Temporal artery biopsy size does not matter
Vascular 2014, Vol. 22(6) 406–410 ! The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1708538113516322 vas.sagepub.com
Sarantos Kaptanis1, Joanne K Perera1, Constantine Halkias2, Nadine Caton1, Lida Alarcon1 and Stella Vig1
Abstract This study aimed to clarify whether positive temporal artery biopsies had a greater sample length than negative biopsies in temporal arteritis. It has been suggested that biopsy length should be at least 1 cm to improve diagnostic accuracy. A retrospective review of 149 patients who had 151 temporal artery biopsies was conducted. Twenty biopsies were positive (13.3%), 124 negative (82.1%) and seven samples were insufficient (4.6%). There was no clinically significant difference in the mean biopsy size between positive (0.7 cm) and negative samples (0.65 cm) (t-test: p ¼ .43 NS). Ninetyfour patients fulfilled all three ACR criteria prior to biopsy (62.3%) and four patients (2.6%) changed ACR score from 2 to 3 after biopsy. Treatment should not be delayed in anticipation of the biopsy or withheld in the case of a negative biopsy if the patient’s symptoms improve.
Keywords Giant cell arteritis, temporal artery biopsy, size, ACR criteria
Introduction Giant cell arteritis (GCA) is a large and medium vessel systemic vasculitis1 aﬀecting, among other vessels, the temporal arteries. The American College of Rheumatology (ACR) has published2 a ﬁve-point scoring system for temporal arteritis (Table 1), which is still widely used, despite its shortcomings; recent critics include the European League Against Rheumatism (EULAR) consensus group,3 where 38% of the committee were dissatisﬁed with the deﬁnition. Temporal artery biopsy (TAB) can establish the diagnosis3 and is considered an important tool (Level of Evidence: Ia); however, a negative biopsy does not exclude GCA. A prompt TAB may lead to early withdrawal of unnecessary corticosteroid treatment4; it is suggested that corticosteroid treatment for one or two weeks5 does not aﬀect the biopsy result, whereas TAB would be less typical after four weeks or more of treatment. TAB length remains a controversial issue. Size of any biopsy should be the minimum required to obtain a diagnosis in most cases. The TAB specimen contracts following harvesting after exposure to air and histologic processing, resulting in diﬀerences between the
preexcision, excision and post-ﬁxation length of the artery.6 Small studies have suggested that this is 20% from excision to ﬁxation (due to contraction of the artery)6 and a further 8.5% following ﬁxation in formalin. According to the latest BSR/BHPR guidelines,7 TAB length should be at least 1 cm. This recommendation is based on a multicentre retrospective study of 1520 biopsies that found no statistically signiﬁcant difference in size between the groups of positive (1.34 cm) and negative (1.33 cm) biopsies, and in fact suggested 0.5 cm as a suﬃcient length8; furthermore, the guidelines do not specify whether the 1 cm target is postﬁxation length or surgical specimen length. Various methods for TAB have been described, by rheumatologists,9 surgeons,10 ENT surgeons,11 dermatologists12 and ophthalmologists.13 Neurosurgeons have described an endoscopic-assisted method of 1 2
Croydon University Hospital, London, UK Imperial College Healthcare NHS Trust, London, UK
Corresponding author: Sarantos Kaptanis, Undergraduate Centre, Croydon University Hospital, 530 London Road, Thornton Heath, CR7 7YE, London, UK. Email: [email protected]
Kaptanis et al.
Table 1. ACR criteria for the diagnosis of GCA 1990 (modified from Hunder et al.2). Criterion
Age 50 years
ESR 50 mm/hour TAB abnormal
Development of symptoms at age 50 or older New onset, or new type, localized Temporal artery tenderness to palpation or abnormal pulses unrelated to atherosclerosis of the cervical arteries Westergren method
ESR: erythrocyte sedimentation rate; GCA: Giant cell arteritis; TAB: temporal artery biopsy.
