Close relationship between melanocytes and neural cells is accepted to reflect their common derivation from the neural crest and tumors combining both elements. We present a series of 10 patients with giant congenital melanocytic nevi (CMN) in which a secondary proliferation (11 lesions) with schwannian and/or perineuriomatous differentiation developed in the course of the disease. The age of the patients (4 male and 6 female) at the time of surgery and histological assessment varied from 3 months to 57 years. Histopathologically, the following subgroups were delineated: (1) nodular/tumoriform "neurotization" in CMN, (2) diffuse neurofibroma-like proliferation within CMN, (3) plexiform neurofibroma-like proliferation within CMN, and (4) diffuse perineuriomatous (hybrid schwannomatous-perineuriomatous) differentiation in CMN. We review the pertinent literature, including the role of recently identified Schwann cell precursors which are believed to represent the nerve-associated state of neural crest-like cells that persists into later developmental stages.

Department of Dermatology Charles University Medical Faculty Hospital Pilsen Czech Republic

Department of Dermatology Medical Military Academy Saint Petersburg Russia

Department of Pathology University Hospital Campus Bio Medico Rome Italy

Division of Pathology UPMC Children's Hospital of Pittsburgh University of Pittsburgh School of Medicine Pittsburgh; and

Dmitry Rogachev's National Medical Research Center of Pediatric Hematology Oncology and Immunology Moscow Russia

IDP Institut für Dermatohistopathologie Pathologie Institut Enge Zürich Switzerland

Russian Children's Clinical Hospital of Pirogov's Russian National Research Medical University of the Ministry of Healthcare Russian Federation Moscow Russia

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Ferreira I, Kind P, Van Den Berghe I, et al. Melanocytic naevi with perineurial differentiation: a distinctive variant of neurotised naevi and a diagnostic pitfall with desmoplastic melanoma. Histopathology. 2018;72:679–684.

Mennemeyer RP, Hallman KO, Hammar SP, et al. Melanotic schwannoma. Clinical and ultrastructural studies of three cases with evidence of intracellular melanin synthesis. Am J Surg Pathol. 1979;3:3–10.

Fetsch JF, Michal M, Miettinen M. Pigmented (melanotic) neurofibroma: a clinicopathologic and immunohistochemical analysis of 19 lesions from 17 patients. Am J Surg Pathol. 2000;24:331–343.

Trufant JW, Brenn T, Fletcher CDM, et al. Melanotic schwannoma arising in association with nevus of Ota: 2 cases suggesting a shared mechanism. Am J Dermatopathol. 2009;31:808–813.

Gray MH, Smoller BR, McNutt NS, et al. Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms. Am J Dermatopathol. 1990;12:234–241.

Kroumpouzos G, Cohen LM Intradermal melanocytic nevus with prominent Schwannian differentiation. Am J Dermatopathol. 2002;24:39–42.

Gerami P, Li G, Pouryazdanparast P, et al. A highly specific and discriminatory FISH assay for distinguishing between benign and malignant melanocytic neoplasms. Am J Surg Pathol. 2012;36:808–817.

Cramer SF. Epithelial membrane antigen staining of melanocytic nevi. Hum Pathol. 1990;21:121–122.

McCalmont TH, Emanuel B, Fung M, et al. Perineuriomatous melanocytic nevi. J Cutan Pathol. 2011;38:940–942.

Doherty SD, George S, Prieto VG, et al. Segmental neurofibromatosis in association with a large congenital nevus and malignant melanoma. Dermatol Online J. 2006;12:22.

Shejbal D, Bedekovic V, Cupic H. Giant congenital nevus with plexiform neurofibroma and malignant peripheral nerve sheath tumor. Fetal Pediatr Pathol. 2012;31:230–235.

Michal M, Kazakov DV, Hadravský L, et al. Multivacuolated mucin-filled cells: a unique cell characteristic of plexiform neurofibroma. A report of 11 cases. Hum Pathol. 2017;60:167–173.

Pizem J, Nicholson KM, Mraz J, et al. Melanocytic differentiation is present in a significant proportion of nonpigmented diffuse neurofibromas: a potential diagnostic pitfall. Am J Surg Pathol. 2013;37:1182–1191.

Ntala C, Biswas A Spectrum of melanocytic proliferation/differentiation in a large series of cutaneous neurofibromas: an under-recognized histopathologic phenomenon and potential clue for neurofibromatosis type 1. Am J Dermatopathol. 2020;42:165–172.

Ball NJ, Kho GT Melanocytic nevi are associated with neurofibromas in neurofibromatosis, type I, but not sporadic neurofibromas: a study of 226 cases. J Cutan Pathol. 2005;32:523–532.

Agaimy A, Michal M. Hybrid schwannoma-perineurioma of the gastrointestinal tract: a clinicopathologic study of 2 cases and reappraisal of perineurial cells in gastrointestinal schwannomas. Appl Immunohistochem Mol Morphol. 2011;19:454–459.

