[The morphological and immunohistochemical characteristics of stratified mucin-producing intraepithelial lesion].

Stratified mucin-producing intraepithelial lesion (SMILE) is a rare premalignant cervical lesion that combines the structural features of cervical intraepithelial neoplasia (CIN) and endocervical adenocarcinoma in situ (AIS).

AIM: to analyze archival materials for the detection of SMILE and its subsequent morphological and immunohistochemical characterization.

MATERIAL AND METHODS: Cervical cone specimens from 53 women with histologically verified CIN3 were examined. The diagnosis of SMILE was based on the positive mucicarmine staining and weak focal expression of p63. The samples containing SMILE were further immunohistochemically examined using the biomarkers P16, Ki-67, Oct4, CD117, CD34, p53, EMA, and CK15. SMILE was detected in 2 of the 53 patients and concurrent with CIN3 in both cases. SMILE was characterized by the stratified arrangement of atypical cells containing mucin, the positive mucicarmine staining of the entire layer of the atypical epithelium, weak focal p63 expression, high Ki-67 expression, and diffuse р16Іnk4а staining. Both SMILE samples showed weak diffuse p53 expression in the presence of single cells with the pronounced nuclear staining pattern for p53 in one female patient. Weak focal CK15 expression was visualized in SMILE. The expression of the stem cell markers Oct4 and CD117 and the angiogenic marker CD34 was absent in the examined cervical epithelial preparations. The diffuse and intense expression of the marker EMA, which was not different from that in the endocervical and stratified squamous epithelium, and CIN3 was established in SMILE.

RESULTS: The findings suggest that SMILE is morphologically and immunohistochemically similar to CIN3. In this investigation, these abnormalities differed only in the mucicarmine staining and expression of p63. This may be indicative of the underdiagnosis of SMILE, attendant СIN3 in the routine practice of a clinical pathologist, as the diagnosis of CIN3 is primarily based on the results of assessment of only the preparations stained with hematoxylin and eosin; the expression of p16 and Ki-67 is evaluated in some cases, which fails to differentiate SMILE and CIN3 in a number of preparations.

CONCLUSION: The diagnosis of SMILE can be made only by immunohistochemical examination.