Primary diffuse large B cell lymphoma (DLBCL) of the prostate presenting with lower urinary tract symptoms (LUTS)

Abstract

Malignant lymphomas of the prostate are very rare tumours and are generally not considered in the clinical or pathological diagnosis of prostatic enlargement. We report a case of a 56-year-old man who presented with long-standing history of low back pain and a 2-month history of voiding lower urinary tract symptoms. He denied any history of urinary retention, trauma, catheterisation or any constitutional symptoms. Examination revealed no lymphadenopathy and hepatosplenomegaly. Digital rectal examination showed an irregular, moderately enlarged nodular prostate. His prostate-specific antigen was 1.54 ng/mL. MRI of the pelvis did not show any focal lesion apart from abnormal signal intensity in the central zone. Bone scan was negative. Transrectal ultrasound-guided prostate biopsy revealed diffuse large B cell lymphoma. Bone marrow biopsy and whole body positron emission tomography/CT were unremarkable. The patient achieved complete remission after receiving six cycles of R-CHOP chemotherapy.

Background

Malignant lymphomas of the prostate are very rare tumours and are generally not considered in the clinical or pathological diagnosis of prostatic enlargement.¹ They account for 0.09% of all prostatic malignancies and 0.2%–0.8% of all extranodal non-Hodgkin’s lymphomas (NHL).^{1 2} Most of the cases present in the sixth decade of life, with majority due to secondary involvement of NHL of a typical site. Primary prostatic lymphomas account for only 35% of these cases, with majority being of diffuse large B cell lymphoma (DLBCL) type. Due to rarity of the disease and the non-specific symptomatology, the diagnosis is generally delayed. These tumours are generally aggressive, with poor short-term outcome. Description of DLBCL localised to prostate without any lymph node involvement or metastasis is extremely rare in the literature.³

Case presentation

A 56-year-old male known case of diabetes and hypertension presented to the urology clinic with a 2-month history of lower urinary tract symptoms (LUTS), particularly poor flow, sense of incomplete bladder emptying, dysuria and hesitancy. He also had long-standing history of lower back pain radiating to the right leg. The patient denied any history of constitutional B symptoms such as fever, weight loss or night sweats. Review of systems was unremarkable and he denied any history of urinary retention, urethral trauma, catheterisation, cancer, sexually transmitted infections or neurological disease. Family history was negative for prostate or breast cancer.

On examination, there were no signs of anaemia or lymphadenopathy. His abdominal examination was unremarkable with no hepatosplenomegaly, and his digital rectal examination (DRE) revealed an irregular, moderately enlarged nodular prostate. His International Prostate Symptom Score was 18 out of 35 and his Eastern Cooperative Oncology Group performance status was 0.

Investigations

The patient underwent the following investigations in chronological order:

Laboratory investigations

• Haemoglobin: 134 g/L.

• Total leucocyte count: 8.6×10⁹/L without any atypical cells.

• Platelets: 286×10⁹/L.

• Prothrombin time/ International normalized ratio (PT/INR): 13/1.1.

• Creatinine: 1.1 mg/dL.

• Electrolytes: normal.

• Urine detailed report: normal.

• Urine culture and sensitivity: no bacterial growth.

• Prostate-specific antigen (PSA): 1.54 ng/mL.

Radiological imaging

• Ultrasound of the kidney, ureter and bladder: normal non-hydronephrotic kidneys with 38 g prostate, with post void residual urine volume of 76 mL.

• Based on suspicion of prostatic malignancy, he underwent MRI of the pelvis and lumbosacral (L/S) spine, whole body bone scan, and transrectal ultrasound (TRUS) guided 12-core needle biopsy of the prostate.

• Bone scan: negative.

• MRI of the pelvis: 4.8×4.1×3.2 cm prostate with abnormal signal intensity area in the central zone appearing hypointense on T2-weighted image. The prostatic capsule and neurovascular bundles were intact. Seminal vesicles were normal and there was no pelvic lymphadenopathy (figure 1).

• MRI of the L/S spine: L5–S1 disc bulge causing nerve root compression on the right side.

Figure 1.

(A) T1-weighted and (B) T2-weighted MRI.

Pathological imaging

• Gross examination: TRUS biopsy showed 12 linear core tissues from both the right and left lobes of the prostate, with the largest measuring 1.1 cm.

