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Brief Report |

Proliferative Nodules vs Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood ONLINE FIRST

Béatrice Vergier, MD, PhD1,2; Elodie Laharanne, PhD1,2; Martina Prochazkova-Carlotti, PhD1,2; Arnaud de la Fouchardière, MD3; Jean-Philippe Merlio, MD, PhD1,2; Natacha Kadlub, MD4; Marie-Françoise Avril, MD5; Christine Bodemer, MD5,6; Caroline Lacoste, MD5,7; Franck Boralevi, MD, PhD8; Alain Taieb, MD, PhD8; Khaled Ezzedine, MD, PhD8; Sylvie Fraitag, MD5,7
[+] Author Affiliations
1Department of Pathology and Molecular Pathology, Hôpital Haut-Lévêque, Centre Hospitalier Universitaire Bordeaux, Pessac, France
2Institut National de la Santé et de la Récherche Médicale U1053-UMR, Bordeaux Research In Translational Oncology, Bordeaux University, Bordeaux, France
3Department of Pathology, Centre Léon Bérard, Lyon, France
4Unit of Maxillofacial and Plastic Surgery, Necker-Enfants Malades Hospital, Paris, France
5Department of Dermatology, Cochin Hospital, Assistance Publique-Hôpitaux de Paris, Paris-Descartes-Sorbonne University, Paris, France
6Department of Dermatology, Necker-Enfants Malades Hospital, Paris, France
7Department of Pathology, Necker-Enfants Malades Hospital, Paris, France
8Department of Dermatology, Centre Hospitalier Universitaire Bordeaux, Bordeaux University, Pessac, France
JAMA Dermatol. Published online August 03, 2016. doi:10.1001/jamadermatol.2016.2667
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Importance  The differential diagnosis between proliferative nodules (PNs) and melanoma arising in congenital melanocytic nevi (CMN) is crucial, as patients with PNs most often experience no increased risk of melanoma with metastases and death.

Objective  To analyze the utility of immunohistochemistry and fluorescence in situ hybridization (FISH) in distinguishing PNs from childhood and adult-onset melanoma arising in CMN.

Design, Setting, and Participants  A case series was conducted from June 29, 1989, to November 12, 2009, of 13 children with PNs arising in CMN in childhood and 5 children with melanomas arising in CMN in childhood. Five patients with giant CMN with no nodules were included as negative controls, and 6 patients with melanomas arising in CMN in adulthood were included as positive controls. Follow-up ranged from 3 to 21 years in all children (mean, 9.9 years) and from 3 months to 7 years in adults. Specimens were selected for immunohistochemistry and FISH. All histopathologic sections were reviewed by 2 dermatopathologists who examined all nodules arising at different ages in the same patient and, in the case of melanoma, all locations. Data analysis was performed from January 1, 2013, to January 31, 2015.

Main Outcomes and Measures  The ability to distinguish melanoma from PN using immunohistochemistry and/or FISH.

Results  Of the 13 patients (5 boys and 8 girls) with PNs present at birth, all PNs were stable (mean follow-up, 9 years). Eight patients with PNs and 4 of 5 patients with childhood-onset melanoma showed homogeneous staining for HMB45, while heterogeneous staining for HMB45 was seen in 3 of 6 patients with adult-onset melanoma. Expression of p16 was strongly positive in most patients with childhood-onset PNs (10 of 11 patients) and melanoma (all patients) but negative in 4 patients with adult-onset melanoma. Patients with PNs and the 5 patients with childhood-onset melanoma had numerical chromosomal aberrations never observed in the adjacent CMN. The 2 children with FISH-positive PNs are melanoma free after 7 and 4 years. Only 1 patient with childhood-onset melanoma had a FISH aberration compared with 4 patients with adult-onset melanoma.

Conclusions and Relevance  Immunohistochemistry and the 4-probe FISH melanoma analysis are not useful for distinguishing PN from childhood-onset melanoma as opposed to adult-onset melanoma. Numerical anomalies seen in PNs but not in the adjacent CMN could be the result of a chromosomal segregation malfunction resulting in the development of nodules.

Figures in this Article

Figures

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Figure 1.
Patients With Congenital Melanocytic Nevi

A, Patient with several proliferative nodules arising in giant congenital melanocytic nevi. B, Patient with melanoma appearing on congenital melanocytic nevi.

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Figure 2.
Histologic Findings of Proliferative Nodules

A, Superficial nodules (hematoxylin-eosin-safran, original magnification ×40). B, Deep nodules (original magnification ×40). C, Epithelioid cytologic findings (original magnification ×400). D, Nevoid cytologic findings (original magnification ×200).

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Figure 3.
Histologic Findings of Melanoma Arising in Giant Congenital Melanocytic Nevi During Childhood

A and B, Melanoma arising in giant congenital melanocytic nevi (hematoxylin-eosin-safran, original magnification ×400). C, Mostly lymphoblastoid cytologic findings (original magnification ×400). D, Epithelioid and hyperpigmented cytologic findings (original magnification ×400).

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