Relationship of tumor thickness in punch biopsy and subsequent

surgical specimens in stage I squamous cell carcinoma of

the lower lip
J. G. A. M. de Visscher, DDS, MD,a M. Schaapveld,b A. J. K. Grond, MD, PhD,c and I. van der
Waal, DDS, PhD,d Leeuwarden, Groningen, and Amsterdam, The Netherlands
MEDISCH CENTRUM LEEUWARDEN, COMPREHENSIVE CANCER CENTRE NORTHERN NETHERLANDS,
LABORATORY OF PUBLIC HEALTH FRIESLAND, AND FREE UNIVERSITY HOSPITAL/ACTA

Objective. Among the histologic features of squamous cell carcinoma of the lower lip, maximum tumor thickness in particular is a predictor of regional nodal metastatic spread and thus an important parameter in treatment planning. The purpose of
this study was to investigate the relationship between maximum tumor thickness in punch biopsies and maximum tumor thickness in subsequent surgical specimens.
Study design. This retrospective study examined the relationship between maximum tumor thickness in punch biopsies with
that in subsequent surgical specimens obtained in 72 patients with clinical stage I squamous cell carcinoma of the lower lip.
Results. A correlation between maximum tumor thickness in punch biopies and in subsequent surgical specimens was found
only for tumors with a thickness less than 3 mm.
Conclusions. Reliable predictive information could be obtained from punch biopsies with a maximum tumor thickness less
than 3 mm. When the maximum tumor thickness exceeds 3 mm, better information may be obtained from either a large incisional biopsy or the surgical specimen.

(Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1999;88:141-4)

The prognosis for patients with squamous cell carcinoma (SCC) of the lower lip is generally favorable.
The most potent predictor of survival is the occurence
of regional lymph node metastasis. In patients in whom
neck metastases develop, 5-year survival rates vary
between 30% and 70%, with an average of 50%.1-5
Most lip cancers are small lesions when diagnosed.
Although stage I lower lip SCCs may metastasize, the
rate of metastasis is low, varying between 4% and 7%5-7;
routine elective treatment of the neck thus seems not to
be justified.
Various clinical and histologic features of the primary
tumor have been identified as important parameters
with respect to predicting the likelihood of the presence
of occult nodal metastasis.4,5,7-10 Among others,
maximum tumor thickness (MTT) seems to be a useful
prognostic indicator of cervical metastatic disease,
whereby carcinomas exceeding 5 mm in size have a
high risk of occult regional lymph node metastasis.7-10
However, in the pertinent studies tumor thickness has
been based on surgical specimens. Accurate pretreataDepartment of Oral and Maxillofacial Surgery, Medisch Centrum
Leeuwarden.
bComprehensive Cancer Centre Northern Netherlands, Groningen.
cDepartment of Pathology, Laboratory of Public Health Friesland.
dDepartment of Oral and Maxillofacial Surgery/Pathology, Free
University Hospital/ACTA.
Received for publication Jan 19, 1999; returned for revision Mar 2,
1999; accepted for publication Apr 7, 1999.
Copyright 1999 by Mosby, Inc.
1079-2104/99/$8.00 + 0 7/12/99133

ment identification of MTT in biopsy specimens may

allow improved treatment planning and facilitate the
decision for elective treatment of the neck.
The punch biopsy is a safe, rapid, and effective
method of obtaining tissue for diagnostic purposes and
is commonly used in dermatology practices.
The objective of the present retrospective study was
to assess the correlation between MTT in punch biopsies and in subsequent surgical specimens of stage I
lower lip SCCs with the aim of determining whether
the biopsy thickness measurement is an accurate basis
for treatment planning.

MATERIAL AND METHODS

Clinical data and histologic material pertaining to 91
consecutive patients who had undergone punch biopsies and subsequently undergone surgery for clinical
stage I primary SCC of the lower lip between 1990 and
1995 were retrieved from the files of the Department of
Pathology, Laboratory of Public Health Friesland,
Leeuwarden, the Netherlands. No patient had had
previous treatment.
The punch instrument used for all biopsies was the
Steifel sterile disposable biopsy punch, the diameter
varying from 2 to 4 mm and the maximum cutting
depth being 10 mm. Subsequent excision was carried
out through use of a standard, full-thickness V- or Wshaped technique.
Histologic sections of the biopsy and surgical specimens from each patient were reviewed by one of the
141

142 de Visscher et al

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

August 1999

Fig 1. Comparison of mean thickness of surgical and biopsy specimens with difference of tumor thickness in
surgical and biopsy specimens after logarithmic transformation of data; n = 72. 2SD, Two times SD.

