Neurocutaneous melanocytosis, with a Giant Congenital Melanocytic Nevus (GCMN) with neurotization, and a deep proliferative nodule.
GCMN, also known as large congenital nevi, bathing trunk nevus, garment nevus, giant hairy nevus, giant pigmented nevus, and nevus pigmentosus are rare, occurring in an estimated 0.002% of births . They are nevi which are present at birth and are characterized by large, often garment-like distributions of deeply pigmented skin often with additional so-called "satellite" lesions. They occur equally in males and females, most patients present with nevi on their trunk and the majority of patients have greater than ten smaller associated (satellite) nevi . Several classification systems are used including the most common being lesions larger than 20 cm in diameter. The alternate systems use lesions larger than 100 cm2 in area or covering more than 2% of total body surface area . GCMN often show mild variation in color and the surface may be macular, papular, mamillated, hyperkeratotic, rugose, and/or nodular. The nevus may be hypertrichotic  and frequently the pigmentation evolves as the child ages. Unfortunately, these lesions are at increased risk for developing melanoma and according to a review of the NYU-Large Congenital Melanocytic Nevus registry, the life-time risk is 2-3%. In addition, this group demonstrated an increased risk of melanoma and neurocutaneous melanoma in patients who develop multiple satellite nevi .
Histologically, these nevi present with deeper involvement of the skin with nests not only at the epidermal-dermal junction, but often within deeper tissues, including the reticular dermis, subcutaneous fat, muscle fascia, and around vessels and nerves and appendage involvement . They are characterized by a proliferation of nevomelanocytes and often lentiginous melanocytic hyperplasia. The nevus cells often have a close association with adnexal structures, penetrating them and frequently splay the dermal collagen bundles. There are frequently "neurotized" structures referred to as "Mason bodies" or Wagner-Meissner-like corpuscles. The epidermis overlying the lesions may be thinned with loss of rete ridges. There are three common patterns in GCMN: compound or intradermal nevus, neural nevus, or a blue nevus. The mitotic rate is typically low within the nevomelanocytes, but can be higher in proliferative nodules (vide infra). There is minimal to no atypia. Immunohistochemical stains usually highlight the nevomelanocytes with S100, HMB-45 (predominantly on the superficial portions of the nevus), and Melan-A. GCMN may also demonstrated heterologous elements including bone, adipose tissue, cartilage, hemangioma, lymphangioma, and schwannoma .
At the molecular level, melanocytic lesions have demonstrated errors related to the RAS/MAPK pathway. Specifically frequently feature activating mutations in NRAS (70%), but less frequently BRAF mutations at the same hotspots as in melanoma (15%) . A recent evaluation of congenital melanocytic lesion in the Chinese population demonstrated a lack of BRAFV600E mutations within 18 GCMN and 3 cases with a NRAS mutation .
A proliferative nodule demonstrates an area of higher cell density and nuclear enlargement with a higher mitotic activity. Proliferative nodules are benign areas of abundant nevomelanocytes. They may have atypical features but generally have a sharp demarcation from the surrounding nevus, no transition between surrounding nevus cells and nodular cells (lack of so-called "maturation") and increased mitotic activity . Cell density, cell size, nuclear aspect and transition with the surrounding nevus vary between the cases. In most cases, mitoses are absent or minimal in number .
Neurocutaneous melanocytosis (NCM) demonstrates deposition of melanocytes in the nervous system. Occasionally, melanocytes may be identified within the cerebral spinal fluid. Radiologically there may be a diffuse or nodular increase in T1 signal on MRI in the affected neural tissue. It is thought to arise due to a development defect in the migration of melanocytes from the neural crest through the leptomeninges to the skin . Dissemination to the peritoneal surface by ventriculo-peritoneal shunting has been exceptionally observed . Factors associated with the development of neurocutaneous melanoma include posterior midline location and multiple satellite lesions .
This case presents the full spectrum of Touraine syndrome, the eponym designation of NCM, featuring a GCMN, CNS involvement and a proliferative nodule. It is thought that cases like this one represent a more severe form of neural crest dysplasia leading to a large number of melanocytic abnormalities covering extensive bodily areas. 
Contributed by Matthew Smith, MD and Miguel Reyes-Mugica, MD