ORIGINAL STUDY
Mitotic Activity in Juvenile Benign Nevi
Megan Anne Brown, MBChB* and Ben Tallon, MBChB, FRACP†
Abstract: Melanocytic nevi are submitted for histological evalu-
ation primarily to exclude a malignant process. Mitotic figures are
one of the factors used in this assessment. However, there is a lack of
data on mitotic activity in juvenile benign nevi. The authors assessed
114 cases of benign melanocytic nevi in children aged 0–15 (inclu-
sive) years old by counting the mitoses present in 2 sections of
hematoxylin and eosin–stained tissue. The authors then calculated
the proportion of cases in which mitotic activity was present, and the
average number of mitoses per case for each age group to get the
mitotic rate. The authors found that there was at least 1 mitoses
present in 40.4% of cases, and that the mitotic rate decreases in older
children compared with younger children. This highlights the need
for careful consideration of the significance of a mitotic figure in
juvenile pigmented lesions, to ensure the lesion is not overinterpreted
as malignant.
Key Words: Mitotic activity, juvenile, benign, nevi, Mitosis, nevus,
compound nevus, intradermal nevus
(Am J Dermatopathol 2017;39:187–188)
KEY POINTS
• There is a lack of data on mitotic activity in juvenile
benign nevi.
• There is high mitotic activity in juvenile benign nevi.
• The mitotic rate decreases in older children compared
with younger children.
INTRODUCTION
B enign melanocytic nevi are commonly submitted for
histological evaluation in both adult and pediatric pop-
ulations. The main reason for removal is to exclude a malig-
nant process. Various histologic characteristics of the lesion
are used to assess whether the lesion is benign or malignant.
One of the key characteristics is the presence of mitotic
figures. Although several studies of mitotically active nevi
support a reduction in mitotic activity with age, there does
not seem to be any studies that look specifically at mitotic
activity in juvenile benign nevi. This study aims to assess
From the *Pathlab Bay of Plenty, Tauranga, New Zealand; and †Pathlab Bay
of Plenty and Skin Dermatology Institute, Tauranga, New Zealand.
The authors declare no conflicts of interest.
Reprints: Dr. Megan Anne Brown, MBChB, Pathlab Bay of Plenty, PO Box
130, Tauranga 3140, New Zealand (e-mail: meganannebrownnz@gmail.
com).
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Copyright Ó 2017 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.
the presence of mitotic activity and the rate of and change in
the mitotic activity with age, in benign nevi, in a juvenile
population.
MATERIALS AND METHODS
Cases were found by searching Delphic AP, a database
of reported cases from a private histology laboratory in
Tauranga, New Zealand. We included 0–15 (inclusive) year
olds with a diagnosis including the term “nevus,” during the
18-month period from July 1, 2014 until December 31, 2015.
We also included 0–8 year olds with a diagnosis including the
term “nevus,” during the period from July 1, 2013 until June
30, 2014. This produced a result of 143 reports.
Each case was examined by 2 researchers—a specialist
dermatopathologist and an anatomical pathology registrar.
Twenty-nine of these reports were excluded. Twenty-one
were due to diagnosis (anything other than a compound or
intradermal nevus), 2 were due to only one section of tissue
being available for assessment, 2 were excluded because of
inflammation or trauma and 4 were excluded as they were not
available. This resulted in a final count of 114 cases.
Each researcher independently counted the mitoses in 2
sections of hematoxylin and eosin–stained tissue. The re-
searchers were blinded as to patient age and to each other’s
findings. Of the 114 cases, 75 had a consensus mitotic count.
Thirty-three cases had an interresearcher discordance of 1 and
6 cases had a discordance of 2. The finding of a mitosis was
accepted as present, and discordant cases were rounded up to
the highest number of mitoses counted by an individual
researcher.
The results were then broken down into age brackets of
1 year. The mitotic rate was recorded as the average number
of mitoses per case in each age group. The correlation
coefficient and a scatterplot were created using the XLSTAT
statistical software in Microsoft Excel.
RESULTS
Our search failed to return any results in the 0–3 year
old age groups, which met the inclusion criteria. There was
one case identified in each of the 4-year-old and 9-year-old
age group categories. In each of the other age categories, at
least 2 cases met the inclusion criteria. A significant propor-
tion of the cases were from patients aged in the 12–15 year
old age groups (Table 1).