authors to reconfirm the initial diagnosis of SCC and to

measure the MTT. Measurements to the nearest 0.1
mm were made from the surface of the tumor to the
maximal depth by means of an ocular micrometer.
Tangential cuts were excluded.
Nineteen (20.9%) of the 91 patients had biopsy specimens that did not reveal the margins of their tumors.
Fourteen (74%) of these patients had surgical specimens that revealed greater tumor thickness than did the
biopsies. Because in these 19 patients the actual MTT
could not be estimated adequately in the biopsy specimens, they were excluded from further analysis; the
remaining 72 patients comprised the study group.
In the study group were 65 men and 7 women. The
mean age at presentation was 65 years (range, 37 to 88
years). The distribution of biopsy punch diameters was
as follows: 5 patients, 2 mm; 61 patients, 3 mm,; 6
patients, 4 mm. The length of the punch biopsy specimens varied from 1.6 to 5.5 mm, with a mean length of
3.3 mm (median, 3.4 mm).
Biopsy results yielded a range of MTTs from 0.5 to
4.7 mm, with a mean thickness of 1.9 mm (median, 1.8
mm). Surgical excision specimen results yielded a
range of MTTs from 0.6 to 13.8 mm, with a mean
thickness of 2.7 mm (median, 2.2 mm).

Statistical analysis
The relationship between the MTT measurement in
the biopsies and the MTT measurement in the surgical
specimens was assessed by comparing the difference
between the 2 measurements with the mean of the 2
measurements.11 The latter was used as an estimate for
the true but unknown value of the MTT. The plot of the
difference against the mean value allowed investigation
of any possible relationship between the measurement
error and the true value. The MTT in the surgical specimen was not used as a gold standard because of the
possible error of the MTT measurement as a result of
taking the biopsy in the thickest part of the tumor.
The MTTs in the biopsy and surgical specimens were
transformed to a logarithmic scale to correct the skewness in the distribution of differences between both
measurements. Logarithmic transformation of the data
allow the use of the statistical properties of a normal
distribution (Gaussian); the limits of agreement of both
measurements are denoted by the mean difference
between both measurements plus or minus 2 times the
standard deviation (SD) of the mean difference. If the
differences are normally distributed, 95% of the differences will lie between these limits. When both measurements correspond well, one would expect a mean differ-

de Visscher et al 143

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

Volume 88, Number 2

14

12

Thickness surgical specimen (mm)

10

B
A

2
0
0

Thickness biopsy specimen (mm)

Fig 2. Tumor thickness, in millimeters, of biopsy specimen versus surgical specimen, with line of equality (A)
and regression line (B); n = 72.

ence between the 2 measurements of approximately 0

and a small SD around the mean value.
Statistical analysis was performed through use of the
SPSS package (SPSS Inc, Chicago, Ill). Statistical
significance was claimed for P < .05.

RESULTS
The surgical specimen revealed an MTT within 0.5
mm of that of the biopsy specimen in each of 40
(55.5%) of the 72 patients. Each of 53 patients (73.6%)
had a surgical specimen with an MTT within 1 mm of
that of the biopsy specimen, and each of 66 patients
(91.7%) had a surgical specimen with an MTT within
1.5 mm of that of the biopsy specimen. Thirteen
patients (18.1%) had biopsy specimens that revealed
greater MTTs than did the surgical specimens; in 3
patients, this difference was greater than 0.5 mm. The
mean difference between the measured thickness in the
surgical and biopsy specimens was 0.7 mm, though the
SD was fairly large (1.6 mm). The limits of agreement
showed that in 95% of the cases the measurement of
the MTT in the biopsy specimen could differ from the
measurement of the MTT in the surgical specimen by
at most 66% (below) to 70% (above; Fig 1).

Fig 2 shows a scatterplot of the MTTs of the surgical

specimens versus the MTTs of the biopsy specimens.
There is perfect agreement only if the points lie along
the line of equality. When the points lie along any other
straight line, there is a perfect correlation. The diagram
illustrates that both measurements are at least partially
correlated. Biopsies with a thickness less than 3 mm
produced quite a high correlation between the 2
measurements (Pearson correlation coefficient, 0.65; P
< .001), the thickness of the surgical specimens being
on average 1.4 times greater than that of the biopsies.
The diameter of the punch instrument that was used
influenced neither the length of the punch biopsy (P =
.80) nor the tumor thickness (P = .68) in the biopsy
specimen.

DISCUSSION
A main problem in this retrospective study is that the
biopsy may have been taken not with the intention of
measuring the thickness of the tumor but merely to
demonstrate the presence of malignancy. However, in 72
biopsies the MTT could be measured. Standardization of
the biopsy technique might result in better correlation
between the 2 measurements.

