Dermatologic
surgery
Surgical margins for excision of primary cutaneous squamous cell carcinoma David G. Brodland, MD,a and John A. Zitelli, MDb Rochester, Minnesota. and Pittsburgh, Pennsylvania
Background: No guidelines for the margin ofresection of cutaneous squamous cell carcinoma have been based on data measuring subclinical tumor extension, as have been formulated for basal cell carcinoma. Objective and methods: Guidelines for appropriate margins of excision of primary cutaneous squamous cell carcinoma were formulated on the basis of a prospective study of subclinical microscopic tumor extension. Results: Four millimeter margins were adequate for most squamous cell carcinomas. However, certain tumor characteristics were associated with a greater risk of subclinical tumor extension and included size of 2 em or larger, histologic grade 2 or higher, invasion of the subcutaneous tissue, and location in high-risk areas. Conclusion: Minimal margins of excision of 4 mm around the clinical borders of the squamous cell carcinoma are proposed for all but the high-risk tumors, in which at least a 6 mm margin is recommended. (J AM ACAD DERMATOL 1992;27:241-8.)
Cutaneous squamous cell carcinoma (SCe) is the second most common skin cancer encountered by dermatologists. Its incidence is currently 38.8 per 100,000 persons! and is increasing at epidemic rates. 2 Surgical excision of SCC includes a margin of normal-appearing skin because it is known that sec often extends beyond the visible margin of the tumor. Current recommended margins of excision are arbitrary and variable, ranging from 2 mm to more than 2 cm. 3-8 No guidelines for the margin of resection of SCC have been based on data measuring the subclinical tumor extension, as have been formulated for basal cell carcinoma. 9 We attempted to define appropriate margins for excision of cutaneous SCC on the basis of such data. We prospectively studied the subclinical lateral tumor extension and the depth of tumor invasion in patients with primary SCC. On the basis of the probability of subclinical tumor extension, we established guidelines for surgical margins that should achieve tumor clearance rates of at least 95%. From the Department of Dermato!ogy, Mayo Clinic and Mayo Foundation, Rochester"; and the Kaufmann Building, Pittsburgh. b Reprint requests: David G. Brodland, MD, Mayo Clinic, 200 First St. SW, Rochester, MN 55905.
16/1/37192
MATERIAL AND METHODS
A prospective study of 111 consecutive patients treated for 141 primary, invasive SCCs was undertaken during a 15-month period. SCC in situ was not included in this study. Informed consent was obtained from the patients: 75 men (68%) and 36 women (32%). The mean age was 70.9 years and the range was 51 to 95 years. A medical history was obtained, with specific attention to immunosuppressive and cytotoxic medications, previous superficial radiation therapy, history of arsenic intake, and 1ymphoreticular malignancies. Preoperatively, under bright surgical lighting, the clinical tumor borders were marked with ink. The borders were delineated on the basis of palpable or visual alterations in surface contour or erosion, erythema, and epidermal changes such as well-defined hyperkeratosis. Presurgical marks were made with gentian violet at 2 mm increments along radial lines in all directions from the tumor borders. With the patient under local anesthesia, the tumor was debulked and a 2 mm margin of normal-appearing skin was excised by Mohs micrographic surgery (fresh-tissue technique).IO This tissue was prepared, stained, and examined microscopically. Residual microscopic tumor was mapped and selectively excised. This process was repeated with additional 1to 2 mm margins until the entire tumor was extirpated. Histologic grade of the biopsy specimen was determined with a four-grade system. II
241
Journal of the American Academy of Dermatology
242 Bradland and Zitelli 99
100
100
80
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o~
c
0
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~
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40
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4
6
Margin of excision, mm Fig. 1. Rate of tumor clearance for various margins of excision in 141 tumors studied. *, One tumor required 9 mm margins for clearance.
Table 1. Tumor size distribution Tumors
Size (mm)
No.
%
0-9 10-19
71 41
29
20+
29
50
21
Postoperatively, the lateral extent of the tumor was measured from the presurgical incremental markings. The vertical extent was determined by the presence or absence of tumor invasion into the subcutaneous fat on biopsy or horizontal frozen section. A tumor clearance standard of 95% or more was selected in determining the guidelines for excisional margins. Vahtes reported for p are based on Fisher's exact test. Statistical evaluation of the relation of tumor characteristics such as size, histologic grade, anatomic location, depth of invasion, and duration to the degree of subclinical tumor extension was performed. The relation of host variables such as age, sex, immune status, radiation exposure, and arsenic intake was similarly evaluated.
