Prognostic value of lymph node involvement in ovarian serous borderline tumors




Objective


This study was conducted to evaluate the prognosis value of lymph node involvement (LN positive) lymph node involvement for borderline ovarian tumor (BOT).


Study Design


This was a retrospective study on 49 patients treated at our institution for advanced-stage serous BOT (International Federation of Gynecology and Obstetrics [FIGO] III or IV). Pathological characteristics and survival were compared according to the lymph node status. The same analysis was performed on 1503 patients of the Surveillance, Epidemiology, and End Results (SEER) database.


Results


In our institution, 14 patients were LN positive. Eight patients have been upstaged after lymph node dissection. No patient has died during follow-up (median 53 months). LN positivity was not associated with recurrence. In the SEER registry, 93 patients (6.2%) had LN positivity. These patients were younger and with more advanced local extension. Survival curves were similar after adjustment for FIGO stage.


Conclusion


Lymph node involvement does not appear as a prognosis factor for advanced-stage BOT.


Borderline tumors of the ovary (BOTs) or ovarian tumors of low malignant potential represent 15-20% of epithelial ovarian tumors. Described for the first time by Taylor in 1929, they are characterized by a slow clinical course with a potential for peritoneal extension but have an excellent prognosis (overall survival estimated 90% at 10 years), which differentiates them from ovarian cancer. BOTs are also distinct from invasive cancer of the ovary because of the age at onset, which is about 10 years younger.


Extraovarian spread is found in about 35% of cases in the form of peritoneal implants. According to their microscopic characteristics, these implants can be divided into noninvasive (papillary structure similar to that of the BOT) or invasive (a similar structure to that of a well-differentiated invasive adenocarcinoma). Invasive peritoneal implants are associated with a poor prognosis.


Although the most frequent extraovarian site of BOT is the peritoneum, pelvic and retroperitoneal lymph node involvement has been described. Since 1995, surgical lymph node staging is no longer among the recommendations for the management of BOTs. Nevertheless, a number of patients undergo lymph node sampling at the time of surgery and lymph node involvement is described in 15-35% of BOTs.


We retrospectively collected data on a large series of patients with advanced-stage serous BOTs, all treated in or referred to our institute. The objective of this study was to focus on the prognostic impact of nodal involvement in patients treated for advanced-stage serous BOTs.


We completed this study by consulting the US Surveillance, Epidemiology, and End Results (SEER) database to evaluate the prognosis of patients with BOTs and documented lymph node involvement.


Materials and Methods


From January 1973 to February 2006, 171 patients treated in or referred to our institution for a serous BOT with peritoneal implants had their histological slides reviewed by the same pathologist in our center . BOT was defined as an ovarian tumor with the following: (1) a stratified epithelial lining; (2) the formation of microscopic papillary projections; (3) nuclear atypia; and (4) above all, the absence of frank stromal invasion. The micropapillary pattern was evaluated according to criteria of Kurman et al. A serous BOT with a micropapillary pattern was confirmed if this appearance continuously occupied greater than 5 mm and greater than 10% of the ovarian tumor. Stromal microinvasion can be observed on the ovarian tumor and was defined as the presence of stromal invasion less than 10 mm 2 .


The staging classification used was the 2000 classification International Federation of Gynecology and Obstetrics (FIGO). The tumor stage was recorded using the macroscopic description during the surgical procedure and reviewing the pathology records. Peritoneal implants were classified as noninvasive (epithelial or desmoplastic type) or invasive according to the criteria previously described by Bell and Scully.


Surgery had consisted of either radical (bilateral salpingo-oophorectomy with or without hysterectomy) or conservative treatment (defined as conservation of the uterus and salvaging at least a portion of 1 ovary). Additional staging surgical procedures had occasionally been performed. This was dependent on the surgical teams, on whether the BOT was diagnosed during or after the surgical procedure, and on disease extension. Patients had undergone either an open or laparoscopic approach performed either during a 1-step surgical procedure, if the diagnosis of BOT was made at a frozen section analysis during the operation, or during restaging surgery. Lymphadenectomy, although not recommended, could have been performed because of enlarged nodes or misdiagnosis of invasive carcinoma.


Adjuvant treatment (chemotherapy, external radiation therapy, and chemotherapy with external radiation therapy) had been administered until 1985. The indications for and the type of adjuvant treatment depended on the pathological results (characteristics of peritoneal implants: noninvasive vs invasive), persistent residual tumor, and the date that treatment had been administered.


Seer program database


Case ascertainment. The SEER Program ( http://seer.cancer.gov/ ) currently collects and publishes cancer incidence and survival data from 15 population-based cancer registries that cover one quarter of the US population. Data on more than 6 million in situ and invasive cancer cases are included in the database. The SEER Program is the only source of population-based historical as well as current information on patient survival and disease stage. The mortality data reported by SEER are provided by the National Center for Health Statistics.


