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Original Research Gynaecological Oncology
Adenocarcinoma in situ of the Cervix – is Loop
Electrosurgical Excision Procedure an Acceptable
Alternative to Cold Knife Cone Biopsy?
Mila Pontremoli Salcedo, 1 Anthony Costales, 2 Mark F Munsell, 3 Preetha Ramalingam, 4 Ricardo Dos Reis, 5
Andrea Milbourne, 2 Patrícia El Beitune 1 and Kathleen M Schmeler 2
1. The Department of Obstetrics & Gynecology, Federal University of Health Sciences/Irmandade Santa Casa de Misericordia, Porto
Alegre, Rio Grande do Sul, Brazil; 2. The Department of Gynecologic Oncology & Reproductive Medicine; 3. The Department of Biostatistics;
4. The Deparment of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, US; 5. The Department of Gynecologic
Oncology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil
O bjective: To compare cone specimen size between loop electrosurgical excision procedure (LEEP) and cold knife cone (CKC), and
evaluate the association between specimen size and margin status. Methods/materials: A retrospective review was performed of
women with adenocarcinoma in situ (AIS) who underwent CKC or LEEP between 1998 and 2013. Specimen size, including length
(distance from the external cervical os to the endocervical margin) and volume were compared between LEEP and CKC, and correlated
with margin status. Results: Eighty-five patients underwent a total of 136 procedures, including 91 CKCs (67%) and 45 LEEPs (33%), with 27
removed as a single specimen (one-piece LEEP) and 18 as two specimens with an ectocervical specimen and a deeper endocervical top-
hat specimen (two-piece LEEP). The two-piece LEEP specimen median length was significantly longer (2.1 cm) versus CKC (1.4 cm, p<0.01)
and one-piece LEEP (0.6 cm, p<0.01). Median specimen volume was greater for two-piece LEEP (7.4 cm 3 ) versus CKC (3.4 cm 3 , p<0.01) and
one-piece LEEP (1.6 cm 3 , p<0.01). A higher rate of positive margins was noted when comparing all LEEP (67.6%) with CKC specimens (34.2%),
p<0.01. However, when the LEEP specimens were analysed separately, one-piece LEEPs had a higher rate of positive margins (81.0%) versus
CKC (34.2%) (p<0.01), but there were no significant differences between two-piece LEEP (50.0%) and CKC (34.2%), p=0.26. Conclusion: Our
results suggest that a two-piece LEEP produces a larger specimen size with similar rates of positive margins compared with CKC. Given the
decreased cost and morbidity compared with CKC, a two-piece LEEP should be considered in the management of women with AIS.
Keywords Cervical adenocarcinoma in situ, AIS, cold
knife cone (CKC), loop electrosurgical
excision procedure (LEEP)
Disclosure: Mila Pontremoli Salcedo, Anthony Costales,
Mark F Munsell, Preetha Ramalingam, Ricardo Dos Reis,
Andrea Milbourne, Patrícia El Beitune and Kathleen M
Schmeler have nothing to disclose in relation to this
article. This research was supported in part by the
National Institutes of Health through MD Anderson’s
Cancer Center Support Grant CA016672. No funding
was received for the publication of this article.
Compliance with Ethics: This study involves a
retrospective review and did not involve any studies
with human or animal subjects performed by any
of the authors. Institutional Review Board approval
was obtained with a waiver of informed consent.
Authorship: All named authors meet the International
Committee of Medical Journal Editors (ICMJE) criteria
for authorship of this manuscript, take responsibility
for the integrity of the work as a whole, and have
given final approval to the version to be published.
Open Access: This article is published under the
Creative Commons Attribution Noncommercial License,
which permits any non-commercial use, distribution,
adaptation and reproduction provided the original
author(s) and source are given appropriate credit.
Received: 4 November 2016
Accepted: 10 February 2017
Citation: European Oncology & Haematology,
2017;13(1):24–7 Corresponding Author: Kathleen M Schmeler,
Department of Gynecologic Oncology and Reproductive
Medicine, Unit 1362, The University of Texas MD
Anderson Cancer Center, 1515 Holcombe Boulevard,
Houston, TX 77030, US. E: firstname.lastname@example.org
24 Cervical adenocarcinoma in situ (AIS) is recognised as a premalignant glandular condition and
is a precursor to invasive cervical adenocarcinoma. 1 It usually affects women of childbearing
age in which a more conservative approach is preferred. 1–3 The incidence of both AIS and
adenocarcinoma of the cervix has been increasing, especially among young women. 4,5 Cervical
conisation, or cone biopsy, can be performed using a scalpel (cold knife cone [CKC]), laser, or
electrosurgery (loop electrosurgical excision procedure [LEEP]). For patients with squamous
dysplasia (cervical intraepithelial neoplasia [CIN]) there appears to be no difference in outcomes
between techniques. 6,7 However, it remains unclear if CKC is preferred over LEEP in patients
with AIS. Studies have consistently shown that patients with AIS with a positive margin after an
excisional procedure of the cervix are at significantly higher risk for residual disease. 2,8,9 In addition,
several studies have shown that a higher proportion of patients with AIS have negative margins if
they undergo CKC versus LEEP. 8,10,11 However, it remains unclear if this is due to a larger specimen
being obtained when CKC is performed compared with LEEP.
For women who desire future fertility, conservative management with cervical conisation is
considered a feasible option. 1 However, the treatment can be challenging in women with AIS
where the lesions are often located high in the endocervical canal, and may be multifocal. Repeat
conisations are often required until negative margins are obtained. 2 In addition, an unnecessarily
large specimen is sometimes removed in an attempt to be certain of obtaining negative margins.
These large and repeat cervical conisations are known to be associated with adverse obstetrical
outcomes, including preterm delivery and low birth weight infants. 12–14 It remains unclear if
CKC should be performed over LEEP in patients with AIS in order to obtain negative margins.
Furthermore, to date, there are limited data comparing specimen size between LEEP and CKC,
and the correlation between specimen size and positive margins is largely unknown. The purpose
of this study was to compare cone specimen size obtained using LEEP compared with CKC in
patients with AIS. In addition, we sought to determine if there was any association between cone
size and positive margins.
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