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Unbiopsied Pigmented Skin Lesion
December  2019

A 39-year-old female is applying for $1 million of life insurance. Records reveal this otherwise healthy woman was recently evaluated for a pigmented lesion on her face. This lesion had been present for years, but she had scratched it recently and it bled slightly. While it seemed to heal normally and there was no appreciable difference in the appearance once healed, she consulted with her dermatologist for further evaluation. She was concerned about the possibility of a malignant melanoma. Her best friend who had been recently diagnosed with a melanoma had encouraged her to seek an opinion.

There was no family history of skin cancer. The dermatologist documented the lesion to be 4-mm in size with uniform color, border and symmetry. A dermascope evaluation was normal. The dermatologist recommended a biopsy to ensure it was benign. The patient refused as she was concerned about the potential scar on her face. Therefore, the dermatologist ordered another test called a Pigmented Lesion Assay (PLA), which was negative. Follow-up was recommended in three months. Records reveal the three-month follow-up was normal and follow-up was now planned in one year.

What are the mortality considerations for someone with a pigmented lesion such as this who has had a biopsy recommended but declined? Should this request be postponed pending favorable review of a biopsy pathology report?
There are several forms of common skin cancer including basal cell carcinoma, squamous cell carcinoma and malignant melanoma.

Malignant Melanoma (MM) has the greatest mortality risk. MM will be diagnosed in approximately 96,000 people annually and will result in more than 7,000 deaths. It is the fifth-most common cancer in men and women. The incidence has been trending upwards during the past few decades. It is important to detect MM early as survival is significantly improved.

The American Joint Committee on Cancer (AJCC) 8th edition describes five stages of melanoma classification:
  • Stage 0 is in situ.
  • Stages I and II involve invasive but localized disease.
  • Stage III involves the regional nodes.
  • Stage IV involves distant metastasis.
The five-year relative survival rate for localized disease is 98%, for regional involvement it is 64%, and for distant disease it drops to 23%.

Figure 1 - A malignant melanoma (not the lesion described in this article)
Image obtained using Google’s “labeled for reuse with modification” search engine

Risk factors
Risk factors for developing MM include sun exposure, indoor tanning, the presence of dysplastic nevi or atypical moles, many moles, congenital melanocytic nevi, fair skin, family history,
previous skin cancer, prior radiation treatment and/or an immunosuppressed system. 

Approximately 10% of all people with melanoma have a family history of melanomas.
Malignant melanomas can occur anywhere on the skin and can also occur in the eye. The malignant melanomas of the skin are most commonly detected by the patient themselves. Unfortunately, MM can be difficult to diagnose based on visual inspection.

Diagnostic techniques
There are several different clues to the presence of MM, and there are several different analysis techniques. The first method to evaluate the skin for malignant melanomas is visual inspection. Features examined include the color, size, regularity of the borders and symmetry of the lesion.

Finally, the lesion is evaluated for change in any of these characteristics, either by good history or by serial examination. Worrisome features could include any of the following:
  • Asymmetry
  • Borders that are irregular
  • Color that is variegated (multiple shades of red, black, gray or other colors within the same mole)
  • Diameter >6mm
  • Evolution of the lesion over time (a new mole or a change in the appearance or size)

Notice these five characteristics establish the rule of melanoma known as “the ABCDE rule”.

Next the lesion is compared to other similar pigmented lesions. On most individuals, moles tend to look like each other. When a pigmented lesion looks different from the other lesions on that
individual, this has been called “the ugly duckling sign.” Even if the ABCDE rule criteria has not been met, the presence of an unusual appearing mole raises the concern that this lesion could be a malignant melanoma.

After visual inspection many suspicious pigmented lesions are evaluated by use of a dermoscope. This device requires special training to be used properly, but use of the device improves not only the sensitivity but also the specificity of the diagnosis of melanoma.

Visual inspection alone has been documented to be 71% sensitive and 80-90% specific. Adding the dermoscopic component to the evaluation increases this to 90% sensitive with a similar degree of specificity.

Another diagnostic aid used for further evaluation of suspicious skin lesions is the reflectance confocal microscopy. This device uses a laser to emit near-infrared light that evaluates the epidermis and is felt to increase both the sensitivity and specificity of the diagnosis of skin cancers. Unfortunately, this technique requires additional training, is more time consuming, more expensive and is not always readily available.

Figure 2 - A dermascope
Image obtained using Google’s “labeled for reuse with
modification” search engine.

Typically, when a lesion is suspected of being a malignant melanoma after one or more of the preceding tests, the next step is to biopsy the lesion for histological evaluation. Even though
the biopsy is considered the “gold standard,” the sensitivity and specificity of this procedure is not perfect.

Several studies have documented a significant degree of variability in the diagnosis among even experienced and well-trained pathologists. One study evaluated this variability and found that
only 82.8% of cases were confirmed when compared to a followup evaluation by three dermatopathologists.

New tools
Recently, several other diagnostic aids for the evaluation of pigmented skin lesions have been introduced. These include use of analysis of autoantibody biomarkers, comparative genomic
hybridization and tumor gene expression evaluation. For pigmented lesions found in areas with significant cosmetic concerns or in patients who are anti-coagulated, making biopsy less desirable, a recent development has been the use of an adhesive skin collection kit. This consists of adhesive strips that are applied to the suspicious lesion, removed and then submitted
to the lab for further analysis.

This noninvasive test uses gene expression profiling to analyze two genes (LINC and PRAME) involved in melanoma. This pigmented lesion assay (PLA) test is reported to be 91% sensitive and 69% specific. It has been reported to have a negative predictive value of 99%.

Another test named Nevome has recently been introduced to further evaluate the genetic material removed by the adhesive patches. DNA mutation analysis is performed analyzing the BRAF, NRAS and TERT promoter genes. This test, when combined with the PLA test, is reported to have a sensitivity of 97% and negative predictive value of >99%.

​Visual inspection
71%​​80% - 90%
​80% - 90%
​Reflectance confocal microscopy
​86% - 100%
​72% - 91%
​Pigmented lesion assay
The Gold Standard but the results are not always agreed upon when secondarily reviewed​
Figure 3 - Testing options for pigmented lesions

Returning to the case
In this case the skin lesion is not described as having any changes using the ABCDE rule and there is no mention of it being “an ugly duckling.” In addition, a dermascope evaluation test was

It isn’t completely clear why a biopsy was recommended, but when this was refused for cosmetic reasons, a PLA test was performed and was negative. While none of these tests are 100% sensitive or specific, the tests that have been done are very reassuring.

Finally, the individual is compliant with follow-up evaluations. The risk of this lesion being a melanoma is extremely low. No increased mortality risk is expected. No postponing is needed.

  • Accessed 11/7/2019
  • American Cancer Society. Accessed 11/7/2019
  • Dermtech: Accessed 11/7/2019
  • Elmore J. Et al Pathologists’ diagnosis of invasive melanoma and melanocytic proliferations: observer accuracy and reproducibility study. BMJ. 2017; 357
  • Geller, A et al. Screening and early detection of melanoma in adults and adolescents. UpToDate. Last accessed 11/7/2019.
  • Gershenwald, J. AJCC Cancer Staging Manual. Evidence-based changes in the American Joint Committee on Cancer. Eight edition cancer staging manual. CA Cancer J Clin 2017: 67
  • Swetter, S et al. Melanoma: Clinical features and diagnosis. UpToDate. Last accessed 11/7/2019.