Use of Frozen Section Analysis in the Treatment of Basal Cell Carcinoma Peter A. Cataldo, MD, Philip B. Stoddard, MD, William P. Reed, MD, Springfield,Massachusetts
Frozen section margin verification has been used in the treatment of basal cell carcinoma at our institution for the past 13 years. A review of the last 4 5 0 cases has shown frozen section to be most helpful in treating recurrent tumors where microscopic tumor foci extend beyond clinical margins in 45% of cases. Frozen section analysis may be of value in selected patients with primary tumors, but its routine use is not indicated for the majority of these lesions, since complete excision is possible without relying on frozen section in 90% of cases.
clinically established margins will contain microscopic tumor in recurrent, as well as primary, basal cell carcinomas.
MATERIAL AND M E T H O D S The records of all patients treated by a single plastic surgeon for basal cell carcinoma during the years 1973 to 1986 were reviewed. These included recurrent as well as primary lesions. To be included in the analysis, patients had to have been followed for a minimum of 2 years after excision and to have had all pathologic diagnoses available. Patients were followed individually and evaluated for recurrence by the operating surgeon. All recurrences were proven by biopsy examination. The results were tabulated and evaluated using the chi-square test for independence [17], with Yates' corrections for continuity when two proportions were compared [18]. Primary and recurrent tumors were evaluated separately. Patients were divided into two groups: those in whom frozen section analysis was used and those in whom frozen section analysis was not used. The presence asal cell carcinoma is the most common form of skin or absence of tumor at the margins of excision (on permacancer, accounting for more than 65% of such tu- nent as well as on frozen section analysis) and its relation mors [1,2]. Metastatic spread and deaths from this dis- to eventual recurrence were noted. Intraoperative frozen sections were used at the discreease have been reported [3] but are rare. The major morbidity associated with these carcinomas is from local tion of the surgeon. Indications included poorly defined recurrence, which may complicate treatment as often as margins on clinical examination, the need to preserve 50% of the time [4]. Factors that contribute to local adjacent structures, recurrent lesions treated previously recurrence include the location of the primary lesion [5]; with radiation therapy, cryosurgery, or electrodesiccaits histologic appearance, such as irregularities of periph- tion, and long-standing lesions or a previous diagnosis of eral palisades and lymphocytic infiltration [6,7]; and, sclerosing basal cell carcinoma. All tumors were excised with a minimum of 2-mm most important, the tendency of these tumors to be incompletely excised because of subclinical extension of margins of normal-appearing skin, marked, and meadisease at the margins [8,9]. Recurrence rates as high as sured preoperatively. At the completion of tumor exci33% to 50% have been reported for incompletely excised sion, a suture was placed at the medical margin for orientumors, in contrast to rates of only 1% to 5% for tumors tation (Figure 1). Sections of the specimens to be analyzed by frozen section were taken from the peripherremoved with free margins [10-13]. Although subclinical tumor extension will result in al margins as well as from the central deep margin (Figtumor being left at clinically apparent margins in as ure 1). Margins positive for tumor were further excised at many as 12.5% of primary tumors [2] and in an undoubt- 2-ram intervals until clear of carcinoma by frozen section. edly higher percentage of recurrent lesions, frozen section One patient required 17 re-excisions before the margins verification of these margins has been advocated on a were free. The resulting defect was closed by whatever routine basis only for eyelid tumors [14], where the rates technique seemed most appropriate to the size of the of incomplete excision reach 50% [15,16]. The current tissue loss. Frozen sections at our institution cost $120 for the study was undertaken to evaluate the effectiveness of intraoperative frozen section analysis as a means of en- first slide and $70 for each subsequent slide. A negative hancing the adequacy of excision. An additional goal of result would therefore entail five slides at a cost of $400, this study was to determine the frequency with which with the added cost of 20 additional minutes of operative From the Department of Surgery, BaystateMedical Center, Spring- and anesthetic time, which amounts to approximately $5 field, Massachusetts. or $15 per minute at our hospital, depending upon whethRequestsfor reprintsshouldbe addressedto WilliamP. Reed,MD, er the procedure is carried out in the day stay center or in BaystateMedicalCenter, 759 ChestnutStreet,Springfield,Massachuthe main operating suite. Re-excision of a lesion not adesetts 01199. quately removed by the initial procedure would entail ManuscriptsubmittedMay 24, 1989,revisedSeptember15, 1989, additional fees for the surgeon, anesthesiologist, operatand acceptedSeptember27, 1989.
