Mantle cell diffuse large B-cell lymphoma revealed by lower urinary tract symptoms: A case report and literature review

Abstract

Introduction

Mantle cell lymphoma with diffuse large B cell lymphoma transformation (MCL-DLBCL) is a rare and aggressive form of lymphoma that typically presents with non-specific symptoms. It is uncommon for this lymphoma to manifest as lower urinary tract symptoms (LUTS), such as dysuria, hematuria, and pelvic pain, often leading to misdiagnosis and delayed treatment.

Case presentation

We present the case of a 62-year-old male patient who presented with irritative urinary symptoms. After a series of diagnostic tests, including imaging (MRI, PET-CT) and histopathological analysis, the final diagnosis was mantle cell lymphoma (MCL) with transformation into mantle cell diffuse large B-cell lymphoma (MCL-DLBCL) involving the prostate, lymph nodes, and stomach. Prostate biopsy and immunohistochemical analysis confirmed this diagnosis.

Discussion

This case highlights the rare presentation of MCL-DLBCL with urinary symptoms. The role of advanced imaging techniques, such as MRI and PET-CT, in identifying the involved organs is emphasized. The study also underscores the importance of prostate biopsy and immunohistochemical analysis to confirm the diagnosis and distinguish between MCL transformation into MCL-DLBCL or a composite lymphoma. A multidisciplinary approach is crucial for early detection and proper management.

Conclusion

The patient received a combination of chemotherapy, including rituximab and other agents, leading to complete remission. After chemotherapy, the patient underwent autologous hematopoietic stem cell transplantation, contributing to his recovery.

Highlights

• •Mantle cell diffuse large B-cell lymphoma (MCL-DLBCL) can sometimes present with lower urinary tract symptoms (dysuria, hematuria, pelvic pain), which is rare and often confused with other benign conditions, thus delaying the diagnosis.
• •MRI and PET-CT play a crucial role in diagnosing this type of lymphoma, allowing for the identification of prostate infiltration, as well as affected lymph nodes and other organs, such as the stomach in this case.
• •Prostate biopsy and immunohistochemical analysis helped confirm the diagnosis of MCL-DLBCL.
• •A combined chemotherapy regimen, including rituximab and other agents, led to complete remission of the patient, followed by autologous hematopoietic stem cell transplantation, highlighting the importance of prompt and effective management.

1. Introduction

Prostatic lymphomas (PL) are rare, with fewer than 300 cases reported in the literature [1]. Diffuse large B-cell lymphoma of the mantle cell type (MCL-DLBCL) is a rare form of non-Hodgkin lymphoma, characterized by the proliferation of B cells in lymphoid tissues. This subtype accounts for about 5 to 10 % of non-Hodgkin lymphomas and is distinguished by its origin in the peripheral zones of lymph nodes and its tendency to invade various organs [1].

The clinical symptoms of MCL-DLBCL are generally non-specific and include systemic symptoms such as fever, weight loss, and night sweats. The isolated presentation with lower urinary tract symptoms is rare. These urological manifestations can include dysuria, hematuria, and pelvic pain, often attributed to other benign conditions [2]. As a result, the diagnosis of lymphoma is frequently delayed, complicating patient management.

This article presents a case of transformation from mantle cell lymphoma (MCL) to diffuse large B-cell lymphoma of mantle cell type (MCL-DLBCL) at the prostate level, revealed by urinary symptoms, followed by a review of the literature on this atypical clinical presentation. This case highlights the importance of an extensive differential diagnosis and a multidisciplinary approach involving urologists, pathologists, radiologists, and hematologists to ensure early diagnosis and a better understanding of the urological manifestations of this rare condition [3].

2. Case report

The patient is a 62-year-old male with a history of psoriasis who presented with irritative lower urinary tract symptoms. Ultrasound revealed a prostate of 120 g with a post-micturition residual volume of 90 cc. The upper urinary tract showed no abnormalities. A digital rectal exam revealed a hard, fixed, and homogeneously enlarged prostate. Clinical examination also highlighted a 3 cm submandibular lymphadenopathy. The prostate-specific antigen (PSA) level was normal (0.123 ng/mL).

