Granuloma formation following cyanoacrylate glue injection in peripheral veins and arteriovenous malformation

Abstract

Background Cyanoacrylate adhesive closure is a technically simple alternative to endothermal ablation of peripheral veins. N-butyl cyanoacrylate is delivered via catheters or by percutaneous injection resulting in occlusion of target veins. The local tissue reaction or the systemic immune response that may follow have not been characterised. Aim To characterise the late local tissue reaction to N-butyl cyanoacrylate glue injected in peripheral vessels. Methods Biopsies were obtained from two patients. In patient one, distal tributaries of the great saphenous vein were injected with VenaBlock™ glue under ultrasound guidance. Ultrasound-guided incisional biopsies were performed at one week, six weeks and 12 months. In patient two, a peripheral arterio-venous malformation was injected with Venablock™ and biopsy was performed 12 months later. Histological analysis was performed using haematoxylin and eosin and immunofixation with CD-4, CD-31, CD-34, CD-68 and D2-40. Results Echogenic material with a strong shadow artefact consistent with the injected N-butyl cyanoacrylate was observed on ultrasound on all follow-up occasions. Biopsies taken at one week showed intravascular glue without histiocytes. Biopsies at six weeks showed isolated foreign body histiocytes coating intravascular fibrillary glue spicules but no granuloma formation. The one-year biopsies showed extravascular changes including fibrosis, lymphoid aggregates and multiple extravascular foreign body cavitated granulomas. Some vessel lumens contained residual spicules of glue but no intravascular granulomas. The extravascular granulomas were deeply located, asymptomatic and not complicated by clinical ulceration. Histologically, there was no evidence of transepidermal elimination. Conclusion Extravascular foreign body cavitated granulomas containing spicules of glue with fibrosis and lymphoid aggregates occur as a delayed finding following the use of N-butyl cyanoacrylate.

Cyanoacrylate glue embolisation for varicose veins – A novel complication

“…We would suggest a potential mechanism may be a chronic immunological reaction to cyanoacrylate with subsequent damage to the vessel wall; this is supported by emerging clinical and preclinical reports of immunological reactions to cyanoacrylate treatment. [9][10][11] An alternative mechanism is that during compression after glue installation, as per the manufacturer's instructions for use, glue may be compressed into a very small tributary leading to its rupture, extravasation and subsequent foreign body reaction. We would therefore suggest that such compression should be light and applied with great care.…”

Cyanoacrylate closure for peripheral veins: Consensus document of the Australasian College of Phlebology

“…21 The second is an Australian study where serial biopsies were taken at one week, six weeks and one year after Venablock TM treatment of peripheral veins. 22 The Russian study reported mast cell degranulation in the peri-vascular space within 10 min of exposure to glue. 21 In AVM studies, acute inflammation consisting mainly of polymorphonuclear cells was observed with foci of intramural haemorrhage within 24-48 h of n-BCA injection.…”

“…No histiocytes or granulomas were present at this stage. 22 The AVM studies showed that by weeks 2-3, there was a granulocytic infiltration of vessel walls and the peri-vascular tissue. The vessel wall showed patchy loss of intima, medial necrosis as well as early foreign body giant cell formation and round-cell infiltration.…”

“…No granulomatous reaction was seen at this stage, but small luminal foci of isolated foreign body histiocytes were present. 22 The AVM studies showed that by week 8, mural angionecrosis was completely replaced by fibrosis with segmental wall thickening, achieving venous closure. Foreign body giant cells were present.…”

“…In the Australian study, all granulomas were found to be extra-vascular and not observed in the vessel walls or within the lumen of the treated vessels, and hence there was no evidence of a granulomatous phlebitis. 22 The foreign body granulomas were observed for as long as 52-60 months.…”