INTRODUCTION
Skin cancer is a multifactorial etiology pathology, resulting mainly from genetic
alterations, environmental and lifestyle factors1. It may present in two forms: melanoma and non-melanoma skin
cancer (NMSC)2, which is the most frequent
malignant neoplasm in white populations and accounts for at least 80% of all
skin cancer. NMSC consists mainly of basal-cell carcinomas BCC (70%), the most
commonly diagnosed worldwide3,4 and squamous
cell carcinoma SCC (20%)3,4. BCC are divided into subtypes with more
or less aggressive behavior and are classified as nodular, micronodular,
superficial, pigmented, cystic, infiltrative, and morpheaform. SCC resembles
nests of abnormal epidermal cells invading the dermis, and its histological
grade depends on the degree of cellular differentiation5, its classification is based on the anatomical body
sites6.
The main cause of skin cancer is chronic exposure to sunlight, which explains the
frequent occurrence of lesions on the body’s areas exposed to the sun, such as
the face, ears, neck, scalp, shoulders, and back. Other etiological factors
include ultraviolet exposure, certain carcinogenic chemicals (arsenic and
hydrocarbons), ionizing radiation, previous skin diseases such as xeroderma
pigmentosum, Bazex, and Gorlin syndromes, chronic irradiation or ulceration,
human papillomavirus (HPV) infection, and chronic stress exposure7. Immunologically compromised patients are
at higher risk8,9. In addition to that, fair-skinned people
often develop skin cancers, and they affect all ethnic groups, primarily those
living in tropical areas that are highly exposed to the sun6-9 where
the highest rate is about 1 to 2% per year10 as in Australia, where this study was developed.
Although the mortality rate from NMSC is low, as reported by Leiter et al., in
20145 such skin cancer impacts
patient’s quality of life causing significant morbidity, the prognosis depends
on tumor type and the chosen treatment. Surgical excision with pre-operatively
identified margins is one of the most common and effective treatment strategies
for basal-cell carcinomas (BCC) and for most squamous cell carcinomas (SCC).
Insufficient compliance with recommended excisional margins among surgeons
represents a very high risk of NMSC recurrence and re-excision for the patient.
This may be caused by the irregular infiltration of these tumours10. The tumor recurrence associated with
incomplete excision in BCCs ranges from 26 to 41% after 2 to 5 years of
follow-up. The maximum number of tumor recurrences has been detected in
morphoeic and facial tumors.11
About the SCCs, when the initial removal is incomplete, theirrecurrence occurs
mostly locally or less frequently in regional lymph nodes. Approximately 75%
of
recurrences occur within two years and 95% within five years after initial
diagnosis.12 So, it is important to
note that the presence (or absence) of tumor cells in the margins is among the
prognostic features for recurrences of SCCs and BCCs. Moreover, when margins
are
involved, the recommendation is usually for re-excision or a close clinical
follow-up. This not only produces adverse effects on patients but also causes
an
increase in additional healthcare costs. So, the optimization of the surgical
management of NMSC is of great importance to ensure the highest quality of
surgical treatments and a subsequent optimal outcome for all patients.
OBJECTIVE
In this context, receiving no funding from any company and without conflict of
interest, this study analyses the risk factors in the follow-up of surgically
removed skin lesions with positive margins during one year of the Royal Perth
Hospital plastic surgery department.
METHODS
This study includes patients who underwent surgical treatment for skin cancer
during December 2016 and December 2017 at the Plastic Surgery Department of
Royal Perth Hospital, Australia. There were selected patients with a
pathological diagnosis of any type of skin cancer, whose initial intention was
the complete removal of the lesion, totalizing 947 incisional biopsies. The
definition of excisional margins recommended by international guidelines (EADV
and EDF) was used as a point of reference for the analysis. Postoperative
pathologic conventional assessment followed all the surgical excisions
considered in the study with histology paraffin-embedded definitive evaluation.
All patients with confirmed incomplete excision (IE) were submitted to a second
surgery or even a third one, according to the clinical procedure of the
Department. All patients with confirmed incomplete excision (IE) were submitted
to a second surgery or even a third one, according to the clinical procedure
of
the Department.
