Primary testicular diffuse large B-cell lymphoma with gonadal vein tumor thrombus: A case report and review of the literature

Abstract

BACKGROUND

Primary testicular lymphoma (PTL) is a rare, aggressive malignancy, representing a small fraction of testicular tumors and non-Hodgkin lymphomas, yet it is the most common testicular malignancy in older men. Diffuse large B-cell lymphoma (DLBCL), which is typically the aggressive subtype, dominates PTL and shows diffuse B-cell infiltration. Venous tumor thrombus, uncommon in lymphomas, is uniquely reported in this case of testicular DLBCL with gonadal vein involvement.

CASE SUMMARY

A 62-year-old man presented with a two-month history of painless left testicular swelling and stiffness. Diagnostic imaging [ultrasonography, computed tomography (CT), and ¹⁸F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG-PET/CT)] revealed bilateral testicular masses and a gonadal vein tumor thrombus (SUVmax 16.5). Left orchiectomy confirmed DLBCL with CD20, Bcl-2, and MUM1 positivity (Ki-67: approximately 80%). The disease was staged as Ann Arbor stage IVA (International Prognostic Index score 3, high-intermediate risk). The patient received Rituximab, Polatuzumab Vedotin, Cyclophosphamide, Epirubicin, and Prednisolone chemotherapy, completing the first cycle with good tolerability. No adverse events were reported, and follow-up is ongoing to assess long-term outcomes. This case highlights the diagnostic utility of ¹⁸F-FDG-PET/CT and the importance of multidisciplinary management in rare PTL presentations with tumor thrombus.

CONCLUSION

This case demonstrates the diagnostic complexities of PTL with gonadal vein tumor thrombus, underscoring the importance of considering lymphoma in elderly patients with testicular masses and venous involvement. A multi-disciplinary team including urologists, hematologists, and radiation oncologists is needed to ensure appropriate therapy.

Key Words: Primary testicular lymphoma; Diffuse large B-cell lymphoma; Gonadal vein tumor thrombus; Positron emission tomography/computed tomography; Chemoimmunotherapy; Case report

Core Tip: This is the first reported case of primary testicular diffuse large B-cell lymphoma presenting with a gonadal vein tumor thrombus, a manifestation previously unrecognized in this malignancy. The case underscores the pivotal role of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography in detecting rare vascular involvement and guiding staging. It also highlights the importance of a multidisciplinary approach in managing advanced-stage primary testicular lymphoma, which remains a rare but aggressive disease with distinct diagnostic and therapeutic challenges.

INTRODUCTION

Primary testicular lymphoma (PTL) is a rare and aggressive disease, with an incidence of approximately 0.09-0.26 per 100000 individuals[1]. PTL accounts for 1%-9% of all testicular malignancies and 1%-2% of all non-Hodgkin lymphoma cases[2]. However, in patients over 60 years old with testicular tumors, PTL is the most common malignancy. Diffuse large B-cell lymphoma (DLBCL) comprises 66%-98% of PTL cases[2-6]. DLBCL is histopathologically characterized by a diffuse infiltrate of large B-lymphocytes throughout the testicular tissue, with positive staining for CD20, CD79a, and PAX5. Further subclassification can be refined by the expression of CD10, BCL6, MUM1, MYC, and BCL2[7,8]. DLBCL can be further subclassified into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) phenotypes via immunohistochemistry. Previously, studies have shown that most testicular DLBCL cases belong to the ABC subtype, which generally exhibits a more aggressive clinical behavior than the GCB subtype. Venous tumor thrombus is typically observed in solid organ tumors, such as renal cell carcinoma, hepatocellular carcinoma, and neuroendocrine tumors[9], making it a rare finding in lymphoma. Here, we report a novel case of testicular DLBCL presenting with a gonadal vein tumor thrombus, the first case of its kind to our knowledge.

CASE PRESENTATION

Chief complaints

A 62-year-old man presented with a two-month history of painless swelling and stiffness in the left testis.

History of present illness

The patient reported no specific past medical history. He tested negative for serum human immunodeficiency virus (HIV) antibodies, indicating no history of HIV infection.

History of past illness

The patient reported a two-month history of painless swelling and stiffness in the left testis. He had no associated systemic symptoms such as fever, night sweats, or weight loss. His Eastern Cooperative Oncology Group (ECOG) performance status was 0, indicating full activity and no functional impairment.