Due to the suspicious findings on the rectal exam, a prostate MRI was performed before biopsy, showing an enlarged prostate with homogeneous infiltration of the peripheral and transitional zones, as well as the seminal vesicles. Inguinal and pelvic lymphadenopathy suggesting prostate lymphoma was also observed (Fig. 1).

Fig. 1.

Pelvic MRI:

(a) Axial T2 sequence: enlarged prostate with diffuse hypointensity.

(b) Axial T2 sequence: encasement of seminal vesicles without invasion.

(c) T1 sequence with contrast injection: diffuse contrast enhancement.

(d) Coronal T2 sequence: right iliac lymphadenopathy.

A systematic transrectal ultrasound-guided biopsy with 12 samples revealed diffuse tissue organization, the absence of well-defined glandular structures, and high cellularity with a proliferation of large B cells with irregular nuclei, clear chromatin, and prominent nucleoli (Fig. 2-a). Immunohistochemical analysis showed positive staining for anti-CD20 antibodies (Fig. 3-a) and anti-CD5 antibodies (Fig. 3-b), with a Ki-67 proliferation index of 40 % (Fig. 3-c). The staining was also positive for cyclin D1 and CD23.

Fig. 2.

Standard HE staining:

(a) Prostatic proliferation of large B cells with irregular nuclei, clear chromatin, and prominent nucleoli.

(b) Gastric proliferation, diffuse tissue organization, absence of well-defined glandular structures, and high cellularity with a predominance of small basophilic lymphoid cells.

Fig. 3.

IHC (Immunohistochemistry):

(a) Anti-CD20 antibody: positive with diffuse membranous and cytoplasmic staining.

(b) Anti-CD5 antibody: positive with diffuse membranous and cytoplasmic staining.

(c) IHC: high expression of Ki-67 at 40 %.

Biological tests revealed an elevated beta-2-microglobulin (> 4 mg/L), a white blood cell count of 11,700/mm3, and a normal lactate dehydrogenase level. A thoracic, abdominal, and pelvic CT scan showed retroperitoneal, iliac, and inguinal lymphadenopathies bilaterally. A PET-CT with 18-FDG showed hypermetabolic lymph nodes and diffuse gastric hypermetabolism (Fig. 4). An esophagogastroduodenoscopy with biopsy confirmed the gastric localization of a B-cell lymphoma consisting of a proliferation of small B cells in the peripheral zones of lymph nodes. These cells showed irregular nuclei and low mitotic activity (Fig. 2-b). Immunohistochemistry showed positivity for CD5, CD20, cyclin D1, with a low expression of Ki-67 at 20 %.

Fig. 4.

PET-CT with 18-FDG: showed hypermetabolic lymph nodes and diffuse gastric hypermetabolism.

The final diagnosis was non-Hodgkin lymphoma of the mantle cell type (MCL) with involvement of the lymph nodes, stomach, and prostate, with transformation into mantle cell diffuse large B-cell lymphoma (MCL-DLBCL) at the prostate level. After discussion in a multidisciplinary committee, chemotherapy with the RDHAOx protocol (rituximab, dexamethasone, oxaliplatin, and cytarabine) was initiated, leading to complete remission confirmed by PET imaging and a negative bone marrow biopsy. The patient subsequently underwent autologous hematopoietic stem cell transplantation. He is currently in complete remission, with 18 months of follow-up.

3. Discussion

Mantle cell lymphoma diffuse large B-cell type (MCL-DLBCL) is a rare form of non-Hodgkin lymphoma characterized by the proliferation of B lymphocytes in the peripheral zones of lymph nodes and infiltration of other organs. It can result from a transformation of mantle cell lymphoma (MCL) into MCL-DLBCL, or from a composite lymphoma involving both types [1]. While this lymphoma is commonly diagnosed with systemic manifestations such as fever, weight loss, and night sweats, it is extremely rare for it to present with lower urinary tract symptoms. In our case, the initial symptoms were irritative urinary disturbances without more specific systemic signs [3].

