Common Lymphoma in an Uncommon Location

FDG avid bilateral ureteral lesions. A 45-year-old man presented with a nodule in his paranasal area. He underwent an excisional biopsy, which showed diffuse large B-cell lymphoma (DLBCL) of germinal center origin. Imaging confirmed advanced stage disease, and the patient was treated with 6 cycles of R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) achieving a complete metabolic response. Two years later, he was noted to have mild hydronephrosis of both kidneys with nonspecific thickening of the right ureter. Repeat imaging 1 year later revealed diffuse thickening of both proximal to mid ureters with mild to moderate bilateral hydroureteronephrosis. His glomerular filtration rate started to decrease gradually over the course of another year to < 45 mL/min. An MRI (T1-post contrast) was performed, showing mild right and severe left dilation of the renal pelvis and calyces with soft tissue encasing the proximal right and left ureter, as well as encasing/replacing the left renal cortex (Figure 1A, left). A PET scan confirmed the soft tissue in the ureters was FDG avid (Figure 1A, right), but failed to show evidence of abnormal FDG uptake elsewhere. A left ureter biopsy was performed, showing an infiltrate of small, mature-appearing lymphocytes (Figure 1B) that are PAX5+ B-cells (Figure 1C) with far fewer reactive CD3+ T-cells (Figure 1D). The B-cells coexpress CD10 (Figure 1E) with variable BCL6 expression (Figure 1F) and dominant BCL2 positivity (Figure 1G). The patient was diagnosed with a follicular lymphoma (FL). There was not an expansion of large cells to suggest the presence of DLBCL. In addition, the Ki-67 proliferation index was 10%. While FL most commonly presents in the lymph nodes, extranodal presentation occurs in around 25% of cases [1-3]. The most common site of extranodal disease is the gastrointestinal tract, but FL has been reported to occur in the head/neck, skin, female genital tract, testes, and eye among other locations, with some of these now recognized as specific subtypes of FL [2-5]. Developing FL in the urinary tract is rare, occurring in only 2.7% of the extranodal presentations in a SEER database cohort [2]. Finding FL in the ureters is even less common, but it has been described in case reports [6]. To evaluate the relationship between the previously diagnosed DLBCL and current FL, comparative immunoglobulin heavy chain (IGH) gene rearrangement PCR studies were performed on both specimens. While a clear monoclonal IGH gene rearrangement was evident in the DLBCL, this was not detectable in the FL, noting that false negative IGH PCR is not uncommon in FL. The finding of FL after treatment for DLBCL might have suggested that the original DLBCL was a transformation from FL, which has now re-emerged after treatment. However, the comparative IGH PCR results suggest otherwise and that they are clonally unrelated. Discordant lymphoma, in which 2 separate lymphoma subtypes are found in 2 different locations, has a reported incidence between 5% and 24% in published studies. The incidence has been reported to be between 5% and 7% for cases of indolent lymphoma in the marrow with DLBCL in the lymph nodes [7]. Treatment options for stage IE follicular lymphoma include involved site radiation (RT) with or without anti-CD20 monoclonal antibody therapy and chemotherapy. Historically, RT alone has 10 year progression-free survival (PFS) and overall survival rates up to 59% and 86%, respectively [8]. A retrospective analysis from ILROG of stage I/IE patients treated with ≥ 24 Gy found no difference in outcome based on extranodal status [9]. The combination of Rituximab and RT has been published in multiple studies, including the phase 2 MIR trial, which found that 8 doses of Rituximab and 30–40 Gy of involved field RT resulted in a 5 year PFS of 78% [10]. An observational study using 4 cycles of Rituximab and RT resulted in a projected 10 year PFS of 64.6% [11]. The patient was treated with 4 weekly doses of rituximab 375 mg/m2 and involved field radiation to the bilateral ureters and renal mass with 4 Gy, achieving a partial response. Since the patient had developed follicular lymphoma less than 24 months after completing RCHOP21, which is a known predictor of worse outcomes [12], he was subsequently treated with axicabtagene ciloleucel. Post CAR-T FDG PET imaging showed a complete metabolic response to therapy. Per institutional policy, the review of medical records for publication of case reports of three or fewer patients does not require IRB review and approval. Stefan K. Barta: Honoraria—Acrotech Biopharma, Bristol Myers Squibb, Citius Pharmaceuticals, Secura Bio, Kyowa Kirin. Data Safety Monitoring Committee—Janssen. Adam Bagg: Speakers Bureau—Recordati Rare Diseases, Consultant—Scopio Labs. The other authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.