Tumor characteristics and survival in patients with extranodal non-Hodgkin lymphoma of the female reproductive tract

Abstract

<h3>Objectives:</h3> Primary extranodal non-Hodgkin lymphoma (NHL) of the female reproductive tract is rare, comprising approximately 1% of all NHL. Studies to date have been limited to case reports without longitudinal follow-up. The objective of this study is to describe tumor characteristics and survival in patients with primary vulvar, vaginal, cervical, uterine and ovarian NHL using the Surveillance, Epidemiology and End Results (SEER) cancer database. <h3>Methods:</h3> Adults with a histologic diagnosis of non-Hodgkin lymphoma (ICD-O-3 9590-9823) and a primary site coded as vulva (ICD-10-CM C51.0-51.9), vagina (C52.9), cervix (C53.0-53.9), uterus (C54.0-C55.9), or ovary (C56.9-C57.4) diagnosed between 1973 and 2015 were included in the analysis. Data was abstracted on variables of interest including age at diagnosis, year of diagnosis, demographics, Ann Arbor stage, histologic subtype, treatment regimens and disease-specific survival (DSS). Descriptive statistics were used to compare characteristics between primary sites. Kaplan-Meier survival curves and multivariable Cox proportional hazards survival analysis were performed using SPSS. <h3>Results:</h3> A total of 793 patients with primary gynecologic NHL were identified, including vulva (n=60), vagina (n=101), cervix (n=187), uterus (n=142) and ovary (n=303). The median age at diagnosis was 55 years old and ranged from 18 to 94 years. Vulvar, vaginal and cervical primary cancers were more likely to be diagnosed at an early stage compared to uterus and ovary (p<0.001) and receive radiation (p<0.001). Ovarian primary NHL was most likely to be diagnosed at an advanced stage (65% stage III or IV) and 88% of patients were treated with surgery. There was no significant difference in chemotherapy administration between the primary sites. The median DSS was not reached. The 5-year disease-specific survival rate was 83.2% for cervical, 81.8% for vaginal, 72.3% for ovarian, 70.9% for vulvar and 69.1% for uterine primary sites (p=0.019). On multivariate analysis, compared to primary ovarian NHL, DSS was significantly improved if the primary site was cervix (hazard ratio 0.61, 95% CI 0.39-0.97) or vagina (HR 0.52, 95% CI 0.29-0.92) with no difference in survival with primary vulvar NHL (HR 0.76, 95% CI 0.43-1.35) or primary uterine NHL (HR 0.90, 95% CI 0.59-1.38). Age at diagnosis (HR 1.04, 95% CI 1.03-1.05), histologic subtype (Burkitt's lymphoma vs other NHL, HR 3.26, 95% CI 1.82-5.84), and advanced stage (Stage II vs I: HR 2.16, 95% CI 1.42-3.28; III vs I: 1.34, 0.60-2.98; IV vs I: 3.50, 2.43-5.06) were associated with worse survival and more recent diagnosis (HR 0.98, 95% CI 0.96-1.00) and treatment with surgery (HR 0.52, 95% CI 0.36-0.73)) were associated with improved survival. <h3>Conclusions:</h3> Overall, extranodal NHL of the female reproductive tract has an excellent prognosis. The clinical characteristics, treatment regimens and survival differ between primary sites.