Late-onset metastatic melanoma arising from a medium-sized congenital melanocytic naevus

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A 58-year-old Indian woman presented with a 6-month history of a rapidly growing nodule within a congenital melanocytic naevus present on her forehead and scalp. She first noticed the nodule a week after sustaining a blunt head injury in a road traffic accident. She was otherwise well, and her past medical and family history were non-contributory. On examination, there was a single cerebriform black-coloured plaque measuring 12 cm × 8 cm, with sparse overlying hair, extending from the left lateral supraorbital area to the ipsilateral fronto-temporal scalp, clinically consistent with a medium-sized congenital melanocytic naevus (CMN). There were no satellite naevi. A 6 cm × 4 cm tender, soft-to-firm, friable nodule with haemorrhagic crusting was noted over the naevus [Figures 1a and 1b]. Dermoscopic examination of the nodule could not be performed due to significant blood-tinged ooze obstructing the view field. There was no loco-regional lymphadenopathy or organomegaly. With the clinical differentials of a malignant transformation or a post-traumatic pyogenic granuloma overlying the CMN, a punch biopsy of the nodule was done. Histopathology from the nodule showed a dermal proliferation of atypical cuboidal cells arranged in sheets, and scattered melanin pigment, suggestive of malignant melanoma [Figures 2a and 2b]. Immunohistochemistry demonstrated diffuse cytoplasmic positivity for Human Melanoma Black-45 (HMB 45) and Melan-A [Figure 2c]. A contrast-enhanced computerised tomographic scan of the chest and abdomen showed multiple hypodense hypo-enhancing lesions in the liver, right upper lobe of lung, and left thyroid gland, suggestive of metastases. The patient was referred to medical oncology for further management, where she chose palliative management.

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Figure 1a:

Lateral view showing an ulcerated nodule over a congenital melanocytic naevus.

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Figure 1b:

Frontal view showing an ulcerated nodule over a congenital melanocytic naevus.

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Figure 2a:

Ulcerated epidermis and dermal proliferation of atypical cuboidal cells in a trabecular pattern and scattered melanin pigment (Haematoxylin & eosin, 40x).

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Figure 2b:

Higher magnification showing oval to polygonal cells with moderate amphophilic cytoplasm, vesicular chromatin, and prominent nucleoli. Melanin pigment in the background (Haematoxylin & eosin, 400x).

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Figure 2c:

Positive immunohistochemical staining with Human Melanoma Black-45 (HMB-45, 40x).

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Congenital melanocytic naevi are benign, neural crest-derived proliferations of melanocytes, classified into small (<1.5 cm), medium (1.5-19.9 cm), and large/giant (≥20 cm) categories based on projected adult size. Around 1% of newborns have a CMN, usually a single small or medium-sized naevus, while large and giant naevi are rare (about 1 in 20,000 births).¹ CMNs result from post-zygotic mutations in the RAF/MAPK signalling pathway, including NRAS, BRAF, MC1R, TP53, and GNAQ during embryonic development, leading to mosaicism. An additional mutation in the same pathways predisposes melanoma development over the CMN.¹

The reported incidence of melanoma in CMN is low, estimated to be around 1-2%.¹ The melanoma risk is stratified based on the projected adult size and location of the CMN. The risk increases with CMN size, with a recent systematic review reporting no melanoma in 29 patients with small CMN, four melanomas in 828 patients (0.48%) with medium-sized CMN, and 87 melanomas in 5923 patients (1.47%) with large/giant CMNs, translating to a risk ratio of 21.9 (95% CI 8.55-56.3) for large-giant size CMN in comparison to small-medium sized CMNs at 15 years of age.² The risk of CMN-associated melanoma was higher for truncal location (0.158%) as compared to head/neck (0.022%) and extremities (0.003%).²

Common histological varieties of melanoma include superficial spreading, nodular, lentigo malignant melanoma, and acral lentiginous melanoma. CMN-associated melanomas are usually superficial spreading melanomas, with initial growth starting at the dermo-epidermal junction. However, melanomas arising in giant CMNs can develop entirely in the dermis, fat, deeper tissues, or even extra-cutaneous sites.³

Our case presents a few points of interest. The patient did not have a high-risk CMN. It was a medium-sized CMN located on the head. Further, the melanoma developed in the sixth decade of life. Such a late onset of melanoma over giant CMN has been rarely reported in the literature.^4,5 Most melanomas are known to occur early in life, with the highest risk during infancy. However, the age at melanoma onset is later in small-to-medium-sized CMN versus large/giant-sized CMN (median 22 vs. 9.5 years).² Finally, our patient was a brown-skinned Indian. While the overall risk of melanoma in this population is known to be considerably low, information on the risk of CMN-associated melanoma is largely limited to isolated case reports in children with giant CMNs. A retrospective study of 39 patients (mean age of presentation 26 months) of Southeast Asian descent with large CMN reported no melanomas over an average follow-up period of 16.9 years.⁶ Our patient correlated the melanoma onset with trauma. While trauma has been sometimes linked with melanoma development, particularly acral melanoma (probably due to the trauma-prone site), a questionnaire-based study including 369 melanoma patients did not find strong evidence linking a single or persistent traumatic event to melanoma.⁷

Through this case, we wish to highlight that low-risk CMNs, such as medium-sized lesions in non-truncal locations, can also develop melanoma even late in life. This reinforces the need for lifelong clinical surveillance, regardless of perceived risk.