Personal and family history

The patient reported no personal or family history, and he had no relevant psychosocial history or familial predisposition to malignancies.

Physical examination

On physical examination, the left testis was enlarged, measuring approximately 7 cm × 5 cm, and was non-tender. Transillumination indicated the presence of a solid mass in the left testis. The right testis appeared normal, and no peripheral lymphadenopathy was noted.

Laboratory examinations

Laboratory tests, including complete blood count, liver and renal function tests, and coagulation parameters, were normal. Specific tumor markers included: Lactate dehydrogenase (LDH), 181 U/L (normal range: 0-250 U/L); alpha-fetoprotein (AFP), 2.1 ng/mL (normal range: ≤ 20 ng/mL); beta-human chorionic gonadotropin (β-HCG), < 0.6 IU/L (normal range: < 5 IU/L); serum HIV antibodies, negative.

Imaging examinations

Ultrasonography revealed an enlarged left testis with heterogeneous echogenicity (5.4 cm × 5.1 cm × 4.0 cm), including patchy high-echo regions and involvement of the spermatic cord. The right testis showed smaller heterogeneous low-echo areas (4.8 cm × 3.2 cm × 2.1 cm). A hydrocele was observed in the left testis with a fluid depth of approximately 2 cm.

Contrast-enhanced CT of the abdomen and pelvis displayed irregularly enhancing bilateral testicular masses, predominantly on the left (5.6 cm × 3.9 cm), with thickening of the left gonadal vein and spermatic cord.

¹⁸F-Fluorodeoxyglucose positron emission tomography/computed tomography showed increased ¹⁸F-fluorodeoxyglucose (FDG) uptake in the left testis (SUVmax 14.1) and multiple areas in the right testis (SUVmax 5.0), indicative of malignancy. A linear uptake along the entire left gonadal vein (SUVmax 16.5) suggested tumor thrombus. Metabolically active lymph nodes were identified in the right clavicular region, mediastinum, paravertebral area, bilateral crura, and retroperitoneum, consistent with possible metastases (Figure 1).

Figure 1 ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography and contrast-enhanced computed tomography images. A: Linear uptake along the left gonadal vein (arrow, SUVmax 16.5); B: Bilateral testicular lesions (left: SUVmax 14.1; right: SUVmax 5.0); C: Paravertebral lymph node uptake (arrow); D: Mediastinal lymph node uptake (arrow); E: Right supraclavicular lymph node uptake (arrow); F and G: Tumor thrombus in the left gonadal vein near the left renal vein (arrow); H and I: Tumor thrombus in the left spermatic cord (arrow).

MULTIDISCIPLINARY EXPERT CONSULTATION

The diagnostic and treatment process involved urologists (for orchiectomy), pathologists (for immunohistochemistry), and oncologists (for staging and Pola-R-CHP chemotherapy). This case underscores that a multidisciplinary team including urologists, hematologists, and radiation oncologists is crucial for managing this condition.

FINAL DIAGNOSIS

The final diagnosis was DLBCL of the testis, stage IVA. This was established based on pathological examination of the left inguinal orchiectomy specimen, which revealed diffuse tumor cell infiltration extending to the spermatic cord margin. The diagnosis was confirmed by immunohistochemistry, showing positivity for CD20, Bcl-2, and MUM1, partial (50%) positivity for Bcl-6, and a Ki-67 proliferation index of approximately 80% (Figure 2). According to the Ann Arbor staging system, the disease was classified as stage IVA. The International Prognostic Index (IPI) score was 3 (high-intermediate risk), determined by age > 60, stage IV disease, and the presence of extranodal involvement.

Figure 2 Pathological findings of left testis tumor. A: Orchiectomy specimen showing an enlarged testis and spermatic cord tumor; B: Lymphatic cellular infiltration with monomorphic, medium-to-large round cells and nuclear pleomorphism, H&E (× 40). C-G: Immunohistochemistry findings. C: MUM1 (× 20, weak positive); D: CD10 (× 20, negative); E: BCL6 (× 20, negative); F: CD20 (× 20, strong positive); G: Ki-67 (× 20, approximately 80% positive, high proliferation rate).

