How Moles Change Over Time in High-Risk Adults: A 16-Year Study

Table of Contents

• Key Points
• Background: Why Study Moles Over Time?
• How the Study Was Conducted
• Who Participated in the Study
• Key Finding: New Moles Keep Appearing
• Key Finding: Very Few Moles Disappear
• Key Finding: Most Moles Grow Larger
• Color Changes in Moles
• Dermoscopic (Microscopic) Changes
• How Melanoma History Affects Mole Behavior
• What This Means for Patients
• Limitations of the Study
• Recommendations for High-Risk Patients
• Frequently Asked Questions
• Source Information

Key Points

• In a 16-year study of 106 high-risk adults, 65% developed at least one new mole, averaging 2.6 new moles per person.
• Most tracked moles grew larger: 49% increased in diameter by at least 25%, while only 6% shrank by that amount.
• Disappearing moles were uncommon; 25.5% of patients had at least one mole disappear, with no more than three per patient.
• Patients with a personal history of melanoma were less likely to develop new moles but more likely to have moles that grew or disappeared.
• Most moles (80.4%) showed no significant color change, and 76% of those with dermoscopic images had no major microscopic changes.

Background: Why Study Moles Over Time?

Having many moles is one of the strongest risk factors for melanoma, the most dangerous form of skin cancer. A large analysis by Gandini and colleagues found that the risk of melanoma increases as the number of moles on a person's body increases. This creates a difficult challenge for doctors. They must find "a needle in a haystack" — identifying the one melanoma among many harmless moles in patients who have dozens or even hundreds of moles.

Change in a mole is an important warning sign for melanoma. However, moles also change naturally over time. To detect changes that might indicate cancer, doctors must first understand how moles normally behave.

Little was known about the long-term natural history of melanocytic nevi (the medical term for moles) in adults. Many studies have looked at mole counts at a single point in time or over short periods. These studies suggest that mole counts are related to age, but the relationship is not straightforward.

Total mole counts tend to increase until people reach their 40s, then decrease in older age. The common explanation for this pattern has been that people develop new moles early in life and lose moles later in life. In children, this mole turnover has been observed directly. Over 3 to 7 years of follow-up, up to 75% of children developed new moles, and 28% had moles that disappeared.

However, in adults, data on how mole counts change with age have been inconsistent. Some studies found that mole counts increase, while others found they decrease. One possible explanation for these conflicting results is that differences across studies are not due to aging at all. Instead, they may reflect differences in ultraviolet (UV) exposure across different generations.

Another problem is that most studies did not track individual moles over time. A study that does not follow individual moles may miss the possibility that different types of moles behave differently. Some moles may develop because of UV exposure and then fade away in midlife. Other moles may develop for reasons unrelated to UV exposure and persist indefinitely.

Total body photography (TBP) offers a way to monitor individual moles over long periods. TBP takes high-resolution overview images of the entire body and is commonly used for patients at high risk for melanoma. The goal of this study was to describe long-term changes in both overall mole counts and individual moles among adult patients undergoing TBP at a high-risk pigmented lesion clinic.

How the Study Was Conducted

The study was approved by the Institutional Review Board at Memorial Sloan Kettering Cancer Center (MSKCC) in New York. The researchers reviewed the medical records of all patients who had their first TBP at MSKCC before January 1, 2005.

Patients were included in a "retrospective" group if they later had a follow-up TBP more than 14 years after their first session. To address the possibility that this group was not representative, the researchers also recruited a "prospective" group. These were consecutive patients who had a TBP more than 14 years earlier but had not returned for follow-up imaging. These patients agreed to undergo a new TBP as part of the study.

Patients were excluded if their original TBP images were not good enough to measure mole size. Two patients were excluded for being younger than 18 at baseline, and two were excluded because they received immunotherapy during follow-up.

Researchers collected demographic information, personal history of skin cancer, and family history of skin cancer from medical charts and patient interviews. All patients had Fitzpatrick skin type I or II, meaning very fair skin that burns easily and tans poorly.

