Excision of periocular basal cell carcinoma guided by en face frozen section

Excision of periocular basal cell carcinoma guided by en face frozen section

Available online at www.sciencedirect.com British Journal of Oral and Maxillofacial Surgery 51 (2013) 520–524 Excision of periocular basal cell carc...

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Available online at www.sciencedirect.com

British Journal of Oral and Maxillofacial Surgery 51 (2013) 520–524

Excision of periocular basal cell carcinoma guided by en face frozen section Mark Tullett, Suresh Sagili, Andrew Barrett, Raman Malhotra ∗ Corneo Plastic Unit, Queen Victoria Hospital, East Grinstead, West Sussex RH19 3DZ, UK Accepted 15 October 2012 Available online 5 December 2012

Abstract We describe a technique for monitoring excision margins in periocular basal cell carcinoma (BCC) using en face frozen sections and report outcomes. We excised periocular BCC with 3 mm margins. An outer 1 mm sliver of the perimeter of the specimen was mapped and sent for evaluation by en face frozen section. The central tumour mass was processed using routine paraffin sections. A further 3 mm level was excised at the site of any affected margin and the outer 1 mm sliver was again evaluated by frozen section. We identified 78 patients from November 2003 to July 2009; 67 had primary tumours and 11 (14%) had recurrent BCC of which 52 (66%) were located on the lower eyelid. Growth patterns were nodular (n = 34, 43%), infiltrative (n = 25, 32%), micronodular (n = 12, 16%), and superficial (n = 7, 9%). A third of BCC with a clinically nodular appearance showed additional histological patterns including infiltrative and micronodular growth patterns. Of 30 clinically nodular carcinomas, 29 were excised completely with one level, and one required 2 levels of excision for clearance after evaluation by frozen section. Mean follow-up was 23 months (range 2–60). There was one recurrence (1%). Excision of margins guided by en face frozen section is justified by the low rates of recurrence, and it can easily be taught or imported into hospital practice. Clinically nodular BCC have subclinical extensions that can be missed on bread loaf sectioning, which makes the sampling of margins a standard for periocular BCC. © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved. Keywords: En-face; Frozen section; Basal cell carcinoma; Excision

Introduction Basal cell carcinoma (BCC) accounts for roughly 90% of malignant tumours of the eyelid. It most often affects the lower lid, followed by the medial canthus, the upper lid, and the lateral canthus.1–6 Recurrence after surgical removal of periocular lesions is high when excision margins are not monitored. Doxanas et al.7 reported recurrence of 23% with 64% of tumours being incompletely excised. However, monitored excisions with Mohs surgery have shown significantly reduced recurrence when followed up over a 5-year period.8 Recurrence is usually the result of incomplete excision because subclinical margins have been underestimated. It is difficult to treat in this region, and reconstruction is

suboptimal and results in serious morbidity. Although Mohs surgery is considered a gold standard for excision it is not always practical as it is offered by a limited number of centres that are often located in the larger teaching hospitals, and many patients are elderly or unable to travel long distances. We describe a technique for monitoring excision margins in cases of BCC in high-risk areas on the face, or when there are pathologically confirmed aggressive histological growth patterns, which can be adapted for practice in any hospital that treats these lesions with or without histopathological examination of frozen sections.

Method ∗

Corresponding author. Tel.: +44 01342 414549; fax: +44 01342 414106. E-mail address: [email protected] (R. Malhotra).

We retrospectively reviewed the medical records of all patients who had margin-controlled excision with en face

0266-4356/$ – see front matter © 2012 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

http://dx.doi.org/10.1016/j.bjoms.2012.10.007

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Fig. 1. The tumour is excised with a 3 mm safety margin marked beyond the clinical margins of the tumour.

frozen section between November 2003 and July 2009 after presenting with clinically and pathologically confirmed periocular BCC. Those who had excision of margins controlled by Mohs surgery or rush paraffin sections were excluded. Informed consent was obtained and all the lesions were excised under local anaesthetic using lidocaine with 1:200,000 adrenaline.

