Carcinoma in situ from the view of complete resection.

Abstract

World Health Organisation (WHO) defined three types of preinvasive epithelial lesions, one of which is preinvasive bronchial squamous lesions consisting of dysplasia and carcinoma in situ (CIS). It is not clear whether or not CIS at the bronchial resection margin is to be considered as incomplete resection in the literature. Follow-up data of such patients using autofluorescence bronchoscopy proved that CIS regresses without further treatment in significant number of patients. It is therefore reasonable to accept any reported CIS lesion on frozen-section examination as complete clearance of the tumor and thus further resection may not be warranted.

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Lung Cancer (2004) 46, 383—385
LETTER TO THE EDITOR
Carcinoma in situ from the view of complete
resection
Accomplishing a curative resection with tumor free
surgical margins is the main concern for the sur-
geon who performs a lung resection for NSCLC.
Previous studies revealed that incomplete resec-
tion invariably have no favorable effect on survival.
Thus, it is universally accepted that resection in
curative intent should not be attempted if the tu-
mor does not appear to be removed completely.
An ‘‘rTNM’’ classification has been described in
order to stage of the disease and delineate the
completeness of resection more accurately. In this
regard, resections are classified as ‘‘r0’’ if all mar-
gins are free of tumor, ‘‘r1’’ if there is microscopic,
or ‘‘r2’’ if there is macroscopic tumor invasion at
one of the resection margins on the final histol-
ogy. Depending on patient’s physiological reserve,
the limits of surgery may be extended to obtain
tumor free margins that results in prolonged sur-
vival. Such extended resections, including en-bloc
removal of extrapulmonary contiguous intratho-
racic structures are commonly performed for this
reason.
Proximal tumor invasion of the bronchial wall is
a different entity from local tumor invasion. There
are couple of historical investigations focusing on
the proximal extend of the tumor at the bronchial
wall [1]. Soorae and Stevenson [2] described four
patterns of microscopic positive margin related to
the bronchus; (a) direct extension, (b) lymphatic
permeation, (c) invasion of peribronchial tissues
and (d) carcinoma in situ (CIS). They have also re-
ported that proximal invasion may be observed up
to more than 2.5cm from the macroscopic tumor
border in some patients. Therefore, intra-operative
frozen-section examination of the bronchial stump
has a great importance for the detection of un-
expected proximal tumor invasion beyond the re-
section margin. If such an invasion is confirmed by
frozen-section, proceeding from lobectomy to a
sleeve resection or even to a pneumonectomy is
warranted to achieve a complete resection in terms
of tumor clearance. Despite all efforts, a significant
number of patients with positive bronchial margin,
ranging from 2.6 to 17% are reported in the litera-
ture [3,4]. Most often, this condition is attributable
to either limited cardiopulmonary reserve of the
patient, so called ‘‘compromised resection’’ or
technical difficulties to extend the limits of resec-
tion. In addition sometimes, tumor cells can only
be noticed on paraffin sections despite negative
frozen-section examination.
In 1999, WHO defined three types of preinva-
sive epithelial lesions, one of which is preinvasive
bronchial squamous lesions consisting of dysplasia
and CIS [5]. Majority of these lesions are observed
in heavy smokers and not all of them progress to in-
vasive carcinoma. Preinvasive bronchial squamous
lesions are described in details depending on the
affected part of the bronchial epithelium. CIS, by
definition,impliespreinvasivechangeswithcellular
and architectural features of carcinoma through-
out the bronchial epithelium without penetration
of its basement membrane. Once detected, chest
physicians tend to follow-up of these lesions using
autofluorescence bronchoscopy in most recent
years [6].
The criteria for the differentiation of dysplasia
from CIS are described for the findings on paraffin
sections [5]. However, pathologists have to make
a decision on the basis of frozen-section examina-
tion concerning bronchial margin peroperatively.
0169-5002/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.lungcan.2004.05.008

