Cervix
Premalignant / preinvasive lesions - H&E
SMILE (stratified mucin producing intraepithelial lesions)
Last author update: 1 August 2017
Last staff update: 25 January 2024
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PubMed Search: Stratified mucin producing intraepithelial lesions cervix
Table of Contents
Definition / general | Essential features | Epidemiology | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Positive stains | Negative stains | Differential diagnosis | Board review style question #1 | Board review style answer #1Cite this page: Hodgson A, Parra-Herran C. SMILE (stratified mucin producing intraepithelial lesions). PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cervixSMILE.html. Accessed April 26th, 2024.
Definition / general
- Rare HPV associated premalignant cervical intraepithelial lesion arising in reserve cells of transformation zone, originally described in 2000 (Am J Surg Pathol 2000;24:1414)
- These cells can transdifferentiate throughout the carcinogenic process
- SMILE shows morphological overlap with both squamous intraepithelial lesions (SIL) and adenocarcinoma in situ (AIS)
- Considered to be a variant pattern of AIS per 2014 WHO classification (Kurman: WHO Classification of Tumours of Female Reproductive Organs, Fourth Edition, 2014)
- Debate exists about whether this lesion should be classified as a variant of adenosquamous intraepithelial lesion due to hybrid features
Essential features
- SMILE often coexists with other preinvasive lesions, including SIL (up to 93% of cases) and AIS (up to 42% of cases) as well as invasive carcinoma (up to 10% of cases)
- Another study showed a high association with AIS (92%) compared to SIL (58%) (Hum Pathol 2016;55:174)
- May be a morphologic indicator of phenotype instability / ambiguity
- Recently proposed to be a precursor to a unique invasive cervical carcinoma termed "invasive stratified mucin producing carcinoma" (Am J Surg Pathol 2016;40:262)
- Mucoepidermoid carcinoma is the principal differential diagnosis of this invasive counterpart
Epidemiology
- Seen in 0.6% of cervical specimens (biopsies and resections) in one study (Histopathology 2015;66:658)
Case reports
- 51 year old woman diagnosed with SMILE on a cervical biopsy (Diagn Cytopathol 2014;42:792)
- 54 year old woman with vaginal bleeding (Basic Appl Pathol 2012;5:72)
Treatment
- Generally managed as AIS, although no clearly documented consensus (Eur J Obstet Gynecol Reprod Biol 2010;148:207)
Microscopic (histologic) description
- Multilayered and stratified cells (resembling SIL) with intracytoplasmic mucin or cytoplasmic vacuoles throughout the thickness of the lesional epithelium
- Associated nuclear pleomorphism, hyperchromasia, mitotic activity and apoptotic bodies
- Most consistent feature is the spacing of nuclei by intracytoplasmic mucin
- Rounded or lobular contour seen at epithelial stromal interface (in keeping with an in situ lesion)
- Overt gland formation not seen (as opposed to AIS)
Microscopic (histologic) images
Images hosted on other servers:
Resembles HSIL but with abundant mucin
Adenocarcinoma in situ stratified type
Cytology description
- Jagged group borders
- Moderate crowding within cell groups
- Distinct and sharp cytoplasmic borders
- Spherical nuclear shape
- Moderate to marked nuclear membrane irregularity
- Fine granular chromatin structure
- Cytologic features of SMILE and AIS overlap, however prominent nucleoli and feathering are not typically described in SMILE (Diagn Cytopathol 2016;44:20)
Positive stains
- Ki67 / MIB1: high index (no threshold stablished)
- p16: block type staining (full thickness strong nuclear and cytoplasmic staining spanning a continuous segment of abnormal epithelium)
- Mucicarmine: positive (pink) intracytoplasmic staining
Negative stains
Differential diagnosis
- Adenocarcinoma in situ (AIS):
- Has gland formation; subtle stratification may exist but epithelium retains a columnar shape and lacks the "squamoid" pattern of stratification of SMILE
- Atypical immature squamous metaplasia:
- Preserved cell polarity, rare mitoses confined to basal layer, lack of mucin
- Squamous intraepithelial lesion (SIL):
- Stratified epithelium with a squamous appearance (polygonal cells with intercellular bridges, lack of intracytoplasmic mucin)
- As a pitfall, mucin may be present superficially if the SIL colonizes endocervical epithelium (which is usually pushed towards the luminal aspect)
- In this setting, mucin containing epithelium is benign (no nuclear enlargement, hyperchromasia or mitotic activity) and p16 will be negative in the mucinous cells (staining of the basal aspect colonized by dysplastic squamous epithelium)
Board review style question #1
Which is of the following staining profiles would be expected for SMILE?
- Ki67 high, block p16, mucicarmine+, IMP3-, CK14-
- Ki67 high, block p16, mucicarmine-, IMP3-, CK14+
- Ki67 low, block p16, mucicarmine+, IMP-, CK14-
- Ki67 low, block p16, mucicarmine-, IMP+, CK14+
Board review style answer #1
A. SMILE has a high MIB1 index, block staining for p16 and is positive for mucicarmine.
Comment Here
Reference: SMILE (stratified mucin producing intraepithelial lesions)
- SMILE is negative for IMP3 and CK14
- Both HSIL and AIS stain strongly and diffusely with p16 and tend to have an elevated MIB1 index
- Mucicarmine is positive in AIS and should be not positive in HSIL
- IMP3 has been shown to be positive in AIS
Comment Here
Reference: SMILE (stratified mucin producing intraepithelial lesions)
