Renal lymphoma is predominantly secondary, potentially arising from hematogenous spread or direct invasion from retroperitoneal lesions[1–3]. PRL is rare since the kidney is not a lymphoid organ and lacks intrinsic lymphatic tissue. Nevertheless, substantial clinical evidence indicates the existence of PRL, primarily as B-cell lymphoma and rarely as T-cell lymphoma[5]. In our study, 13 cases were B-cell lymphomas and one case was extranodal NK/T-cell lymphoma, consistent with literature reports. Several theories propose the origin of PRL:It may originate from lymphatic vessels in the renal capsule or subcapsular tissue, where lymphocytes progressively infiltrate and invade the renal parenchyma, undergoing carcinogenic transformation in situ to develop lymphoma[2, 3, 6].Chronic inflammation within the kidney or autoimmune diseases causing lymphocyte aggregation could be related[7].
PRL can occur at any age but is more common in middle-aged and elderly individuals, with a slight male predominance. It typically presents unilaterally, although 20% of PRL cases involve bilateral kidneys, primarily in children[6, 8]. In this study, all patients was unilateral, with right-sided involvement being more common. The patients' ages ranged from 34 to 79 years, with a mean age of 60.4 years, and 78.6% were over 50 years old, aligning with previous reports[6]. The equal gender distribution in our study might be due to the small sample size.
PRL's clinical manifestations are non-specific and resemble renal cell carcinoma, with the most common symptoms being flank pain, abdominal mass, hematuria, and abnormal urinalysis. Some patients may exhibit B symptoms (night sweats, unexplained fever > 38°C, weight loss > 10% within six months), and in rare cases, the tumor may compress the kidney, leading to renal dysfunction[9]. In our cohort, flank pain was the primary symptom in most cases, with two patients also experiencing fever. PRL in transplant kidneys is often Epstein-Barr virus (EBV)-associated, possibly linked to immunosuppressive therapy. One case of EBV-positive DLBCL in a non-transplant kidney was noted, with only one such case reported previously.
Due to its rarity, preoperative imaging is crucial for the diagnosis and management of PRL. Imaging findings are relatively specific: ultrasound typically shows solid hypoechoic masses, sometimes mimicking cysts due to uniform echo distribution. PRL's homogeneity is due to lymphocyte origin, leading to fewer reflective interfaces. As a poorly vascularized tumor, perirenal hemorrhage is uncommon in PRL.
On CT, PRL masses often present as isodense or slightly hypo- or hyperdense compared to the renal cortex, with smooth borders and homogeneous density. Enhanced CT reveals mild enhancement, significantly lower than normal renal parenchyma. In our series, CT scans showed slightly lower density than normal parenchyma on plain scans, with indistinct margins or mild patchy or mild-to-moderate heterogeneous enhancement post-contrast. The soft tumor tissue frequently encircles but does not invade surrounding vessels, a phenomenon known as the "floating vessel sign," which is characteristic of lymphomas due to the predominant proliferation of uniform cells and the preservation of existing vascular structures[10]. This sign was observed in one case, with the renal artery traversing the tumor(Fig. 3). PRL can present as nodular, perirenal mass, renal pelvis, or diffuse enlargement types, with nodular and diffuse types being most common in our study. PRL often invades the retroperitoneal space, initially asymptomatic due to the deep location and ample space until significant tumor growth occurs[11].
In our study, 10 patients underwent MRI, revealing slightly low signal on T1-weighted images, slightly high signal on T2-weighted images, but lower than normal renal parenchyma, and mild enhancement post-contrast. DWI showed high signal intensity. MRI aids in differentiating PRL from common renal malignancies and monitoring treatment response. PRL is a poorly vascularized tumor, as evidenced by imaging features. Research by Ye et al.[12]indicates higher FDG uptake in lymphomas than in renal cell carcinoma, suggesting PET-CT can assist in lymphoma diagnosis preoperatively. Additionally, PET-CT can perform whole-body scans, providing comprehensive disease assessment for staging, grading, and prognosis evaluation.
