Disease Distribution in Low-stage Tubo-ovarian High-grade Serous Carcinoma (HGSC): Implications for Assigning Primary Site and FIGO Stage

Abstract

The latest FIGO and TNM (eighth edition) staging systems for ovarian, tubal, and peritoneal neoplasms require primary site assignment as tubal/ovarian/peritoneal, but provide no guidance or criteria. Fewer than 10% of extrauterine high-grade serous carcinoma (HGSC) cases present at low stage (stage I/II). Low-stage cases offer a unique opportunity to understand the pattern of disease early in its evolution prior to wide dissemination and provide valuable evidence for guiding specimen handling and tumor staging. This study aimed to examine disease distribution in low-stage tubo-ovarian HGSC. Anonymized pathology reports of 152 stage I/II extrauterine HGSCs from 6 teaching hospitals were analyzed: group 1 (n=67) comprised cases with complete tubal examination by Sectioning and Extensively Examining the FIMbriated end of the tube (SEE-FIM) and group 2 (n=85) consisted of cases without documentation of both tubes being fully examined by the SEE-FIM or a SEE-FIM-like protocol. The stage, site/pattern of involvement, site/size of largest tumor focus and laterality of tubal and ovarian involvement were recorded. Tubal mucosal involvement was present in 95% of optimally examined cases and many factors influenced detection of tubal disease. Bilateral involvement, suggestive of metastasis, was significantly more frequent in the ovaries (35%) than the tubes (9%) (P<0.0001, Fisher exact test). No case showed a complete absence of tubal/ovarian involvement, questioning the biological existence of primary peritoneal HGSC. Disease distribution in low-stage cases supports a tubal origin for most HGSCs. Detailed tubal sampling upstages some apparent stage I cases through detection of microscopic tubal involvement.

Diagnosis Shift in Site of Origin of Tubo-Ovarian Carcinoma

“…25,26 It has also been shown that application of the SEE-FIM protocol increases the detection of premalignant and malignant tubal lesions. 27 Occult invasive cancer and serous tubal intraepithelial carcinoma lesion are identified in 0.9-8.5% of patients undergoing riskreducing salpingo-oophorectomy. 28 It is therefore possible that there has been increased detection of premalignant and malignant tubal lesions when combined with increased application of the SEE-FIM protocol and the state-of-science updated pathology protocols.…”

Primary fallopian tube adenocarcinoma: A case report and review of the literature

“…They are frequently confused with ovarian cancers in case of locally advanced disease and are clearly underestimated. They are unilateral in 85 % of cases [2] , with an average of 20 to 30 new cases reported each year [3] .…”

“…Thus, an oncogenetic opinion is most often sought. Tubal cancer is also associated with overexpression of p53, HER-2/neu and c-myc [2] .…”

“…Primary cancers of the tube are distinguished from ovarian cancers by their more noisy symptomatology, with pain appearing rapidly due to early tubal distension. Metrorrhagia with negative endometrial curettage is also a warning sign [2] .…”

“…Averages of 20 to 30 new cases are reported each year. The incidence of this cancer varies between 0.3 and 1.1 % among all gynecological cancers [1] , [2] . We report a case of primary tubal adenocarcinoma in a 42-year-old woman, discovered following an abdomino-pelvic mass and treated by surgery and chemotherapy.…”