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

Margareta Strojan Fležar,Neža Nedelko,Anja Oštrbenk Valenčak,Mario Poljak,Helena Gutnik

doi:10.3390/cells10082039

Margareta Strojan Fležar, Neža Nedelko + Show 3 more

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https://doi.org/10.3390/cells10082039

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Journal: Cells	Publication Date: Aug 10, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: University of Ljubljana

Abstract

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare high-grade cervical precancerous lesion designated a variant of adenocarcinoma in situ (AIS) in the WHO classification. We aimed to determine HPV genotypes, immunohistochemical phenotype and mucin presence in SMILE. Between 2010 and 2018, SMILE was diagnosed in 34 out of 6958 (0.5%) cervical biopsies, in 23 patients. Twenty-six tissue samples from twenty-one patients were available for further analysis, including 13 with SMILE alone, 12 with SIL and/or AIS and one with HSIL, AIS and endocervical adenocarcinoma. HPV genotyping was performed using the Seegene Anyplex II HPV 28 assay. Of the 26 samples, a single HPV genotype was identified in the majority of cases (n = 22), including 12/13 SMILEs associated with SIL/AIS. All but one were high-risk HPV genotypes (23/24; 96.8%). We identified seven different HPV genotypes, the most common being HPV16 (n = 10; 43.5%), HPV18 (n = 8, 34.8%) and HPV 31 (n = 5, 21.7%). All SMILEs showed a strong positive reaction to p16, CK7, CK19 and high Ki67 expression comparable to adjacent HSIL and/or AIS if present. SMILE showed variable mucin presence and p40-positive squamous differentiation suggesting phenotypic diversity in cervical precancerous lesions infected by single HPV.

Highlights

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare cervical precancerous lesion exhibiting architectural features encompassing cellular stratification similar to squamous intraepithelial lesions (SIL), crowding, an increased nuclear/cytoplasmic ratio, hyperchromasia, mitoses and apoptosis
One SMILE combined with both high-grade squamous intraepithelial lesions (HSIL) and adenocarcinoma in situ (AIS) was associated with an endocervical adenocarcinoma of the uterine cervix, FIGO stage IA1, but was no longer present in deeper tissue sections for adjunct studies
A single human papillomavirus (HPV) genotype was found in the majority of combined lesions (12/13, 92.3%), except for one SMILE with AIS, in which two genotypes, HPV 16 and 18, were found

Summary

Introduction

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare cervical precancerous lesion exhibiting architectural features encompassing cellular stratification similar to squamous intraepithelial lesions (SIL), crowding, an increased nuclear/cytoplasmic ratio, hyperchromasia, mitoses and apoptosis. In the 2014 World Health Organization (WHO) and recently in the 2020 WHO classification of cervical tumors, SMILE has been categorized as a subtype of endocervical adenocarcinoma in situ (AIS), while initial and later reports acknowledged a double histomorphological differentiation, namely, glandular and squamous [1,2,3,4]. In the majority of cases reported, SMILE was associated with conventional high-grade squamous intraepithelial lesions (HSIL), adenocarcinoma in situ (AIS) or both [1,2,5,6,7,8]. SMILE has recently been described as a precursor of invasive stratified mucin-producing carcinoma [9]

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