Melanocytic nevus pathophysiology
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Editors-In-Chief: Martin I. Newman, M.D., FACS, Cleveland Clinic Florida, [1];Associate Editor(s)-in-Chief: Qurrat-ul-ain Abid, M.D.[2] Michel C. Samson, M.D., FRCSC, FACS [3]
Overview
Melanocytic nevus is a benign growth on the skin (usually tan, brown, or flesh-colored) that contains a cluster of melanocytes and surrounding supportive tissue.
Pathophysiology
Congenital melanocytic nevi (CMN)
- When melanocytic nevi are present at birth or within the first few months of life they are known as Congenital melanocytic nevi (CMN).
- Congenital melanocytic nevi (CMN) are hamartomas lesions.
- Small melanocytic nevi that appear during early childhood between three months and two years of age, resemble true CMN clinicaly and histologicaly and are known as "tardive CMN," "early-onset nevi," and "congenital nevus-like nevi.[1]
- During embryogenesis clonal proliferations of benign melanocytes may give rise to melanocytic nevi.[2][3]
- BRAF V600E mutations have a very high corelation with small congenital melanocytic nevi (CMN), acquired melanocytic nevi and cutaneous melanomas.[4][5]
- While giant congenital melanocytic nevi (CMN) have somatic gain-of-function mutations in NRAS.[6][7]
- Compared to acquired melanocytic nevi, CMN penetrate into deeper layers of dermis.[8]
- Melanocytes in CMN follow pathyway of nerves and vessels and grow along adenxal structures (eg, hair follicles, sebaceous glands, eccrine ducts) and settle between collagen bundles in a single arrangement.[9][10]
Dermoscopic features of Congenital melanocytic nevi (CMN)
- CMN and acquired melanocytic nevi appear as pigment network, aggregated globules, or diffuse homogeneous brown pigmentation on dermoscopy.[11]
- Dermoscopic patterns that are commonly seen in CMN are:[12]
- Reticular
- Globular/cobblestoning
- Homogenous
- Or a mixture of these (ie, multicomponent)
- CMN may exhibit exaggerated attributes on dermoscopy compared to acquired melanocytic nevi, they may show:[13][14][14]
- Perifollicular hypopigmentation
- Marked follicular structures
- Skin hyperpigmentation
- Hypertrichosis
- Pigment changes surrounding follicles such as hypopigmentation
Gross Pathology
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Proliferative nodules Melanocytic nevus
- Benign melanocytic proliferations may occasionally appear within large or giant CMN.[15]
- They may be congenital or develop in infancy or childhood.
- They may grow rapidly with clinical characteristics of firmness or ulceration, in that case, a biopsy should be performed to eliminate melanoma.
- Large, atypical melanocytes and mitoses may be present on microscopy that make it difficult to differentiate from Melanoma.
- In case of difficulty in differentiating benign melanocytic proliferation from Melanoma on microscopy, an evaluation of an experienced doctor may be helpful. Other modalities of evaluation are comparative genomic hybridization or mass spectroscopy imaging proteomic analysis.[15] [16]
References
- ↑ Makkar HS, Frieden IJ (August 2002). "Congenital melanocytic nevi: an update for the pediatrician". Curr. Opin. Pediatr. 14 (4): 397–403. PMID 12130901.
- ↑ Tannous ZS, Mihm MC, Sober AJ, Duncan LM (February 2005). "Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management". J. Am. Acad. Dermatol. 52 (2): 197–203. doi:10.1016/j.jaad.2004.07.020. PMID 15692463.
- ↑ Price HN, Schaffer JV (2010). "Congenital melanocytic nevi-when to worry and how to treat: Facts and controversies". Clin. Dermatol. 28 (3): 293–302. doi:10.1016/j.clindermatol.2010.04.004. PMID 20541682.
- ↑ Ichii-Nakato N, Takata M, Takayanagi S, Takashima S, Lin J, Murata H, Fujimoto A, Hatta N, Saida T (September 2006). "High frequency of BRAFV600E mutation in acquired nevi and small congenital nevi, but low frequency of mutation in medium-sized congenital nevi". J. Invest. Dermatol. 126 (9): 2111–8. doi:10.1038/sj.jid.5700366. PMID 16691193.
- ↑ Wu J, Rosenbaum E, Begum S, Westra WH (December 2007). "Distribution of BRAF T1799A(V600E) mutations across various types of benign nevi: implications for melanocytic tumorigenesis". Am J Dermatopathol. 29 (6): 534–7. doi:10.1097/DAD.0b013e3181584950. PMID 18032947.
