Low-grade Serous Carcinoma of the Ovary: Clinicopathologic Analysis of 52 Invasive Cases and Identification of a Possible Noninvasive Intermediate Lesion.

Low-grade serous carcinoma (LGSC) is an uncommon but distinct histologic subtype of ovarian carcinoma. Although the histologic features and natural history of LGSC have been described in the literature, there is no robust correlative study that has specifically addressed histologic features in correlation with clinical follow-up. To refine the criteria for invasion patterns of LGSC and determine additional clinically pertinent morphologic features of LGSC predisposing to a more aggressive clinical course, the clinicopathologic features of 52 LGSCs were evaluated and compared with those of a large series of serous borderline tumors (SBT), with and without invasive implants. To qualify for LGSC, the tumor needed to demonstrate destructive invasion, nuclear atypia that was mild to moderate at most (grade 1 or 2), and a mitotic index that did not exceed 12 mitoses per 10 high-power fields. On the basis of histologic evaluation, destructive invasion was classified into 7 primary architectural patterns: (1) micropapillary and/or complex papillary; (2) compact cell nests; (3) inverted macropapillae; (4) cribriform; (5) glandular and/or cystic; (6) solid sheets with slit-like spaces; and (7) single cells. Five-year overall survival and disease-free survival for LGSC were 82% (median, 72 mo) and 47% (median, 54 mo), respectively. All the patients with fatal outcome demonstrated tumors showing invasion with predominant patterns of cribriform glands, micropapillae and/or complex papillae, or compact cell nests. Notably, 2 of 9 patients with fatal outcome had only small foci of destructive invasion (2 and 3 mm, respectively) with compact cell nests and cribriform glands as the predominant patterns. There was no statistically significant association between pattern of invasion and disease-free survival. Classic stromal microinvasion, as defined by nondestructive stromal invasion <5 mm was identified in 52% of LGSC and was statistically more frequent in LGSC than in SBT (P<0.001). In 2 LGSCs, there were areas demonstrating an intraluminal solid proliferation of tumor cells with grade 1 or 2 nuclear atypia, which we hypothesize may represent a noninvasive form of LGSC, as similar non-invasive proliferations of morphologically low-grade serous carcinomatous cells were also identified in 8 SBTs, in either solid or compact glandular/papillary formations. One patient with this isolated noninvasive pattern in SBT developed LGSC 40 months after initial operation. LGSC was typically high stage (FIGO stages II to IV, 86%) and bilateral (68%), with multiple foci of invasion (82%). Bilaterality was significantly more common in high-stage disease (P=0.009). LGSC was associated with SBT in 84% of cases, most commonly usual type (27%), followed by cribriform (18%), micropapillary (11%), or mixed cribriform and micropapillary (7%) types; focal micropapillary and/or cribriform features were present in an additional 16%. The presence of intraluminal proliferations of cells resembling LGSC occurring in SBT should prompt additional tumor sampling and assiduous evaluation of implants (if present), as this appears to represent a form of intraepithelial carcinoma, which may be associated with invasion elsewhere.

Classification of Extraovarian Implants in Patients With Ovarian Serous Borderline Tumors (Tumors of Low Malignant Potential) Based on Clinical Outcome.

The classification of extraovarian disease into invasive and noninvasive implants predicts patient outcome in patients with high-stage ovarian serous borderline tumors (tumors of low malignant potential). However, the morphologic criteria used to classify implants vary between studies. To date, there has been no large-scale study with follow-up data comparing the prognostic significance of competing criteria. Peritoneal and/or lymph node implants from 181 patients with high-stage serous borderline tumors were evaluated independently by 3 pathologists for the following 8 morphologic features: micropapillary architecture; glandular architecture; nests of epithelial cells with surrounding retraction artifact set in densely fibrotic stroma; low-power destructive tissue invasion; single eosinophilic epithelial cells within desmoplastic stroma; mitotic activity; nuclear pleomorphism; and nucleoli. Follow-up of 156 (86%) patients ranged from 11 to 264 months (mean, 89 mo; median, 94 mo). Implants with low-power destructive invasion into underlying tissue were the best predictor of adverse patient outcome with 69% overall and 59% disease-free survival (P<0.01). In the evaluation of individual morphologic features, the low-power destructive tissue invasion criterion also had excellent reproducibility between observers (κ=0.84). Extraovarian implants with micropapillary architecture or solid nests with clefts were often associated with tissue invasion but did not add significant prognostic value beyond destructive tissue invasion alone. Implants without attached normal tissue were not associated with adverse outcome and appear to be noninvasive. Because the presence of invasion in an extraovarian implant is associated with an overall survival analogous to that of low-grade serous carcinoma, the designation low-grade serous carcinoma is recommended. Even though the low-power destructive tissue invasion criterion has excellent interobserver reproducibility, it is further recommended that the presence of an invasive implant be confirmed by at least 2 pathologists (preferably at least 1 of whom is an experienced gynecologic pathologist) in order to establish the diagnosis of-low grade serous carcinoma.

[Mucinous ovarian neoplasms. Prognostically mostly excellent, infrequently a wolf in sheep's clothing]. / Muzinöse Ovarialtumoren. Prognostisch meist exzellent, selten Wölfe im Schafspelz.

Mucinous ovarian neoplasms represent the second largest group of epithelial ovarian tumors after serous neoplasms, of which benign cystadenomas constitute more than 80 %. Mucinous cystadenomas and carcinomas cannot be distinguished by the clinical features or the mean age of onset of the disease. They typically occur unilaterally, are confined to the adnexae (FIGO stage I) and clinically present with non-specific abdominal symptoms or are diagnosed by chance. The mean age of disease onset is around 50 years old. The prognosis is excellent. Implants, peritoneal metastases and bilateral occurrence of ovarian mucinous neoplasms should lead to the suspicion of metastasis particularly from a gastrointestinal tumor. Neither microinvasion defined as a maximum extent of invasion of 5 mm, nor intraepithelial carcinoma characterized by high grade atypia without invasion, affect the prognosis of mucinous borderline tumors. Mucinous carcinomas typically show confluent glandular, expansile growth that leads to a labyrinth-like pattern. A destructive infiltrative or nodular growth pattern, however, should lead to the consideration of metastasis. Mural nodules that may reveal a spindle cell sarcomatous or anaplastic carcinomatous pattern occur infrequently in mucinous and do not affect the prognosis. Pax8 positivity is indicative of a primary ovarian neoplasm. In this case, however, mucinous tumors associated with teratomas may show the colonic immunoreaction pattern (CK7-/CK20+/CDX2+). The rare mucinous tumors with endocervical differentiation are now designated as seromucinous tumors and consist of two or more distinct cell types, are frequently associated with endometriosis and seem to show a molecular genetic relationship to endometrioid neoplasms.