The medical record included in this study was reviewed for the following
parameters of patients with incomplete excisions: gender, age, anatomical
localization of the lesions, perineal invasion, size of the lesion,
histopathological profile of the lesion, multiple or single skin lesions, size
of safety margins and metastasis. The statistical analysis of Pearson’s
chi-square test was used to study the association of the main variables with
compromised surgical margins. The level of significance was set at 5% (p
<0.05) and the relative risk of incomplete excision at (RR) >1. Thus, the
main risk factors for a re-assessment were defined. For this type of study,
formal ethical research committee consent is not required. This article does
not
contain any studies with animals performed by any of the authors.
All procedures performed in studies involving human participants were following
the institutional and/or national research committee’s ethical standards and
with the 1964 Helsinki declaration and its later amendments or comparable
ethical standards. For this type of study, formal consent is not required. This
article does not contain any studies with animals performed by any of the
authors.
RESULTS
Incisional biopsy (first surgery)
According to the departmental records review, 947 patients underwent their
first resection of skin cancer at the surgical center. In this universe,
eight hundred and eighty (93.3%) had complete excision (CE), and sixty-two
(6.6%) had IE. Of those who had CE, five hundred and sixty-five (65%) had a
BCC diagnosis, and two hundred and thirty (26%) had a diagnosis of SCC, the
other sixty-seven (7.6%) had melanoma. Of the patients who had IE,
forty-seven (75%) had BCC diagnosis while the other twelve (21.4%) had SCC,
no case (0%) of melanoma had IE. The association between the exposure to SCC
when compared to BCC leads to a relative risk of 2.8 and a p-value of 0.041,
suggesting that it is a risk factor for the presence of surgical compromised
margins (Table 1)
Table 1 - Correlation between the histopathological lesion and the
occurrence of incomplete excision in the first surgical approach
(incisional biopsy).
Histopathological Lesion |
Complete incisional biopsy |
Incomplete incisional biopsy |
Risk factor of incomplete
incisional biopsy
|
|
N |
% |
N |
% |
Relative risk (RR) of incomplete excision at
the incisional biopsy
|
P-value (chi-square correlation between risk
factors versus the occurrence of incomplete incisional
biopsy)
|
SCC |
230 |
26 |
12 |
21.4 |
2.8 |
0.041 |
BCC |
575 |
65 |
47 |
75 |
Melanoma |
67 |
7.6 |
0 |
0 |
Table 1 - Correlation between the histopathological lesion and the
occurrence of incomplete excision in the first surgical approach
(incisional biopsy).
Second look (second surgery)
After the first surgery and based on the anatomopathological results, the
team evaluated the cases with compromised margins, deciding each patient’s
follow-up. Imaging examinations were necessary to stage the recurrent cases
(6,6% IE) and decide the conduct.. We performed 28% of CT scans, 14% of
nuclear magnetic resonances, and 28.5% of PET-Scans. From the staging, the
need for the second surgical abortion was evaluated in 61.29% of the
patients, 20.9% were under observation, 3.2% were absent from the service,
8% were direct to chemotherapy or radiotherapy, and 6.4 % rescheduled
surgery.
The male prevalence was observed for IE. In a universe of 62 patients, 48
(77.4%) were men, and 14 (22.5%) were women. The mean age of the patients
was 70.2 years in a range of 41 to 86 years old with a standard deviation of
12,9.
In a topographic evaluation of the lesions with an incomplete incisional
biopsy, the face and neck areas were the most commonly affected (91,7%),
precisely nose areas (23%) followed by ear areas (19,2%). The incidence of
the tumors in occipital regions, frontal and neck were the same (11,5%). In
the patients analyzed, 20,8% presented a single lesion, whereas 79,1%
presented multiple lesions. Histologic subtypes were not identified in this
study.
