Refined Diagnostic Criteria for Implants Associated With Ovarian Atypical Proliferative Serous Tumors (Borderline) and Micropapillary Serous Carcinomas

Abstract

Characterization of invasive peritoneal implants from patients with noninvasive serous ovarian tumors has important prognostic and treatment implications, but the criteria for distinguishing invasive and noninvasive implants vary among investigators and can be difficult to apply. The authors studied 148 implants from 60 patients, 33 with primary atypical proliferative serous tumor, and 27 with primary noninvasive micropapillary serous carcinoma, with a mean follow-up of 62 months (median follow-up, 52 months). Previously reported and newly proposed histologic features for implant classification were evaluated and correlated with clinical outcome. Three criteria were applied for the diagnosis of "invasive" implants: invasion of underlying normal tissue, micropapillary architecture, and solid epithelial nests surrounded by clefts. Implants displaying any one of these three features were classified as "invasive," whereas those lacking all three features were classified as "noninvasive." Sixty-six implants were invasive and 82 were noninvasive. Of the 31 patients with invasive implants, six were dead of disease (DOD), 13 were alive with progressive disease (AWPD), and 12 were alive with no evidence of disease (NED). Of the 29 patients with noninvasive implants, two were DOD, one was dead of uncertain causes, one was AWPD, and 25 were alive with NED. Eighty-nine percent of invasive implants had a micropapillary architecture and 83% had solid epithelial nests surrounded by clefts. A minority of invasive implants (14% of those with underlying normal tissue) demonstrated invasion of normal underlying tissue. Nuclear atypia, mitoses, calcification, necrosis, and identification of individual cells "infiltrating" the stroma did not correlate with implant type. The proposed criteria permitted recognition of implants that correlated strongly with adverse outcome. Sixty-one percent of patients with implants displaying any one of the three features used to diagnose invasive implants were AWPD or DOD compared with 10% of patients whose implants lacked these features (p = 0.00001). Because implants associated with an adverse outcome can be identified before they invade underlying normal tissue, the term invasive implant to describe them is inaccurate and misleading. These implants resemble patterns of growth in micropapillary serous carcinoma of the ovary and the recurrent tumor that is obvious carcinoma. Accordingly, we propose that these extraovarian lesions be designated "well-differentiated serous carcinoma."

A Meta-Analysis on the Impact of Platinum-Based Adjuvant Treatment on the Outcome of Borderline Ovarian Tumors With Invasive Implants

“…Bell et al included a large cohort of patients with invasive implants, followed for a median of 53 months [31]. The study included 31 patients with invasive implants, 48.4% of whom received platinum-based treatment; of those, 26.7% died, whereas none of the patients who did not receive chemotherapy died [31].…”

Data set for reporting of ovary, fallopian tube and primary peritoneal carcinoma: recommendations from the International Collaboration on Cancer Reporting (ICCR)

“…Not all gynaecological pathologists accept these expanded criteria, 29,51 but they have been shown to correlate with poor outcome. 61 We feel this is an area where further studies are needed to clarify the prognostic significance of these expanded criteria.…”

“…As some peritoneal staging biopsies may be superficial without sufficient underlying tissue to assess invasion, expanded criteria for invasive implants have been proposed for cases without classic patterns of invasion. 61 These criteria include micropapillary architecture resembling micropapillary serous borderline tumour and clusters of tumour within clear lacunar spaces. Not all gynaecological pathologists accept these expanded criteria, 29,51 but they have been shown to correlate with poor outcome.…”

“…29,30,51,52,61 51 but a recent study of a large population-based cohort has shown that the vast majority of implants are clonally related to the primary ovarian tumour. 63 Most of the cases from that study were non-invasive implants; however, all 10 invasive implants had the same mutational status (KRAS mutation, BRAF mutation or wild-type KRAS/BRAF) as the corresponding serous borderline tumour, suggesting that invasive implants are clonally related to the primary ovarian tumour as opposed to representing independent primary peritoneal lesions.…”

Histopathological features and prognostic significance of the micropapillary pattern in lung adenocarcinoma

“…Factors including smoking history, serum level of carcinoembryonic antigen, and tumor size, as well as lymphatic and venous invasion have been identified as poor prognostic factors for lung adenocarcinoma. [8][9][10][11][12] Recently, a pathological entity called the micropapillary pattern has been reported to have worse outcomes in breast, 13 colon, 14 urinary tract, 15 ovary, 16 salivary gland, 17 and lung 18,19 cancer. The micropapillary pattern in lung adenocarcinoma is characterized by small papillary tufts lying in alveolar spaces or in spaces encased by connective tissues, with the tufts having no fibrovascular core, 18,19 and it has been reported as an important factor for poor prognosis.…”