PRL is highly aggressive, with early diagnosis and differentiation aiding in precise treatment to improve prognosis. PRL typically lacks a capsule and does not invade vessels, with minimal venous thrombus and necrosis, unlike clear cell renal carcinoma which often exhibits degeneration, hemorrhage, necrosis, and frequent vascular invasion forming tumor thrombus. Enhanced CT/MR scanning helps distinguish PRL from clear cell renal carcinoma. PRL must also be differentiated from other poorly vascularized renal tumors. In elderly patients, small, well-defined, homogeneous PRL can be challenging to distinguish from papillary and chromophobe renal cell carcinomas, which also show similar enhancement patterns on CT. On MRI, PRL signals lower or equal to normal renal parenchyma on T1WI and T2WI sequences aid differentiation as renal carcinoma usually shows slightly higher or high signal on T2WI. PRL exhibits more pronounced diffusion restriction on DWI. MRI is recommended for difficult-to-diagnose renal tumors[13]. Chromophobe renal cell carcinoma may resemble PRL but often presents with central scars and calcification, aiding differentiation[14].
PRL in the renal sinus requires differentiation from renal pelvic carcinoma, which typically presents with hematuria. CT urography aids in differentiation as renal pelvic carcinoma shows filling defects, whereas PRL does not invade the renal pelvis and often encircles and compresses it along with the ipsilateral renal artery. Perirenal and diffuse PRL must be distinguished from pyelonephritis, which shows renal enlargement and heterogeneous enhancement on imaging, improving with anti-inflammatory treatment, a feature absent in PRL. In cases where anti-inflammatory treatment is ineffective, fever, weight loss, and elevated LDH should raise suspicion for PRL[2, 15].
For bilateral renal masses with atypical preoperative imaging, ultrasound or CT-guided biopsy can provide a definitive diagnosis[16]. When histological and immunophenotypic features are atypical, molecular testing is needed for accurate subtyping, guiding treatment, and prognosis. DLBCL is the most common histological subtype, followed by marginal zone lymphoma (MZL) and follicular lymphoma (FL)[17], with other B-cell lymphomas comprising less than 5%[18]. In our study, 57.1% were DLBCL and 35.7% were MZL. Most DLBCL cases are non-germinal center B-cell type with high proliferative activity. Among eight DLBCL cases, seven were non-germinal center B-cell type with Ki-67 ≥ 50%.
Lymphomas are multicentric, and despite localized detectable lesions, undetectable disease may exist elsewhere, making local treatment limited. PRL treatment has shifted from surgery alone to a multimodal approach with chemotherapy being central. Combined surgery and chemotherapy have better outcomes than either modality alone[19]. For bilateral involvement, surgery intolerance, or extensive perirenal lymph node infiltration, chemotherapy is chosen post-pathological confirmation. The recommended chemotherapy regimen is CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) every 21 days, for at least six cycles. Studies indicate adding rituximab (R-CHOP) significantly improves DLBCL prognosis, with a 5-year OS rate of 43%, compared to 41% for CHOP alone over three years[20].
In our cohort, four of five patients undergoing surgery alone died within two years. Among those receiving surgery combined with R-CHOP, one died at 28 months postoperatively, while three survived. Of those receiving surgery and CHOP, two died at 32 and 14 months respectively, while two survived. One patient with extranodal NK/T-cell lymphoma received COP-L combined with chidamide and survived.
PRL has a poor prognosis, and factors significantly affecting prognosis remain challenging to assess. Khan et al.[3]found Ki-67 expression correlates with lymphoma aggressiveness. PRL with unclear margins or necrosis/cystic changes indicates high malignancy and invasiveness, often involving surrounding lymph nodes. Morel et al.[21]reported tumor size > 10 cm, renal hilum involvement, and diffuse renal infiltration as poor prognostic factors. In our study, three patients with tumors > 10 cm had significantly shorter PFS than those with tumors < 10 cm (19 vs. 60 months). Age > 60 years was an independent OS risk factor[16], and patients > 60 had shorter PFS (30 vs. 45 months). Elevated LDH indicates poorer prognosis and higher recurrence rates[3, 15]; our study showed lower median PFS in patients with elevated LDH (33 vs. 45 months). Chen et al.[19]found unilateral PRL had longer survival (average 68 months) compared to bilateral cases (average 21 months).
Despite combined surgery and chemotherapy, PRL has a high recurrence rate and low overall survival. Emerging therapies like lenalidomide and ibrutinib offer new treatment possibilities. Lenalidomide has direct cytotoxic and anti-angiogenic effects[22], while ibrutinib inhibits B-cell proliferation by targeting Bruton’s tyrosine kinase in the B-cell receptor pathway[23], representing new therapeutic avenues. Additionally, PD-1/PD-L1 antibody studies show potential benefits for DLBCL prognosis but require more clinical evidence[24]. Early postoperative PET-CT can detect minimal residual disease, and for recurrent PRL, combining novel agents like ibrutinib, lenalidomide, and PD-1/PD-L1 antibodies with chemotherapy is suggested.