Fiche publication
Date publication
juillet 2024
Journal
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Auteurs
Membres identifiés du Cancéropôle Est :
Pr AUBIN François
,
Pr CRIBIER Bernard
,
Dr NARDIN Charlée
Tous les auteurs :
Kervarrec T, Lei KC, Sohier P, Macagno N, Jullie ML, Frouin E, Goto K, Taniguchi K, Hamard A, Taillandier A, Tallet A, Collin C, Sahin Y, Barry F, Taibjee S, Cokelaere K, Houben R, Schrama D, Nardin C, Aubin F, Doucet L, Pissaloux D, Tirode F, de la Fouchardière A, Balme B, Laurent-Roussel S, Becker JC, von Deimling A, Samimi M, Cribier B, Battistella M, Calonje E, Guyétant S
Lien Pubmed
Résumé
Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/β-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/β-catenin pathway without evidence of matrical differentiation, as well as four combined tumors in which a similar Wnt/β-catenin activated carcinoma component was associated with Merkel cell carcinoma or pilomatrical carcinoma. Among the pure tumor cases, 6/16 patients were female with a median age of 80 years (range: 58-98). Tumors were located on the head and neck (n=7, 44%), upper limb (n=4, 25%), trunk (n=3, 18%), and leg (n=2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in one patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%) and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but one case. Nuclear β-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%) and RB1 (n=47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogenous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, Merkel cell carcinoma and squamous cell carcinoma) while the 3 other cases lacking such morphologic features did not. In addition, we identified four combined neoplasms in which there was a component showing a similar poorly differentiated rosette forming carcinoma demonstrating Rb loss and beta-catenin activation associated with either Merkel cell carcinoma (n=3) or pilomatrical carcinoma (n=1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/β-catenin activated rosette-forming carcinoma", morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.
Référence
Mod Pathol. 2024 07 31;:100586
