Introduction
Congenital melanocytic nevi are brown-black skin lesions caused by
benign proliferation of melanocytes. They are mostly present at birth,
however some authors consider melanocytic nevi developing within 2 years
of life congenital as well (1). The incidence of CMN (congenital
melanocytic nevi) is about 1%. They are mostly sporadic, caused by
somatic mutations, although familial cases have also been reported (2).
CMN are categorized into three groups: small (<1.5 cm), medium
(1.5-20cm) and large or giant CMN (>20cm) (3).
There is a risk of malignant transformation both in prepubertal and post
pubertal patients which is higher in larger lesions. The risk of
transformation of GCMN(giant congenital melanocytic nevi) to melanoma is
estimated between 0 to 3.8% (4, 5). Another complication associated
with GCMN is neurocutaneous melanosis (NCM), characterized by abnormal
melanosis of the central nervous system (6).
Typical histopathological findings in CMN include; the presence of
nevomelanocytes within the lower dermis, extension of nevomelanocytes
between collagen bundles, around hair follicles, eccrine apparatus and
sebaceous glands. CMN are often removed by surgery (7).
Here we report a 12-year old female immigrant from Afghanistan with
multiple melanocytic nevi on the face and trunk and a giant congenital
cerebriform melanocytic nevus on the scalp.
Case Report
A twelve year-old female immigrant from Afghanistan was admitted in the
dermatology department of Alzahra hospital in 2020 with multiple brown
lesions on the trunk and face and a large cerebriform plaque on the
right side of her scalp.
She was born with multiple brown papules and nodules on the trunk and
face and a brown patch on the right side of her scalp. She reported a
small increase in the size of the lesions on her body and face over time
and there was no associated pain or itching. According to her parents,
the lesion on the scalp was a small brown flat patch at birth and had
increased in size and thickness over the last 8 years and in the past 5
years it became nodular and cerebriform. The patient complained about
intense itching and discharge which had recently become malodorous.
Her birth and developmental history were normal. The family history was
negative for congenital nevi or melanoma and she was born of a
non-consanguineous marriage. The patient had normal intelligence without
any history of traumatic brain injury, dermatological disorder,
endocrine disorder, or cancer and there were no similar cases in her
family.
In physical examination, her developmental and nutritional status was
normal. The head circumference was in normal range and her neurologic,
cardiovascular, musculoskeletal and ophthalmic examinations didn’t show
any abnormalities.
On skin examination, there were multiple non-tender brown papules and
nodules on her back, abdomen and face (Figure 1-a). There was no
hypertrichosis or ulcer. The mass on the scalp sized 22 cm × 18 cm x 2.5
cm approximately with a nodular surface spread across the right side of
the scalp. There was focal ulceration and yellow discharge on the mass.
(Figure 1-b)
Laboratory examination showed normal blood, urine and stool routine with
normal liver and kidney functions. MRI, brain CT, and ultrasonography of
the abdomen did not reveal any abnormalities. Three biopsy specimens
were obtained from one of the nodules on the face and two different
sites of the mass on the scalp.
Histopathologic examination of the biopsy from the pigmented lesions
revealed junctional and dermal melanocytic nests. Nests of nevus cells
extend deeply in the dermis and around hair follicles. There were also
some melanophages in papillary dermis. Cellular atypia, necrosis and
atypical mitoses were not seen in these specimens. ( Figure 2-a,b,c)
Discussion
Melanocytic nevi are benign proliferation of melanocytes arranged in
nests. Melanocytic nevi are mostly present at birth although some may
develop within two years after birth. (6)
The prevalence of congenital pigmented lesions is estimated about 2.5%
but biopsy-confirmed melanocytic nevi are reported only in 1% of
infants. The prevalence of CMN ranges from 0.005 to 2.7% depending on
the size of the lesion in greatest diameter. (8)
CMN are caused by gain-of-function somatic mutations in either BRAF at
V600 or NRAS at Q6. These mutations affect the microtubule-associated
protein kinase (MAPK) signal trans-duction pathway, leading to abnormal
proliferation of embryonic melanoblasts. These abnormal melanoblasts
scatter to various parts of the body, leading to nevi. CMN are
predominantly caused by sporadic de novo mutations, although familial
cases have been reported. (2)
The clinical presentation varies depending on size, location and age.
Based on their size in greatest diameter, CMN are categorized into three
groups: small (<1.5 cm), medium (1.5–19.9 cm) and large or
giant (≥20 cm). The size of CMN is extremely important since it
increases the risk of malignancy transformation and is a decisive factor
in cosmetic and therapeutic approaches. (9)
GCMN are mostly characterized as brownish lesions with distinct borders
and hypertrichosis. In comparison to acquired melanocytic nevi, CMN have
a heterogeneous morphology and they’re larger in size. The clinical
presentation may vary in different stages of life. At birth they are
usually flat and as the child grows they become darker in color, thicker
and develope coarse hair. However in our case, the patient was born with
dark brown nodules and papules on the trunk and face, rather than flat
lesions and associated hypertichosis was absent. GCMN typically appear
on trunk (38 %) and extremities (38 %). Head and neck lesions are less
common (14 %). (9, 10)
In histologic examination, epidermal changes of CMN are similar to
acquired melanocytic nevi however they cab be distinguished by the
presence of nevus cells in the deep dermis and subcutaneous tissue;
arrangement of these cells among the collagen bundles of the lower
reticular dermis; the involvement of sebaceous glands, blood vessels,
erector muscles of hair follicles, eccrine glands and lymphatic vessels.
(6)
A major concern about CMN is malignant transformation to melanoma which
can develop within the nevus or elsewhere, especially the central
nervous system. Size, location, and type of histology are important
factors which help to assess the risk of developing melanoma in CMN. The
risk increases in larger lesions and for GCMN, the risk of developing
melanoma has been reported to be as high as 5-7% by the age of 60
years. The nevi located on the posterior scalp, neck, back, and buttock
are at more risk of developing melanoma than lesions on the face and
limbs. (4 ,11)
Malignant transformation occurs in the first decade of life in most of
the cases. In our case in histologic examination, there was no evidence
of cellular atypia, atypical mitoses or focal necrosis within these
three samples.
Another associated complication in congenital melanocytic nevi is
neurocutaneous melanosis (NCM) defined as melanocytic proliferation
within the leptomeninges and brain parenchyma and is divided into
symptomatic and asymptomatic. Symptomatic NCM frequently manifests in
the first 2–3 years of life with signs of raised intracranial pressure
due to hydrocephalus or mass effect and is accompanied by poor
prognosis. The risk of neurocutaneous melanosis is higher in large or
giant nevi with a greater number of satellite lesions and a posterior
axial location (involving the head, neck, back and buttocks) (12 ,13).
Since our patient was at risk for neurocutaneous melanosis and had not
been screened for it earlier, MRI imaging of head and spine was
requested for the patient that showed no abnormality. Her parents were
provided guidance for detecting signs and symptoms of NCM.
The patient was referred to the plastic surgery department for providing
tissue expander and serial excision.
Conclusion
Giant congenital melanocytic nevi are caused by benign proliferation of
melanocytes which are larger than 20 cm. They can be associated with
complications such as neurocutaneous melanoma and there is a risk of
malignancy which is higher in larger lesions. Thus, it is important to
monitor patients for such conditions and remove the nevi to reduce the
cosmetic burden.