From a total of 95,000 ovarian tumors registered, we selected 6017 for further analysis based on the following International Classification of Diseases for Oncology (third edition) codes: 8442 (serous cystadenoma of borderline malignancy), 8451 (papillary cystadenoma of borderline malignancy), 8462 (serous papillary cystic tumor of borderline malignancy), 8472 (mucinous cystic tumor of borderline malignancy), and 8473 (papillay mucinous cystadenoma of borderline malignancy). Only histopathologically diagnosed tumors that represented either the only primary tumor or the first primary tumor diagnosed for each patient were included. Analysis of vital status data were collected until death or the last contact before or until December 2004.


For descriptive purposes, we tabulated data using SEER*Stat software (National Cancer Institute, Bethesda, MD): the variables studied were age, stage (American Joint Committee on Cancer stage third edition), number of lymph nodes examined, number of positive lymph nodes, cause of death, and survival time at recode. Staging of BOT was based exclusively on histologically diagnosed extraovarian lesions (called implants). Implants removed from undesignated sites were coded as abdominal involvement. The presence of implants increased the stage of a BOT, but the data on the subclassification of noninvasive or invasive implants were unavailable.


Statistical analysis


Recurrence-free interval rates were determined using the Kaplan-Meier method. Recurrence-free intervals were calculated including patients who had relapsed. Patients who had died of intercurrent disease were censored at the time of their death. Univariate analysis was performed. The log-rank test was used to compare the survival curves and to determine the P value. A P < .05 was considered significant. Categorical variables were compared using the χ 2 or Fisher’s test, when appropriate. Continuous variables were compared using the Student t test, the Mann-Whitney U test, or the analysis of variance test, when appropriate.




Results


Our series concerned 49 patients who had undergone a lymphadenectomy and had a final diagnosis of BOT: 14 of them (28.6%) had lymph node metastases from BOT. Patient characteristics and histopathological results are detailed in Table 1 .



TABLE 1

Characteristics of the Institute Gustave Roussy patients according to lymph node involvement














































































































































































































































Characteristics All Lymph node not involved (n = 35) Lymph node involved (n = 14) P value
Age (mean) (y) 36.6 37.0 35.6
Age (median) (y) 34.9 31.4 36.0 .94
Infertility 16.7% 6 of 29 1/13 .41
Ovulation induction 7.5% 2 of 27 1/13 1.00
CA 125 (median) 257 179 417.5 .22
Type of surgery
Radical 89.8% 30 of 35 14 of 14 .30
Conservative 10.2% 5 of 35 0 of 14
Type of lymph node surgery
Pelvic 91.8% 33 of 35 12 of 14 .56
Lumbar-aortic 59.2% 17 of 35 12 of 14 .024
Number of nodes removed
Mean 15.3 11.3 24.1
Median 11.0 4.0 20.0 .006
No residual disease (R0) 65.3% 23 of 35 9 of 14 1.00
Adjuvant chemotherapy 44.9% 15 of 35 7 of 14 .75
Pathological results (%)
Microinvasion 51.1 16 of 32 7 of 13 1.00
Micropapillary pattern 53.3 15 of 31 9 of 14 .36
Noninvasive implants 93.6 32 of 33 12 of 14 .21
Invasive implants 23.4 7 of 33 4 of 14 .71
Endosalpingiosis 57.1 14 of 29 10 of 13 1.00
Number of sites greater than 3 68.8 23 of 34 10 of 14 1.00
Omentum microscopically involved 54.2 19 of 34 7 of 14 .76
Omentum macroscopically involved 10.4 1 of 34 4 of 14 .021
Serosa of the corpus uteri 37.5 12 of 34 6 of 14 .75
Douglas pouch 20.8 7 of 34 3 of 14 1.00
Peritoneum between bladder and uterus 27.1 8 of 34 5 of 14 .48
Pelvic peritoneum 41.7 17 of 34 3 of 14 .11
Paracolic gutters 22.9 6 of 34 5 of 14 .26
Rectum 4.2 2 of 34 0 1.00
Diaphragmatic peritoneum 10.4 5 of 34 0 .30
Salpinx 38.8 13 of 34 6 of 14 1.00
Nodal endosalpingiosis 28.6 7 of 35 7 of 14 .08
Ovarian macroscopic implants 83.7 30 of 35 11 of 14 .67
Peritoneal washing positive 73.2 21 of 28 9 of 13 .72
Recurrence 23.9% 8 of 34 3 of 12 1.00
Invasive recurrence (per recurrences) 36.4% 2 of 7 2 of 3 .50

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Jun 14, 2017 | Posted by in GYNECOLOGY | Comments Off on Prognostic value of lymph node involvement in ovarian serous borderline tumors

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