Emanuel P, Pertsemlidis DS, Gordon R, et al. Benign hybrid perineurioma-schwannoma in the colon. A case report. Ann Diagn Pathol. 2006;10:367–370.

Kuroda N, Kazakov DV, Hes O, et al. Hybrid peripheral nerve sheath tumor of the nasal cavity showing schwannomatous, neurofibromatous, and perineuriomatous areas. Med Mol Morphol. 2010;43:82–85.

Zamecnik M, Michal M. Perineurial cell differentiation in neurofibromas. Report of eight cases including a case with composite perineurioma-neurofibroma features. Pathol Res Pract. 2001;197:537–544.

Feany MB, Anthony DC, Fletcher CD. Nerve sheath tumours with hybrid features of neurofibroma and schwannoma: a conceptual challenge. Histopathology. 1998;32:405–410.

Hornick JL, Bundock EA, Fletcher CD. Hybrid schwannoma/perineurioma: clinicopathologic analysis of 42 distinctive benign nerve sheath tumors. Am J Surg Pathol. 2009;33:1554–1561.

Kazakov DV, Pitha J, Sima R, et al. Hybrid peripheral nerve sheath tumors: schwannoma-perineurioma and neurofibroma-perineurioma. A report of three cases in extradigital locations. Ann Diagn Pathol. 2005;9:16–23.

Ohata C, Imai N, Hinogami H, et al. Hybrid schwannoma/perineurioma: a report of two cases including a possible radiation-induced case. J Cutan Pathol. 2012;39:56–62.

Shelekhova KV, Danilova AB, Michal M, et al. Hybrid neurofibroma-perineurioma: an additional example of an extradigital tumor. Ann Diagn Pathol. 2008;12:233–234.

Zamecnik M. Hybrid neurofibroma/schwannoma versus schwannoma with Antoni B areas. Histopathology. 2000;36:473–474.

Michal M, Kazakov DV, Belousova I, et al. A benign neoplasm with histopathological features of both schwannoma and retiform perineurioma (benign schwannoma-perineurioma): a report of six cases of a distinctive soft tissue tumor with a predilection for the fingers. Virchows Arch. 2004;445:347–353.

Harder A, Wesemann M, Hagel C, et al. Hybrid neurofibroma/schwannoma is overrepresented among schwannomatosis and neurofibromatosis patients. Am J Surg Pathol. 2012;36:702–709.

Michal M, Kazakov DV, Michal M. Hybrid peripheral nerve sheath tumors: a review. Cesk Patol. 2017;53:81–88.

Kacerovska D, Michal M, Kuroda N, et al. Hybrid peripheral nerve sheath tumors, including a malignant variant in type 1 neurofibromatosis. Am J Dermatopathol. 2013;35:641–649.

Macarenco AC, Macarenco RS. Intradermal monophasic hybrid schwannoma-perineurioma: a diagnostic challenge. Am J Dermatopathol. 2010;32:526–528.

Wang L, Wang G, Gao T. Congenital melanocytic nevus with features of hybrid schwannoma/perineurioma. J Cutan Pathol. 2013;40:497–502.

Furlan A, Adameyko I. Schwann cell precursor: a neural crest cell in disguise? Dev Biol. 2018;444(suppl 1):S25–S35.

Joseph NM, Mukouyama YS, Mosher JT, et al. Neural crest stem cells undergo multilineage differentiation in developing peripheral nerves to generate endoneurial fibroblasts in addition to Schwann cells. Development. 2004;131:5599–5612.

Adameyko I, Lallemend F, Aquino JB, et al. Schwann cell precursors from nerve innervation are a cellular origin of melanocytes in skin. Cell. 2009;139:366–379.

Nitzan E, Pfaltzgraff ER, Labosky PA, et al. Neural crest and Schwann cell progenitor-derived melanocytes are two spatially segregated populations similarly regulated by Foxd3. Proc Natl Acad Sci U S A. 2013;110:12709–12714.

Dyachuk V, Furlan A, Shahidi MK, et al. Neurodevelopment. Parasympathetic neurons originate from nerve-associated peripheral glial progenitors. Science. 2014;345:82–87.

Kaukua N, Shahidi MK, Konstantinidou C, et al. Glial origin of mesenchymal stem cells in a tooth model system. Nature. 2014;513:551–554.

Uesaka T, Nagashimada M, Enomoto H. Neuronal differentiation in Schwann cell lineage underlies postnatal neurogenesis in the enteric nervous system. J Neurosci. 2015;35:9879–9888.

Espinosa-Medina I, Outin E, Picard CA, et al. Neurodevelopment. Parasympathetic ganglia derive from Schwann cell precursors. Science. 2014;345:87–90.

Furlan A, Dyachuk V, Kastriti ME, et al. Multipotent peripheral glial cells generate neuroendocrine cells of the adrenal medulla. Science. 2017;357:eaal3753.

Kastriti ME, Adameyko I. Specification, plasticity and evolutionary origin of peripheral glial cells. Curr Opin Neurobiol. 2017;47:196–202.