Giant melanocytic nevi with neurocutaneous melanosis masquerading as neurofibromas.

Neurocutaneous melanosis is congenital melanocytic nevus with neurological manifestations. We report a 4-year-old female child presenting with hyperpigmented and nodular skin lesion associated with developmental delay and convulsions. The child had multiple brownish-black nevi on the face and chest and giant melanocytic nevi on thoraco-abdomen, back, and gluteal region. Computed tomography scan of the brain showed calcification in the pons, right cerebellar hemisphere, and left medial temporal lobe. Skin biopsy done from nodular hyperpigmented site was suggestive of melanocytic nevi. Electroencephalogram showed multifocal epileptiform discharges.

Introduction

Congenital melanocytic nevi (CMNs) are proliferation of melanocytic cells that can be present at birth or may develop after a few weeks of life.[1] Giant congenital melanocytic nevus (GCMN) can increase up to 20 cm in adult life.[1] CMN associated with neurological manifestation is defined as neuromelanosis.[2] Neurocutaneous melanosis (NCM) is seen in 2–45% of patients with GCMNs. We report an unusual case where GCMN was associated with neuromelanosis and neurofibroma-like lesions.

Case Report

A 4-year-old child born of nonconsanguineous marriage presented with nodular skin lesions all over the body including palms, soles, and scalp since 6 months of age. There was a history of multiple episodes of convulsion since the age of 1 year. The child had global developmental delay. On examination, weight, height, and head circumference were appropriate for age. Multiple brownish-black nevi were seen on the face and chest [Figure 1a] and giant melanocytic nevi on the thoraco-abdomen [Figure 1b], back, and gluteal region [Figure 1c] including palms and soles. Hypertrophy of genital region is present [Figure 1b].

Figure 1

(a) Multiple brownish-black nevi present on the face, chest. (b) Giant melanocytic nevi present on the thoracoabdominal region extending to thighs along with multiple satellite nevi. Hypertrophy of genital region is present. (c) Giant melanocytic nevi with nodularity on the back and gluteal region

Routine investigation, complete blood counts, and renal and liver function tests were within normal limit. Multifocal interictal epileptiform discharges were noted in electroencephalogram. Computed tomography of the brain shows calcification in the pons and right cerebellar hemisphere [Figure 1a] and in the left medial temporal lobe and right cerebellar hemisphere [Figure 2a and b]. Magnetic resonance imaging (MRI) of the brain shows extensive folds in the scalp of both parietal regions with nodular enhancing lesion in the scalp of left frontal region [Figure 3a and b]. Gradient-echo images of the MRI show punctuate areas of blooming in the pons and left medial temporal lobe [Figure 4a and b]. Skin biopsy done from nodular hyperpigmented site was suggestive of melanocytic nevi. Hence, final diagnosis of GCMN with NCM was made.

Figure 2

(a) Axial noncontrast computed tomography image demonstrating calcifications in the pons and right cerebellar hemisphere. (b) Axial noncontrast computed tomography image demonstrating calcifications in the right cerebellar hemisphere and left medial temporal lobe

Figure 3

(a and b) Axial pre- and post-contrast T1-weighted images demonstrating extensive folds in the scalp of both parietal regions with a nodular enhancing lesion in the scalp of left frontal region

Figure 4

(a and b) Axial gradient-echo images showing punctuate areas of blooming in the pons and left medial temporal lobe

Discussion

GCMN is defined by size >20 cm diameter or as a lesion that occupies a region considered major such as the face, or one that cannot be excised without resulting in significant deformity.[3] It presents at birth in 1 in 500,000 newborns with a female predominance. The mode of inheritance is probably multifactorial. No family history was noted in our case. Eighty-two percent of the GCMNs occur in an axial distribution (trunk, head, and/or neck).[3] In our case, predominant axial distribution is noted. GCMN usually presents as a brown lesion, with flat or mammilated surface, well-demarcated borders, and hypertrichosis. CMN is primarily a clinical diagnosis. Congenital nevi are histologically distinguished from acquired nevi mainly by their larger size, the spread of the nevus cells to the deep layers of the skin, and their more varied architecture and morphology.[1]

NCM is characterized by the presence of benign or malignant melanocytic proliferations in the central nervous system (CNS) associated with the occurrence of congenital melanocytic lesions.[1] Melanocytic cells are found in large number in the leptomeninges of the brain and spinal cord.[1] NCM is thought to be a result of an error occurring during morphogenesis in the neuroectoderm; however, its exact pathogenesis is unclear.[1] The exact pathogenesis of NCM is not entirely clear although there are several schools of thoughts that contribute to the development of NCM. One factor that may contribute to the development of NCM is the abnormal postzygotic development of melanoblasts. This mutation would possibly occur within the neural crest of the ectoderm. After the mutation occurs, these cells would then migrate to the meninges as the precursors to the malignant or benign melanocytes. This mutation may be due to abnormal expression of hepatocyte growth factor/scatter factor by the mesenchymal cells within the neural crest. Another proposed cause of NCM is mutation of the NRAS gene at codon 61. This mutation has been detected in patients with CMNs, as well as those with melanocytic tumors of the CNS. The mutation would also likely occur within the neural crest.

NCM is currently diagnosed according to the following criteria put forth by Kadonaga and Frieden in 1991: (1) Large and/or multiple congenital melanocytic lesion in association with meningeal melanosis or melanoma, (2) no evidence of cutaneous melanoma, except in patients with histologically benign meningeal lesions, or (3) no evidence of meningeal melanoma, except in patients with histologically benign cutaneous lesions.[4] GCMN can occur in 5% of von Recklinghausen's neurofibromatosis Type I.[5] In our child, neurofibromatosis was ruled out as diagnostic criteria were not met. Based on classical skin lesion with developmental delay and convulsions, we made diagnosis of NCM. Clinical and histopathological similarity between the GCMN and neurofibromas is likely to result from the fact that both melanocytes and Schwann cell originate from the neural crest.[6] Various CNS malformations described with NCM are arachnoid cysts, choroid plexus papilloma, cerebellar astrocytoma, spinal dysraphism, Type I, and Arnold–Chiari. Approximately 10% of patients with NCM can present with Dandy–Walker syndrome and associated Dandy–Walker malformation.[1] Previously multiple intracranial calcifications have not been described in the literature.

In our case, unusual presentation is giant congenital hypermelanotic nevi with neurocutaneous hypermelanosis, neurofibromatosis-like lesion, and intracranial calcifications.

Conclusion

NCM should be considered if any child with CMN with neurological abnormalities. Clinicians should aware that not all lesions resembling neurofibromas occurring on GCMN are real neurofibromas.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.