144 de Visscher et al

ORAL SURGERY ORAL MEDICINE ORAL PATHOLOGY

August 1999

It is clear that there is a strong relationship between

MTT in lower lip SCC and lymph node metastasis.
Because there seems to be a discerning point at 5 mm of
MTT at which regional metastasis is probable, for reliable predictive information from the punch biopsy the
length of the biopsy specimen should be greater than 5
mm. In a biopsy of a suspicious lip lesion, inclusion of a
zone of adjacent, clinically uninvolved tissue is usually
recommended. For measurement of the MTT, the best
site at which to perform a biopsy may be the central part
of the tumor. Because a punch biopsy specimen is small,
it may not represent the thickest part of the tumor.
Furthermore, there are well-known problems as to what
should be measured in tumor thickness. In our study, for
punch biopsy and surgical specimens the actual tumor
thickness was determined; in contrast, the reconstructed
tumor thickness, measured from the theoretically reconstructed surrounding normal mucosal surface to the
deepest extent of tumor growth, seems to be more useful
in predicting cervical lymph node metastasis.12 However,
in most studies on the value of tumor thickness in
predicting cervical metastasis of primary SCC of the
lower lip, the actual tumor thickness is measured.7-10
The results of this study show considerable discrepancies between the 2 measurements. The wide intervals
between the upper and lower limits reflect the great
variation of the differences. Fig 2 shows that there is no
perfect agreement between the measurementsie,
they do not lie along the line of equality. However, if
the tumor is less than 3 mm thick, a correlation
between the 2 variables has been found. Biopsies with
a tumor thickness greater than 3 mm were too variable
to be of predictive value for the definitive pretreatment
evaluation of SCCs of the lower lip. A pretreatment
punch biopsy with an MTT less than 3 mm might be a
useful guide for preoperative assessment of the MTT in
lower lip SCC. This seems to be of clinical relevance,
inasmuch as lower lip SCCs with an MTT less than 3
mm hardly ever metastasize.7-10

CONCLUSION
In punch biopsies of stage I SCC of the lower lip, an
MTT less than 3 mm is useful for predicting the actual
MTT. When the biopsy thickness is greater than 3 mm,
better information may be obtained either from a large
incisional biopsy or from the surgical specimen.
REFERENCES
1. Jrgensen K, Elbrnd O, Andersen AP. Carcinoma of the lip: a
series of 869 patients. Acta Otolaryngol 1973;75:312-3.
2. Baker SR, Krause CJ. Carcinoma of the lip. Laryngoscope
1980;90:19-27.
3. Cruse CW, Radocha RF. Squamous cell carcinoma of the lip.
Plast Reconstr Surg 1987;80:787-91.
4. Rowe DE, Carroll RJ, Day CL. Prognostic factors for local recurrence, metastasis, and survival rates in squamous cell carcinoma
of the skin, ear and lip. J Am Acad Dermatol 1992;26:976-90.
5. Zitsch RP, Park CW, Renner GJ, Rea JL. Outcome analysis for
lip carcinoma. Otolaryngol Head Neck Surg 1995;113:589-96.
6. Luce EA. Carcinoma of the lower lip. Surg Clin North Am
1986;66:3-11.
7. de Visscher JGAM, van den Elsaker K, Grond AJK, van der Wal
JE, van der Waal I. Surgical treatment of squamous cell carcinoma of the lower liplong-term results and prognostic factors:
retrospective analysis of 184 patients. J Oral Maxillofac Surg
1998;56:814-20.
8. Frierson HF, Cooper PH. Prognostic factors in squamous cell
carcinoma of the lower lip. Hum Pathol 1986;17:346-54.
9. Stein AL, Tahan SR. Histologic correlates of metastasis in
primary invasive squamous cell carcinoma of the lip. J Cutan
Pathol 1994;21:16-21.
10. Teuber S, Klss M, Lautenschlger C. Anamnestische, klinische
und prognostische Faktoren beim Lippenkarzinom. Deutsche
Zeitschrift fr Mund-, Kiefer- und Gesichts-Chirurgie 1995;19:814.
11. Bland JM, Altman DG. Statistical methods for assessing agreement between two methods of clinical measurement. Lancet
1986;I:307-10.
12. Moore C, Kuhns JG, Greenberg RA. Thickness as prognostic aid
in upper aerodigestive tract cancer. Arch Surg 1986;121:1410-4.

Reprint requests:
J. G. A. M. de Visscher, DDS, MD
Department of Oral and Maxillofacial Surgery
Medisch Centrum Leeuwarden
Henri Dunantweg 2, 8934 AD Leeuwarden
The Netherlands