The researchers compared baseline and follow-up torso images. They evaluated:

• The total number of moles, new moles, and disappearing moles
• The number of seborrheic keratoses (benign, waxy skin growths) and actinic keratoses (rough, scaly patches caused by sun damage)
• The diameter of each mole at both time points
• Color changes in each mole
• The presence of clinical atypia (moles that look unusual under examination)
• Dermoscopic features (detailed microscopic examination of moles) when available

Only moles measuring at least 4 millimeters (mm) on the torso were included. The researchers had previously found that counting and measuring moles of this size on flat body surfaces gave more reproducible results. The torso was defined as the area from the collarbones in front and the tips of the shoulders in back. The torso extended down to the iliac crests (the top of the hip bones).

Baseline images were 2D photographs, while follow-up images were 3D photographs, reflecting technological improvements over the study period. All images were taken by trained clinical photographers using standardized lighting, patient postures, and camera settings. Before each session, patients were asked to trim body hair and remove jewelry and undergarments.

Diameter measurements on 2D images were performed manually using ImageJ software, calibrated to dermoscopy images. Measurements on 3D images were performed automatically using VECTRA software. To account for measurement inaccuracy, a mole was considered to have grown or shrunk only if it showed at least a 25% change in diameter.

When dermoscopic images were available at both time points, researchers noted the main features at the center and edge of each mole. They defined dermoscopic "fading" as pigment network or globules disappearing, or the pigment network becoming lighter, patchier, or having thinner lines. They defined dermoscopic "enhancement" as pigment network or globules appearing, or the pigment network becoming darker, more widespread, or showing thicker lines.

For the statistical analysis, the researchers used Poisson regression to assess the rate of new moles and logistic regression to analyze disappearing moles. Because moles within the same patient are not independent of each other, mole-level outcomes were analyzed using a generalized estimating equations (GEE) approach.

Who Participated in the Study

Of 836 patients who had TBP at MSKCC before January 1, 2005, 66 had a follow-up TBP that met the inclusion criteria. An additional 63 consecutive patients agreed to undergo a follow-up TBP for the study. After exclusions, a total of 106 patients participated.

The median follow-up time was 16.4 years, with a range of 14.2 to 19.8 years. The average age at baseline was 40.6 years (standard deviation 10.1 years). Fifty-eight patients (55%) were male, and 48 (45%) were female.

In total, 71 patients (67%) had a history of melanoma. Of these, 50 patients (47%) had their first melanoma before their baseline TBP, and 21 patients (20%) were diagnosed during follow-up. Thirty-five patients (33%) had never had melanoma.

Regarding family history, 44 patients (42%) had a family history of melanoma, 59 (56%) did not, and 3 (3%) had an unknown family history.

At baseline, patients had an average of 29.2 moles on the torso (standard deviation 27.4). The average number of actinic keratoses at baseline or follow-up was 0.5 (standard deviation 2.2), and the average number of seborrheic keratoses was 14.5 (standard deviation 23.1).

Forty-nine patients were in the retrospective group, and 57 were in the prospective group. The two groups were similar in age and melanoma history. However, patients in the retrospective group had a higher average baseline mole count (36 moles versus 23 moles, P = 0.017).

Key Finding: New Moles Keep Appearing

Most patients continued to develop new moles throughout the study period. Sixty-nine patients (65.1%, 95% confidence interval 55.6% to 73.5%) had new moles appear on the torso. The average number of new moles per patient was 2.6 (standard deviation 4.8).

Excluding moles that were removed, 62 of 106 patients (58%) had an absolute increase in their total mole count. Only 9 of 106 patients (8%) had an absolute decrease in their total mole count over the follow-up period.

The average number of new moles was higher among younger patients and decreased with age. However, new moles appeared even in the oldest patient in the study at baseline imaging.

New moles appeared more commonly among male patients. Women had 46% fewer new moles than men per 15 years, a statistically significant difference (P = 0.001).

Patients with a higher baseline mole count also developed more new moles. Additionally, patients who had at least one mole disappear were more likely to develop new moles.

When the researchers looked at the number of new moles by category:

• Overall, 73% of patients (n=73) had 0 to 3 new moles, and 27% (n=32) had 4 or more new moles
• Among patients with 1 to 10 baseline moles, 72% had 0 to 3 new moles and 28% had 4 or more
• Among patients with 10 to 20 baseline moles, 92% had 0 to 3 new moles and 8% had 4 or more
• Among patients with 20 to 40 baseline moles, 83% had 0 to 3 new moles and 17% had 4 or more
• Among patients with 40 or more baseline moles, 72% had 0 to 3 new moles and 28% had 4 or more

The rate of new moles was significantly associated with baseline mole count (P < 0.001). Patients with 10 to 20 baseline moles had an adjusted rate ratio of 1.29 (95% CI 1.05 to 3.57) compared to patients with 1 to 10 moles. Patients with 20 to 40 baseline moles had an adjusted rate ratio of 2.3 (95% CI 1.25 to 4.49). Patients with 40 or more baseline moles had an adjusted rate ratio of 4.17 (95% CI 1.10 to 4.32).

