Melanocytic Neoplasm With KIT and APC Mutations: A New Subtype of Melanocytoma?
Journal
The American Journal of dermatopathology
ISSN: 1533-0311
Titre abrégé: Am J Dermatopathol
Pays: United States
ID NLM: 7911005
Informations de publication
Date de publication:
14 Nov 2023
14 Nov 2023
Historique:
medline:
20
11
2023
pubmed:
20
11
2023
entrez:
20
11
2023
Statut:
aheadofprint
Résumé
We report a very unusual case of melanocytic neoplasm appearing clinically as a 0.5-cm dome-shaped pigmented papule on the chest of a 63-year-old man. Microscopically, it was an asymmetric, entirely dermally based neoplasm characterized by a multinodular, vaguely plexiform architecture composed of moderately pleomorphic spindled melanocytes with ample, dusty pigmented cytoplasm and scattered multinucleated cells. The tumor cells were strongly positive for Melan-A, HMB45, S100, and PRAME, whereas p16 showed diffuse nuclear loss. β-catenin presented a strong and diffuse cytoplasmic staining, while nuclei were negative. Despite an increased cellularity, mitotic count was low (1/mm2). Fluorescence in situ hybridization revealed no copy number alteration in melanoma-related genes (CDKN2A, MYB, MYC, CCND1 and RREB1). DNA and RNA sequencing identified KIT c.2458G>T and APC c.6709C>T mutations. No further genetic alteration was detected including TERT-promoter (TERT-p) hot-spot mutation. A re-excision was performed. A sentinel lymph node biopsy was negative. Clinical investigations revealed no extracutaneous involvement. The patient is disease-free after a follow-up period of 8 months. Given the peculiar morphologic and molecular findings, we hypothesize the lesion may represent a novel subtype of an intermediate grade melanocytic tumor (melanocytoma).
Identifiants
pubmed: 37982490
doi: 10.1097/DAD.0000000000002556
pii: 00000372-990000000-00264
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest.
Références
Cerroni L, Barnhill R, Elder D, et al. Melanocytic tumors of uncertain malignant potential: results of a tutorial held at the XXIX Symposium of the International Society of Dermatopathology in Graz, October 2008. Am J Surg Pathol. 2010;34:314–326.
Gerami P, Jewell SS, Morrison LE, et al. Fluorescence in situ hybridization (FISH) as an ancillary diagnostic tool in the diagnosis of melanoma. Am J Surg Pathol. 2009;33:1146–1156.
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.
Ebbelaar CF, Jansen AML, Bloem LT, et al. Genome-wide copy number variations as molecular diagnostic tool for cutaneous intermediate melanocytic lesions: a systematic review and individual patient data meta-analysis. Virchows Arch. 2021;479:773–783.
Wiesner T, Murali R, Fried I, et al. A distinct subset of atypical Spitz tumors is characterized by BRAF mutation and loss of BAP1 expression. Am J Surg Pathol. 2012;36:818–830.
Yeh I, Lang UE, Durieux E, et al. Combined activation of MAP kinase pathway and β-catenin signaling cause deep penetrating nevi. Nat Commun. 2017;8:644.
Zembowicz A, Knoepp SM, Bei T, et al. Loss of expression of protein kinase a regulatory subunit 1alpha in pigmented epithelioid melanocytoma but not in melanoma or other melanocytic lesions. Am J Surg Pathol. 2007;31:1764–1775.
Wiesner T, He J, Yelensky R, et al. Kinase fusions are frequent in Spitz tumours and spitzoid melanomas. Nat Commun. 2014;5:3116.
Lee S, Barnhill RL, Dummer R, et al. TERT promoter mutations are predictive of aggressive clinical behavior in patients with spitzoid melanocytic neoplasms. Sci Rep. 2015;5:11200.
Cohen JN, Yeh I, Mully TW, et al. Genomic and clinicopathologic characteristics of PRKAR1A-inactivated melanomas: toward genetic distinctions of animal-type melanoma/pigment synthesizing melanoma. Am J Surg Pathol. 2020;44:805–816.
Isales MC, Khan AU, Zhang B, et al. Molecular analysis of atypical deep penetrating nevus progressing to melanoma. J Cutan Pathol. 2020;47:1150–1154.
Donati M, Šteiner P, Kazakov DV. BAP1-Inactivated melanoma arising from BAP1-inactivated melanocytic tumor in a patient with BAP1 germline mutation: a case report and review of the literature. Am J Dermatopathol. 2023;45:117–122.
Cellier L, Perron E, Pissaloux D, et al. Cutaneous melanocytoma with CRTC1-TRIM11 fusion: report of 5 cases resembling clear cell sarcoma. Am J Surg Pathol. 2018;42:382–391.
Macagno N, Pissaloux D, Etchevers H, et al. Cutaneous melanocytic tumors with concomitant NRASQ61R and IDH1R132C mutations: a report of 6 cases. Am J Surg Pathol. 2020;44:1398–1405.
Goto K, Pissaloux D, Fraitag S, et al. RASGRF1-rearranged cutaneous melanocytic neoplasms with spitzoid cytomorphology: a clinicopathologic and genetic study of 3 cases. Am J Surg Pathol. 2022;46:655–663.
Yeh I. New and evolving concepts of melanocytic nevi and melanocytomas. Mod Pathol. 2020;33(suppl 1):1–14.
Gerami P, Cooper C, Bajaj S, et al. Outcomes of atypical spitz tumors with chromosomal copy number aberrations and conventional melanomas in children. Am J Surg Pathol. 2013;37:1387–1394.
Seab JA Jr., Graham JH, Helwig EB. Deep penetrating nevus. Am J Surg Pathol. 1989;13:39–44.
Strazzula L, Senna MM, Yasuda M, et al. The deep penetrating nevus. J Am Acad Dermatol. 2014;71:1234–1240.
de la Fouchardière A, Caillot C, Jacquemus J, et al. β-Catenin nuclear expression discriminates deep penetrating nevi from other cutaneous melanocytic tumors. Virchows Arch. 2019;474:539–550.
Manca A, Sini MC, Cesinaro AM, et al. NGS-based analysis of atypical deep penetrating nevi. Cancers (Basel). 2021;13:3066.
Yasuda T, Kurosaki T. Regulation of lymphocyte fate by Ras/ERK signals. Cell Cycle. 2008;7:3634–3640.
Curtin JA, Busam K, Pinkel D, et al. Somatic activation of KIT in distinct subtypes of melanoma. J Clin Oncol. 2006;24:4340–4346.