SENTIX (ENGOT-CX2/CEEGOG-CX1) is an international, multicentre, prospective observational trial evaluating sentinel lymph node (SLN) biopsy without pelvic lymph node dissection in patients with early-stage cervical cancer. We report the final preplanned analysis of the secondary end-points: SLN mapping and outcomes of intraoperative SLN pathology. Forty-seven sites (18 countries) with experience of SLN biopsy participated in SENTIX. We preregistered patients with stage IA1/lymphovascular space invasion-positive to IB2 (4 cm or smaller or 2 cm or smaller for fertility-sparing treatment) cervical cancer without suspicious lymph nodes on imaging before surgery. SLN frozen section assessment and pathological ultrastaging were mandatory. Patients were registered postoperatively if SLN were bilaterally detected in the pelvis, and frozen sections were negative. ClinicalTrials.gov (NCT02494063). We analysed data for 395 preregistered patients. Bilateral detection was achieved in 91% (355/395), and it was unaffected by tumour size, tumour stage or body mass index, but it was lower in older patients, in patients who underwent open surgery, and in sites with fewer cases. No SLN were found outside the seven anatomical pelvic regions. Most SLN and positive SLN were localised below the common iliac artery bifurcation. Single positive SLN above the iliac bifurcation were found in 2% of cases. Frozen sections failed to detect 54% of positive lymph nodes (pN1), including 28% of cases with macrometastases and 90% with micrometastases. SLN biopsy can achieve high bilateral SLN detection in patients with tumours of 4 cm or smaller. At experienced centres, all SLN were found in the pelvis, and most were located below the iliac vessel bifurcation. SLN frozen section assessment is an unreliable tool for intraoperative triage because it only detects about half of N1 cases.

Atypical polypoid adenomyoma (APA) is an uncommon uterine lesion that commonly recurs after local excision and is occasionally associated with or precedes the development of atypical hyperplasia or endometrioid adenocarcinoma. Despite the fact that about 230 cases have been reported in the literature, only 2 studies of 6 and of 7 cases have investigated the molecular aspects; as such, molecular alterations that occur in APA remain largely unknown. We undertook a comprehensive immunohistochemical and molecular analysis of 21 cases of APA in 17 patients (including 4 recurrent/persistent lesions). The analyzed genes were PTEN and TP53 (by fluorescence in situ hybridization) and KRAS, BRAF, EGFR, and NRAS (all by polymerase chain reaction). Immunohistochemical staining was performed for PTEN, p53, mTOR, β-catenin, HNF-1β, and GLUT1 and for the mismatch-repair proteins MLH-1, MSH-2, MSH-6, and PMS-2. In most cases, there was nuclear expression of β-catenin in squamous morules and expression of HNF-1β, mTOR, and GLUT1 in the glandular component. All cases exhibited “wild-type” expression of p53. A common finding was loss of PTEN expression (6/19 cases). In 1 of these cases, loss of PTEN expression was accompanied by PTEN deletion. Mutation of the KRAS gene was found in 5/19 cases. Intact mismatch-repair protein expression was present in all cases, and TP53 abnormalities or mutations of EGFR, NRAS, or BRAF genes were not found. Given the association with atypical hyperplasia and endometrioid adenocarcinoma and the shared immunohistochemical and molecular features, we feel that, conceptually, APA is best regarded as analogous to a localized form of atypical hyperplasia.