Ovarian Borderline Tumor

Ovarian borderline tumors have low malignant potential. WHO defines them as tumors whose growth pattern and cytologic features are intermediate between clearly benign and clearly malignant counterparts, without destructive stromal invasion, and which generally have a much better prognosis than ovarian cancer at the same clinical stage. Lymph-node metastasis may occur, mostly involving pelvic and para-aortic nodes.

Common Symptoms

Pelvic mass

Causes and Pathogenesis

(A) Etiology: The cause of ovarian borderline tumors is unclear. Pseudomyxoma peritonei associated with borderline tumors was formerly thought to arise from the ovary; now the appendix is considered the most likely source. (B) Pathogenesis: Main histologic types are serous and mucinous; endometrioid and clear-cell types exist but are rare. 1. Histologic diagnosis of serous borderline tumors — Katzenstein criteria: ① stratified epithelial cells and/or budding clusters; ② cellular atypia; ③ mitoses; ④ no stromal invasion. Russell requires at least two of the four in the absence of true stromal invasion. Many authors have added refinements. Stromal invasion is sometimes hard to judge; some serous borderline tumors have peritoneal implants; diagnosis should be based on the primary tumor morphology. Recently microinvasive serous borderline tumors were reported. Bell and Scully define microinvasion as: in the stroma of a typical serous borderline tumor, focal or multifocal single cells, irregular small nests, papillary or cribriform nests with atypia, but without destructive stromal change or desmoplastic reaction, lesion diameter <3 mm or area <10 mm². Most studies consider microinvasion does not affect prognosis and remains within borderline-tumor category. Scully adds: when such focal tumor cells show disordered growth in stroma, malignant cytology, and cause some stromal destruction or desmoplasia, it should be diagnosed as 'microinvasive carcinoma' — especially with extraovarian disease, it threatens the patient. 2. Histologic diagnosis of mucinous borderline tumors — Piura criteria: epithelial proliferation without stromal invasion, plus at least two of: ① villoglandular proliferation; ② mitoses or cellular atypia; ③ epithelium no more than 4 layers. Rutgers and Seully recently divided mucinous borderline tumors into endocervical-like and intestinal types. Scully: endocervical-like mucinous borderline tumors resemble serous borderline tumors but papillae have rich stroma and cell buds; may implant on peritoneum and metastasize to nodes but without pseudomyxoma peritonei; peritoneal spread is scattered nodules of mucinous glands and fibrous stroma; prognosis better than intestinal type. Riopel's criteria for intestinal mucinous tumors: ① stratified/clustered mucinous epithelium without stromal invasion; ② microinvasion shows crowded glands, fused or back-to-back growth, lack of fibrous stroma, cribriform pattern, possible necrosis, mitoses <5/10 HPF, invasion <5 mm; cases with pseudomyxoma peritonei are mostly intestinal type. Riopel relaxed stromal-invasion cutoff from <3 mm to <5 mm since prognosis does not differ significantly. 3. Peritoneal implants: The traditional view treats all extraovarian lesions as 'implants'; this classification is flawed. Bell: noninvasive implants have sparse epithelium surrounded by reactive fibroblasts, so epithelium blends with stroma and is hard to find; invasive implants have abundant epithelium with highly complex proliferation or micropapillary structures and small nests irregularly distributed in stroma. Sliva's criteria: ① single or clustered epithelial cells in stroma reaching a certain number = 'invasive implant'; ② no fibrous reaction on peritoneal surface but epithelium penetrates underlying tissue = 'invasive implant'; ③ if implant site shows extensive fibrosis with only a few single cells in stroma = 'implant with early invasion'. Regardless of whether peritoneal lesions are multicentric primaries or implants, primaries occur in ~88% with 10-year survival 95%-98%; implants are 12% with 10-year survival only 33%, closely resembling invasive carcinoma. Therefore current practice treats invasive peritoneal implants as carcinoma regardless of ovarian lesion. Seidman reviewed 4129 serous borderline tumors with median follow-up 7.4 years: survival 95% for noninvasive peritoneal implants vs 66% for invasive; invasive peritoneal implants are currently the most reliable prognostic indicator — thus surgeons should perform careful multiple peritoneal biopsies. In serous borderline tumors, invasive implants are the only cause of death; only such patients need chemotherapy. Intestinal-type mucinous borderline tumors spread as diffuse mucin pools floating with mucinous epithelium. Pseudomyxoma peritonei associated with borderline tumors was once thought ovarian in origin; appendix is now the most likely source. Treatment of pseudomyxoma peritonei remains unsatisfactory; borderline mucinous tumors with pseudomyxoma peritonei have aggressive biology and poor prognosis; stromal invasion >5 mm is the only poor-prognostic indicator.

Treatment

Drug therapy, supportive therapy, surgery

Preventive Measures

Ovarian borderline tumors should be followed up like ovarian cancer: transvaginal ultrasound, gynecologic exam and serum CA125 are routine postoperative items; transvaginal ultrasound is currently the most effective means to detect recurrence. CA125 is elevated in many serous borderline tumors. Gotlieb reviewed 91 patients: 75% of serous borderline tumors had elevated preoperative CA125 (mean 156 U/ml), while only 30% of mucinous tumors were elevated (mean 28 U/ml); Stage Ia patients had only 35% elevated (mean 67 U/ml); those with extraovarian spread had 89% elevated (mean 259 U/ml). Engelen reported 57% of mucinous borderline tumors had elevated preoperative CA19-9, and recommends CA19-9 for follow-up of mucinous tumors.

Department to Visit

It is recommended to visit the Gynecology department; an appointment can be booked on this platform before the visit.

Warm reminder: The above information is for health science reference only and cannot replace professional medical diagnosis. If you have related symptoms, please seek medical attention at a regular hospital promptly.