Urological symptoms, although often associated with benign prostatic conditions such as benign prostatic hyperplasia (BPH), can sometimes be the first manifestation of prostatic lymphoma. Several studies have reported cases of prostatic lymphoma, but these presentations remain rare (Table 1).

Table 1.

Main published cases of prostatic lymphoma.

Publication	n	Histology	Symptoms	Therapeutic management
Sarris et al. [4]	3	NHL	LUTS	CT
Bostwick et al. [5]	22	NHL	LUTS	CT (5), RT (8), CT/RT (2), PR (3), 2-year OS: 50 %
Bostwick et al. [6]	7	NHL	LUTS	CT, median survival: 15 months
Chargari et al. [7]	1	NHL	LUTS	CT, TURP,RT
Wazait et al. [8]	1	NHL	LUTS	RT, TURP
Singh et al. [9]	1	NHL	LUTS	RT, TURP, CT, CR

CT: Chemotherapy, RT: Radiotherapy, TURP: Transurethral Resection of the Prostate

LUTS: Lower Urinary Tract Symptoms, NHL: Non-Hodgkin Lymphoma, CR: Complete Remission, OS: Overall Survival.

Clinically, the urological symptoms are generally dominated by lower urinary tract symptoms (LUTS) of a benign nature, mimicking benign prostatic hyperplasia or prostatitis. Common irritative symptoms include frequency, nocturia, urgency, and dysuria. Obstructive symptoms, such as weak urinary flow, the sensation of incomplete bladder emptying, and, less commonly, urinary retention, may also be present. Additionally, hematuria, pelvic pain, or a homogeneous, hard prostatic mass on digital rectal examination may suggest a more serious pathology [3].

Prostatic lymphoma is distinguished from other prostatic conditions by its diffuse infiltration of the gland, often bilateral, and the absence of well-defined nodules on rectal examination, as observed in our patient [10].

Imaging techniques, such as MRI and PET-CT, play a crucial role in diagnosing mantle cell lymphoma, especially in assessing the extent of the disease. In our case, the MRI revealed homogeneous infiltration of the peripheral and transitional zones of the prostate, as well as inguinal and pelvic lymphadenopathy, suggesting prostatic lymphoma. PET-CT confirmed the presence of hypermetabolic lymph nodes and diffuse gastric hypermetabolism, suggesting secondary stomach involvement by lymphoma. This suspicion was confirmed by an esophagogastroduodenoscopy with biopsy. The combination of these exams allows the detection of secondary infiltration sites and helps guide treatment and prognosis [11].

The diagnostic challenge in our case was distinguishing between a transformation from MCL to MCL-DLBCL or a composite lymphoma. Prostate and gastric biopsies with histological and immunohistochemical analysis allowed us to differentiate between these two entities. The transformation from MCL to MCL-DLBCL is a process where the initially indolent lymphoma becomes more aggressive. This transformation is often associated with an unfavorable prognosis and can occur in a significant proportion of cases, especially in patients who are inadequately treated or who do not respond well to conventional treatments. Histopathologically, transformation to DLBCL is characterized by a diffuse architecture and larger cells compared to the initial MCL. The tumor cells acquire a more aggressive morphology, with increased proliferation and larger, irregular nuclei [1].

Immunohistochemically, the transformation of MCL to DLBCL can result in a more prominent expression of Ki-67 (proliferation index) and the loss of certain MCL characteristics, such as cyclin D1 expression. In some cases, DLBCL may also show expression of markers like CD10, BCL6, or MUM1, which are not typical of MCL [11].

In our observation, the final diagnosis of non-Hodgkin lymphoma of mantle cell type with aggressive transformation to DLBCL at the prostatic level was confirmed by prostate biopsy followed by immunohistochemical analysis with specific markers. The histological results explain that gastric involvement remained completely asymptomatic due to the low aggressiveness of MCL in the stomach, while the transformation of MCL into MCL-DLBCL was more pronounced and symptomatic, allowing the diagnosis to be established based on urinary symptoms that prompted the consultation.

