Cytomorphologic and molecular analyses of fallopian tube fimbrial brushings for diagnosis of serous tubal intraepithelial carcinoma

Abstract

BACKGROUND:The paradigm shift localizing the origin of ovarian high-grade serous carcinoma (HGSC) to the fallopian tube underscores the rationale for meticulous microscopic examination of salpingectomy specimens. The precursor, termed "serous tubal intraepithelial carcinoma," is often a focal lesion, which poses difficulties for histologic diagnosis. METHODS:The authors describe a method to examine exfoliated epithelial cells from fallopian tube fimbria by gentle brushing, thereby enabling thorough sampling of the mucosal surface. Fimbrial brushings were collected from 20 fresh salpingectomy specimens from 15 patients, including 5 who had pathologically confirmed ovarian HGSC. Samples taken only from tubes that were grossly negative for tumor were processed for Papanicolaou staining, p53 immunocytochemistry, and tumor protein 53 (TP53 ) mutation analysis. RESULTS: Cells with malignant cytomorphologic features were identified only in tubal brushings from patients with ovarian HGSC. In all cases, atypical/malignant cells on cytology corresponded to lesions with similar morphology and immunostaining pattern in permanent sections, demonstrating the sensitivity of the technique while providing reassurance that specimen integrity was not disrupted by the procedure.Targeted next-generation sequencing confirmed the presence of TP53 mutations in fimbrial brushings from HGSC, but not in benign samples, and demonstrated concordance with the immunostaining pattern. Identical mutations were observed in matched lesions microdissected from formalin-fixed tissue sections. CONCLUSIONS: The described technique enables cytologic evaluation of the fallopian tube fimbria for a diagnosis of serous tubal intraepithelial carcinoma, serving as a complement to histology while offering distinct advantages with respect to the procurement of cellular material for ancillary testing and research.

The Utility of Fallopian Tube Cytology in the Early Detection of Extrauterine Serous Gynecological Malignancies: A Narrative Literature Review

“…Five studies with a total of 278 patients and 423 specimens were investigated. The included studies [13][14][15][16][17] showed variations in the method of obtaining the samples, the cytopreservatives used, and the stains applied for cytological analysis (Table 2). Table 2 indicates that sample obtaining was performed ex vivo in the majority of the studies (4/5), and cytological evaluation was mostly performed on Papanicolaou stains.…”

“…The most commonly used brush was the cytobrush, while an electric toothbrush repurposed as a Tubebrush© was applied on fresh specimens in one study. Nonetheless, the most recent obtaining method utilized the Cytuity™ cell collection catheter to collect samples via hysteroscopy [13][14][15][16][17].…”

“…In an attempt to assess the diagnostic ability of cytological evaluation, 5 studies [13][14][15][16][17] correlated the cytological with the histopathological diagnosis, reporting promising results in the detection of atypical and malignant alterations of the salpingeal cells. All of these studies showed a high concordance rate (81.8-100%).…”

“…Interestingly, in the study by Dhanani et al [14], one of the 3 discrepant cases referred to the single malignant diagnosis, a STIC that was diagnosed as benign during the cytological evaluation. Nevertheless, another case of STIC was correctly diagnosed in the study by Chui et al [15] which yielded a concordance rate of 100%. Only 2 cases of early OC (FIGO I) were not discovered by cytology in the study of Powell et al [16] (4.5%).…”