• Microscopic examination: sections from 4 cores out of 12 (2 each from the apical prostatic tissues of the right and left lobes) revealed prostate parenchyma infiltrated by atypical medium-sized to large-sized lymphoid cells arranged in diffuse sheets. These lymphoid cells exhibited scant to moderate amount of eosinophilic cytoplasm and nuclei with irregular contours, dispersed chromatin and occasional prominent nucleoli. The rest of the eight prostate tissue cores revealed benign prostate parenchyma showing glands lined by double-layered epithelium.

• Immunohistochemical studies: tumour cells were strongly positive for leucocyte common antigen, CD20 (Pan-B marker), BCL-2 and CD10. Other markers, that is, CD3 (Pan-T marker), cyclin D1 and cytokeratin AE1/AE3, were negative. The Ki-67 proliferation index was expressed by approximately 80% nuclei (figure 2).

Figure 2.

(A) Low-power magnification (10×) H&E: prostatic parenchyma exhibiting diffuse sheets of atypical lymphoid cells. (B) High-power magnification (40×) H&E: prostatic glands and stroma infiltrated by moderate to markedly pleomorphic and hyperchromatic lymphoid cells. (C) Immunohistochemistry (20×): CD20 immunostain showing diffuse strong membranous positivity. (D) Immunohistochemistry (20×): proliferation index (Ki-67): approximately 80% nuclear positivity.

The patient subsequently had a bone marrow biopsy and whole body positron emission tomography (PET/CT) scan. There was no marrow involvement, and biopsy showed normocellular marrow with multilineage haematopoiesis. Whole body PET/CT scan did not reveal tumour in any other parts of the body.

Differential diagnosis

The most likely differential diagnosis is adenocarcinoma of the prostate due to nodular prostate and history of low back pain. However, PSA in this case was low and MRI did not show any lesion(s) in the prostate. Another differential is sarcoma of the prostate, but again MRI of the pelvis showed an intact prostate capsule with no periprostatic involvement. Benign prostatic hyperplasia may have a low/normal PSA but would have a firm, smooth prostate on DRE. Chronic pelvic pain syndrome and granulomatous prostatitis are other differentials but are associated with long history of LUTS.

Treatment

The patient received alpha-adrenergic blocker tamsulosin with finasteride for LUTS with good response. For his radicular pain, he received diclofenac sodium and pregabalin. Following discussion in a multidisciplinary tumour board meeting, he received six cycles of R-CHOP (Rrituximab, Cyclophosphamide, Doxorubicin hydrochloride, Vincristine sulfate, and Prednisone) regimen at an outside cancer treatment facility.

Outcome and follow-up

The patient achieved complete remission after six cycles of chemotherapy. He is currently doing well after 6 months of completion of chemotherapy and follow-up imaging did not show any abnormal findings.

Discussion

Prostate cancer is the most commonly diagnosed neoplasm in men, accounting for 28% of new cancer cases in the USA.⁴ Adenocarcinoma of the prostate accounts for 95% of all prostatic cancers, with NHL contributing to only 0.1% of these cases. Data are limited with regard to the natural history and management options for prostatic lymphoma. Lymphoma of the prostate should be suspected in a patient with obstructive LUTS in the absence of any other lower tract pathology and with normal PSA.⁵ Patients with secondary lymphoma of the prostate may also give history of primary lymphoma elsewhere. There is a lack of systematic study on the clinical features, diagnostic modalities, treatment and prognosis of primary prostatic lymphoma as majority of the literature is limited to individual case reports.

Most cases of NHL involving the prostate are DLBCL, but primary prostatic small cell lymphomas, Burkitt lymphomas, follicular lymphomas, mucosa-associated lymphoid tissue lymphomas and mantle cell lymphomas are also described.^{1 2 6} Primary lymphoma of the prostate is thought to have origin in the rudimentary lymphoid nodules or due to proliferation within the capillaries or postcapillary venules.^{7 8} Gene expression profiling has identified two distinct molecular subtypes of DLBCL: the germinal centre B cell-like and activated B cell-like groups, the cell-of-origin classification. These groups have different genetic mutations, pathogenesis and outcomes following treatment.⁹

Terris et al⁶ found 13 cases (1.2%) of prostatic lymphomas in 1092 specimens of radical prostatectomy done for prostate cancer, with DLBCL being the most common subtype. Chu et al¹⁰ examined 4831 prostate samples, including needle biopsy, transurethral resection and radical prostatectomy specimens, and found lymphoma/leukaemia in 15 (0.3%) cases only.

