Keywords
margins of excision - lip cancer - squamous cell carcinoma
Introduction
Squamous cell carcinoma is the most common malignant tumor on the lower lip. As age
increases, the risk of this condition rises, with the highest incidence in 70-to 80-year
olds. Sun exposure, tobacco use, and genetic causes act in a multifactorial way to
promote the development of squamous cell carcinoma, although its exact cause has not
been identified. It is thought to be more prevalent in certain occupations, such as
farmers and fishermen, but that is not necessarily the case, and the role of occupation
as a risk factor remains a matter of debate. In general, it shows a male predominance,
and most cases of lip cancer in the United States occur in men. There is also an inverse
correlation between latitude and the incidence of squamous cell carcinoma, suggesting
that ultraviolet radiation contributes to the occurrence of squamous cell carcinoma.
Early detection of squamous cell carcinoma is often possible because it occurs in
a position where it is easy to see. Therefore, its prognosis is generally favorable,
with a 5-year survival rate exceeding 90% according to various studies.[1]
[2]
[3]
The treatment methods for squamous cell carcinoma include surgery and radiotherapy.
However, since radiotherapy takes a long time and the recurrence rate is high, surgical
treatment is the most standard treatment method for patients without metastasis.[4]
[5]
When wide excision is performed, a gross inspection of the surgical field cannot confirm
whether the lesion has been completely excised. Furthermore, wide excision involves
the removal of a substantial amount of normal tissue. Reconstruction should also consider
the burden on the patient in terms of finances and time, and extensive reconstruction
significantly reduces patients' functional and cosmetic satisfaction after surgery.
Mohs micrographic surgery (MMS) is a useful method for ensuring complete cancer removal,
but it is time-consuming and costly. The authors have performed surgery on other parts
of the face using the conventional MMS method. However, for tumors on the eyelid and
lip, it is often difficult to select an appropriate reconstruction method, so MMS
is not performed.
At many centers, the surgical method varies depending on the surgeon. When frozen
biopsy is possible for patients with stage I/II cancer, some cases have been reported
where frozen biopsies were performed with a 3-mm margin, but this has only been described
in a single study.[1] Researchers have recommended securing a margin of at least 6 mm, and some surgeons
prefer a surgical margin of at least 10 mm.[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
Therefore, we performed the first frozen biopsy at an appropriate distance from the
gross boundary of the lesion. If negative, the remaining cancer tissue was removed,
and if positive, frozen biopsy was performed again at an appropriate distance after
additional resection. This proceeded until the negative frozen biopsy results were
reported. In this workflow, the distance of the first frozen biopsy from the visual
boundary and the location of the next frozen biopsy in case of positive frozen biopsy
results greatly affected the operation time and results.
Accordingly, we analyzed patients with squamous cell carcinoma of the lower lip for
23 years (from 1997–2020). We investigated where the initial frozen biopsy was performed,
at what interval, and the width of the final surgical margin. The aim of this study
was (1) to evaluate the appropriate initial margin and additional intervals and (2)
to establish a reference value of the surgical margin and length through a long-term
follow-up study. We expect that the results of this study will be helpful in the treatment
of squamous cell carcinoma of the lower lip in the future.
Methods
Patients
We retrospectively studied 44 patients treated from November 1997–October 2020 for
squamous cell carcinoma on the lower lip. We performed surgery with frozen biopsy
to determine the excision margin. The average age of the patients was 69.09 years
(range, 43–90 years), and there were 24 men and 20 women.
Surgical Method
The gross margin was marked based on palpation of the lesion, and the first surgical
margin was flexibly designed to be 5–10 mm left and right from the gross margin, considering
the tumor location and size. On the lower side, the surgical margin was the skin above
the sulcus boundary.
Frozen biopsy (frozen section) was performed at the left, right, and lower margins.
When the frozen biopsy result was positive, an additional frozen biopsy was performed
5 mm away from where the initial frozen biopsy was performed. This process continued
until negative results on frozen biopsy were reported. After securing a negative margin,
full-layer excision was performed along the surgical margin. The excised tissue was
subjected to permanent fixation and a definitive histopathologic examination, and
the defect was reconstructed ([Fig. 1]).
Fig. 1 Surgical method. (A) The initial frozen biopsy is done at the right margin (1), the left margin (2),
and the lower margin (3). (B) The biopsy result is positive at the right margin (1) and negative at the left margin
(2) and lower margin (3). (C) An additional frozen biopsy is done 5-mm lateral from the initial right margin (4).
(D) The biopsy result is negative in (4). Then, full layer excision is done and the
excised mass is sent for permanent fixation and a definitive histopathologic examination.
