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Feature Story

Using Ancillary Tests in the Diagnosis of Melanoma

September 2021

Introduction

The number of ancillary tests to diagnose, stage, and help with prognosis in the management of melanoma and other skin cancers is increasing, and the question of how, when and why to employ them is omnipresent. As the debate over the usefulness of sentinel node biopsy and polymerase chain reaction tests for melanomas and squamous cell carcinomas (SCCs) continues, other tests have been developed to hasten results and provide simple, possibly in home “starter” tests for more expeditious diagnosis.1,2 The increase of teledermatology during the COVID-19 pandemic has shown some of these may have a place; however, nothing replaces clinical judgment, the use of the dermatoscope, and biopsy for a definitive pathological diagnosis.3,4 What is the appropriate placement of these tests?  Can a simple test have a benefit psychologically and encourage a patient to seek medical attention for a more accurate diagnosis? Can such a test be done “at home” and be useful when going to a physician’s office? These tests may alleviate patient denial and reticence by patients to undergo a diagnostic surgical procedure such as an excisional biopsy.5,6

Case

A 69-year-old White man presented with a history of poison plant dermatitis and a recent exposure. He was arrogant and called “to get steroids.” He had seen other physicians over the past years and indicated he had no other major problems.

On physical examination, there was erythema and vesicles on the anterior aspect of the upper extremities and excoriations on the legs with edema around the neck area. This poison plant dermatitis was treated appropriately with oral and topical steroids. However, a 2.5-cm2; irregular; brown, black, and gray flat lesion was noted on the back (Figure 1). Dermatoscopic examination showed irregular granular areas consistent with melanoma, and an excisional biopsy was indicated. The situation was explained to the patient with pain-staking time and pamphlets were provided to educate him and encourage him to have this biopsy/removal immediately. He would not allow it.

Figure 1

In an effort to convince him, a novel tape diagnostic test was employed. The lesion was irritated with a cotton gauze and then the tape was placed on the lesion to transfer cells onto it for examination.7 The specimen on the diagnostic tape should not have blood in it because this may interfere with results. Though no blood was present in the initial specimens, due to the type of lesion, the laboratory thought there was sanguineous contamination and wanted the test repeated. The second attempt also produced “darkened” cells, and a note to this affect indicated the absence of blood. (This may be a problem with the test.)

It is obvious that such a test is truly not needed or clinically appropriate with an obvious melanoma; however, this patient needed a fast, noninvasive technique to convince him to go further. The molecular pathology report indicated gene expression was positive with LINC00518 and PRAME detected, meaning a high (red) risk status. This combination has a sensitivity of 91%, and surgical biopsy is recommended consistent with the American Academy of Dermatology treatment guidelines for lesions clinically suggested of melanoma.8 (Consider complete removal to full depth and breadth with clear margins.)

Following the tape test report, the patient finally scheduled the definitive treatment excision. Excision documented a melanoma in situ (Figure 2).

Figure 2

 

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Discussion

This case shows the complications of many aspects of real-world medicine. First, it emphasizes the importance of a complete skin evaluation in all presentations. Since the patient’s chief complaint was minor and he was defiant, the melanoma on his back would have gone unnoticed had he not been fully undressed. Second, a simple noninvasive test may be unnecessary and frustrating for an astute clinician, but it can be useful to convince a non-cooperative or fearful patient of the necessity for surgery (biopsy).9-11 Third, if the dermatologist suspects something is awry with test results, call the laboratory and discuss it and/or repeat it. If the suspicion is high, follow through.

There is also a learning curve for a new test and those who developed it. In this case, the test is meant to delineate early, nonspecific lesions and provide advice for the necessity of further evaluation. This lesion was blatantly obvious to the clinician that the darker cells were removed easily onto the tape, making the technicians think it was blood, not dark cells. It is hoped the technicians also have learned things could be misleading and that they should speak to the clinician for further information before they dismiss evidence. The instincts of the clinician must always remain the highest form of guidance.

Lastly, the question of the usefulness of such a study for an at home test remains including cost/benefits.12,13 Can a patient follow the directions of the test sent to them and returned to the laboratory? Is it useful in times when the patient cannot come for an in-person examination? Can the test be sent directly to the patient ordered by a physician after a video encounter? During this COVID-19 isolation, the use of teledermatology has expanded and raised many questions as to what should or could be done. A positive result on such a test would determine the timeline of the necessity for the physical removal. It could encourage the patient to seek help immediately or alleviate extra worries...or could it muddle the situation with confusion? More studies and statistical evaluation must be done to know; however, everything seems to have a place and must be considered in that light.

References

1.  Nakamura Y.  The role and necessity of sentinel node biopsy for invasive melanoma. Front Med.  2019;6:231. doi:10.3389/fmed.2019.00231

2. Arnot SP, Han G, Fortino J, Han D, Fowler G, Vetto JT. Utility of a 31-gene expression profile for predicting outcomes in patients with primary cutaneous melanoma referred for sentinel node biopsy. Am J Surg. 2021;221(6):1195-1199.

3.  Elmore JG, Barnhill RL, Elder DE, et al. Pathologists’ diagnosis of invasive melanoma and mm melanocytic proliferations: observer accuracy and reproducibility study. BMJ. 2017;357:j2813. doi:10.1136/bmj.j2813

4. Levine A, Markowitz O. In vivo reflectance confocal microscopy. Cutis. 2017;99(6):399-402.

5. Fink C, Haenssle HA. Non-invasive tools for the diagnosis of cutaneous melanoma. Skin Res Technol. 2016;23(3):261-271. doi:10.1111/srt.12350

6. Orzan OA, Sandru A, Jecan CR. Controversies in the diagnosis and treatment of early cutaneous melanoma. J Med Life. 2015;8(2):132-141.

7.  Creel J, Boudreaux B, Harrington H. Noninvasive diagnosis of malignant melanoma for today’s dermatologist. The Dermatologist. 2020;28(2):40-43. Accessed September 1, 2021. https://www.hmpgloballearningnetwork.com/site/thederm/article/noninvasive-diagnosis-melanoma-todays-dermatologist

8. Swetter SM, Tsao H, Bichakijan CK, et al. Guidelines of care for the management of primary cutaneous melanoma. J Am Acad Dermatol. 2019;80(1):208-250. doi:10.1016/j.jaad.2018.08.055

9. Ferris LK, Rigel DS, Siegel DM, et al. Impact on clinical practice of a non-invasive gene expression melanoma rule-out test: 12-month follow-up of negative test results and utility data from a large US registry study. Dermatol Online J. 2019;25(5):13030/qt452297hk.

10. Gerami P, Yao Z, Polsky D, et al. Development and validation of a noninvasive 2-gene molecular assay for cutaneous melanoma. J Am Acad Dermatol. 2017;76(1):114-120.e2. doi:10.1016/j.jaad.2016.07.038

11. Ferris LK, Gerami P, Skelsey MK, et al. Real-world performance and utility of a noninvasive gene expression assay to evaluate melanoma risk in pigmented lesions. Melanoma Res. 2018;28(5):478-482. doi:10.1097/CMR.0000000000000478

12. Pellacani G, Witkowski A, Cesinaro AM, et al. Cost-benefit of reflectance confocal microscopy in the diagnostic performance of melanoma. J Eur Acad Dermatol Venereol. 2016;30(3):413-419. doi:10.1111/jdv.13408

13. Hornberger J, Siegel DM. Economic analysis of a noninvasive molecular pathologic assay for pigmented skin lesions. JAMA Dermatol. 2018;154(9):1025-1031. doi:10.1001/jamadermatol.2018.1764

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