The reliability of a second biopsy for determining residual tumor

The reliability of a second biopsy for determining residual tumor

Dermatologic surgery The reliability of a second biopsy for determining residual tumor Abel Torres, MD,a Jack Seeburger, MD,a Dixon Robison, MD,a and ...

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Dermatologic surgery The reliability of a second biopsy for determining residual tumor Abel Torres, MD,a Jack Seeburger, MD,a Dixon Robison, MD,a and Richard Glogau, MDb

Loma Linda and San Francisco, California Background: Often after biopsy a skin cancer appears to resolve clinically and a repeat bi-

opsy may be done on the area in question before proceeding with further treatment. Objective: Our purpose was to assess the value of a subsequent biopsy in the treatment ofskin cancers previously diagnosed by biopsy results. M etllods: The results of a subsequent biopsy were compared with the results of Mohs micrographic surgery in 291 patients with biopsy-established basal cell carcinoma and squamous cell carcinoma. Pre-Mohs surgery curettings were examined in 60 of these patients to evaluate whether these could have caused false-negative Mohs results. Results: One hundred nineteen patients had a negative second biopsy, of which 75 (63%) had residual tumor at surgery. Eight of 60 patients in whom the curettings were examined had negative results from both biopsy and Mohs surgery; tumor in the curettings was shown in six of these eight patients (75%). Conclusion: This study suggests that 63% or more of subsequent biopsy specimens for skin cancer may yield false-negative results and casts doubt on the usefulness of a subsequent biopsy before surgery. (J AM ACAD DERMATOL 1992;27:70-3.)

Often, after a diagnosis of a skin cancer has been established by biopsy, the biopsied lesion clinically appears to resolve. One option, when this occurs, is to perform a second biopsy on the area in question with therapy determined by the results of the second biopsy. To our knowledge the validity of this approach is unproved and holds the potential for inadequate tissue sampling, leading to a false-negative result and thus inadequate treatment of the lesion. We describe our experience with 291 patients referred for Mohs micrographic surgery. The significance of a second biopsy for the determination of treatment in these patients was evaluated.

PATIENTS AND METHODS Three hundred consecutive patients referred for Mohs micrographic surgery between July 1985 and June 1986 were included in this study. The patients consisted of 167 men from 23 to 95 years of age and 133 women from 28 to 93 years of age. All patients were referred for Mohs micrographic surgery because of a high-risk tumor as de-

From Lorna Linda University" and the University of California, San Francisco.b Reprint requests: Abel Torres, MD, Lorna Linda University Faculty Medical Offices, Suite 2600, Lorna Linda, CA 92354.

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fined by (1) size greater than 2 cm; (2) inadequatelyexcised tumor; (3) recurrent tumor; (4) histologically aggressive tumor such as morpheaform basal cell carcinoma (BCC); (5) anatomic sites associated with a high recurrence rate; and (6) occurrence in areas in which tissue sparing was important.]' 2 All lesions had previously been sampled by punch, shave, or excisional biopsy with a histologically proven diagnosis of BCC in 91.8% and squamous cell carcinoma (SCC) in 8.2%. Just before undergoing Mohs micrographic surgery, shave biopsies (saucerization) of the areas to be treated were performed in 291 patients (nine patients did not undergo repeat biopsy because of unintentional operator omission). The shave biopsy specimens were obtained with a No. 15 blade such that the previously biopsied site and adjacent tissue were sampled. Since Mohs micrographic surgery was to be performed, cosmesis was not a primary consideration and the repeat biopsy specimens were large with depth to the reticular dermis and width of 5 mm in more than 80% of cases. Curettage was subsequently performed on all biopsied lesions to help determine the extent of the tumor. 3 Mohs micrographic surgery was then performed in the usual fashion and the presence or absence of residual tumor established and treated with further Mohs micrographic surgery if needed. It later became apparent that if a lesion was curetted, it could result in the removal of tumor and thus lead to a false correlation between a negative biopsy result and no

Volume 27 Number 1 July 1992

Reliability ofsecond biopsy 71

Table I. Location of all lesions Nose Forehead Ear Cheeks Temple Eyes Lips Scalp Other

Table III. Data from curettings

No.

%

108

37.7 13.7 12.4

40

36 30 23 21 18

10.3

7.9 7.2 6.2 3.1 5.2

9 15

No. of cases curetted Curettings that were BX+ Curettings that were BXCurettings that were BX- jMohs+ Curettings that were BX- jMohsBX- jMohs- currettings with tumor found BX- jMohs- curettings with tumor absent

60 29 31 23 (38.3%) 8 6 (75%)

2 (25%)

BX, Biopsy results.

