Differentiated High-Grade Squamous Intraepithelial Lesion of the Uterine Cervix (d-HSLI, d-CIN 3) as a Distinct Precursor Lesion in Keratinising HPV-negative Squamous Cell Carcinoma of the Uterine Cervix

Purpose In contrast to the relatively high frequency of uterine prolapse, the coexistence with cervical carcinoma is extremely rare, and the knowledge about its morphologic and molecular characteristics is very scarce. Furthermore, morphologic features of HPV-independent squamous precursor lesions are very limited.

Methods Detailed histopathological and immunohistochemical analyses of p16, p53 and CK 17 were performed, as was a molecular evaluation for HPV-DNA and p53-mutation of four consecutive cervical squamous cell carcinomas associated with uterine prolapse with the definition of a hitherto not well-described precursor lesion and molecular tumorigenetic pathway.

Results The cases were diagnosed during a period of seven years with a mean age of 75 (range 69-83) years and a mean tumor size of 7.3 cm (range 5.2-9.4cm). All patients presented with locally advanced disease, and one woman died within four, another within 14 months of follow-up. Histopathologically, all keratinizing squamous cell carcinomas (SCC) with infiltrative growth and their adjacent precursor lesions were negative for p16, showed an aberrant p53-expression and diffuse and strong staining for CK 17 on immunohistochemistry. On the molecular level, both the SCCs and their precursors were negative for HPV-DNA but harbored a TP53-mutation. The precursor lesions were characterized by epithelial thickening with superficial keratinization, the presence of basal and parabasal keratinocytes with mitotic figures beyond the basal layer, thus showing features similar to those seen in differentiated types of vulvar intraepithelial lesions (d-VIN), suggesting the terminology of cervical d-HSIL (syn. d-CIN 3). An HPV-independent pathogenetic pathway with a p53-alteration was identified for these cases.

Conclusions The coexistence of cervical SCC with uterine prolapse is extremely rare. These specific SCCs represent highly keratinized, HPV-independent tumors harboring a TP53-mutation. For the first time, a precursor lesion of HPV-independent SCC of the uterine cervix was been described with a d-VIN-like morphology, and a separate tumorigenic pathway was defined.

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Artikel online veröffentlicht:
10. Juni 2022