The Histologic and Molecular Spectrum of Highly Differentiated HPV-independent Cervical Intraepithelial Neoplasia.
Female
Humans
Tumor Suppressor Protein p53
/ genetics
Papillomavirus Infections
/ complications
Reproducibility of Results
Vulvar Neoplasms
/ pathology
Carcinoma in Situ
/ pathology
Carcinoma, Squamous Cell
/ pathology
Papillomaviridae
/ genetics
Uterine Cervical Dysplasia
Cyclin-Dependent Kinase Inhibitor p16
/ metabolism
Journal
The American journal of surgical pathology
ISSN: 1532-0979
Titre abrégé: Am J Surg Pathol
Pays: United States
ID NLM: 7707904
Informations de publication
Date de publication:
01 08 2023
01 08 2023
Historique:
medline:
19
7
2023
pubmed:
7
6
2023
entrez:
7
6
2023
Statut:
ppublish
Résumé
Recently, the World Health Organization (WHO) recognized the existence of human papillomavirus (HPV)-independent invasive cervical squamous cell carcinoma (SCC), but HPV-independent precursor lesions were not included due to the lack of description of this rare entity. We present the histologic spectrum of highly differentiated squamous HPV-negative and p16 ink4a -negative precursor lesions adjacent to and/or preceding invasive HPV-negative cervical SCC in 3 patients. The histologic features resembled those described for vulvar HPV-negative precursor lesions. One precursor featured a proliferation of atypical basal keratinocytes with mitotic activity, premature squamatization in elongated epithelial rete, and mostly regular superficial squamous differentiation with TP53 mutation and immunohistochemical p53 overexpression termed differentiated cervical intraepithelial neoplasia (d-CIN). The other 2 precursors included verruciform acanthosis with plump rete, minimal atypia, and an EGFR mutation that resembled vulvar acanthosis with altered differentiation, and an exophytic papillary proliferation with a PIK3CA mutation resembling the differentiated exophytic vulvar intraepithelial lesion. Two precursors that preceded the invasive SCC harbored an additional pathogenic SMARCB1 mutation. The cytologic smears of d-CIN revealed 3-dimensional branched basaloid tubular structures and eosinophilic squamous cell clusters mimicking the histologic features. In conclusion, highly differentiated cervical HPV-negative precursors are characteristic intraepithelial squamous lesions with somatic mutations that resemble those described in vulvar HPV-independent carcinogenesis. For optimal reproducibility, we propose a simplistic classification of these HPV-negative cervical precursors in TP53 -mutated d-CIN and p53 wild-type verruciform intraepithelial neoplasia.
Identifiants
pubmed: 37283469
doi: 10.1097/PAS.0000000000002067
pii: 00000478-990000000-00175
doi:
Substances chimiques
Tumor Suppressor Protein p53
0
Cyclin-Dependent Kinase Inhibitor p16
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
942-949Informations de copyright
Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
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