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TABLE
A
I
Proportion of Positive Margins after Excision
Silk Suture On Medial Margin
Excised B.C.C. With 2mm Margins
Primary tumors Recurrent tumors p Value
Total (%)
Frozen Section (%)
Permanent Section (%)
45/347 (13) 411103 (40) 0.0001
21/102 (21) 35/78 (45) 0.0009
241245 (10) 6/25 (24) 0.07
B TABLE Individual Frozen Sections For Immediate Margin Verification
I
II
Proportion of Positive Margins at Recurrence by Type of Prior Therapy Initial Treatment Cryosurgery Radiation Excision Electrodesiccation Chemotherapy
Center Slice For Deep Margin Evaluation
Figure 1. Technique of frozen section margin verification. The specimen is labeled with a suture for orientation (A). After inking the raw surface of the specimen, sections are taken from the periphery of each quadrant and through the center of the lesion (B) for evaluation of the peripheral and deep margins, respectively. BCC = basal cell carcinoma.
ing room, and recovery room. In 1989, charges would have amounted to $1,200 to $1,500, assuming an operative time of 45 minutes in the day stay center or main operative suite, respectively. We would feel obligated to rely on frozen section margin verification the second time, so that the real cost of the second procedure would have been nearer to $1,700 to $2,200.
Proportion/Percent Positive* 16/51 4/11 24165 0/7 212
31% 36 % 37 % 0% 100 %
* Chi-square = 7.91 with 4 degrees of freedom; p ~ 0.09 (difference not significant).
sion (65), radiotherapy (11), electrodesiccation (7), and topical 5-fluorouracil (2), There were no statistically significant differences in the rates of positive frozen section between these groups (Table II). Minimal follow-up of 2 years was available for 279 patients. Four percent of patients with primary basal cell carcinomas developed a recurrence, whereas 5% of patients in the recurrent group developed further recurrences, a difference that was not statistically significant.
RESULTS Four hundred fifty patients with basal cell carcinoma were treated from 1973 to 1986. These included 347 patients with primary tumors and 103 patients with recurrent lesions. Of these, 180 patients (102 with primary tumors and 78 with recurrent tumors) underwent frozen section analysis at the time of operation. When intraoperative frozen section was utilized, at least one margin was positive for tumor in 21% of patients with primary tumors and in 45% of patients with recurrent tumors. This difference was statistically significant. Two hundred seventy patients (245 with primary tumors and 25 with recurrent tumors) underwent excision without the use of intraoperative frozen sections. In this group, permanent sections revealed residual tumor at the resection lines in 11% of patients (10% with primary tumors, 24% with recurrent tumors). All patients with residual tumor underwent re-excision at a later time with eventual margins that were tumor-free (Table I). In the group of patients with recurrent lesions, previous treatments included cryosurgery (51), previous exci-
COMMENTS Local recurrence is the major failure in the treatment of basal cell carcinoma. The best means available to reduce the recurrence rate is to completely excise the lesion. When completely excised, basal cell carcinoma has a 99% cure rate [1,2]. When tumor comes to within one highpower field of the surgical margin, 12% of patients will experience a recurrence. This rate increases to 33% of patients when tumor involves the margins of excision [10]. Increased rates of recurrence have also been noted for tumors in young women and for tumors involving the face [19], presumably due to the use of minimal margins of excision to promote cosmetic results. Although incomplete excision rates have been reported in from 5.5% to 12.5% of cases of primary basal cell carcinomas [2], intraoperative frozen sections have been reported to be useful only in the treatment of eyelid tumors. The utility of frozen section in the treatment of basal cell carcinomas in other locations has not been previously documented. This study addresses the role of intraoperative frozen section analysis of the margins of excision and its relation to the completeness of excision and eventual recurrence. Frozen sections were used in lesions with poorly defined clinical margins, in long-standing lesions, in recur-
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rent lesions, and in lesions where tissue preservation was desirable. Using these criteria, 21% of patients with primary lesions and 45% of patients with recurrent tumors had cancers extending to the margins of excision as demonstrated by frozen section. These patients underwent further excision until margins were negative for tumor, thereby avoiding the eventual need for a second surgical procedure. Patients with primary tumors who lacked indications for intraoperative frozen sections had clear margins on permanent section 90% of the time. The added cost of $500 to $700 for frozen section margin verification would obviously not be justified in this group of patients. However, 24% of patients with recurrent tumors underwent incomplete excision when frozen section was not employed. These patients then required re-excision at a greater cost than would have been incurred by using frozen section initially. In fact, the cost of secondary procedures for the 24% equaled or exceeded the projected cost of frozen section verification for the 76% who had free margins. These data suggest an important, but selective, value for the use of intraoperative frozen section margin verification in the treatment of basal cell carcinoma. The benefit is particularly important in recurrent lesions where microscopic tumor foci often extend beyond clinically detectable margins. The use of frozen section margin verification in the treatment of recurrent tumors decreases the rate of incomplete excision, the need for reoperation, and the overall recurrence rate. This benefit is independent of the treatment modality used for the primary tumor. Complete excision is possible in 90% of patients with primary tumors having clinically distinct borders. Routine use of frozen section for margin verification is of little benefit in this group of patients. When margins are indistinct, however, or when preservation of surrounding structures is deemed important, frozen section may be of value even for primary tumors. Eyelid tumors constitute one such group where the benefits of frozen section have been well documented.
