Primary Female Genital Lymphoma: Prognostic and Therapeutic Considerations
Authors: Steffanoni Sara , Agazzi Alberto , Laszlo Daniele , Liptrott Sarah Jane , Negri Mara , Peccatori Fedro Alessandro , Martinelli Giovanni 
Published: April 2020

Abstract
Primary Female Genital Lymphoma (PFGL) is very rare, representing 1.5% of all Non-Hodgkin’s Lymphomas (NHLs) and 0.5% of female genital malignant tumours; uterus is the main commonly genital site involved by NHL. Most PFGLs are B-cell lymphomas; usually they occur in 5th decade of life. Because of PFGL rarity, a standard treatment has not been identified yet. This is a retrospective study on 20 women with PFGL, treated at European Institute of Oncology. The median age was 52 yrs (range 30–79 yrs); at diagnosis 6 pts were asymptomatic, 11 reported pelvic symptoms and 3 B symptoms. According to the International Prognostic Index, 7 pts had low, 6 intermediate, 6 high risk and one pt not known. Eleven pts had uterine involvement, with a concomitant extension to vagina in 5 of them, ovary NHL was recognised in 4 pts, vaginal NHL in 4 pts and vulvar NHL in one pt. Diffuse large B-cell NHL (DLBCL) was diagnosed in 14 pts, marginal extranodal NHL in 3 pts and follicular in 3 pts. According to Ann Arbor staging system: 8 pts were in early stage (IE–IIE) and 12 pts in stage IVE; considering FIGO system: 11 pts were in early stage (I–II), 6 pts in stage III for regional lymph node involvement and 3 in stage IV for concomitant non-genital extranodal localization; 12 pts presented with bulky disease. At diagnosis no pts had bone marrow involvement. The diagnostic biopsy was performed by endoscopy in 13 pts and by ultrasound-guided in 2 pts, whereas 5 pts underwent laparotomy. One pt with vulva-limited marginal NHL did not receive any treatment until disease progression (PD) and transformation to DLBCL. Five pts underwent laparotomy and adjuvant chemotherapy (CT) alone (n=4) or in combination with radiotherapy (RT) (n=1); 14 pts received CT alone (n=8) or in combination with RT (n=6) as first line therapy.
Anthracycline-containing CT was delivered to all pts with DLBCL (n=14) and to one pt with high grade follicular NHL, 12 of them received concurrent immunotherapy anti-CD20 (Rituximab). Central nervous system (CNS) chemo-prophylaxis with i.v. high dose methotrexate was delivered to 3 pts because of advanced or bulky disease. Two pts with follicular and 2 with marginal subtype received alkylating-containing CT alone (n=2) or with Rituximab (n=2). The Overall Response Rate (ORR) to first line therapy was 80%; the response did not improve by the addition of local treatment to CT. Three pts did not response to first line therapy: one with marginal NHL in stable disease did not receive any additional treatment because of asymptomatic disease; two with DLBCL in PD underwent salvage treatment with high dose CT and died in PD, concurrent intrathecal therapy was mandatory in one pt because of CNS relapse. Three pts with follicular NHL, in response to first line therapy, relapsed: one went on to receive maintenance Rituximab, one resulted refractory to different rescue CT regimens and died in PD, one underwent autologous bone marrow transplantation obtaining CR. After a median follow up of 51 months (range 11–164 months), 17 pts are still alive: 10 in CR and 7 in PR, 3 pts died in PD. The Overall Survival (OS) at 3 and 14 yrs was 84.8% and 42.4% respectively. According to the literature the most common histological subtype of PFGL occurred in our population was DLBCL and the most frequent genital site involved was uterus (55% of cases) [Lagoo et al. 2006]. An additional local treatment did not seem to give an advantage in terms of ORR, PFS and OS in comparison with systemic therapy alone, as stated by the literature [Signorelli et al. 2006]. Concerning the pts treated with anthracycline-containing CT with or without Rituximab (n=15), 8 pts (53%) and 5 pts (33%) achieved CR and PR respectively, 2 pts (13%) had a PD during treatment, only one pt in CR relapsed after 65 months from the first line therapy. After a median follow up of 27 months 12 pts (80%) are alive, 3 (20%) died in PD. The Response Rate and OS in the subgroup of pts that received anthracycline-containing CT resulted similar to those reported in the literature [Coiffier 2002]; therefore female genital involvement by NHL doesn’t seem to represent a negative prognostic factor.