Technique We identified and delineated clinical tumour margins and marked a 3 mm margin beyond the clinical margin (Fig. 1). The tumour was excised at the 3 mm margin and was then oriented and placed on a cutting board in the operating theatre. Sections 1 mm thick were cut around the perimeter using a

Fig. 2. Diagram showing en face margins and the preparation of 1 mm outer slivers for examination by frozen section.

number 10 blade according to the map drawn earlier (Fig. 2), and were then placed in previously labelled dry pots for frozen section. A sliver of the deep margin was also assessed by frozen section. The main remaining tumour specimen was oriented with a suture and placed in formalin. The map was copied on the histopathology request form. The sliver samples were placed flat on labelled freezing plates, coated with optimum cutting temperature compound to ensure correct orientation, then placed in a cryostat and frozen at −20 to −30 ◦ C (Fig. 3). They were then shaved on a microtome and slides were prepared. If tumour was present anywhere in the specimen the margin was considered invaded. The surgeon was informed and the patient was returned to the operating theatre. A further

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Discussion

Fig. 3. Sliver samples placed in a cryostat.

3 mm was taken at that margin, and the outer 1 mm strip around the perimeter of the new mapped margin was removed for frozen section. Once clearance was ascertained the defect was reconstructed.

Results We retrospectively reviewed 78 patients (42 male and 36 female), mean age 74.5 years (range 35–97). A total of 52 BCC (66%) were on the lower eyelid, 12 (15%) were at medial canthus, 8 (10%) on the upper eyelid, and the remaining tumours were around the rest of the ocular adnexa. There were 67 primary tumours and 11 recurrent basal cell carcinomas. The histological growth pattern was nodular in 34 (43%), infiltrative in 25 (32%), micronodular in 12 (16%), and superficial in 7 (9%). Of the lesions that appeared nodular on clinical examination, 37% showed a different pattern histologically including infiltrative and micronodular growth patterns. A total of 59 patients (76%) had clear margins after single level excision, 19 (24%) required more than one level of excision and of these, 3 (4%) required 3 levels. The mean level of excision for all growth patterns was 1.29 (range 1–3). Lesions with a micronodular growth pattern required more levels of excision (mean 1.53, range 1–3) than those with histologically nodular growth patterns (1.03, range 1–3). Of the 30 clinically nodular lesions, 29 were excised completely with one level and one required 2 levels after assessment by frozen section. Mean follow-up was 23 months (range 2–60 months) and 58 patients (74%) had follow-up of more than one year. Overall recurrence was 1% (1/78); one tumour had been incompletely excised and was clinically evident at 4 months.

The en face method of assessing tumour margins looks at the whole of the excised specimen and gives the surgeon accurate information about the extent of local spread. Traditional bread loaf sectioning looks at specific points of the margin (usually with 3–5 slices) and assesses clearance, but as the whole outer margin is not examined there is a considerable potential for false-negative margins. The Cochrane Review of 2009 suggested that there is not enough evidence to dictate which method of excision should be used, but it did suggest that Mohs surgery is the preferred method for recurrent BCC.9 In 2004, Malhotra et al. reported that 5-year recurrence after excision of periocular BCC with Mohs surgery could be as low as 0% for primary, and 7.8% for recurrent tumours.8 By contrast, unmonitored excision with a 4 mm margin was reported by Doxanas et al. to show recurrence of 23%; 64% of tumours had been incompletely excised.7 Although the Mohs technique ideally achieves complete excision with minimal loss of normal tissue, it is costly and time-consuming, and requires multiple tissue excisions and histological examinations. We had one recurrence with evidence of BCC at 4 months after initial operation, which suggests incomplete excision. This tumour had previously recurred and had an infiltrative growth pattern. After repeat excision controlled by en face frozen section there has been no recurrence at 48 months follow-up. Our overall recurrence rate of 1% with en face frozen section is comparable with results from excision by Mohs surgery and shows that the technique is an acceptable alternative to Mohs for most periocular BCC. Of particular note is the number of tumours that were considered clinically nodular, but histologically showed more aggressive growth patterns and needed more attempts to excise (more levels of frozen section). The number of levels of excision raises the possibility that, for a classic 4 mm margin, and certainly for more conservative margins between 2 and 4 mm, a proportion will be incompletely excised because histologically they have more aggressive and unsuspected growth patterns. Hamada et al.10 excised BCC with defined margins of between 2 and 4 mm depending on the histological growth type. They included histological subtypes other than nodular. With traditional margins and standard bread loaf sectioning they reported clearance of 84% and recurrence of 4.35%, of which all showed an infiltrative growth pattern. Conway et al.11 assessed periocular BCC that was excised with margins between 4 and 8 mm. Frozen sections were examined from the medial and lateral margins, and in some cases from the deep surface, if there was clinical doubt regarding the adequacy of excision. Their results showed that after 5-year follow-up there were no recurrences in the group treated with excision guided by frozen section compared with 3 recurrences (9.7%) in those treated with large margins of 4–8 mm and no histological control. Wong et al.12 did modified en face excision controlled by frozen section in 423 primary BCC and reported overall recurrence of 0.71%. A