harvesting the entire artery for the purpose of anastomosis with the middle cerebral artery.14 Identiﬁcation of the temporal artery is by palpation or portable Doppler; the course of the artery is marked. Some surgeons shave the hair over the artery if they choose to harvest the parietal branch; then local anaesthetic is inﬁltrated with or without adrenaline. The area is prepared and draped. An incision, 2–8 cm long, is made through the epidermis and dermis just until subcutaneous fat presents. The superﬁcial temporalis muscle fascia envelops the STA, and it should be carefully divided. An adequate length of artery is dissected and then ligated with ties before dividing the specimen and ﬁxing it in formalin for histopathology; some surgeons use diathermy on the cut ends of the artery or on small branches; others prefer ties. Skin closure and dressings vary according to surgeon’s preference. Bilateral biopsies are rarely performed; most surgeons operate on the side where symptoms are most prominent. This retrospective audit aimed to explore the potential association between TAB specimen length and diagnosis of GCA in a single centre, and highlight the diﬀerences in surgical technique leading to the wide variation of collected specimen sizes.
Methods The operation TAB is performed mostly by junior surgeons in our institution, under Consultant supervision. Our method aims to avoid the danger zone where the temporal branch of the facial nerve may be injured, minimize scar, infection rates, wound dehiscence, bleeding, hematoma formation and damage to hair follicles which may lead to bald patches.
After marking the artery, a mixture of lidocaine and bupivacaine local anaesthetic (5–10 cc) is inﬁltrated; this provides adequate post-operative pain control. We do not use epinephrine to prevent arterial spasm. We aim to biopsy the frontal branch whenever possible, about 2 cm above the zygoma; this avoids the temporal branch of the facial nerve. We use a 2-cm incision to harvest a 2–3 cm specimen. Operating loupes are not routinely used. The artery and any branches are ligated prior to division with 3/0 Polyglactin 910 ties. Skin closure is with Polyglactin 910 deep dermal sutures and Poliglecaprone 25 subcuticular suture. Steri-strips or surgical tape is also used.
Histopathological examination The specimen is embedded in 10% formalin. We examine hematoxylin-eosin sections at three levels. The specimen is examined for the characteristic histological ﬁndings in GCA: inﬂammation (sometimes transmural), the presence of giant cells, intimal hyperplasia, fragmentation and disruption of the internal elastic lamina, arterial lumen occlusion.
Data collection A retrospective audit was registered with the hospital’s audit department, which provided ethics approval for the study. In all, 151 patients who had temporal artery biopsies from April 2006 to February 2012 were identiﬁed from pathology and theatre records. Erythrocyte sedimentation rate (ESR) results were retrieved from the patient information system. Data was entered in a Microsoft Excel (2010) spreadsheet. Statistical analysis was performed with Stata version 11.15
Literature review and audit criteria A literature review in Ovid Medline (MESH terms: giant cell arteritis, temporal arteries, biopsy and keywords: length or size) identiﬁed 29 reports of positive artery biopsy rate compared with sample length. Further studies were identiﬁed by cross-referencing. We sought to clarify whether our positive biopsies had a greater sample length than negative biopsies, in which case we would need to change our practice (biopsy method) to obtain larger samples. We set an arbitrary target of less than 10% insuﬃcient samples for biopsy.
Results In all, 111 females (74.5%) and 38 males (25.5%) underwent a total of 151 temporal artery biopsies.
Table 2. Demographics and results.
71.4 (SD 9.8)
68.8 (SD 12)
64.7 (SD 12)
82.9 (SD 35.5))
61.4 (SD 33.4)
79.9 (SD 37.7)
TAB length (mm)
7 (SD 3.2)
6.4 (SD 3)
3.5 (SD 1.3)
ESR: erythrocyte sedimentation rate; TAB: temporal artery biopsy.