Age also mattered. Compared to patients younger than 35, those aged 35 to 45 had an adjusted rate ratio of 0.30 (95% CI 0.22 to 0.40) for new moles. Those older than 45 had an adjusted rate ratio of 0.22 (95% CI 0.14 to 0.33). Both findings were statistically significant (P < 0.001).

Key Finding: Very Few Moles Disappear

Disappearing moles were uncommon. Twenty-seven patients (25.5%, 95% CI 18.1% to 34.5%) had at least one mole that disappeared during follow-up. The number of disappearing moles ranged from 0 to 3 per patient, with an average of 0.3 (standard deviation 0.6).

The disappearance of moles was not related to age. This phenomenon was uncommon even among the oldest participants in the study.

The average number of disappearing moles was higher among patients with a higher baseline mole count. However, this finding was not statistically significant.

Patients with a history of melanoma were less likely to acquire new moles and more likely to have disappearing moles compared to patients with no history of melanoma. Specifically:

• Patients diagnosed with melanoma during follow-up had an adjusted rate ratio of 0.75 (95% CI 0.41 to 0.70) for new moles compared to patients who never had melanoma (P < 0.001)
• Patients whose first melanoma occurred before follow-up had an adjusted rate ratio of 0.56 (95% CI 0.41 to 0.76) for new moles (P < 0.001)
• Patients diagnosed with melanoma during follow-up had an adjusted odds ratio of 4.58 (95% CI 1.17 to 23.62) for having at least one disappearing mole (P = 0.035)
• Patients whose first melanoma occurred before follow-up had an adjusted odds ratio of 3.43 (95% CI 0.99 to 14.14) for having at least one disappearing mole (P = 0.066)

The number of seborrheic keratoses on the torso ranged from 0 to 190, and the number of actinic keratoses ranged from 0 to 19. Both were positively associated with age.

Key Finding: Most Moles Grow Larger

This was one of the most striking findings of the study. Of the 2,890 moles that could be evaluated at both time points, 49% (1,416 moles) increased in diameter by at least 25%. Only 6% (159 moles) decreased in diameter by at least 25%. The average change in diameter was 1 mm (standard deviation 1.7 mm).

All but three patients experienced at least one growing mole. Fifty-nine patients (55.7%) had at least one shrinking mole on their torso.

Several factors influenced whether moles grew or shrank:

• Melanoma history: Moles in patients with a personal history of melanoma were more likely to increase in size. Compared to patients who never had melanoma, those diagnosed during follow-up had 2.36 times the odds of mole growth (95% CI 1.60 to 3.48, P < 0.001). Those whose first melanoma occurred before follow-up had 2.55 times the odds of mole growth (95% CI 1.83 to 3.57, P < 0.001).
• Disappearing moles: Moles in patients with at least one disappearing mole were more likely to decrease in size. The adjusted odds ratio was 2.1 (95% CI 1.31 to 3.37, P = 0.002).
• Baseline mole count: The likelihood of mole size decrease was positively associated with the total count of baseline torso moles (P = 0.002 for trend).
• Color change: Moles that became lighter in color were more likely to decrease in size (adjusted odds ratio 5.65, 95% CI 3.91 to 8.15, P < 0.001). Moles that became darker were more likely to increase in size (adjusted odds ratio 2.01, 95% CI 1.23 to 3.28, P = 0.005).

The number of new and disappearing moles, as well as the likelihood of growth and shrinkage, were similar in all four sections of the torso. The four sections were chest, abdomen, upper back, and lower back.