Table IV. Location of BX-/Mohs + lesions* Table II. Subsequent biopsy results Total No. of cases Total No. with second BX+ for tumor Total No. with BXfor tumor Total No. of BX+ jMohs+ Total No. of BX+ jMohsTotal No. of BX-jMohs+ Total No. of BX-jMohsTotal No. of BX? jMohs+

_ _ _ _I

291 172 (59.1%) 116 (39.9%)

144 (49.5%) 28 (9.6%) 75 (25.8%) 41 (14.1%) 3 (1.0%)

BXI, Uninterpretable results.

tumor seen with Mohs micrographic surgery. Unfortunately the bulk of Mohs micrographic surgery curettage specimens were not histologically evaluated for this variable because we realized this late in the study. As a result, when we did study this variable, only 60 patients could be evaluated. Of these 60 patients, the curettings of the lesions were preserved in formalin and submitted for processing only if findings the biopsy specimen and Mohs micrographic surgery were negative for tumor. The location of all lesions including those lesions that were shave biopsy-negative and Mohs micrographic surgery-positive were collated and tabulated (Table 1).

RESULTS Of the 291 patients studied, 172 (59.1 %) had a second biopsy specimen that was positive for tumor. Of these 172, 144 (83.7%) had residual tumor found with Mohs micrographic surgery and 28 (16.2%) had no residual tumor found with Mohs micrographic surgery. Of the remaining 119 patients (40.9%) with a negative second biopsy specimen, 63% had residual tumor found with Mohs micrographic surgery and 41 (34.5%) had no residual tumor found with Mohs micrographic surgery. The remaining three patients (2.5%) had results as outlined in Table II.

Nose Forehead Cheeks Ear Lips Eyes Temple Scalp Other

No.

31

10 10 6 4 3

2 1

8

1

%

41.3 13.3 13.3 8 5

4 2.6 1.3

10.6

*Total of BX-/Mohs+ that were Bee, 70 (93.3%); total of BX-/ Mohs + that were sec, 5 (6.6%)

As previously explained, 60 of the 291 patients were evaluated for the presence or absence of tumor in the curettings from their lesions (Table III). Of these 60 patients, 29 (48.3%) had a positive biopsy specimen and thus the curettings were not sent for pathologic evaluation. Thirty-one patients (51.7%) had a biopsy specimen that did not show tumor. Of these 31, 23 (74.2%) had residual tumor found with subsequent Mohs micrographic surgery and the curettings were not submitted for evaluation. Thus, only eight patients (25.8%) had a curettage specimen submitted for evaluation. Of these six specimens (75%) revealed tumor and two (25%) had no tumor present. The location of the lesions was the head and neck in 285 patients, (95%), 61% were located on the nose, ears, lips, and periorbital regions. The remaining 15 patients (5%) had lesions in other locations (Table I). Of the 75 patients with biopsy-negative, Mohs micrographic surgery-positive tumors, 67 (89.3%) had lesions in the head and nec~ whereas two (2.7%) were located in another region and six (8.0%) did not have the site of the lesion recorded (Table IV). Seventy of these 75 patients (93.3%) had a Bee and five (6.6%) had an sec.

72 Torres et al. DISCUSSION In the evaluation of cutaneous neoplasms a biopsy is normally required for a complete assessment. The choice of biopsy depends foremost on a knowledge of the disease so that adequately and properly sampled tissue can result in a diagnosis. The type of biopsy chosen should also allow the best choice of therapeutic modalities and whenever possible the best cosmetic results. eosmesis is particularly important because a significant number of neoplasms are located in the head and neck. Shave biopsy (saucerization) is one modality that lends itself to the principles discussed earlier. 4,5 It can provide a diagnosis while maintaining a large choice of therapeutic modalities and, more often than not, allows a good cosmetic result. However, although shave biopsies are useful in the evaluation of largely exophytic hyperplasias and neoplasias, they are not useful in the evaluation oflargely endophytic tumors. Fortunately, many cutaneous neoplasms of the head and neck are exophytic and are suitable for shave biopsy. As a result, results ofshave biopsies are frequently used to diagnose lesions that are suspected of being Bee or sec. However, if a neoplasm is predominantly endophytic or occurs in a scarred area, a shave biopsy may be too superficial to provide adequate and proper sampling. 6, 7 This may be true even if the biopsy is carried out deep into the dermis because the tumor may be extending beneath or around a thick scar or extend deep along a fascial plane. By the same token, an inadequately excised tumor or recurrent tumor may be predominantly endophytic with only one or a few superficial extensions. Thus, if an initial biopsy removes the superficial extensions, a second shave (superficial) biopsy may result in a false-negative assessment of tumor. Shave biopsies, for the reasons previously described, are also commonly used in the evaluation of tumors in cosmetically important areas. Because of cosmetic concerns, one may be tempted to perform a second shave biopsy to confirm whether further treatment is needed. Therefore it is important to establish whether this technique provides an adequate assessment of the presence or absence of tumor. In our study of 291 patients with biopsy-established Bee or sec, a second biopsy was performed before the patient underwent Mohs micrographic surgery. In 172 patients, (59.1 %) the biopsy specimen showed tumor and would not have changed the decision for further therapy. However, in 119 pa-