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384Letter to the Editor
Dysplasia, either mild or severe, is not a problem
for the surgeon in view of obtaining tumour free
margins. On frozen-section examination, bronchial
stump with dysplasic changes is reported as neg-
ative surgical margin. In this situation, lung re-
section is considered complete by means of tumor
clearance. Furthermore, surgeons do not hesitate
to anastomose those two bronchial orifices with
dysplasic changes during a sleeve resection. This
approach must be adequate enough because such
precancerous changes might be seen throughout
bronchial tree, so it may not be possible for the
surgeon to find a mucosa without such changes. On
the other hand, cancer cells are detected at the
resection margin on frozen-section examination if
the margin contains mucosal changes featuring CIS.
Although it is difficult to identify whether or not
these changes are confined within the bronchial
epithelium, the pathologist has to report any suspi-
cious malignant changes regardless of localization.
This reveals an impression that the resection is in-
complete due to malignant changes at the bronchial
margin. Then, it is the surgeons’ dilemma to resect
more lung or bronchial tissue for complete resec-
tion. The indications for treatment of preinvasive
bronchial squamous lesions are yet to be defined in
the literature [6] however, it is generally accepted
that patients with these lesions are not surgical
candidates.
To date, it is also unclear whether CIS at the re-
section margin is to be considered as positive. Only
a few series of positive bronchial margin included
those cases of CIS in the literature. The 5-year sur-
vival rate in this group of patients was comparable
to those who had resection with tumor free margins
(54%versus58%)[7].Similarresults(41%versus52%)
were also reported by Gebitekin et al. [4] in 1994.
This excellent retrospective study however, did not
state the type of microscopic invasion in details.
Previous reports suggest that microscopic dis-
ease that is limited to the bronchial mucosa (CIS)
has no adverse effect on survival following surgery.
Massard et al. [8] also advocated that CIS at the
bronchial margin does not require further treat-
ment. Bota et al. [6] reported the results of a
prospective study addressing the natural progress
of CIS in heavy smokers. This study proved that
severe dysplasia and CIS regress in a significant
number of patients without any treatment. The
results are also confirmed by others [9]. This find-
ing might explain the comparable survival rates in
patients with CIS at the resection margin. More-
over, Bota in his report, concluded that the bio-
logical behavior of severe dysplasia and CIS were
similar. Thus, dysplasia and CIS as peroperative
findings should be managed in the same way from
the thoracic surgeons’ standpoint. It seems if any
bronchial margin that is reported as positive on
frozen-section examination due to CIS may be ac-
cepted as complete clearance of the tumor and
therefore it is not necessary to extend the limits
of the resection. As outlined by Soorae and Steven-
son [2], it is the surgeon’s liability to distinguish
whether the positive margin is due to CIS rather
than the other patterns of microscopic invasion on
the basis of gross tumor findings at thoracotomy.
Inconclusion,wesuggestthatCISatthebronchial
resection margin, like dysplasia, is to be classified
within the subset of ‘‘r0’’ while other patterns of
microscopic disease remain as ‘‘r1’’. Such data
should be extracted and re-analyzed accordingly
from the centers with large reproducible databases
of lung cancer worldwide. This will in turn, not only
allow us to report more reliable long term results
regarding the fate of more homogeneous patient
groups with residual tumor at the bronchial resec-
tion margin but also add considerable influence on
the decision making while operating such patients.
References
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Letter To The Editor 385
Cemal Asim Kutlu∗
Department of Thoracic Surgery
Yedikule Hospital for Chest Diseases
and Chest Surgery, Zeytinburnu
Istanbul, Turkey
Nur Urer
Department of Pathology
Yedikule Hospital for Chest Diseases
and Chest Surgery, Zeytinburnu
Istanbul, Turkey
Guven Olgac
Department of Thoracic Surgery
Yedikule Hospital for Chest Diseases
and Chest Surgery, Zeytinburnu
Istanbul, Turkey
∗Corresponding author. Tel.: +90 212 296 1680
fax: +90 212 247 4122
E-mail address: cakutlu@tnn.net
(C.A. Kutlu)
3 May 2004