When analyzed by baseline mole count category, the percentage of moles that grew by at least 25% varied:

• Patients with 1 to 10 baseline moles: 59% of moles grew
• Patients with 10 to 20 baseline moles: 44% of moles grew
• Patients with 20 to 40 baseline moles: 39% of moles grew
• Patients with 40 or more baseline moles: 53% of moles grew

For moles that shrank by at least 25%:

• Patients with 1 to 10 baseline moles: 4% of moles shrank
• Patients with 10 to 20 baseline moles: 10% of moles shrank
• Patients with 20 to 40 baseline moles: 8% of moles shrank
• Patients with 40 or more baseline moles: 4% of moles shrank

Color Changes in Moles

Most moles did not change color during the follow-up period. Of all moles assessed, 80.4% showed no significant color change. However, 15.6% of moles became lighter, and 3.9% became darker.

Color change was strongly linked to size change. Moles that became lighter were much more likely to shrink. Moles that became darker were much more likely to grow. Specifically, 80% of moles that became darker grew by at least 25%, compared to 52% of moles with no color change and 24% of moles that became lighter.

For shrinkage, 21% of moles that became lighter shrank by at least 25%, compared to only 3% of moles with no color change. No moles that became darker shrank by at least 25%.

Dermoscopic (Microscopic) Changes

Dermoscopy is a technique that allows doctors to examine moles under magnification to see structures not visible to the naked eye. Of the 2,890 moles included in the study, only 773 had dermoscopic images available at both time points for comparison.

Most moles (76%) did not have major dermoscopic changes between the two imaging sessions. This finding is important because it suggests that most moles remain stable when examined closely over many years.

When dermoscopic changes did occur, they followed patterns related to mole growth or shrinkage:

• Fading at the center of the mole was noted in 15% of moles that grew, compared to 35% of moles that shrank (P < 0.001)
• Dermoscopic enhancement at the center was less common, noted in only 4% of moles that grew and 2% of moles that shrank

The researchers noted that moles with major dermoscopic changes were more likely to be removed (excised) during the study. This removal could have contributed to the relatively unchanged dermoscopy seen in the remaining moles.

How Melanoma History Affects Mole Behavior

The study found important differences in mole behavior between patients with and without a personal history of melanoma.

Patients with a history of melanoma were less likely to develop new moles. This finding was statistically significant for both patients diagnosed during follow-up and those diagnosed before follow-up.

However, patients with a history of melanoma were more likely to have moles that grew larger. Their moles had approximately 2.4 to 2.6 times the odds of increasing in diameter by at least 25% compared to patients without melanoma history.

Patients with a history of melanoma were also more likely to have disappearing moles. This finding was statistically significant for patients diagnosed during follow-up (P = 0.035) and showed a trend for patients diagnosed before follow-up (P = 0.066).

Family history of melanoma did not show a statistically significant association with new moles, disappearing moles, or mole size change in this study.

What This Means for Patients

This study provides several important insights for high-risk patients and their doctors.

First, patients continue to develop new moles throughout adulthood, even into their 50s and beyond. This finding contradicts the common belief that adults stop developing new moles. The study found that 65% of patients developed at least one new mole over an average of 16 years.

Second, most moles in adults grow larger over time rather than shrinking. Nearly half of all tracked moles increased in diameter by at least 25%, while only 6% shrank by that amount. This finding challenges previous assumptions that moles naturally shrink with age.

Third, very few moles disappear completely. Only about one in four patients had even one mole disappear over the 16-year study period, and no patient had more than three disappearing moles.

Fourth, most moles do not change significantly when examined with dermoscopy. This stability is reassuring and suggests that most moles are biologically stable over long periods.

These findings have practical implications for clinical practice. As total body photography becomes more widely used, doctors will identify many new moles. This study suggests that many of these new moles are likely to be benign and not require biopsy, and that follow-up may be considered if a new mole is not an outlier, has no melanoma-specific dermoscopic structure and shows dermoscopic features that fit its body location and the patient's age. Similarly, most growing moles in high-risk patients are not melanoma.

However, the study also found that patients with a history of melanoma have moles that are more likely to grow. This finding suggests that doctors should pay particular attention to growing moles in melanoma survivors.

Limitations of the Study

The study had several limitations that patients should understand.

First, the study included only 106 patients, all of whom had Fitzpatrick skin type I or II and were treated at a single high-risk pigmented lesion clinic. The findings may not apply to patients with darker skin types or to the general population.

Second, the baseline and follow-up images were taken using different technologies (2D versus 3D photography). While the researchers took steps to ensure accurate measurements, this difference could have affected the results.

