Abstract
Primary follicular lymphoma of the prostate is rare. This case report and literature review literature describes a 74-year old male patient who presented with worsening urinary symptoms, and imaging showing prostatomegaly compressing and displacing the rectum. He ultimately underwent a Millen retropubic prostatectomy for a prostate of 692 cc. The histology and immunohistochemistry confirmed the diagnosis as follicular lymphoma. His lymphoma underwent high-grade transformation with leptomeningeal involvement.
Keywords: Follicular lymphoma, Prostatic neoplasm, Prostatomegaly
1. Introduction
Primary non-Hodgkin's lymphoma of the prostate is rare, and there have been very few cases reported regarding primary follicular lymphoma of the prostate (see Table 1).
Table 1.
Case reports.
| Author/year | Age/diagnosis | PSA/size | Treatment/outcomes |
|---|---|---|---|
| Bostwick et al., 1998 | 62 cases. 3 primary follicular lymphomas | Individual case outcomes not reported | |
| Bouet et al., 2004 | 69 M | 62 cc | Patient outcomes not reported |
| Hard, fixed prostate on DRE | |||
| Biopsy/histology revealed follicular lymphoma | |||
| Gorgel et al., 2014 | 74 M open prostatectomy low intermediate grade non-hodgkin follicular lymphoma | PSA 2.4 | Patient did not receive chemotherapy, and remained disease free at 24 months |
| Uroflow flow rate max 8ml, average 4.4. Prostate 106 cc | |||
| Terada 2016 | 65 M primary follicular lymphoma | PSA 4.6ng/ml | Patient underwent low-dose R–CHOP chemotherapy and local radiation (40 Gy), with no recurrence 5 months post |
| 65g from TURP | |||
| Nerli et al., 2020 | 73 M presented with AUR | 147 cc | Patient referred to medical oncology, however refused further treatment |
| Follicular variant of non-Hodgkin lymphoma grade 2 | PSA 46.83 |
B-cell lymphomas are broken into categories: Diffuse large B-cell lymphoma (DCBCL), follicular lymphoma, chronic lymphocytic leukaemia (CLL)/small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), marginal zone lymphomas, Burkitt lymphoma amongst others.1 Follicular lymphoma is subclassified into Grade 1, 2 and 3 depending on the amount of centroblastic cells.1
Diagnosis of primary follicular lymphoma of the prostate is based on lower urinary tract symptoms, computed tomography (CT), magnetic resonance imaging (MRI) and histopathological examination.2 Bostwick et al. noted that for a lesion to be primary prostatic lymphoma, there needed to be 1) symptoms attributable to prostatic enlargement with tumour limited to the prostate or adjacent soft tissues, 2) involvement of the prostate predominantly, with or without involvement of adjacent tissue, and 3) absence of involvement of liver, spleen, or lymph nodes within 1 month of diagnosis of the prostatic involvement.2
There have been no cases of primary follicular lymphoma of the prostate, with prostatomegaly to this degree reported in the literature.
2. Case presentation
A 74-year old male, presented with a history of progressive lower urinary tract symptoms (LUTS) and a prostate specific antigen (PSA) of 16.3 in 2010. He had two transrectal ultrasound guided prostate biopsies in 2010 and 2011 showing no malignancy. He was commenced on Tamsulosin (an α-blocker) and dutasteride (a 5α-reductase inhibitor). His PSA incremented to 23 in 2012, with subsequent prostate biopsy showing no malignancy. Prostate MRI at this time showed an enlarged prostate with features of benign prostatic hyperplasia (BPH).
Due to worsening LUTS, and a prostate volume of 73 cc, he underwent an elective aqua-ablation of the prostate (TURP) in 2016.
In 2021, he had significant deterioration in LUTS over several months (nocturia x5, urge incontinence, weak stream, increased urinary frequency), associated with constipation and overflow faecal incontinence. His uroflow Qmax was 4.7mml/s and post void residual volume of 360ml. His repeat ultrasound showed a prostate volume of 692 cc. Computed Topography imaging showed massive prostatomegaly compressing and displacing the rectum, and obstructing bilateral ureters. His renal function was not impaired, and he had a normal full blood count (Fig. 1).
Fig. 1.
CT imaging. A) axial, B) coronal and C) sagittal computer tomography (CT) imaging showing prostatomegaly.
He underwent a Millen retropubic prostatectomy in 2022, with 350g prostate (measuring 170x179 × 45mm).