The presence or absence of at least 1 mitosis in each
case was noted and expressed as a percentage (Table 1).
The average number of mitoses per case in each age
group was calculated by dividing the total number of mitoses
by the total number of cases in each age group (Fig. 1). The
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Brown and Tallon Am J Dermatopathol  Volume 39, Number 3, March 2017

cases, and pooled the results to the highest value, which may
TABLE 1. Cases With Mitotic Figures by Age Group
elevate the apparent mitotic activity compared with previous
Number of Number of Cases With Percentage of Cases studies and routine assessment.
Age Cases Mitoses Present With Mitotic Figure
Our data, which assessed mitotic rate in yearly age groups,
4 1 1 100 shows a progressive decline in mitotic rate as age increases. This
5 2 1 50 seems to be not only a significant difference compared with rates
6 2 1 50 seen in adult benign nevi, but here also shows a measurable
7 3 3 100 decline across the years of 4–15. This suggests that proliferative
8 5 3 60 activity may begin to fall from a very early age.
9 1 0 0 From a clinical perspective, this is important in our
10 7 4 57 assessment of melanocytic lesions, where mitotic figures form
11 8 3 38 part of the diagnostic criteria for malignancy. Although this
12 10 4 40 variation in mitotic rate with age has been appreciated from
13 21 8 38 previous studies, our data show that it can significantly decline
14 27 8 30 even by the age of 15. There is although, presence of a mitotic
15 27 10 37 figure in 40% of cases on average and still 37% in the 15-year-
114 46 40.4 old age bracket. Therefore, careful consideration of the signifi-
cance of a mitotic figure in juvenile pigmented lesions is still
warranted to ensure the lesion is not overinterpreted as malignant.
correlation coefficient was 0.1315, indicating a positive asso- The role of immunohistochemistry using markers such
ciation between increasing age and reduced mitotic rate. as phosphohistone H3 or MPM2, to routinely detect mitoses,
has yet to be established. An increased detection rate from
19.5% on hematoxylin and eosin to 31.3% with phosphohi-
DISCUSSION stone H3 has been described in banal nevi.4 A recent study in
Our study shows high mitotic activity in juvenile thin melanoma although, shows no benefit over careful eval-
benign nevi, and that the mitotic rate decreases in older uation of hematoxylin and eosin sections.5 Given the high
children compared with younger children. O’Rourke et al1 frequency of finding a small number of mitotic figures in
found that patients aged in the first, second, and third decades benign nevi, the addition of immunohistochemistry may
had mitotic activity present in over 10% of cases each, com- therefore be of limited value.
pared with all other groups, which had mitotic activity in less Our study was limited by the lack of data from patients in
than 10% of cases. Lu et al2 found that the presence of mitotic the youngest age groups. This is most likely due to the rarity
activity varied between 14% and 56% of cases in the first 2 and perceived benign nature of nevi in this age group. In
decades compared with all other age groups, which had addition, we did not adjust for the size of the nevus, and
mitotic activity in less than 10% of cases. Our study showed therefore the number of melanocytes, which had the potential to
at least 1 mitosis present in at least 30% of cases in all age be mitotically active. Interobserver variability was also a factor
groups except for the 9-year-old age group. Of the 114 benign which was demonstrated by discordant counts in some cases.
melanocytic nevi reviewed, 46 (40.4%) contained at least 1 This study shows a relatively high presence of mitotic
mitotic figure. This is significantly higher than that found in activity, and a high mitotic rate in pediatric benign nevi,
most previous study data,1–4 which demonstrated mitotic which is consistent with other published data. We were
activity to be present in between 0.91% and 19.5%, with an further able to document the reducing mitotic rate across
outlying 56% (5 of 9) in cases ,1-year-old in one study. yearly age groups, with a significant reduction occurring by
These studies differed in that a wider range of patient ages the age of 15. There is although, a persisting high presence of
were included in the studies, as well as different types of nevi. mitotic activity, with at 15 years of age, on average one in
Our high rate may reflect the small number of cases available, every 3 cases showing a mitotic figure.
particularly in the very young. We also heavily scrutinized the
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