TREATMENT

The patient received Rituximab, Polatuzumab Vedotin, Cyclophosphamide, Epirubicin, and Prednisolone (Pola-R-CHP) chemotherapy, completing the first cycle. A chronological summary of the patient’s clinical course is presented in Table 1.

Table 1 Timeline of case report: Primary testicular diffuse large B-cell lymphoma with gonadal vein tumor thrombus.

Time point	Event	Details
Month 0	Onset of symptoms	A 62-year-old man noticed painless swelling and stiffness in the left testis, lasting for two months. No associated systemic symptoms (e.g., fever, night sweats, weight loss). ECOG performance status: 0
Month 2	Initial clinical evaluation	Physical examination: Left testis enlarged (7 cm × 5 cm), non-tender, with a solid mass on transillumination. Right testis normal. No peripheral lymphadenopathy. Laboratory tests: Complete blood count, liver/renal function, and coagulation parameters normal. Tumor markers: LDH 181 U/L (normal: 0-250 U/L), AFP 2.1 ng/mL (normal: ≤ 20 ng/mL), β-HCG < 0.6 IU/L (normal: < 5 IU/L). HIV antibodies negative
Month 2 (cont.)	Diagnostic imaging	Ultrasonography: Left testis enlarged (5.4 cm × 5.1 cm × 4.0 cm) with heterogeneous echogenicity, spermatic cord involvement, and hydrocele (fluid depth approximately 2 cm). Right testis showed smaller heterogeneous low-echo areas (4.8 cm × 3.2 cm × 2.1 cm). Contrast-enhanced CT (abdomen/pelvis): Irregularly enhancing bilateral testicular masses (left: 5.6 cm × 3.9 cm), thickened left gonadal vein and spermatic cord. 18F-FDG-PET/CT: Increased FDG uptake in left testis (SUVmax 14.1), right testis (SUVmax 5.0), and linear uptake along left gonadal vein (SUVmax 16.5, suggestive of tumor thrombus). Metabolically active lymph nodes in right clavicular region, mediastinum, paravertebral area, bilateral crura, and retroperitoneum, indicating possible metastases
Month 2-3	Surgical intervention	Left inguinal orchiectomy: Performed for diagnosis. Pathological findings: Diffuse tumor cell infiltration in testicular tissue, extending to spermatic cord margin. Immunohistochemistry confirmed DLBCL (positive for CD20, Bcl-2, MUM1; 50% Bcl-6 positivity; Ki-67 approximately 80%)
Month 3	Staging and additional tests	Bone marrow biopsy and cerebrospinal fluid analysis: Normal, no malignant cells detected. Staging: Ann Arbor stage IVA, International Prognostic Index score 3 (high-intermediate risk, based on age > 60, stage IV, extranodal disease)
Month 3 (cont.)	Treatment initiation	Chemotherapy: Patient received first cycle of rituximab, polatuzumab vedotin, cyclophosphamide, epirubicin, and prednisolone. Outcome: Good tolerability to the first cycle, with ongoing follow-up to assess long-term outcomes

ECOG: Eastern Cooperative Oncology Group; LDH: Lactate dehydrogenase; AFP: Alpha-fetoprotein; β-HCG: Beta-human chorionic gonadotropin; HIV: Human immunodeficiency virus; CT: Computed Tomography; 18F-FDG-PET/CT: Fluorine-18 fluorodeoxyglucose positron emission tomography/ computed tomography; FDG: Fluorodeoxyglucose; SUVmax: Maximum standardized uptake value; DLBCL: Diffuse large B-cell lymphoma; Ann Arbor stage IVA: Standard lymphoma staging system; IPI: International Prognostic Index.

OUTCOME AND FOLLOW-UP

The patient demonstrated good tolerability to the first cycle of Pola-R-CHP chemotherapy. Follow-up is ongoing to assess long-term outcomes, with no adverse events reported at the time of writing. Postoperatively, bone marrow biopsy and cerebrospinal fluid analysis were normal, with no malignant cells detected.