Study Method
For each patient, the total number of sessions, final surgical margin, and recurrence
were investigated. One patient died of hematologic cancer unrelated to squamous cell
carcinoma 2 months after surgery. Except for this patient, the average follow-up was
67.4 months (range, 12–227 months).
Results
All 44 patients had negative results of the inferior frozen biopsy. Among the 88 initial
left and right margins, the initial frozen margin was 5 mm in 60 margins (68.2%),
7 mm in 8 margins (9%), 8 mm in 2 margins (2.3%), and 10 mm in 18 margins (20.5%;
[Table 1]).
Table 1
Initial frozen margins
|
Initial frozen margin (mm)
|
Number of margins (%)
|
|
5
|
60 (68.2)
|
|
7
|
8 (9.0)
|
|
8
|
2 (2.3)
|
|
10
|
18 (20.5)
|
In total, 44 patients underwent frozen biopsy for the first safety margin. Three patients
had positive findings on the first frozen biopsy. In those patients, the first safety
margin was 10, 5, and 5 mm, respectively. An additional frozen biopsy was done 5-mm
lateral from the initial margin. Two patients had negative results from the second
frozen biopsy, while one patient (with a first safety margin of 5 mm) had positive
results. An additional frozen biopsy was performed 5 mm lateral from the second margin.
Finally, the third frozen biopsy was negative. Thus, 41 cases ended at the first session,
two cases ended at the second session, and one case ended at the third session ([Fig. 2]). The final surgical margin was 5 mm (58 margins, 66%), 7 mm (8 margins, 9%), 8 mm
(2 margins, 2.3%), 10 mm (18 margins, 20.4%), and 15 mm (2 margins, 2.3%; [Table 2]). There were no positive margin results in the final pathology findings.
Table 2
Final surgical margins
|
Final surgical margin (mm)
|
Number of margins (%)
|
|
5
|
58 (66.0)
|
|
7
|
8 (9.0)
|
|
8
|
2 (2.3)
|
|
10
|
18 (20.4)
|
|
15
|
2 (2.3)
|
Fig. 2 Arrow diagram for the frozen biopsies. In total, 44 patients underwent frozen biopsy
for the first safety margin. Three patients had positive findings on the first frozen
biopsy. In those patients, the first safety margin was 10, 5, and 5 mm, respectively.
An additional frozen biopsy was done 5 mm lateral from the initial margin. Two patients
had negative results from the second frozen biopsy result, and one patient (with a
first safety margin of 5 mm) had positive results. An additional frozen biopsy was
performed 5-mm lateral from the second margin. Finally, the third frozen biopsy was
negative.
In an average follow-up of 67.4 months (range, 12–227 months), there was only one
case of recurrence.
All patients received physical examinations, including palpation, during the follow-up
period. Follow-up computed tomography (CT) was routinely performed at 6 months, 1
year, and 2 years after surgery to determine whether the disease had recurred. Follow-up
was performed twice a week until the second week, then every month until 6 months,
at 3-month intervals for up to 1 year, and then at 6-month intervals for up to 5 years.
One patient experienced recurrence. This patient refused surgery under general anesthesia
due to the patient's general condition. Therefore, at the time of the first operation,
metastasis to the neck lymph node was suspected, but neck dissection was not performed.
After 20 months of follow-up, local recurrence was observed, but additional surgery
was rejected.
Two patients simultaneously underwent radiation therapy after neck dissection at the
otolaryngology department. These two patients both had T1N2bM0 (stage 4a) disease,
and modified neck dissection was performed. In total, 60 Gy and 54 Gy of radiation
therapy was administered to each of these patients, respectively, in 30 sessions over
a 5-week period.
Case 1
A 70-year-old was diagnosed with squamous cell carcinoma on the lower lip. The patient
had no specific medical history and the patient had noticed the mass 8 months before
surgery. The size of the tumor was 9 × 7 mm, and it was located in the center of the
lower lip. Facial, neck, and chest CT scans were taken, and no metastasis was observed.
The stage was T1N0M0. The margins were all negative in the first session (left 5 mm,
right 5 mm). Wide excision was performed, followed by reconstruction using a double
barrel-shaped excision and local advancement flap. The follow-up period was 58 months.
No recurrence or metastasis was found, and there were no complications following reconstruction.
The patient was also satisfied with the postoperative scar in terms of cosmesis ([Fig. 3]).
Fig. 3 A case where frozen biopsy ended in the first session. (A) A preoperative photograph. (B) The preoperative design. (C) An intraoperative photograph after excision. (D) An immediate postoperative photograph. (E) A photograph at follow-up at postoperative 58 months.
Case 2
A 63-year-old was diagnosed with squamous cell carcinoma on the lower lip. The patient
had a history of hypertension and cerebral hemorrhage, and 3 years before surgery,
laser removal was performed once at a local clinic. However, the tumor recurred thereafter.
