Angiosarcoma associated with a vascular graft: Case report

International Journal of Angiology 5:157-159 (1996)

Angiosarcoma Associated with a Vascular Graft: Case Report Dulce A. Brito, M.D., l Filomena Carneiro, M.D., ~ Mdnica Pedro, M.D., 1 Lina Salgueiro, M.D., 1 Maria J. Palhano, M.D., 2 Jos6 S. Nunes, M.D., 3 Fernando de P~idua, PhD., F.E.S.C., 1 Hugo C. Madeira, PhD., F.E.S.C., F.I.C.A. 1 ~IV Department of Internal Medicine, Hospital Universit~irio de Santa Maria, Lisboa, Portugal, 2Department of Anatomo-Pathology, Hospital Universit,-iriode Santa Maria, Lisboa, Portugal, 3Department of Vascular Surgery, Hospital Universitfirio de Santa Maria, Lisboa, Portugal

Abstract. W e d e s c r i b e a case o f r e t r o p e r i t o n e a l a n g i o s a r c o m a in a s s o c i a t i o n with an a o r t a - b i f e m o r a l D a c r o n graft. Surgery was not p e r f o r m e d and the p a t i e n t died. A t a u t o p s y , a local e x t e n s i v e , h i g h - g r a d e a n g i o s a r c o m a w a s c o n f i r m e d and a left p u l m o n a r m e t a s t a s e w a s found. A s a r c o m a s h o u l d a l w a y s be c o n s i d e r e d in the differential d i a g n o s i s o f any m a s s a s s o c i a t e d with v a s c u l a r grafts, and an e x t e n s i v e investigation o f p o s s i b l e and u n s u s p e c t e d distant m e t a s t a s i s is m a n d a t o r y in all cases.

Introduction A n i m a l studies h a v e i m p l i c a t e d plastic p o l y m e r s c a p a b l e o f i n d u c i n g s a r c o m a [1-3]. In h u m a n s , a l t h o u g h rare, this risk also exists [3]. W e d e s c r i b e a case o f a n g i o s a r c o m a in association with an aortic D a c r o n graft, b e i n g a w a r e that only five cases w e r e r e p o r t e d p r e v i o u s l y [4-8]. T h e aim o f this report is to d r a w attention to the o c c u r r e n c e o f t u m o r s arising in relation to v a s c u l a r i m p l a n t s and also to the i m p o r tance o f looking for the p r e s e n c e o f distant m e t a s t a s i s bec a u s e its e x i s t e n c e ( s o m e t i m e s u n s u s p e c t e d ) m a y h a v e important t h e r a p e u t i c i m p l i c a t i o n s .

markable. The chest radiograph and gastrointestinal studies were normal. The electrocardiogram showed sinus rythm and discrete, nonspecific repolarization alterations. On abdominal CT scanning, a retroperitoneal solid mass (Fig. l) was identified encircling the right arm of the prosthesis and extending from below the right kidney to the superior pelvis. There was also hydroureter with right hydronephrosis. No other abnormalities were found. Diagnosis included a pseudoaneurysm vs graft infection or a tumor. Aortography showed a patent bypass without evidence of pseudoaneurysm and a leucocyte cintigraphy--99Tcm-hexamethylpropyleneamine oxime (HMPAO)labeled white blood cell--was negative. The patient refused a laparotomy and a needle biopsy of the mass was than considered and performed. The histopathologic diagnosis was compatible with angiosarcoma. Staging and combined therapy (radiation and chemotherapy) were planned but the patient died suddenly. At autopsy, there was a firm and partially necrotic mass measuring 20 x 14 x 10 cm, localized in the right retroperitoneum and encircling the right arm of the graft. The tumor encroached on adjacent vertebra and was neither fixed to any intraabdominal structure nor did it invade the graft, which was patent (Fig. 2). No tumor emboli were seen within any organs but a metastasis was discovered in the upper lobe of the left lung. No other metastases were found. The right kidney was small and there was right hydroureter with hydronephrosis. The left kidney was normal. Extensive examination revealed marked and generalized atherosclerosis. No direct cause was found for the sudden death. Microscopic examination of the tumor (Fig. 3) revealed spindle-shaped cells forming irregular cords within a fine fibrous stroma. Nuclei were pleomorphic, and moderate numbers of mitosis were noted. In some areas there was formation of vascular spaces of irregular size and shape lined by neoplastic endothelial cells. Various foci of necroses were present. Immunoperoxidase study for factor VIII was positive. The final diagnosis was high-grade angiosarcoma.