DISCUSSION

Testicular lymphoma can present as a primary testicular mass without involvement of other extranodal organs, referred to as PTL, or as secondary testicular lymphoma due to involvement from other sites. Distinguishing primary from secondary involvement is challenging in stage IV cases. PTL primarily affects older adults, with a median onset age of 66-69 years, and is more common than testicular germ cell tumors in individuals over 60[10]. Clinically, PTL typically presents as painless testicular swelling in approximately 80% of cases, often with a mass around 6-8 cm in diameter, slightly more frequent in the left testis. About 40% of patients may also exhibit hydrocele. LDH levels are elevated in around 60% of PTL cases, and systemic B symptoms (fever, chills, night sweats, or weight loss) appear in 13%-41% of advanced-stage cases[1,2,10,11]. The most common pathological subtype is DLBCL, with up to 90% of cases diagnosed at stage I (60%) or stage II (30%)[12]. Additionally, HIV infection is a recognized risk factor for PTL and increases the likelihood of extranodal involvement, including testicular involvement[10,13].

Diagnostic methods

Ultrasound and MRI are key in identifying PTL. Ultrasonography typically shows diffuse hypoechogenicity with increased vascularity in an enlarged testis[1]. MRI allows detailed assessment of both testes and paratesticular structures. Positron emission tomography/computed tomography, bone marrow biopsy, and CNS staging (CSF analysis and brain MRI) are recommended for comprehensive staging in PTL cases[1]. When a diagnosis of PTL is made or suspected, inguinal orchiectomy is considered the gold standard for diagnosis, as it provides more precise histological characterization and local tumor control[14]. If a patient cannot tolerate surgery, an ultrasound-guided needle core testicular biopsy may be considered[15]. Percutaneous testicular biopsy is minimally invasive and requires only local anesthesia; however, it may increase the risk of tumor seeding due to scrotal violation.

Differential diagnosis of tumor thrombus

Differentiating tumor thrombus from bland thrombus is essential, as the former typically shows FDG avidity and an enhancement pattern similar to the primary tumor. Venous tumor thrombus is commonly seen in solid tumors (e.g., renal cell carcinoma and hepatocellular carcinoma) and is extremely rare in lymphoma, often leading to diagnostic challenges that may result in misdiagnosis as solid organ tumors[16]. Misdiagnosis of lymphoma-associated tumor thrombus can lead to unnecessary surgical interventions, as in a previous case where a patient with IVC tumor thrombus from lymphoma was misdiagnosed with renal cell carcinoma and underwent nephrectomy[17].

In our patient, ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography revealed intense, homogeneous tracer uptake along the entire course of the left gonadal vein (SUVmax 16.5), nearly matching the activity of the left testis (SUVmax 14.1). This metabolic pattern is consistent with tumor thrombus rather than bland thrombus. Notably, venous tumor thrombus is less common in germ cell tumors, with incidence rates of IVC thrombus ranging from 0.6% to 11%, and other veins (renal, gonadal, and lumbar) occasionally affected[18-22]. Tumor thrombus in testicular cancer is particularly associated with more aggressive subtypes, such as embryonal carcinoma or mixed non-seminomatous germ cell tumors with embryonal carcinoma components[23], which frequently demonstrate elevated serum levels of AFP and β-HCG. Christopher et al[19] reported a case of testicular embryonal germ cell cancer with tumor thrombus in the gonadal and renal veins. However, our patient’s normal AFP and β-HCG levels suggested a higher likelihood of seminoma. This raised suspicion regarding the pathological hypothesis in relation to the gonadal vein tumor thrombus symptom. Currently, reports of lymphoma with venous tumor thrombus are mainly limited to case reports or case series, with the most commonly affected veins being the renal vein, IVC, and portal vein. There are also occasional reports of involvement of the superior vena cava, superior mesenteric vein, splenic vein, common iliac vein, and central adrenal vein[24-28]. The most common lymphoma subtype associated with venous tumor thrombus is DLBCL, followed by follicular lymphoma (FL), a combination of FL and DLBCL, Hodgkin disease, and T-cell lymphoma[27]. Given that PTL is the most common testicular malignancy in men over 60, particularly when associated with lymphadenopathy and systemic symptoms, the presence of lymphoma should be carefully considered in older patients with testicular masses and venous thrombus.