Microscopically, there were sections showing high cellular proliferation of lymphoid cells of variably-shaped follicles without mantle zones separated by bands of collagenous tissue, lacking body macrophages. Other sections showed benign prostatic hyperplasia (Fig. 2). For immunohistochemistry stains, the atypical cells are positive for CD20, CD79A, OCT-2, BOB-1, PAX5, Bcl-2, Bcl-6 and CD10. CD23 is negative. CD21 highlights the follicular dendritic cell network in the follicles. CD3 and CD5 highlight non-neoplastic T cells, primarily seen in the tissue between the follicles. Cyclin D1 is negative. Ki67 is elevated within the follicles, up to approximately 50–60% and is scant in the interfollicular areas. EBER-ISH, Kappa and Lambda-ISH are all negative (Fig. 3). These findings are all consistent with follicular lymphoma, grade 1.
Fig. 2.
Histopathology. A) H&E at x4 magnification – shows multiple confluent follicles of tumour cells. Eosinophilic fibrous tissue is seen between the follicles. B) H&E at x40 magnification – The cells within the follicles are mostly small and uniform, with somewhat angulated hyperchromatic nuclei and scant cytoplasm; these cells are consistent with centrocytes. There is an occasional larger cell with an oval nucleus, vesicular chromatin and larger amounts of cytoplasm (arrow); these are consistent with centroblasts. ); the number of centroblasts seen per high power field (HPF) is used to grade follicular lymphoma – in this case there are less than 6 centroblasts per HPF, which is consistent with grade 1.
Fig. 3.
Immunohistochemistry. A) CD20 at x2 magnification – The neoplastic cells within the follicles are diffusely and strongly positive for CD20, which is a B cell marker. A subset of the cells in the interfollicular region are also CD20 positive. CD3-positive reactive T cells are seen most densely in the interfollicular areas, but are rare in the follicles (CD3 stain not shown). B) Bcl2 x4 magnification – Bcl2 inhibits apoptosis and is negative in reactive follicles. Bcl2 expression is retained in follicular lymphoma because of t(14;18)/Bcl2-IgH. C) Bcl6 and D) CD10 at x2 magnification – Bcl6 and CD10 stain germinal centre B cells and are positive within the follicles of follicular lymphoma since it is a tumour of germinal centre B cells.
Two months later his follicular lymphoma underwent high-grade transformation with leptomeningeal involvement. He was commenced on two cycles of rituximab and cyclophosphamide followed by rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone (R–CHOP) chemotherapy and intrathecal methotrexate, with good clinical response 6 months later.
3. Discussion
Primary non-Hodgkin's lymphoma (NHL) of the prostate is rare, with very few cases of primary follicular lymphoma reported in the literature. Bostwick et al., presented an analysis of 62 prostatic lymphoma cases, of which 30 were secondary lymphomas, 22 were primary prostatic lymphomas, and 10 unable to be classified.2 Of the primary prostatic lymphomas, only 3 were follicular lymphoma. Due to the rarity of primary prostatic lymphoma, there is no current consensus regarding optimal management. Treatment modalities include chemotherapy, radiotherapy and radical prostatectomy.2
Patients found to have non-hodgkin lymphoma of the prostate have typically presented with lower urinary tract symptoms including increased urinary frequency, urgency and acute urinary retention.3,4 One case of primary follicular lymphoma of the prostate was asymptomatic, discovered by digital rectal examination.5 The prostate specific antigen (PSA) level is often within the normal range for non-hodgkins lymphomas.3,6, 7, 8 For case reports specifically finding follicular lymphoma of the prostate, only Gorgel et al. found a normal PSA of 2.4 ng/ml, with the other two cases both having elevated PSA levels.8 Nerli et al. (2020) presented a 73-year-old male with primary follicular lymphoma with a PSA of 46.83 ng/ml, and similarly Oosterheert et al. reported a follicular NHL of the prostate with PSA of 62 ng/ml.9 There has been a report of a primary low grade B cell lymphoma of the prostate with a PSA of 903 ng/ml, which following TURP decreased to 8.6ng/ml.9
Those diagnosed with primary follicular lymphoma of the prostate, need referral to a medical oncologist. Terada (2016) reported following low-dose R–CHOP chemotherapy and local radiation (40 Gy), there was no recurrence 5-months post.10
Majority of cases of primary lymphoma of the prostate have shown some degree of prostatomegaly, which lead to the symptoms that are detected. However, the largest found in the literature is 286 cc.6 Imaging is an important aspect of investigating prostatomegaly, however ultrasonography, CT and MRI lesion appearances are non-specific. The histopathological examination provides the diagnosis. Follicular lymphomas typically positive for CD10, CD20, BCL2, BLC6.11,12
4. Conclusion
Primary follicular lymphoma of the prostate is a rare condition that can progress with potential detrimental outcomes. It cannot be diagnosed clinically or radiologically, and requires histological diagnosis. There is currently insufficient evidence to recommend a particular treatment, with current management tailored to individual patient and disease factors. Lymphoma should be considered in the differential diagnosis of a rapidly growing prostate.
Consent
A written patient consent form has been signed by the patient and archived.
Declaration of competing interest
There are no conflicts of interest to declare.
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