Unlike isolated MCL, transformation to DLBCL is often associated with a more aggressive clinical evolution, as seen in our observation.

The treatment of MCL, particularly in advanced or transformed stages, relies on a multimodal approach. In our patient’s case, the RDHAOx protocol (Rituximab, Dexamethasone, Oxaliplatin, Cytarabine) was used. This combined chemotherapy regimen is effective in treating MCL-DLBCL and has shown promising results in transformed MCL forms. It combines a cytotoxic agent with targeted therapy using Rituximab, a monoclonal antibody directed against CD20, which has proven effective in treating MCL [12].

Bruton's tyrosine kinase (BTK) inhibitors, notably Ibrutinib, represent another therapeutic option for refractory forms or patients with transformations to MCL-DLBCL. These treatments target a critical signaling pathway in B cell survival, contributing to a clinical response in cases of relapse or transformation. A recent study demonstrates the effectiveness of Ibrutinib in managing mantle cell lymphomas, including those that transform into DLBCL [13]. This treatment is particularly beneficial in advanced or refractory cases to first-line chemotherapy. Targeted therapies, such as BTK inhibitors, are particularly effective in patients refractory to conventional chemotherapy. These drugs block a key survival signaling pathway in tumor cells and have shown high response rates, even in the presence of genetic mutations related to resistance [13].

Autologous stem cell transplantation (autograft) remains an option for some patients after remission induced by chemotherapy or targeted treatments. This approach allows for prolonged remission and increases the chances of long-term survival [[12], [13], [14]].

Local treatment by transurethral prostate resection (TURP) has been necessary in certain reported cases of acute urinary retention, leading to rapid improvement of urinary symptoms [[7], [8], [9]].

In our case, first-line chemotherapy led to complete remission, as shown by molecular imaging and a negative bone marrow biopsy. Autologous hematopoietic stem cell transplantation was subsequently performed to consolidate this remission and prevent relapse [14].

A multidisciplinary approach involving urologists, hematologists, internists, and pathologists is crucial for the rapid diagnosis and treatment of this rare lymphoma. Close follow-up, particularly with imaging and biological tests, is essential to detect any recurrence and adapt treatment accordingly [15].

In addition to the rarity of prostatic involvement by lymphoma in general, to our knowledge, this is the first reported case in the literature of the transformation of MCL into mantle cell type diffuse large B-cell lymphoma in the prostate.

4. Conclusion

Mantle cell lymphoma diffuse large B-cell type (MCL-DLBCL) with prostatic involvement is very rare but significant, and should be considered in the differential diagnosis of urinary disorders, especially when accompanied by clinical or biological signs suggesting lymph node involvement. The histopathological study with immunohistochemical analysis enabled the establishment of a definitive diagnosis. Prompt management with a chemotherapy protocol and possibly autologous stem cell transplantation can offer a favorable prognosis, as demonstrated by this clinical case.

Author contribution

Idriss ZIANI, Majdouline BOUAOUAD, and Aziz AQIRA: study concept and design, data collection and interpretation, data analysis and interpretation, writing the paper. Jamal AOUIFI, and Hassan En-NOUALI: data collection, writing the paper. Yassine NOUINI And Aziz AQIRA: study design, correcting the manuscript, Validation.

Registration of research studies

Not applicable.

Patient consent

Informed written consent was obtained from the patient for the publication of this case report and any associated images.

Ethical approval

Ethical approval is not required as the case report does not contain any personal data. This decision was made in accordance with the guidelines of the Ibn Sina Hospital and University Mohammed V of Rabat Institutional Review Board.

Guarantor

Idriss ZIANI

Methods

The work was reported in accordance with the SCARE criteria [16].

Funding sources

No funding sources to declare.

Declaration of competing interest

The authors declare no conflict of interest.