3.b.ii.1 Adenocarcinoma In Situ Endocervical-Type

Adenocarcinoma in situ Endocervical type

Adenocarcinoma in situ Endocervical type

Adenocarcinoma in situ (AIS) is the precursor lesion to invasive endocervical adenocarcinoma. AIS is an HPV induced lesion that is mainly associated with the oncogenic HPV type 18. On histology, AIS is characterised by the presence of atypical glandular cells replacing the normal glandular mucosa of the endocervix while preserving its normal lobular architecture. The demarcation between the benign and neoplastic glandular cells is usually abrupt. The diagnostic features include nuclear stratification, loss of the normal nuclear polarity, increased nuclear size, hyperchromasia, altered chromatin pattern, mitotic activity and apoptosis. Some atypical glandular lesions fall short of the diagnostic criteria of AIS and can be diagnosed as glandular dysplasia. Less common subtypes of AIS are recognized, including the intestinal type of AIS and the stratified type.

AIS should be differentiated from its benign mimics, which include tubal metaplasia, endometriosis and reactive changes. Tubal metaplasia shows cilia and intercalated cells and usually does not have mitotic activity. Endometriosis can mimic AIS because it will show stratified elongated nuclei and mitotic activity; identification of endometrial type stroma and hemosiderin should help render the proper diagnosis. As for benign glands with reactive changes, they usually are not mitotically active, they often have non-stratified nuclei with nucleoli and the transition between reactive mucosa and normal mucosa is usually gradual, with no sharp demarcation. In difficult cases, immunohistochemistry can be performed; AIS is usually positive for CEA, p16 (strong and diffuse nuclear and cytoplasmic staining) and ki67. Tubal metaplasia and endometriosis can be focally positive for p16, but AIS is strongly and diffusely positive with both nuclear and cytoplasmic staining. Finally, care should be taken to exclude an invasive endocervical adenocarcinoma.

For patients who desire to preserve their fertility, conservative surgical excision of AIS by LEEP or conisation is an acceptable management option. Clear margins should be obtained to reduce the risk of having residual AIS or invasive adenocarcinoma. However, careful patient follow-up is necessary even if clear margins were obtained as AIS may be multifocal and recur. A circumferential involvement by AIS of more than 50% in a LEEP or cone specimen is a significant predictive factor for residual/recurrent disease (Ref 1).

Reference:
1. Plotkin A, Khalifa MA, Ismiil N, Saad RS, Dubé V, Ghorab Z, Nofech-Mozes S. The Circumferential Extent of Disease Should Be Reported in Cervical Adenocarcinoma In Situ (AIS) Excised by LEEP and Cone Biopsies. Mod Pathol 2009 Jan; 22 Suppl 1: 1058a.