Case Report A 77-year-old man was admitted with a 4-month history of right lower quadrant and back pain, constipation, and marked weight loss. Physical examination revealed a painful right abdomen but no palpable mass. No bruits were heard. Femoral, popliteal, and distal pulses were markedly diminished. He was afebrile. Past medical history included intermittent claudication (stage lib LericheFontaine). Three years ago, an arteriogram showed the characteristic picture of severe arterial atherosclerotic obstruction of both iliac arteries. An aorta-bifemoral bypass graft (woven double-velour Dacron) was placed. Laboratory studies revealed leucocytosis (21.400/ram 3) with neutrophilia (90%) and raised sedimentation rate (90 mm) but were otherwise unre-

Correspondence to: Hugo C. Madeira, Ph D. F.I.C.A., Medicine IV, Hospital Universit~iriode Santa Maria. Lisboa, Portugal

Discussion P r i m a r y t u m o r s o f the m a j o r b l o o d v e s s e l s are rare, e x c e p t for t h o s e r e l a t e d to the large arteries, w h i c h are the rarest o f all [9]. A r e v i e w o f the w o r l d literature d i s c l o s e d 32 rep o r t e d c a s e s [10], 31 r e l a t e d to the aorta and 1 to the f e m o r a l artery. In five o f t h e s e c a s e s (15,6%) the t u m o r w a s a sarc o m a [4-8] and d e v e l o p e d a r o u n d a p r e v i o u s l y p l a c e d aortic v a s c u l a r p r o s t h e s i s , s u g g e s t i n g a p o s s i b l e causal relationship b e t w e e n the graft and the tumor. V a s c u l a r graft i m p l a n t s are c o m m o n t r e a t m e n t p r o c e d u r e s in v a s c u l a r o c c l u s i v e or a n e u r i s m a t i c disease. Graft occlusion, p s e u d o a n e u r y s m , or a o r t o e n t e r i c fistula are the m o s t

158

D. Brito et al.: Sarcoma Associated with Vascular Grafts

Fig. 1. Abdominal CT scan showing a retroperitoneal mass (M) encircling the right arm of the graft (arrow).

Fig. 2. Irregularly anastomosing channels (C), some with blood, lined by pleomorphic endothelial cells (Van Gieson stain; original magnification 325x). frequent detected complications related to graft implants. The occurrence of m e s e n c h y m a l - d e r i v e d tumors in association with synthetic material is c o m m o n in experimental works but it is an extremely rare finding in clinical practice. Our report is the sixth case described of a sarcoma associated also with an aortic vascular prosthesis in h u m a n s .

Fig. 3. Gross specimen showing the mass (M) and longitudinal section of the right (R) and left (L) arms of the Dacron graft (the lumen is clear).

In 1941, T u r n e r [11] described the appearance of sarcomas in sites of baquelite implants in rats. O p p e n h e i m e r et al. [1 ], e m b e d d i n g plastic films of various types, subcutaneously in rats, induced the d e v e l o p m e n t of sarcomas in 7 - 5 0 % of cases, after a latent period of 7 months to 2.5 years. He also demonstrated that the physical form of the e m b e d d e d material played an important role in sarcoma induction, the film form h a v i n g the greatest carcinogenicity potential. After implant, the film was encapsulated by a sheath of connective tissue and the inner surface of this sheath formed a pocket from which the film could be easily removed. W h e n a t u m o r was induced, it arose in the inner layer of the pocket wall, after a variable latent period. In the first 6 months after implant, the plastic film seemed to be the most potent carcinogenic stimulus, and its removal prevented tumor induction. After that time, the pocket wall itself became the most important carcinogenic factor and its removal was also necessary for preventing tumor formation. In humans, a latent period of 1 5 - 2 0 years was suggested before carcinogenesis b e c a m e manifest. Karp et al. [2] and Brand and Brand [3] showed that the carcinogenic potential varied directly with the size of the material porus. The smaller the size (less than 0.4 micra), the greatest the carcinogenic potential. This finding can be explained by a fagocitosis p h e n o m e n o n allowed by the free

Table 1. Graft-associated sarcomas: principal features

Author

Graft type and location

Histology

[4]

Woven Teflon-Dacron femoral bypass Woven Dacron abdominal aorta Woven Dacron thoracic aorta Woven Dacron abdominal aorta Woven double-velour Dacron abdominal aorta Woven double-velour Dacron aorta-femoral bypass

Fibrosarcoma

[5] [6] ]7] [8l This case

Time between implant and tumor presentation 10 yr

Metastasis

Tumor thrombus

Treatment

Follow-up

No

No

Surgery

Alive (1.5 yr) Death(8 too) Death

Fibrosarcoma

4 mo

No

Yes

Malignant histiocytoma Angiosarcoma

14 mo

No

Yes

Combined therapy -

12 yr

No

-

-

Death (7 mo)

Angiosarcoma

3.5 yr

Liver

No

Alive (7 mo)

