Cutaneous metastasis of chordoma.

BACKGROUND: Chordomas are rare neoplasms that arise from the notochord remnant. They develop in the sacrococcygeal (50%) or cervical (15%) region and are generally regarded as a locally aggressive tumor with a slow progressive growth rate and a metastatic incidence ranging from 3 to 48%. Skin involvement by chordoma is rare, but can occur by direct extension, by local recurrence and by metastases. OBJECTIVE: To illustrate by a case report the clinical presentation and management of this disease. METHODS: We present a case of sacral chordoma with metastases over a 10-year period to the lungs, the soft tissue of the chest wall, the triceps tendon, and distant cutaneous metastases to the back and the nose. RESULTS: The cutaneous metastases were treated by excision. CONCLUSION: Chordoma is a slow growing tumor of the notochord remnant that may metastasize to the skin. Physicians and pathologists should be aware of this entity.

Variations in the composition of arterial wall isomeric chondroitin sulfate proteoglycans among different animal species.

1. Isomeric chondroitin sulfate proteoglycans were extracted from human, bovine, swine and rabbit aortas by 4 M guanidine-HCl and were fractionated and purified by CsCl isopycnic centrifugation, Sepharose CL-4B gel filtration, DEAE-Sepharose ion-exchange chromatography and octyl-Sepharose hydrophobic interaction chromatography. 2. The molecular size and the composition of isomeric chondroitin sulfate proteoglycans varied among species. Variations were also noted in the composition and molecular weight of constituent glycosaminoglycan chains. 3. Observations made on chondroitinase ABC and chondroitinase AC digests of proteoglycans indicate that dermatan sulfate is linked to the core proteins through chondroitin sulfates.

Composition of proteoglycans from human atherosclerotic lesions.

Proteoglycans from human atherosclerotic lesions and from uninvolved aortic intima were isolated and their composition was studied. The tissues were sequentially extracted by guanidine hydrochloride followed by hydrolysis of the tissue by elastase. Chondroitin sulfate/dermatan sulfate proteoglycans were predominant in guanidine hydrochloride extracts of the tissue. Most of the heparan sulfate proteoglycans were released from the tissue by hydrolysis with elastase. The content of proteoglycan material, measured as uronate per unit weight of wet tissue, was lower in fatty streaks and fibrous plaques than in uninvolved tissue (0.58 and 0.48 mg vs. 0.7 mg/g wet tissue). The distribution of different glycosaminoglycans in guanidine hydrochloride-extracted proteoglycans was similar among the lesions and uninvolved tissue, but varied in the elastase-hydrolyzed extracts. Gel filtration studies suggested that the major proteoglycan material, chondroitin sulfate proteoglycans, from lesions had greater molecular weight than proteoglycans from uninvolved tissue. The studies indicate that alteration in intrinsic composition and molecular size of proteoglycans occurs in atherosclerotic lesions.

Studies of arterial wall glycosaminoglycans and collagen during experimental regression of atherosclerotic lesions in cynomolgus monkeys.

The effect of various antiatherogenic regimens on glycosaminoglycan and collagen concentrations in aortas from cynomolgus monkeys with diet-induced atherosclerosis was studied. The drugs and materials that were studied included d-thyroxine, [4-chloro-6-(2,3-xylidino)-2-pyrimidinyl]thioacetic acid, cholestyramine, alfalfa, and glucophage. The treatments resulted in varied degrees of regression of lesions. The mean hydroxyproline concentration in aortas among groups of animals treated with different regimens was significantly different within the groups (p less than 0.001) and correlated with the severity of the lesions (p less than 0.01). The mean total glycosaminoglycan concentration among different groups did not differ significantly but correlated positively (p less than 0.05) with the severity of lesions. Heparan sulfate and hyaluronic acid increased with regression and decreased with increasing severity of lesions, whereas chondroitin sulfates followed an opposite trend. These observations show connective tissue components are intimately involved in remodeling the aorta during regression of diet-induced atherosclerosis.

The effect of various dietary regimens and cholestyramine on aortic glycosaminoglycans during regression of atherosclerotic lesions in rhesus monkeys.

The effect of various diets on the aortic glycosaminoglycan (GAG) composition was studied in rhesus monkeys. Aortas were obtained from monkeys fed diets containing cholesterol and comparative fats including coconut oil--butter and peanut oil and with and without cholestyramine. Additional groups in each experiment were placed on regression diets of low-fat, low-cholesterol with and without cholestyramine. Further, an atherogenic diet of coconut oil--butter was alternated every 2 months with a diet enriched with corn oil. GAG isolated from intima and media--adventitia indicated slight variations in the concentration of total GAG among different dietary groups but major differences in the concentration of individual GAG. The concentrations of hyaluronic acid and heparan sulfate were generally greater in aortas of monkeys fed corn oil diets than in those fed coconut oil--butter or peanut oil diets. The concentration of dermatan suulfate generally decreased during regression of lesions induced by the saturated fat--cholesterol diet. Furthermore, the aortas of monkeys with lesions from feeding peanut oil showed higher levels of dermatan sulfate and lower levels of chondroitin 4-sulfate than the saturated fat-fed groups. The addition of cholestyramine enhanced the effects of regression. These observations show that the composition of GAG of the arterial wall can be influenced by various dietary programs and that GAG play a role in induction and regression of experimental atherosclerotic lesions.

Studies of glycosaminoglycan composition and biologic activity of Vessel, a hypolipidemic agent.

Heparin-like glycosaminoglycans (GAG) were isolated from commerical Vessel and their biologic properties studied. Vessel was found to be a mixture of chondroitin sulfates, dermatan sulfate and heparin-like GAG. Chondroitin sulfates and dermatan sulfate in Vessel were hydrolyzed by chondroitinase ABC and the residual Vessel was fractionated on a Dowex-1 Cl- column eluting with a stepwise-increasing concentration of NaCl (1.2--4.0 M). The major fractions eluted at 1.6 M and 1.8 M NaCl were tentatively identified by chemical analysis as heparin-like GAG with somewhat lower sulfate content than standard heparin. Both fractions had lipoprotein lipase-releasing activity and anticoagulant activity similar to heparin, but 1.6 M NaCl fraction had a third of the anticoagulant activity of standard heparin. The 1.8 M NaCl fraction complexed with serum lipoproteins similarly to heparin. In preliminary studies cholesterol-fed rabbits treated with Vessel exhibited somewhat less atherosclerosis than controls.

Connective tissue composition of aortas from non-human primates. A comparative study.

Connective tissue composition of aortas from several non-human primate species has been studied in an effort to relate collagen, elastin, ang glycosaminoglycan (GAG) content to species susceptibility to atherosclerosis. Among the species studied the baboon contained the highest content of GAG in the aorta. While the distribution of individual GAG varied from species to species, heparan sulfate (HS) was the highest GAG in aortas from most of the species. The ratio of HS to chondroitin sulfates (CS) plus dermatan sulfate (DS) was lowest in the baboon, a species relatively less susceptible to atherosclerosis, and highest in the squirrel monkey, a very susceptible primate. If a relationship exists between HS to CS + DS ratio in the aorta and atherosclerosis, the primates can be arranged in the following decreasing order of susceptibility: squirrel, chimpanzee, stump-tailed, rhesus, African green, patas, baboon. In studies of other connective tissue components, the proportion of total collagen to elastin was found lowest in the baboon. Such observations emphasize the importance of connective tissue in the pathogenesis of atherosclerosis.