Journal of the American Academy of Dermatology

tients (39.9%) a second biopsy specimen was free of or equivocal for tumor and could have resulted in no further therapy, if our decision was based on this finding. Of the latter patients, 75 (63%)* showed tumor to be present on Mohs micrographic surgery; thus the decision not to perform surgery on the basis of negative results from a second biopsy could have had serious consequences. In 41 (34.5%) of these patients, a negative second biopsy specimen did appear to correlate with the absence of tumor. However, because curettage was performed on all lesions before Mohs micrographic surgery, there exists the possibility that negative results from biopsy and Mohs micrographic surgery did not really correlate with an absence of tumor. Our further study evaluating the histologic results of the curettage in 60 patients seems to confirm this suspicion. Of the 60 patients studied, only eight (13.3%) showed negative biopsy results and absence of tumor at Mohs micrographic surgery. Of these, six (75%) had tumor present in the curettings. An understanding of the process of Mohs micrographic surgery raises the possibility that a biopsynegative/Mohs-negative result does not necessarily mean that tumor was not present in the tissue. In most cases the Mohs surgeon is looking for the absence of tumor, not its presence. Usually only the bottoms and sides (deep and lateral margins) ofeach piece of excised tissue are examined and the entire specimen is not always sectioned to see how much tumor lies within the specimen. Thus, because not all specimens were completely sectioned, it cannot be stated for certain that the 41 patients (31.5%) with biopsy-negative/Mohs-negative results did actually have an absence of tumor. The possible inadequacies of a second shave biopsy have been presented. The question arises as to whether a second punch or excisional biopsy could present the same inadequacies. Our study did not examine this possibility. However, we believe that the results of this study should raise strong doubts about the adequacy of or need for a second punch or excision biopsy in the management of an established tumor. A proper punch biopsy would certainly provide deeper tissue for evaluation. 8 However, our shave biopsy specimens were greater than 5 mm in diameter in more than 80% of the patients. Thus, to sample the same amount of superficial tissue, the *The 63% is statistically significant with a 95% confidence interval with the use of the Z test for proportions.

Volume 27 Number 1 July 1992

punch would have to have a larger diameter or multiple punch biopsies would have to be performed. However, multiple biopsies or a large punch biopsy could increase the difficulty ofmaintaining adequate cosmesis and resemble more closely an excisional biopsy. An excisional biopsy would provide deeper tissue but it probably would make more sense therapeutically to simply excise the lesion. Of interest is whether the nature of the original biopsy (shave vs punch or incisional) could have influenced the results of this study. This is a question left unanswered because the majority of original biopsies were of the shave variety and the number of original punch or incisional biopsies was too small to yield any useful (statistically significant) results. Also of interest is the difference in outcome depending on the location of the lesions. It is easy to speculate why nose lesions showed so many biopsynegative/Mohs-positive results. However, the biopsy-negative/Mohs-positive results for ear and eyelid lesions seemed lower than expected. Similarly the forehead and cheeks, which are not typically highrisk locations, showed many biopsy-negative/Mohspositive results. These results may have been because physicians referring patients for Mohs micrographic surgery are more likely to refer histologically or clinically aggressive forehead and cheek lesions

Reliability ofsecond biopsy 73

while equally likely to refer less histologically or clinically aggressive ear and eyelid lesions. Finally we caution against overinterpretation of our results. In our study 41 of 291 patients (14.1 %) showedbiopsy-negative/Mohs-negativeresults. One possible interpretation is that the original biopsy reo suIted in a cure of the skin cancer in those patients. However, as we noted previously, an understanding of Mohs micrographic surgery tissue processing and the results ofthe "curettings" study sheds significant doubt as to how many patients were actually biopsy negative and tumor free. REFERENCES 1. SwansonNA.Mohssurgery.ArchDermatol1983;119:76173. 2. Zitelli J A. Mohs surgery: concepts and misconceptions. Int J Dermatol1983;1l9:541-8. 3. Johnson T, Tromovitch T, Swanson N. Combined curettage and excision: a treatment method for primary basal cell carcinoma. J AM ACAD DERMATOL 1991;24:613-7. 4. Arnold H, Odorn R, James W. Andrews' Diseases of the skin. 8th ed. Philadelphia: WB Saunders, 1990:1009-10. 5. Robinson JK. Fundamentals of skin biopsy. Chicago: Year Book, 1986:24-6. 6. Kopf AW, Popkin GL. Shave biopsies for cutaneous lesions. [Letter]. Arch Dermatol1974;1l0:637. 7. Ackerman AB. Shave biopsies: the good and right, the bad and wrong. Am J Dermatopathol1983;5:21l-2. 8. Crollick J8, Klein LE. Punch biopsy diagnostic technique. J Dermatol Surg Oneol 1987;13:839.