Angiosarcoma

3 yr

Lung

No

Combined therapy -

Death

D. Brito et al.: Sarcoma Associated with Vascular Grafts passage of cells in large porus. Factors accounting for the low incidence o f tumors in association with D a c r o n prosthesis in humans could be not only the large size of the porus ( 2 0 - 3 0 micra) in these grafts, but also a low genetic predisposition, a conclusion m a d e by Brand [3] after d e m onstrating that humans, like guinea pigs, w e r e highly resistent to foreign body-related neoplasms. All previously reported cases o f s a r c o m a related to vascular prostheses were in association with D a c r o n material (Table 1) as in the present one. In the first four reports, a w o v e n Dacron graft was placed. In our case and in the case reported by Weiss, the prostheses were both w o v e n , doublevelour Dacron grafts. Our case is similar to the cases described by Burns et al. [4], W e i n b e r g and Maini [6], and Weiss et al. [8] in that a tumor mass surrounded the graft material. The time interval b e t w e e n the implant and the diagnosis of the n e o p l a s m varied b e t w e e n 4 months and 12 years. The presence of neoplastic thrombus was responsible for the clinical presentation in two cases [5,6]. In the others, tumor was clinically manifest by pain and/or local c o m p r e s sion. K e v o r k i a n and Cento [9] reported an important i n c i d e n c e (21%) of p u l m o n a r metastases in n e o p l a s m s arising f r o m inferior v e n a cava, large veins (40%), p u l m o n a r y artery (20%), and other large arteries (40%). In tumors related to vascular prosthesis, p u l m o n a r metastases are only described in our case, although hepatic metastases w e r e noted in the case reported by Weiss et al. [8]. C o n c e r n i n g the treatment o f these tumors, an adequate and wide en bloc excision, if possible, and a c o m b i n a t i o n o f radiotherapy plus c h e m o t h e r a p y can a c h i e v e a appreciable success [8]. In the present case, the patient refused a laparotomy, but a curative ressection or e v e n an adequate paliative one w o u l d n e v e r be feasible. The t u m o r was extensive, showed a high-grade of malignancy, and distant metastases were already present (stage I V B - A J C Staging system). The occurrence of sudden death p r e c l u d e d any further evaluation or treatment option. N o evident cause for death

159 could be found and a m a l i g n a n t arrhythmia was considered as a probable event. The p r e s e n c e o f important and generalized atherosclerosis (coronary system included) helps to support this idea e v e n in the absence of areas o f m y o c a r d i a l scarring, as was the case with this patient. The consideration of a s a r c o m a in the differential diagnosis of all masses associated with grafts is important. A n agressive a p p r o a c h is m a n d a t o r y in these patients in order to i m p r o v e survival and also quality o f life. It is our b e l i e f that an e x h a u s t i v e investigation to e x c l u d e the p r e s e n c e of metastasis at r e m o t e sites is m a n d a t o r y as their p r e s e n c e can alter patient m a n a g e m e n t .

References 1. Oppenheimer BS, Oppenheimer ET, Stout AP, et al (1958) The latent period in carcinogenesis by plastics in rats and its relation to the presarcomatous stage. Cancer 11:204-213. 2. Karp RD, Johnson KH, Buoen LC, et al (1973) Tumorigenesis by millipore filters in mice: Histology and ultrastructure of tissue reactions, as related to pore size. J Natl Cancer Inst 51:1275. 3. Brand KG, Brand I (1980) Risk assessment of carcinogenesis at implantation sites. Plast Reconstr Surg 66:591-594. 4. Bums WA, Kanhouwa S, Tillmann L, et al (1972) Fibrosarcoma occurring at the site of a plastic vascular graft. Cancer 29:66-72. 5. O'Connell TX, Fee HJ, Golding A (1976) Sarcoma associated with Dacron prosthetic material. J Thorac Cardiovasc Surg 72:94-96. 6. Weinberg DS, Maini BS (1980) Primary sarcoma of the aorta associated with a vascular prosthesis. A case report. Cancer 46:398-402. 7. Fehrenbacher JW, Bowers W, Strate R, et al (1981) Angiosarcoma of the aorta associated with a Dacron graft. Ann Thorac Surg 32:297301. 8. Weiss WM, Riles TS, Gouge TH, et al (1991) Angiosarcoma at the site of a Dacron vascular prosthesis: A case report and literature review. J Vasc Surg 14:87-91. 9. Kevorkian J, Cento DP (1973) Leiomyosarcoma of large arteries and veins. Surgery 73:39~400. 10. Schipper J, van Oostayen JA, den Hollander JC, et al (1989) Aortic tumors: Report of a case and review of the literature. Br J Radiol 62:35-40. 1I. Turner FC (1941) Sarcomas at sites of subcutaneously implanted Bakelite disks. J Natl Cancer Inst 2:81-83.