Clinical presentation is with voiding LUTS and frequency and urgency. Pain or haematuria may be the presenting symptom in some of the patients. Urinary retention, perineal and anal pain, dyschezia and flank pain due to obstructive uropathy are other symptoms.¹¹ Systemic/constitutional symptoms may be present in some patients. Due to non-specific symptoms and normal PSA, this condition can often be mistaken for Benign prostatic hyperplasia (BPH) or chronic prostatitis, leading to delay in diagnosis.¹¹

Bostwick et al² proposed diagnostic criteria for primary prostatic lymphoma to clarify whether malignant lymphoma of the prostate is primary or secondary based on three conditions: (1) symptom presentation attributed to enlarged prostate; (2) prostate as the predominant site of involvement; and (3) absence of involvement of other sites, such as the lymph nodes, blood, liver and spleen within 1 month of diagnosis of prostate involvement. This is the largest study of primary prostatic lymphoma to date, with 22 pooled cases from three tertiary care referral centres.²

Cross-sectional imaging such as CT scan and MRI of the prostate are generally non-specific for its diagnosis, while PET scan can help to determine the metabolic activity at suspicious sites and to monitor the disease and response to treatment.³

The treatment modalities for primary NHL are chemotherapy and/or radiation and surgery in some cases; however, guidelines are not clear with regard to the management of this rare tumour and there is no consensus on therapeutic modalities. Good responses have been reported with rituximab and anthracycline-based combination chemotherapy regimen in the literature.¹² Generally six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is the chemotherapy regimen of choice and has shown better disease-free survival in primary prostatic lymphomas compared with secondary one or with extensive disease.³

Radical surgery was not found to be an appropriate treatment option for prostatic lymphoma. Fukutani et al¹³ summarised a series of 22 Japanese patients with prostatic lymphoma. Three patients were treated with radical prostatectomy alone but had evidence of early progression and died, while patients who received chemotherapy alone or in combination with other treatment had a complete response.

Jafari et al¹⁴ reported a case of a 71-year-old man who presented with LUTS and haematuria. There were no constitutional symptoms and they found a diffusely enlarged prostate on DRE with normal PSA. His cross-sectional imaging did not reveal any pathology. Prostate biopsy confirmed it to be primary DLBCL. Bone marrow examination was done, which was normal. He was treated with R-CHOP regimen followed by pelvic radiotherapy (50 Gy) and did well 3 years post treatment.

Ezekwudo et al³ reported a case of a 54-year-old man who presented with history of urinary retention with normal PSA and enlarged benign-feeling prostate. He had history of ileocolectomy for tubulovillous adenoma. The patient underwent Transurethral resection of prostate (TURP) and the prostate tissue was found to have DLBCL based on morphology and immunohistochemistry. Bone marrow biopsy was normal with multilineage haematopoiesis. The patient was treated with chemotherapy and was disease-free on surveillance 2 years after the treatment.

Kakkar et al¹⁵ reported two cases of primary DLBCL of the prostate diagnosed on TRUS-guided biopsy in a 35-year-old and a 65-year-old patient who presented with LUTS, normal PSA levels and nodular prostates. Both had negative B symptoms and a normal bone marrow. PET scan, however, found increased uptake not only in the prostate but also in the regional lymph nodes. Both of these patients were successfully treated with six cycles of R-CHOP regimen.

In our case, the diagnosis was established on prostate biopsy done for a nodular prostate raising the suspicion for prostate cancer; however, diagnosis using DRE can be challenging as studies have reported prostates to appear diffusely enlarged with benign consistency,^{3 14 16} irregular or nodular¹⁵ and even stony hard.¹¹ Our case was fortunately diagnosed early and had a localised disease to the prostate only, with no extraprostatic extension, nodal involvement and distant metastasis. He responded well to chemotherapeutic regimen and is on remission on interim imaging.

The study of Bostwick et al² showed that 73% of patients with primary prostatic lymphoma developed extraprostatic disease between 1 and 59 months after diagnosis, with 1-year, 2-year and 5-year survival rate of 64%, 50% and 33%, respectively.

Learning points.

• Prostatic lymphomas are very rare and are challenging tumours to diagnose due to rarity and non-specific symptomatology.

• Most patients present with voiding lower urinary tract symptoms and have normal prostate-specific antigen at presentation.

• Diagnosis is established on prostate biopsy and on cross-sectional imaging such as MRI and positron emission tomography/CT.

• Diagnostic criteria for ‘primary’ prostatic lymphoma are based on symptoms attributed to prostatic enlargement and absence of involvement of other lymphohaematopoietic organ systems.

• Rituximab and anthracycline-based combination chemotherapy is the first-line treatment of choice, with radiation and surgery reserved for specific cases.