of serum lipids. If possible, total serum lipid determination with partition is desirable, especially in the obscure cases. At least an accurate estimation of serum cholesterol is needed before a logical prognosis and course of treatment can be provided. The Schoen-heimer-Sperry cholesterol method has the widest acceptance. Patients with xanthomas can be divided into those with normal serum lipids and those with elevated lipids. A. Xanthoma disseminatum lesions are the most frequent and the most benign, and are associated with normal serum cholesterol values. B. Xanthomas without elevation of serum lipids are also found in patients with the "eosinophilic granuloma syndromes," and occasionally with other chronic diseases. C. In xanthoma tuberosum the serum cholesterol is markedly elevated, and the frequent cardiac involvement gives the full-blown patient a poor prognosis. D. Secondary or eruptive xanthomas can accompany most of the conditions with chronic hyperlipemia irrespective of the cause, but they are most common in diabetes mellitus and idiopathic familial hyperlipemia. Another case of idiopathic familial hyperlipemia in an infant is reported, with a total serum lipid level of 6.2%, as well as two cases of the nephrotic syndrome in childhood with secondary xanthomas, a case of xanthomas complicating chronic obstructive liver disease, an example of eruptive xanthomata in von Gierke's disease, and a description of a diabetic girl with a serum total lipid level of 19.4%. The basic cause for the accumulation of cholesterol in any of these conditions is unknown. Surgical removal of the lesions is rarely advisable, and dietary treatment is indicated only in certain of the hypercholesterolemic syndromes.

HEREDITARY XANTHOMATOSIS

In accordance with the classification accepted by Thannhauser and Magendantz,¹Montgomery²and other investigators, primary essential xanthomatosis may be divided into two main types, xanthoma tuberosum and xanthoma disseminatum. The distinction between these forms rests on a variety of clinical and biochemical differences, which concern the cholesterol content of the blood as well as the type and localization of the cutaneous and visceral lesions. In xanthoma disseminatum there are numerous fine papules and plaques on the flexor surfaces of the extremities, especially in the axillary folds. The mucous membranes of the mouth, pharynx and larynx are often affected, and as a result of involvement of the pituitary gland there is frequent occurrence of diabetes insipidus. Thannhauser and Magendantz also associated with this disease involvement of the bones, lungs and brain and Schüller-Christian disease. The cholesterol content of the blood is usually normal in patients with this disease, which has been designated, therefore,