- ↑ Dessars B, De Raeve LE, Morandini R, Lefort A, El Housni H, Ghanem GE, Van den Eynde BJ, Ma W, Roseeuw D, Vassart G, Libert F, Heimann P (January 2009). "Genotypic and gene expression studies in congenital melanocytic nevi: insight into initial steps of melanotumorigenesis". J. Invest. Dermatol. 129 (1): 139–47. doi:10.1038/jid.2008.203. PMID 18633438.
- ↑ Charbel C, Fontaine RH, Malouf GG, Picard A, Kadlub N, El-Murr N, How-Kit A, Su X, Coulomb-L'Hermine A, Tost J, Mourah S, Aractingi S, Guégan S (April 2014). "NRAS mutation is the sole recurrent somatic mutation in large congenital melanocytic nevi". J. Invest. Dermatol. 134 (4): 1067–1074. doi:10.1038/jid.2013.429. PMID 24129063.
- ↑ Mark GJ, Mihm MC, Liteplo MG, Reed RJ, Clark WH (September 1973). "Congenital melanocytic nevi of the small and garment type. Clinical, histologic, and ultrastructural studies". Hum. Pathol. 4 (3): 395–418. PMID 4756859.
- ↑ "Precursors to malignant melanoma. National Institutes of Health Consensus Development Conference Statement, Oct. 24-26, 1983". J. Am. Acad. Dermatol. 10 (4): 683–8. April 1984. PMID 6715623.
- ↑ Kokta V, Hung T, Al Dhaybi R, Lugassy C, Barnhill RL (April 2013). "High prevalence of angiotropism in congenital melanocytic nevi: an analysis of 53 cases". Am J Dermatopathol. 35 (2): 180–3. doi:10.1097/DAD.0b013e318260908c. PMID 22771898.
- ↑ Haliasos EC, Kerner M, Jaimes N, Zalaudek I, Malvehy J, Hofmann-Wellenhof R, Braun RP, Marghoob AA (2013). "Dermoscopy for the pediatric dermatologist part III: dermoscopy of melanocytic lesions". Pediatr Dermatol. 30 (3): 281–93. doi:10.1111/pde.12041. PMID 23252411.
- ↑ Changchien L, Dusza SW, Agero AL, Korzenko AJ, Braun RP, Sachs D, Usman MH, Halpern AC, Marghoob AA (August 2007). "Age- and site-specific variation in the dermoscopic patterns of congenital melanocytic nevi: an aid to accurate classification and assessment of melanocytic nevi". Arch Dermatol. 143 (8): 1007–14. doi:10.1001/archderm.143.8.1007. PMID 17709659.
- ↑ Seidenari S, Pellacani G, Martella A, Giusti F, Argenziano G, Buccini P, Carli P, Catricalà C, De Giorgi V, Ferrari A, Ingordo V, Manganoni AM, Peris K, Piccolo D, Pizzichetta MA (July 2006). "Instrument-, age- and site-dependent variations of dermoscopic patterns of congenital melanocytic naevi: a multicentre study". Br. J. Dermatol. 155 (1): 56–61. doi:10.1111/j.1365-2133.2006.07182.x. PMID 16792752.
- ↑ 14.0 14.1 Ingordo V, Iannazzone SS, Cusano F, Naldi L (2006). "Dermoscopic features of congenital melanocytic nevus and Becker nevus in an adult male population: an analysis with a 10-fold magnification". Dermatology (Basel). 212 (4): 354–60. doi:10.1159/000092286. PMID 16707885.
- ↑ 15.0 15.1 Phadke PA, Rakheja D, Le LP, Selim MA, Kapur P, Davis A, Mihm MC, Hoang MP (May 2011). "Proliferative nodules arising within congenital melanocytic nevi: a histologic, immunohistochemical, and molecular analyses of 43 cases". Am. J. Surg. Pathol. 35 (5): 656–69. doi:10.1097/PAS.0b013e31821375ea. PMID 21436676.
- ↑ Lazova R, Yang Z, El Habr C, Lim Y, Choate KA, Seeley EH, Caprioli RM, Yangqun L (September 2017). "Mass Spectrometry Imaging Can Distinguish on a Proteomic Level Between Proliferative Nodules Within a Benign Congenital Nevus and Malignant Melanoma". Am J Dermatopathol. 39 (9): 689–695. doi:10.1097/DAD.0000000000000849. PMC 5647999. PMID 28248717.