RESULTS Tumor size varied from 3 mm to 6 cm (Table 1). The minimal lateral margin required for tumor clearance was determined for each lesion (Fig. 1). Four millimeter margins were required to achieve a greater than 95% tumor clearance rate in the 141 tumors studied. Minimal lateral margins for clear-
ance were determined for subgroups of these tumors on the basis of various characteristics of the tumors. Those subgroups that required greater or lesser lateral margins to obtain the 95% tumor clearance rate are discussed later. The relation of tumor size to the minimum tumor clearance margin was determined (Fig. 2). Tumors were grouped according to maximum diameter: 0 to 9 mm, 10 to 19 mm, or 20 mm and larger. A 4 mm margin cleared 95% or more of the secs in the 0 to 9 mm and the 10 to 19 mm groups. However, 6 mm margins were required to clear 95% of the tumors that were 20 mm or larger. These results indicate a tendency for greater subclinical tumor extension in large tumors (p = 0.001). The histologic grade of all tumors was determined. The effect of the histologic grade on the margins of excision necessary for tumor clearance was studied (Fig. 3). The standard of 95% tumor clearance was met with 4 mm margins in the grade 1 sce and with 6 mm margins with grade 2 and 3/4 tumors. These data suggest that higher grade tumors are more prone to subclinical lateral tumor extension (p = 0.002). The locations of the tumors were recorded and evaluated. The tumors were equally distributed on the right and left sides. Of the 141 tumors, 92 (65%) were located on the head and neck. Previous studies of cutaneous tumors identified high-risk areas where subclinical tumor extension and tumor recurrence
Volume 27 Number 2, Part 1 August 1992
Cutaneous squamous cell carcinoma 243
100 95lll>
4
6
9'
Margin of excision, mm
Fig. 2. Rate of tumor clearance as function of tumor size.
Histologic grade
m, In - 104) (74%) 02 (n=
surgery
Surgical margins for excision of primary cutaneous squamous cell carcinoma David G. Brodland, MD,a and John A. Zitelli, MDb Rochester, Minnesota. and Pittsburgh, Pennsylvania
Background: No guidelines for the margin ofresection of cutaneous squamous cell carcinoma have been based on data measuring subclinical tumor extension, as have been formulated for basal cell carcinoma. Objective and methods: Guidelines for appropriate margins of excision of primary cutaneous squamous cell carcinoma were formulated on the basis of a prospective study of subclinical microscopic tumor extension. Results: Four millimeter margins were adequate for most squamous cell carcinomas. However, certain tumor characteristics were associated with a greater risk of subclinical tumor extension and included size of 2 em or larger, histologic grade 2 or higher, invasion of the subcutaneous tissue, and location in high-risk areas. Conclusion: Minimal margins of excision of 4 mm around the clinical borders of the squamous cell carcinoma are proposed for all but the high-risk tumors, in which at least a 6 mm margin is recommended. (J AM ACAD DERMATOL 1992;27:241-8.)
Cutaneous squamous cell carcinoma (SCe) is the second most common skin cancer encountered by dermatologists. Its incidence is currently 38.8 per 100,000 persons! and is increasing at epidemic rates. 2 Surgical excision of SCC includes a margin of normal-appearing skin because it is known that sec often extends beyond the visible margin of the tumor. Current recommended margins of excision are arbitrary and variable, ranging from 2 mm to more than 2 cm. 3-8 No guidelines for the margin of resection of SCC have been based on data measuring the subclinical tumor extension, as have been formulated for basal cell carcinoma. 9 We attempted to define appropriate margins for excision of cutaneous SCC on the basis of such data. We prospectively studied the subclinical lateral tumor extension and the depth of tumor invasion in patients with primary SCC. On the basis of the probability of subclinical tumor extension, we established guidelines for surgical margins that should achieve tumor clearance rates of at least 95%. From the Department of Dermato!ogy, Mayo Clinic and Mayo Foundation, Rochester"; and the Kaufmann Building, Pittsburgh. b Reprint requests: David G. Brodland, MD, Mayo Clinic, 200 First St. SW, Rochester, MN 55905.
