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05.08.2019 | Original Article – Clinical Oncology | Ausgabe 10/2019

Journal of Cancer Research and Clinical Oncology 10/2019

Invasive stratified mucin-producing carcinoma (i-SMILE) of the uterine cervix: report of a case series and review of the literature indicating poor prognostic subtype of cervical adenocarcinoma

Journal of Cancer Research and Clinical Oncology > Ausgabe 10/2019
Lars-Christian Horn, Romy Handzel, Gudrun Borte, Udo Siebolts, Anja Haak, Christine E. Brambs
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The online version of this article (https://​doi.​org/​10.​1007/​s00432-019-02991-3) contains supplementary material, which is available to authorized users.

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Invasive stratified mucin-producing carcinoma (i-SMILE) represents a recently recognized subtype of cervical adenocarcinoma (AC) developing in a background of a stratified mucin-producing intraepithelial lesion (SMILE). Clinical and prognostic data on i-SMILE are limited.


We report a series of five cases with histopathological, immunohistochemical (p16) and PCR analyses. The cases as well as the patients previously published in the literature were reviewed for follow-up information.


Thirteen cases were identified. The mean age of 47.1 years (range 34–66) was not different from the usual type of cervical AC. 10/13 cases presented with tumors > 2 cm and a polypoid-exophytic appearance. Regardless of tumor size and stage of the disease, 7 out of 11 patients developed recurrent disease after a mean of 7.8 months (range 6 weeks–36 months). Five patients developed distant metastases (three of them in the lungs). Five out of the 11 informative cases died of the disease. All reported cases were positive for high-risk HPV (mainly HPV type 18) and associated with p16-overexpression.


i-SMILE represent a distinct subtype of invasive endocervical AC, associated high-risk HPV infection and strong p16-overexpression. Clinically, i-SMILE may represent an aggressive tumor with early recurrent disease and substantial risk of distant metastatic disease, especially to the lungs.

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