The authors address the specific question of when frozen section control ought to be used in treating basal cell carcinoma of the skin. This is especially pertinent in
today's cost-conscious medical climate and seems to have highest merit when treating recurrent basal cell carcinoma.
REFERENCES 1. Casson P. Basal cell carcinoma. Clin Plast Surg 1980; 7:301-11. 2. Koplin L, Zarem HA. Recurrent basal cell carcinoma. Plast Reconstr Surg 1980; 65: 656-64. 3. Domarus H, Stevens PJ. Metastatic basal cell carcinoma: report of five cases and review of 170 cases in the literature. J Am Acad Dermatol 1984; 10: 1043-60. 4. DeSilva SP, Dellon AL. Recurrence rate of positive margin basal cell carcinoma: results of a five-year prospective study. J Surg Oncol 1985; 28: 72-4. 5. Shanoff LB, Spira M, Hardy SB. Basal cell carcinoma: a statistical approach to rational management. Plast Reconstr Surg 1967; 39: 619-24. 6. Dellon AL. Histologic study of recurrent basal cell carcinoma. Plast Reconstr Surg 1985; 75: 853-9. 7. DeUonAL, DeSilva S, Connolly M, Ross A. Prediction of recurfence in incompletely excised basal cell carcinoma. Plast Reconstr Surg 1985; 75: 860-71. 8. Burg G, Hirsch RD, Konz B, Braun-Falco O. Histographic surgery: accuracy of visual assessment of the margins of basal cell epithelioma. J Dermatol Surg 1975; 1: 21-4. 9. Wolf DJ, Zitelli JA. Surgical margins for basal cell carcinoma. Arch Dermatol 1987; 123: 340-4. 10. Pascal RR, Hobby LW, Lattes R, Crickelair GF. Prognosis of "incompletely excised" versus "completely excised" basal cell carcinoma. Plast Reconstr Surg 1968; 41: 328-32. 11. Richmond JD, Davie RM. The significance of incomplete excisionin patients with basal cell carcinoma. Br J Plast Surg 1987; 40: 63-7. 12. Gooding CA, White G, Yatsuhashi M. Significance of marginal extension in excised basal-cell carcinoma. N Engl J Med 1965; 273: 923-4. 13. Rintala A. Surgical therapy of basal cell carcinoma. Scand J Plast Reconstr Surg 1971; 5: 87-90. 14. Older J J, Quickert MH, Beard C. Surgical removal of basal cell carcinoma of the eyelids utilizing frozen section control. Trans Am Acad Opthal Otol 1975; 79: OP658-663. 15. Einaugler RB, Henkind P. Basal cell epithelioma of the eyelid: apparent incomplete removal. Am J Ophthalmol 1969; 67: 413-17. 16. Rakofsky SI. The adequacy of the surgical excisionof basal cell carcinoma. Ann Ophthalmol 1973; 5: 596-600. 17. Dixon WJ, Massey F. Introduction to statistical analysis. New York: McGraw-Hill, 1969: 240-3. 18. Everitt BS: The analysis of contingency tables. London: Halstead Press, 1977: 12-14. 19. Robins P, Albom MJ, Recurrent basal cell carcinomas in young women. J Dermatol Surg 1975; 1: 49-51.
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