Detection of HPV RNA molecules in stratified mucin-producing intraepithelial lesion (SMILE) with concurrent cervical intraepithelial lesion: a case report

Abstract

Background Stratified mucin-producing intraepithelial lesion (SMILE) is a rare precursor lesion in the uterine cervix that is considered a variant of adenocarcinoma in situ (AIS). Although human papillomavirus (HPV) is thought to be related to the development of SMILE, there is little information available on the detection of HPV integrated into the lesion. Case presentation A 30-year-old female underwent a routine uterine cervical cancer screening, and her Pap smear indicated the possible existence of atypical glandular cells. A cervical biopsy with endocervical curettage was performed. The histopathological analysis showed that she had SMILE and high-grade squamous intraepithelial lesion (HSIL) on her cervix. The lesion was found to be positive for HPV genotypes 52 and 68 by multiplex PCR. In situ hybridization with HPV RNA probes revealed that these HPV types were involved in the onset of HSIL and SMILE, respectively. Conclusions Rare, high-risk HPV genotypes may contribute to the development of SMILE, and their detection can be useful for preventing the progression to carcinoma and ensuring adequate patient management.

Stratified Mucin-Producing Intraepithelial Lesion (SMILE) of the Uterine Cervix: High-Risk HPV Genotype Predominance and p40 Immunophenotype

“…In accordance with the transforming HPV infection indicated by diffuse p16 positivity in all SMILE cases, the proliferation activity of cells was also increased, as detected by Ki67 immunostaining, and the results are consistent with previous reports [1,2,10]. Ki67 expression was limited to the lower two-thirds of epithelial thickness in about onethird of cases, which may nonetheless reflect lesions with a lesser grade of intraepithelial neoplastic changes.…”

“…Similar to previous studies, all SMILEs in this study exhibited strong block diffuse nuclear and cytoplasmic positive p16 immunostaining consistent with transforming HPV infection [1,2,5,[8][9][10]. Except in one SMILE, when only a possibly carcinogenic HPV70 genotype was identified, high-risk HPV genotypes were detected in all other SMILEs.…”

“…Among published SMILE case reports, one case was positive for HPV16 and another for HPV18 by multiplex PCR and ISH with an HPV16/18 probe [8]. Another case was positive for HPV52 and 68 by multiplex PCR and subsequently with RNA fluorescent ISH [10]. Compared to other studies, we found HPV16-positive SMILE cases more frequently, although both HPV16 and HPV18 were predominant genotypes, similar to other reports.…”

“…SMILE has also recently been described as a precursor of invasive stratified mucin-producing carcinoma [9]. By analogy to squamous intraepithelial lesions (SIL) and AIS, SMILE has been considered etiologically linked to persistent infection with high-risk human papillomavirus (HPV) genotypes, mostly due to strong diffuse block p16 nuclear and cytoplasmic positivity, although HPV genotyping has only been reported in a very small number of studies on a limited number of cases [5,6,8,10]. SMILE presumably originates from reserve cells of the transformation zone (TC), which are capable of multidirectional differentiation [1,2].…”