Original contributionStratified mucin-producing intraepithelial lesion with invasive carcinoma: 12 cases with immunohistochemical and ultrastructural findings☆
Introduction
High-grade squamous intraepithelial lesion (HSIL) and adenocarcinoma in situ (AIS) are precursor lesions for invasive carcinomas [1], [2]. Stratified mucin-producing intraepithelial lesion (SMILE) is a rare columnar cell cervical neoplasm, first described in 2000 [3]. It overlaps morphologically with HSIL and AIS and is considered to be a variant of AIS [4] or adenosquamous carcinoma in situ [5]. IMP3 is a member of insulin growth factor II protein and is a useful marker for AIS, HSIL, and invasive carcinomas [6]. Recently, Boyle and McCluggage [7] suggested that SMILE is more similar to squamous epithelial tumor than adenocarcinoma because SMILE and HSIL were negative for IMP3 in their study.
A few studies have reported the association between SMILE and invasive carcinomas. Park et al [3] reported 12 cases (67%) of SMILE with invasive carcinomas (4 invasive adenocarcinomas, 1 adenocarcinoma and separated squamous cell carcinoma, 5 adenosquamous carcinomas, and 2 papillary lesions) but did not describe their morphological findings in detail. Lastra et al [8] recently reported the similarity in appearance between invasive components and SMILE and proposed the invasive form of SMILE to be “invasive stratified mucin-producing carcinoma” (ISMC). However, the immunohistologic features of SMILE and ISMC have not been well documented.
Therefore, we studied the immunohistochemically characteristics of 12 cases of SMILE with or without invasive carcinoma components, and the ultrastructural study of 1 case was also described.
Section snippets
Materials and methods
This study was approved by the Ethics Committee of the University of Miyazaki (approval no. 2014-05). We retrospectively reviewed specimens obtained from 445 patients (mean age, 44 years; age range, 19-80 years) with uterine cervical tumors, diagnosed as HSIL, AIS, SMILE, or invasive carcinoma, who were treated at the University of Miyazaki Hospital between 2004 and 2014. Of the 445 patients, 250 (56%; mean age, 39 years) had only intraepithelial lesions, and 195 patients (44%; mean age, 50
Clinical features
Of 445 patients, 12 showed SMILE histologically (2.7%; mean age, 44 years; age range, 30-66 years; Fig. 1; Table 1). Of 12 patients, 3 (25%; mean age, 37 years; range, 30-48 years) had only intraepithelial lesions, and 9 patients (75%; mean age, 47 years; range, 37-66 years) had invasive cancer elements. In the group with only intraepithelial tumors, 1 patient presented with genital bleeding; and 2, with abnormal cytology; in the invasive group tumor, 6 patients presented with genital bleeding;
Discussion
SMILE is an uncommon intraepithelial lesion. Determining its incidence and clinicopathological features from the few reports in the literature is difficult. The initial 2000 proposal by Park et al [3] and the recent 2014 World Health Organization classification [4] described SMILE as a cervical glandular premalignant lesion; however, SMILEs are probably still underrecognized or misclassified. Actually, we could not make the diagnosis of SMILE for 6 cases in the original diagnoses. We documented
Acknowledgments
The authors thank Dr Tohru Hayashi for his valuable advice and Takako Tokumitsu, Kyoko Ohashi, and Ritsuko Sotomura for their excellent technical assistance.
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2022, Seminars in Diagnostic PathologyCitation Excerpt :Furthermore p63 is characteristic for SMILE highlighting the basal layer of the lesion.34 Similar to uAIS SMILE is block positive for p16 and usually positive for HPV16/18 by in situ hybridization.35 It frequently occurs with concurrent lesions been HSIL the most common (79%) followed by uAIS (39%) EAC (5%) and invasive squamous cell carcinoma (6%).36
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2022, PathologyCitation Excerpt :In situ and invasive lesions are consistently associated with high-risk HPV and, hence, are immunoreactive with p16. p63 is at most focally positive.40 Though rare, anal invasive stratified mucin-producing carcinomas show similar histological features as their cervical counterparts, and the few cases we have encountered have been positive for high-risk HPV in addition to CK7 (CK20 negative) and CDX2 (focal).
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Disclosures: There is no relationship with industry to declare, and no authors have competing financial interests or conflicts of interest.