Two patients (one male, one female) had bilateral biopsies (all negative) in diﬀerent occasions (21 months apart and 2 months apart, respectively). Mean age at biopsy was 68.9 years (range 19 to 95, SD 11.8); 144 biopsies were performed on people over 50 years old. An ESR result was available for 148 cases (98%). Mean ESR was 65.2 (SD 34.6); 95 cases had an ESR greater than 50. In total there were 20 positive (13.3%) and 124 negative (82.1%) biopsies; in seven (4.6%) cases the specimen was insuﬃcient for diagnosis. The characteristics of the three groups are in Table 2. Out of the seven biopsies performed in patients less than 50 years old, six were negative and one was an insuﬃcient sample. Out of the 53 cases with an ESR less than 50, four (7.5%) had temporal arteritis, 47 (88.7%) were negative and two (3.8%) were insuﬃcient samples. Length of specimen (post-ﬁxation) was available for 148 cases. Mean length was 6.4 mm (median 6, range 2 to 1.8, SD 3 mm). For positive biopsies mean was 7 mm (median 7, range 2 to 1.5, SD 3.2 mm). For negative biopsies mean was 6.4 mm (median 6, range 2 to 1.8, SD 3 mm) and for insuﬃcient samples length of tissue mean was 3.6 mm (range 2 to 5, SD 1.3 mm). Excluding insuﬃcient samples from further analysis, a t-test showed that the diﬀerence between positive and negative specimen length (0.6 mm, 95% conﬁdence interval -0.9 to 2 mm) was not statistically signiﬁcant (p ¼ .43). Logistic regression identiﬁed only ESR as a statistically signiﬁcant predictor of positive biopsy (p ¼ .02), and not age (p ¼ .46), biopsy size (p ¼ .271) or sex (p ¼ .401). Twenty-seven (18.2%) specimens had a post-ﬁxation length of 1 cm or greater; 76 (48.1%) specimens had a post-ﬁxation length of 0.7 cm or greater. Introduction of the BSR/BHPR guidelines for the management of GCA in 20107 made no diﬀerence to harvested specimens. All patients presented with a headache; combining this with ESR, age and biopsy results, 94 patients
fulﬁlled all three criteria prior to biopsy. Four patients changed ACR classiﬁcation after biopsy, as their ESR was below 50.
Discussion GCA is the most common systemic vasculitis in the elderly in the western world.16 It can result, without treatment, in irreversible visual loss due to arteritic anterior ischaemic neuropathy,17 arm or leg claudicatio,18 or even aortic dissection.19 Current practice is such that corticosteroids are commenced when a patient’s presentation is suspicious of GCA based on the ACR criteria (Table 1) and they are subsequently referred for a TAB. This procedure should then be undertaken within 2 weeks of initiating corticosteroid therapy to ensure that the inﬂammatory changes corresponding to a diagnosis of GCA have not resolved, thus leading to a false-negative result.5 Presently, the main implication of a positive temporal artery biopsy result is to clarify a decision on prolonging corticosteroid therapy in cases where the clinical presentation is not entirely diagnostic of GCA, i.e., in patients presenting with less than three of the ﬁve criteria, and in whom initial response to corticosteroids is not satisfactory. Conversely, corticosteroids are often continued despite a negative biopsy result, particularly in those with more than three criteria present. In our series, seven patients had a biopsy which resulted in an insuﬃcient sample for diagnosis, only four of whom fulﬁlled three ACR criteria; none of these patients had a repeat biopsy requested. In this study, we examined length of biopsy and its impact on diagnosis of GCA. One would expect that the longer the segment, the higher the sensitivity, particularly as skip inﬂammatory lesions can occur in this condition. It has previously been suggested that an increased length of biopsy increases the sensitivity and several studies have recommended a segment length ranging between 2 and 7 cm. This is a strategy not supported by clinical data, as in all studies diﬀerence in mean length of positive and negative biopsies is only a few millimetres. The old recommendation for bilateral temporal artery biopsies20 has been abandoned after a number of studies demonstrated minimal beneﬁt.21–23 We ﬁnd it surprising that discussion continues regarding the optimum length of the unilateral biopsy. Ypsilantis et al.24 recently suggested that specimen length is important, on a retrospective cohort of 966 biopsies where median length of positive specimens was 1.2 cm and median length of negative specimens 1.0 cm; a 0.7 cm minimum post-ﬁxation length was suggested. Mahr et al.8 previously studied 1534 biopsies with similar lengths (mean 1.34 cm for positive and 1.33 cm for negative biopsies, median 1.2 cm), ﬁnding
