SMILE-type endocervical adenocarcinoma in situ: the importance of the correlation between cytology and biopsy for the early diagnosis of rare diseases

Abstract

Adenocarcinoma is a type of cervical tumor originating in the lining epithelium of the endocervical mucosa, constituting between 10-20% of malignant epithelial tumors of said location. Mucin-producing stratified intraepithelial lesion (SMILE) is a variant of adenocarcinoma in situ (AIS) that was first reported in 2000 as a lesion with some overlap between squamous intraepithelial lesion (SIL) architecture and AIS, due to  its presumably origin in the reserve cells of the transformation zone, considering it a rare cervical precancerous lesion. Like squamous cell carcinoma, it is etiologically related to persistent high-risk HPV infection due to strong nuclear and cytoplasmic positivity for p16 by immunohistochemistry. Cytological diagnosis requires a high index of suspicion, since it is more difficult to detect in early stages and its location in the upper part of the endocervical canal may limit obtaining a representative biopsy for histopathological diagnosis.

Case presentation: 43-year-old patient who consulted for postmenstrual spotting. Colposcopy with a dense acetowhite lesion and dilated vessels at hour 12 within the transformation zone. Cervicovaginal cytology reports squamous cells compatible with Low-Grade Squamous Intraepithelial Lesion (L-SIL) and atypical glandular cells (AGUS). A biopsy of the lesion was performed, which revealed adenocarcinoma in situ, SMILE type. Immunohistochemistry: diffuse p16 positive, Ki-67 70%, ER positive and CDX-2 negative.

Cervical adenocarcinoma constitutes a fraction of malignant neoplasms with limitations for cytological diagnosis. SMILEs are a relatively recently recognized rare variant of AIS, it express p16  and have a high Ki-67 proliferation rate. It is important to recognize the morphological spectrum of this lesion in order to promptly suspect  from cytology and be able to confirm  with biopsy, since they are potentially aggressive tumors compared to the usual type and are usually diagnosed in more advanced stages. Finally, it is essential that gynecologists are familiar with the diagnosis in order to guarantee proper management of these patients.