Vulvar Pigmented Epithelioid Melanocytoma With a Novel HTT-PKN1 Fusion: A Case Report.
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:
Jul 2020
Jul 2020
Historique:
pubmed:
24
1
2020
medline:
17
4
2021
entrez:
24
1
2020
Statut:
ppublish
Résumé
Pigmented epithelioid melanocytoma is a highly pigmented, predominantly dermal melanocytic neoplasm composed by epithelioid and spindled melanocytes. It is characterized by a limited number of specific genomic alterations principally involving protein kinase A regulatory subunit alpha (PRKAR1A) and fusion of protein kinase C alpha isoform (PRKCA). However, in some of these neoplasms, no genetic aberrations have been detected. We performed genomic analysis of a nodular heavily pigmented intradermal proliferation composed of monomorphic epithelioid melanocytes with slight cytologic atypia consisting with pigmented epithelioid melanocytoma occurring on the vulva of a 24-year-old woman. A novel fusion transcript HTT-PKN1 and an ATM (Val410Ala) missense mutation were found. No other mutations including TERT-promoter hotspot mutation analysis were detected. The data expand the spectrum of molecular alterations in pigmented epithelioid melanocytoma.
Identifiants
pubmed: 31972666
doi: 10.1097/DAD.0000000000001600
pii: 00000372-202007000-00014
doi:
Substances chimiques
HTT protein, human
0
Huntingtin Protein
0
protein kinase N
EC 2.7.1.-
ATM protein, human
EC 2.7.11.1
Ataxia Telangiectasia Mutated Proteins
EC 2.7.11.1
Protein Kinase C
EC 2.7.11.13
Types de publication
Case Reports
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
544-546Références
Zembowicz A, Carney JA, Mihm CMJ, et al. Pigmented epithelioid melanocytoma, a low-grade melanoma indistinguishable from animal type melanoma and epithelioid blue nevus. Am J Surg Pathol. 2004;28:31–40.
Levene A. Disseminated dermal melanocytosis terminating in melanoma: a human condition resembling equine melanotic disease. Br J Dermatol. 1979;101:197–205.
Kazakov DV, Rütten A, Kempf W, et al. Melanoma with prominent pigment synthesis (animal-type melanoma): a case report with ultrastructural studies. Am J Dermatopathol. 2004;26:290–297.
Crowson AN, Magro CM, Mihm MC Jr. Malignant melanoma with prominent pigment synthesis: “animal type” melanoma—a clinical and histological study of six cases with a consideration of other melanocytic neoplasms with prominent pigment synthesis. Hum Pathol. 1999;30:543–550.
Carney JA, Ferreiro JA. The epithelioid blue nevus: a multicentric familial tumor with important associations, including cardiac myxoma and psammomatous melanotic schwannoma. Am J Surg Pathol. 1996;20:259–272.
Carney JA, Gordon H, Carpenter PC, et al. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine. 1985;64:270–283.
Mandal RV, Murali R, Lundquist KF, et al. Pigmented epithelioid melanocytoma: favorable outcome after 5-year follow-up. Am J Surg Pathol. 2009;33:1778–1782.
Bax MJ, Brown MD, Rothberg PG, et al. Pigmented epithelioid melanocytoma (animal-type melanoma): an institutional experience. J Am Acad Dermatol. 2017;77:328–332.
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.
Bahrami A, Lee S, Wu G, et al. Pigment-synthesizing melanocytic neoplasm with protein kinase C alpha (PRKCA) fusion. JAMA Dermatol. 2016;152:318–322.
Isales MC, Mohan LS, Quan VL, et al. Distinct genomic patterns in pigmented epithelioid melanocytoma: a molecular and histologic analysis of 16 cases. Am J Surg Pathol. 2019;43:480–488.
Cohen JN, Joseph NM, North JP, et al. Genomic analysis of pigmented epithelioid melanocytomas reveals recurrent alterations in PRKAR1A, and PRKCA genes. Am J Surg Pathol. 2017;41:1333–1346.
Mukai H. The structure and function of PKN, a protein kinase having a catalytic domain homologous to that of PKC. J Biochem. 2003;133:17–27.
Yasui T, Sakakibara-Yada K, Nishimura T, et al. Protein kinase N1, a cell inhibitor of Akt kinase, has a central role in quality control of germinal center formation. Proc Natl Acad Sci USA. 2012;109:21022–21027.
Marinissen MJ, Chiariello M, Gutkind JS. Regulation of gene expression by the small GTPase Rho through the ERK6 (p38 γ) MAP kinase pathway. Genes Dev. 2001;15:535–553.
Stransky N, Cerami E, Schalm S, et al. The landscape of kinase fusions in cancer. Nat Commun. 2014;5:4846.
Yoshihara K, Wang Q, Torres-Garcia W, et al. The landscape and therapeutic relevance of cancer-associated transcript fusions. Oncogene. 2015;34:4845–4854.
James RG, Bosch KA, Kulikauskas RM, et al. Protein kinase PKN1 represses Wnt/b-catenin signaling in human melanoma cells. J Biol Chem. 2013;288:34658–34670.
Siroy AE, Boland GM, Milton DR, et al. Beyond BRAF(V600): clinical mutation panel testing by next-generation sequencing in advanced melanoma. J Invest Dermatol. 2015;135:508–515.
Massi G, LeBoit PE. Regressing and regresses melanoma. In: Massi G, LeBoit PE, eds Histological Diagnosis of Nevi Melanoma. Darmstadt, Germany: Springer; 2004:625.
Goto K, Pissaloux D, Paindavoine S, et al. CYSLTR2-mutant cutaneous melanocytic neoplasms frequently simulate “pigmented epithelioid melanocytoma.” Expanding the morphologic spectrum of blue tumors: a clinicopathologic study of 7 cases. Am J Surg Pathol. 2019;43:1368–1376.