However, there is still a failure rate of 26,3% at the end of this second
approach. Where 9.6% of the patients had metastasis, and 22.5% had to
undergo lymph node dissection. (Table 2)
Table 2 - Assiciation between risk factors and the occurrence of incomplete
excision in the second look
Rick Factor of incomplete Excision
(IE) at the Second Look
|
Complete Second look
excision
|
Incomplete second look
excision
|
Relative risk (RR) of incomplete
excision at the second look
|
P-value (chi-square correlation
between risk factors versus the occurrence of incomplete
excision)
|
N |
% |
N |
% |
Male |
20 |
62.5 |
12 |
37.5 |
1.46 |
0.84 |
Female |
4 |
66.6 |
2 |
33.3 |
> 70 years |
24 |
60.0 |
16 |
40.0 |
0.75 |
0.49 |
< 70 years |
8 |
50.0 |
8 |
50.00 |
Size of tumor > 15mm |
6 |
50.0 |
4 |
50.0 |
1.8 |
0.07 |
Size of tumor < 15mm |
8 |
28.5 |
20 |
71.4 |
Safety margin < 15mm |
22 |
73.3 |
8 |
26.6 |
2.88 |
0.012 |
Safety margim > 15 mm |
2 |
25.0 |
6 |
75.0 |
Multiple lesions |
20 |
71.4 |
8 |
28.5 |
0.47 |
0.077 |
Single lesion |
4 |
40.0 |
6 |
60.0 |
IE - deep and peripheral |
4 |
66.6 |
8 |
33.3 |
4.44 |
0.013 |
IE - deep |
6 |
60.0 |
4 |
40.0 |
IE - peripheral |
14 |
87.5 |
2 |
12.5 |
SCC |
8 |
80.0 |
2 |
20.0 |
3.80 |
0.001 |
BCC |
22 |
78.5 |
6 |
21.4 |
Perineural Invasion |
2 |
33.3 |
4 |
66.6 |
2.86 |
0.038 |
Non invasive tumor |
6 |
23.0 |
20 |
76.9 |
Table 2 - Assiciation between risk factors and the occurrence of incomplete
excision in the second look
DISCUSSION
Our case series was consistent with the current literature findings concerning
cutaneous carcinomas, which will be described below. Data reveal that most
incomplete excisions are in the head and neck12,13,14 and that the
leading risk factor associated with skin cancer is chronic exposure to
ultraviolet light. It is most often diagnosed in the body’s most exposed
sites15,16 contributing to the association of
direct exposure to ultraviolet light being a risk fator.17,18,19 We did not
evaluate this criterion in this study. However, 91.5% of the lesions present
and
analyzed were from the face.
Tan et al., in 200720 have associated the
higher rates of incomplete resection, the lesion’s invasion characteristic and
an increased number of re-excisions. However, age, sex, tumor size, and surgery
experience were not statistically significant risk factors. In our study using
the chi-square test, the statistically significant risk factors for incomplete
excision includes the diagnosis of SCC (p <0.01), perineural invasion (p =
0.038), safety surgical margin <15mm (p = 0.012) and characteristic of a deep
and peripheral excision (p = 0.013). Other factors such as age (p = 0.49), tumor
size> 15mm (p = 0.07) and sex (p = 0.84) were not found to be significant, in
agreement with the literature findings.
CONCLUSION
The findings of this study are consistent with those in the literature. Locations
of greater sun exposure are at all times increasing the incidence of the
development of skin cancers. It is then necessary to improve our knowledge to
make the procedure curable in a single approach. Knowing the risk factors for
an
ineffective approach, such as diagnosing SCCs, is possible to prepare for
continued treatment. Statistically, significant risk factors were SCC diagnosis
and previously incompletely excised lesions referred for re-excision.
The authors recommend more care with tumor markings, taking margins >15 mm,
using deeper margins, and referring patients to more experienced centers. In
addition to that, the significant number of patients with multiple lesions
emphasizes the importance of periodic examination.
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1. University Nove de Julho, UNINOVE, São Paulo,
SP, Brazil.
2. Royal Perth hospital, Plastic Surgery
Department, Perth, Austria.
Corresponding author: João Vitor Pithon Napoli Rua
Pamplona, 1119, Jardim Paulista, São Paulo, SP, Brazil. Zip Code: 01405-200
E-mail: joaovitorpithon@gmail.com
Article received: September 21, 2019.
Article accepted: January 10, 2021.
Conflicts of interest: none