The size of the tumor was 16 mm × 16 mm, and it was located in the center and right
side of the lower lip. Facial, neck, and chest CT scans were taken, and no metastasis
was observed. The stage was T1N0M0. The margin was positive in the first session (right:
5 mm). The margin was negative in the second session (right 5 mm). Wide excision was
performed, followed by reconstruction using the bilateral Webster modification of
the Bernard technique. No recurrence or metastasis was found, and there were no complications
following reconstruction. The patient was also satisfied with the postoperative scar
in terms of cosmesis ([Fig. 4]).
Fig. 4 A case where frozen biopsy ended in the second session. (A) A preoperative photograph. (B) The preoperative design. (C) An immediate postoperative photograph. (D) A photograph at follow-up at postoperative 60 months.
Case 3
A 59-year-old was diagnosed with squamous cell carcinoma on the lower lip. The patient
had a history of hypertension. The size of the tumor was 15 × 12 mm, and it was located
in the center and left side of the lower lip. Facial, neck, and chest CT scans were
taken, and no metastasis was observed. The stage was T1N0M0. The margin was positive
in the first and second sessions (right 5 mm). The margin was negative in the third
session (right 5 mm). Wide excision was performed, followed by reconstruction using
the bilateral Webster modification of the Bernard technique. No recurrence or metastasis
was found, and there were no complications following reconstruction. The patient was
also satisfied with the postoperative scar in terms of cosmesis ([Fig. 5]).
Fig. 5 A case where frozen biopsy ended in the third session. (A) A preoperative photograph. (B) The preoperative design. (C) An intraoperative photograph after excision. (D) An immediate postoperative photograph. (E) A photograph at follow-up at postoperative 15 months.
Discussion
Squamous cell carcinoma is the most common malignant tumor on the lower lip. It occurs
more frequently in men than in women, and the average age of diagnosis is 66.1 years.[3]
[14]
[15]
For complete excision of cancer cells, as described above, we performed frozen biopsy
on the left and right from the gross margin, considering the tumor location and size.
On the lower side, the margin was the skin above the sulcus boundary. After securing
additional margins at intervals of 5 mm until negative results were obtained, full-thickness
excision was performed according to the final surgical margin.
In this retrospective study of 44 patients, the final surgical margin was 5 mm in
66% (58/88) of margins, and 86 (97.7%) were 10 mm or less. During an average of 67.4
months of follow-up (range, 12–227 months), only one patient experienced recurrence
(1/44; 2.3%). Based on these results, we recommend setting the first frozen biopsy
margin at 5 mm, and if needed, additional biopsies can be performed at intervals of
5 mm.
Previous studies recommended excising 10 mm of normal-looking tissue beyond the border
of the tumor as a safe margin.[6]
[7]
[8]
[9]
[10]
[11]
[12] Another study suggested a margin of at least 6 mm.[13] However, surgery involving the excision of such a large amount of normal tissue,
coupled with the subsequent reconstruction, is financially burdensome and time-consuming
for patients, and their functional and cosmetic satisfaction after surgery may be
significantly reduced.
A previous study reported that 3 mm was suitable for the first surgical margin in
early-stage cancers (stage I/II). However, no additional studies have investigated
the feasibility of a 3-mm margin. This recommendation is also limited to patients
with early-stage disease,[1] underscoring the importance of research on a broader patient population. Moreover,
metastasis easily occurs from squamous cell carcinoma on the lower lip to the lymph
node of the neck, especially if the maximal thickness of the tumor is more than 6 mm.[16] In this study, metastasis was determined by biopsy when an enlarged lymph node in
the neck was observed on a CT scan. The authors surgically removed the tumors in all
patients. Two patients with neck metastases also underwent neck dissection surgery
and radiotherapy at the otolaryngology department.
This study has several limitations. First, patients who underwent surgery recently
had a relatively short follow-up period, which was sometimes shorter than the average
recurrence time (67.4 months). Additional follow-up will be required in the future.
Second, in the early period of the study, the first frozen margin was determined according
to the operator's experiential competency, and in some cases, it was more than 5 mm.
To summarize, we performed surgery in 44 patients diagnosed with squamous cell carcinoma
on the lower lip over a 23-year period from 1997–2020. Only one patient had recurrence
during follow-up. Of the 88 left and right final surgical margins, 86 (97.7%) were
within 10 mm, and 58 (66.0%) were within 5 mm. Only three cases lasted beyond the
second session.
Therefore, the method described herein is efficient in terms of time and cost, and
it is safe from the risk of recurrence. Based on these findings, 5 mm is considered
appropriate as the first frozen biopsy margin. We expect that these findings will
be helpful for the surgical treatment of squamous cell carcinoma on the lower lip.