Kaptanis et al. no signiﬁcant diﬀerence. The vast majority of smaller studies report mean and median lengths in this region.5,25–28 Small studies with biopsies of greater size achieve a similar positive rate.29 The 1983 study by Hall et al.,30 achieving median biopsy lengths of 4 cm for positive cases and 5 cm for negative cases, had a 34% positive rate over 134 cases. We doubt that a biopsy length of 17.5 cm would be deemed acceptable today. Arguably, large biopsies avoid the problem of skip lesions, which could occur, according to the Mayo Clinic series,31 in up to 28% of cases. A more recent study by Poller et al.32 has suggested that foci of discontinuous inﬂammation would occur in around only 10% of cases. This study also stated that skip lesions should be apparent on one set of sections from each segment of temporal artery from a specimen at least 6 mm long. If this is the case, then a post-ﬁxation length of 6 mm should be adequate for histological diagnosis of GCA, negating the need for a more extensive biopsy and thus keeping the incision size to a minimum. It has been suggested that deeper sections,33 multiple levels25 or anti-CD83 immunohistochemistry34 may improve diagnostic accuracy; when quantitatively assessed, these methods have provided at most a 10% increase in sensitivity. It is important to consider the need for temporal artery biopsy given that in most cases, the ACR scoring system is able to provide a clinical diagnosis of GCA. Furthermore, the impact on management rarely diﬀers with a negative TAB result. This has been concluded by Varma and O’Neill35 who studied the clinical application of TAB and discovered that it is of most beneﬁt to patients whose diagnosis is less clear as the result impacts on the decision to continue corticosteroid therapy, which of course has its own adverse eﬀects. The beneﬁt of TAB needs to be carefully considered in those who have 3 of the ACR criteria as although TAB is a relatively simple local anaesthetic procedure, it does have recognised complications such as bleeding, infection, damage to the facial nerve,36 a scar which may be considered cosmetically undesirable and insuﬃcient biopsy sample: these need to be mentioned to the patient while obtaining informed consent. Regarding samples insuﬃcient for diagnosis, our rate of 4.6% is unfortunate. Previously, Mahr et al.37 reported 23/1821 (1.3%) biopsies to have sampling errors; we could not identify other major studies referring to this biopsy outcome. Possibly other authors tend to exclude such specimens from further analysis. In our experience, repeat or contralateral biopsies were not requested for these patients where an ‘‘insuﬃcient sample’’ was reported. If TAB is still to be considered an integral component of GCA diagnosis despite the advent of methods such as ultrasound, CT arteriography, MRI
409 and FDG-PET,18 then perhaps the focus should be put on the minimum length of biopsy that is adequate for histological diagnosis to keep complications to a minimum. The largest meta-analysis comparing ultrasound and temporal artery biopsy so far38 included 988 patients in 17 studies, with a sensitivity of 75% and speciﬁcity of 83%. We await the results of the Temporal artery biopsy vs ultrasound (TABUL) in diagnosis of giant cell arteritis study to see whether ultrasound can replace TAB as a ﬁrst-line investigation. Limitations of our study, because of its retrospective nature, are that there was no way to assess whether patients were already on corticosteroid treatment and for how long prior to the biopsy. Histological ﬁndings have not been correlated with follow up. As length of biopsies is not routinely measured or recorded by the operating surgeon in theatre, all measurements refer to post-ﬁxation length measured by histopathology.
Conclusions Temporal artery biopsy is a procedure commonly requested of general and vascular surgeons for the conﬁrmation of the diagnosis of GCAs. Our ﬁndings suggest that it can be competently performed by junior surgeons with minimal morbidity. There is no clear beneﬁt in harvesting specimens longer than 0.6 cm post ﬁxation. Corticosteroid treatment should not be delayed in anticipation of the biopsy or withheld in the case of a negative biopsy if the patient’s symptoms improve. Funding This research received no speciﬁc grant from any funding agency in the public, commercial, or not-for-proﬁt sectors.
Conflict of interest None declared
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