Therapeutic approach

Testicular lymphoma is aggressive, and treating PTL is challenging due to the risk of late relapses. Despite recent advances and aggressive treatment, the prognosis remains relatively poor[14]. There is still no specific guideline for testicular DLBCL. Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the most common first-line chemoimmunotherapy regimen, with CNS prophylaxis and contralateral testicular radiation advised to reduce recurrence risk[14,29]. For the ABC subtype of DLBCL, lenalidomide added to R-CHOP (R2CHOP) has shown improved progression-free survival (PFS) and overall survival (OS)[30] due to inhibition of B-cell receptor-dependent nuclear factor-kappa B activation[31]. Recent studies, including the POLARIX trial, support the addition of Polatuzumab Vedotin for untreated intermediate-risk or high-risk DLBCL, showing reduced progression and relapse rates[32]. Various chemo-free regimens have emerged in recent years, such as Bruton’s tyrosine kinase (BTK) inhibitors in mantle-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, and programmed death 1/programmed death ligand 1 inhibitors in classical Hodgkin lymphoma and natural killer cell/T-cell lymphoma. For DLBCL, BTK inhibitors and lenalidomide are recommended for second-line treatment in certain cases, and the XPO1 inhibitor selinexor and anti-CD19 CAR T-cell therapy for third-line treatment. Nevertheless, chemo-free regimens are rarely used in PTL, with limited case reports[33-35].

Prognosis

Age, year of diagnosis, laterality, elevated LDH level, presence of B symptoms, Ann Arbor stage, IPI score, and treatment modality are risk factors for PT-DLBCL[3,36]. For stage I/II PTL patients treated with R-CHOP along with radiation to the contralateral testis and intrathecal methotrexate, the five-year PFS rate is 74%, and the OS rate is 85%[17,29]. PFS is significantly lower in patients with stage IV disease, IPI score ≥ 2, B symptoms, and elevated LDH levels[36]. To date, no prognostic studies have specifically examined PTL with tumor thrombus. However, data from lymphomas at other anatomical sites suggest that tumor thrombus does not substantially alter clinical outcomes (Table 2).

Table 2 Treatment response of lymphoma with tumor thrombus reported in the literature.

Ref.	Primary tumor site	Tumor thrombus site	Pathology	Treatment	Prognosis
Wagner et al[17], 1993	Right kidney	Renal vein and IVC	DLBCL	Right radical nephrectomy followed by 6 courses of CHOP chemotherapy	Significant mass reduction after 1 year
Yoneyama et al[24], 1998	Hepatic tumor of the left and caudate lobes	Portal vein	DLBCL	Left hepatic trisegmentectomy, caudate lobectomy and portal tumour thrombectomy followed by 6 courses of combination chemotherapy including CHOP and VP-16	4.5 years without recurrence after surgery
Matsumoto et al[37], 2004	Mesentery nodal	Portal vein and superior mesenteric vein	DLBCL	An open surgical biopsy followed by 7 courses of CHOP	7.5 years without recurrence after diagnosis
Hiraga et al[38], 2006	Porta hepatis	Portal vein	DLBCL	Biopsy followed by 8 courses of THP-COP	6 years without recurrence after the initial diagnosis
Natsuizaka et al[28], 2009	Liver and left spermatic cord	Portal vein	DLBCL	Percutaneous liver biopsy and left testis and spermatic cord were surgically resected followed by 6 courses of R-CHOP	Complete response maintained for 16 months after chemotherapy
Samlowski et al[39], 2011	Right upper pole of kidney, right adrenal gland and liver	Renal vein and IVC	DLBCL	Biopsy followed by R-CHOP	Partial response after 3 courses of chemotherapy
Chen et al[25], 2013	Left solid renal mass, retroperitoneal extension and adenopathy	Renal vein, IVC	DLBCL	Biopsy followed by R-CHOP	Complete response maintained for 47 months

IVC: Inferior vena cava; DLBCL: Diffuse large B-cell lymphoma; CHOP: Cyclophosphamide, doxorubicin, vincristine, and prednisone; THP-COP: Cyclophosphamide, pirarubicin, vincristine, and prednisone; R-CHOP: Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab.

CONCLUSION

This case demonstrates the diagnostic complexities of PTL with gonadal vein tumor thrombus, underscoring the importance of considering lymphoma in elderly patients with testicular masses and venous involvement. A multi-disciplinary team including urologists, hematologists, and radiation oncologists is needed to ensure appropriate therapy.

ACKNOWLEDGEMENTS

We thank the patient for his consent to the publication of this case report and the clinical team for their support.