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total of 97 lesions were followed up for at least 5 years and recurrence was 2.2%. Secondary recurrences treated with excision guided by frozen section resulted in recurrence of 3.8%. In 2009 Levin et al.13 described a similar en face technique for excision of periocular BCC with stereoscopic microdissection of surgical margins under frozen section control in 200 patients. They reported overall recurrence of 1.0% with a mean follow-up period of 4 years. They used only 1 mm excision margins and reported that 34% needed more than one level of excision to obtain clear margins. There seems to be a wide variability in the safety margin adopted and it is a compromise between operating time and loss of tissue. A larger initial margin enables a balance to be made between achieving histological clearance of tumour and limiting the number of excision levels and the operating time. In periocular disease the uncertainty of the growth pattern suggests that monitoring the excision margins with en face frozen sections is particularly appropriate. Aggressive growth patterns are not always evident in incisional biopsy specimens and therefore the potential for subclinical extension is not always apparent. Infiltrative and micronodular growth patterns are not displayed uniformly around the margin so if the sample is assessed using a bread loaf technique then islands of invasive tumour can be missed, and can cause recurrence. The en face frozen section method allows the tumour to be assessed for clearance and the defect reconstructed on the same day. As patients are usually older (mean 74.5 years, maximum age 97) a single visit will be better tolerated. In our experience the en face sections took 15 min/margin and an average of 4 margins were analysed/lesion (average time for preparation of slides is 45–75 min). This timing allows for multiple levels of excision and still enables the defect to be reconstructed on the same day. Certain considerations are important if the technique is to be successful: an on-site histopathology service is vital, appropriate personnel must be available, and communication between the operating theatre and the histopathology laboratory must be possible. Diagrammatic and written communication is important. It can be difficult to process the marginal slices because of their minimal size, and to section the sample on the microtome. It can also be technically difficult to obtain representative cross-sections, and several attempts may be required, which can slow the process down and means that a longer time elapses between the primary excision and subsequent levels or the final reconstruction. This initial problem improves with practice and the delay is, in our experience, part of the learning process. Traditionally, histopathologists have used bread loaf sections as they are quicker to examine than en face preparations. However, the histopathologist’s time can be saved if slivers of outer tissue are prepared in the operating theatre by the surgeon. It also reduces the possibility of the specimen being incorrectly oriented as the surgeon labels the tissue margins soon after excision.

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A limitation of the data presented here is the variability in follow-up period. Ideally, to be compared like-for-like with the Mohs database, all patients treated for periocular BCC would have to be followed up for a period of 5 years.9 However, our data are comparable with those of other studies on the monitoring of excision margins with en face histological techniques. In the absence of facilities for frozen sections, this method of preparing specimens in the operating theatre can easily be applied to paraffin sectioning. It can therefore be incorporated as the preferred technique to sample margins for delayed examination of paraffin sections. We do margincontrolled excision for all the periocular BCC. Excision with examination by en face paraffin section and delayed repair is adopted for lesions that may be considered for laissez faire healing such as medial canthal BCC or small tumours in the preseptal region where there is laxity in the adjacent skin. Relatively younger patients with minimal laxity in the eyelid, poorly defined lesions, tumours close to the puncta lacrimalia, or with recurrent BCC, and those willing to travel to the centres that provide Mohs surgery for 2-stage excision and reconstruction are referred for Mohs micrographic surgery. The remainder are usually considered appropriate for excision guided by frozen section.

Conflict of interest Authors have no financial interest in this article.

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