Third, dermoscopic images were available for only 773 of the 2,890 moles at both time points. The dermoscopic findings may not represent all moles in the study.

Fourth, the study could not determine whether the observed changes were due to aging, UV exposure, or other factors. The researchers could only describe what changed, not why it changed.

Fifth, patients in the retrospective group had a higher average baseline mole count than those in the prospective group. This difference could have influenced some of the findings.

Sixth, the study did not track moles smaller than 4 mm. Smaller moles may behave differently from the larger moles included in this study.

Recommendations for High-Risk Patients

Based on this study, high-risk patients and their healthcare providers should consider the following:

1. Continue regular skin examinations. Because new moles continue to appear throughout adulthood, ongoing monitoring is important for high-risk patients.
2. Do not assume a growing mole is cancer. Most growing moles in this study were benign. However, growing moles should still be evaluated by a dermatologist.
3. Understand that moles rarely disappear. If a mole does disappear, it is uncommon but not necessarily dangerous. However, patients with a history of melanoma were more likely to have disappearing moles.
4. Pay attention to color changes. Moles that become darker are more likely to grow, while moles that become lighter are more likely to shrink. Both patterns can be normal, but changes should be evaluated.
5. Use total body photography if available. TBP allows doctors to track individual moles over time and may reduce unnecessary biopsies.
6. Discuss your personal risk factors with your dermatologist. Patients with a personal history of melanoma may need more frequent monitoring because their moles are more likely to grow.

Patients should remember that this study describes average patterns across a group. Individual mole behavior can vary widely. Any concerning change in a mole should be evaluated by a qualified dermatologist.

Frequently Asked Questions

How common is it for adults to keep getting new moles?

In a 16-year study of 106 high-risk adults with fair skin, 65% developed at least one new mole on the torso, averaging 2.6 new moles per person. New moles appeared even in the oldest participant. Men developed more new moles than women, and people with more moles at the start tended to develop more over time.

Does a personal history of melanoma change how moles behave?

Yes. Among 106 high-risk adults, those with a personal history of melanoma were less likely to develop new moles and more likely to have moles that grew larger or disappeared. Their moles had about 2.4 to 2.6 times the odds of growing by at least 25% compared with people who never had melanoma.

What did the study find about color changes in moles?

Most moles (80.4%) showed no significant color change over 16 years. When color did change, it was linked to size: 80% of moles that became darker grew by at least 25%, while 21% of moles that became lighter shrank by that amount. Any color change should still be evaluated by a dermatologist.

What are the limitations of this mole study?

The study included only 106 patients with very fair skin (Fitzpatrick type I or II) at a single high-risk clinic, so results may not apply to people with darker skin or the general population. Baseline and follow-up photos used different technologies, and dermoscopy was available for only 773 of 2,890 moles.

I have many moles and a history of melanoma — when should I get a second opinion about whether my moles are changing normally or need a biopsy?

Most moles in high-risk adults grow rather than shrink: 49% of tracked moles increased in diameter by at least 25%, while only 6% shrank that much, and 65% of patients developed new moles over about 16 years. Moles in people with a personal history of melanoma had roughly 2.4 to 2.6 times the odds of growing. Because most growing moles are benign, a second opinion can help distinguish expected change from something needing biopsy. Diagnostic Detectives Network provides independent expert second opinions.

Source Information

Original article title: The long‐term evolution of melanocytic nevi among high‐risk adults

Authors: O. Reiter, N.R. Kurtansky, S.T. Musthaq, S. Dusza, A.C. Halpern, M.A. Marchetti, A.A. Marghoob, A. Scope, V. Rotemberg

Author affiliations: Dermatology Service, Memorial Sloan Kettering Cancer Center, New York, NY, USA; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; The Kittner Skin Cancer Screening and Research Institute, Sheba Medical Center, Ramat Gan, Israel

Publication: Journal of the European Academy of Dermatology and Venereology (JEADV), 2022, volume 36, pages 2379-2387

DOI: 10.1111/jdv.18470

Funding: The study was funded by a Melanoma Research Alliance Dermatology Fellowship grant (A#654544). This research was funded in part through the MSKCC institutional NIH/NCI Cancer Center Support Grant P30CA008748.

Conflicts of interest: None declared.

This patient-friendly article is based on peer-reviewed research. It is intended for educational purposes and should not replace consultation with a qualified healthcare provider.