16/1/37192
MATERIAL AND METHODS
A prospective study of 111 consecutive patients treated for 141 primary, invasive SCCs was undertaken during a 15-month period. SCC in situ was not included in this study. Informed consent was obtained from the patients: 75 men (68%) and 36 women (32%). The mean age was 70.9 years and the range was 51 to 95 years. A medical history was obtained, with specific attention to immunosuppressive and cytotoxic medications, previous superficial radiation therapy, history of arsenic intake, and 1ymphoreticular malignancies. Preoperatively, under bright surgical lighting, the clinical tumor borders were marked with ink. The borders were delineated on the basis of palpable or visual alterations in surface contour or erosion, erythema, and epidermal changes such as well-defined hyperkeratosis. Presurgical marks were made with gentian violet at 2 mm increments along radial lines in all directions from the tumor borders. With the patient under local anesthesia, the tumor was debulked and a 2 mm margin of normal-appearing skin was excised by Mohs micrographic surgery (fresh-tissue technique).IO This tissue was prepared, stained, and examined microscopically. Residual microscopic tumor was mapped and selectively excised. This process was repeated with additional 1to 2 mm margins until the entire tumor was extirpated. Histologic grade of the biopsy specimen was determined with a four-grade system. II
241
Journal of the American Academy of Dermatology
242 Bradland and Zitelli 99
100
100
80
a>
o~
c
0
co
.~
~
Q)
60
~co
0~ :J
o E
E :J
I-
40
:J 0
20 (;)
4
6
Margin of excision, mm Fig. 1. Rate of tumor clearance for various margins of excision in 141 tumors studied. *, One tumor required 9 mm margins for clearance.
Table 1. Tumor size distribution Tumors
Size (mm)
No.
%
0-9 10-19
71 41
29
20+
29
50
21
Postoperatively, the lateral extent of the tumor was measured from the presurgical incremental markings. The vertical extent was determined by the presence or absence of tumor invasion into the subcutaneous fat on biopsy or horizontal frozen section. A tumor clearance standard of 95% or more was selected in determining the guidelines for excisional margins. Vahtes reported for p are based on Fisher's exact test. Statistical evaluation of the relation of tumor characteristics such as size, histologic grade, anatomic location, depth of invasion, and duration to the degree of subclinical tumor extension was performed. The relation of host variables such as age, sex, immune status, radiation exposure, and arsenic intake was similarly evaluated.
RESULTS Tumor size varied from 3 mm to 6 cm (Table 1). The minimal lateral margin required for tumor clearance was determined for each lesion (Fig. 1). Four millimeter margins were required to achieve a greater than 95% tumor clearance rate in the 141 tumors studied. Minimal lateral margins for clear-
ance were determined for subgroups of these tumors on the basis of various characteristics of the tumors. Those subgroups that required greater or lesser lateral margins to obtain the 95% tumor clearance rate are discussed later. The relation of tumor size to the minimum tumor clearance margin was determined (Fig. 2). Tumors were grouped according to maximum diameter: 0 to 9 mm, 10 to 19 mm, or 20 mm and larger. A 4 mm margin cleared 95% or more of the secs in the 0 to 9 mm and the 10 to 19 mm groups. However, 6 mm margins were required to clear 95% of the tumors that were 20 mm or larger. These results indicate a tendency for greater subclinical tumor extension in large tumors (p = 0.001). The histologic grade of all tumors was determined. The effect of the histologic grade on the margins of excision necessary for tumor clearance was studied (Fig. 3). The standard of 95% tumor clearance was met with 4 mm margins in the grade 1 sce and with 6 mm margins with grade 2 and 3/4 tumors. These data suggest that higher grade tumors are more prone to subclinical lateral tumor extension (p = 0.002). The locations of the tumors were recorded and evaluated. The tumors were equally distributed on the right and left sides. Of the 141 tumors, 92 (65%) were located on the head and neck. Previous studies of cutaneous tumors identified high-risk areas where subclinical tumor extension and tumor recurrence
Volume 27 Number 2, Part 1 August 1992
Cutaneous squamous cell carcinoma 243
100 95lll>
4
6
9'
Margin of excision, mm
Fig. 2. Rate of tumor clearance as function of tumor size.
Histologic grade
m, In - 104) (74%) 02 (n=
