INTRODUCTION
Primary hematolymphoid tumors of the genitourinary tract are uncommon. Primary lymphoma of the prostate comprises about 0.1% of all non-Hodgkin lymphomas (NHLs) and 0.09% of all prostatic malignancies.[1,2]
An analysis of the Surveillance, Epidemiology, and End Results (SEER) data (1998–2015) showed that primary extranodal lymphomas of the testis, kidney, urinary bladder, and prostate accounted for 3.04%, 0.22%, 0.18%, and 0.01%, respectively, of all localized tumors in those organs.[3]
The diagnosis of this entity depends on the correlation between clinical and histopathological findings with a thorough radiological workup to exclude secondary involvement of the prostate by primary lymphoma elsewhere.
CASE REPORT
A 61-year-old gentleman presented in the emergency room with hematuria of recent onset. There was no history of fever, night sweats, dysuria, or weight loss.
On digital rectal examination, the prostate appeared enlarged with an obliterated median sulcus. The surface was smooth without nodularity. Ultrasound revealed multiple bladder clots and bladder outlet obstruction due to prostatomegaly. On general examination, no organomegaly or lymphadenopathy was noted. Testes were normal. Serum prostate-specific antigen (PSA) was normal (1.1) throughout the course of the disease. Complete blood counts were normal, with an hemoglobin (Hb) of 12 gm%, a white blood cell (WBC) count of 7870/cmm, platelet count of 3,28,000, and an erythrocyte sedimentation rate (ESR) of 60 mm/hr. Kidney function test and liver function tests were normal.
In view of acute clot retention, an urgent cystoscopy was planned. On cystoscopy, the bladder was full of clots with generalized oozing from the prostate region. The patient underwent evacuation of clots and transurethral resection of the prostate (TURP). Good operative hemostasis was achieved, and the postoperative course was uneventful. The patient was discharged after the removal of Foley’s per urethral catheter on postoperative day 2. Resected prostatic chips were sent for histopathological examination elsewhere. A histopathological diagnosis of benign prostatic hyperplasia was given.
Within 15 days following discharge from the hospital, the patient presented to the emergency room with hematuria and clot retention. A contrast-enhanced computed tomography of the kidneys, ureters, and bladder (CT KUB) was performed to rule out any other sources of hematuria, which could have been missed. A CT scan revealed a normally excreting kidney with no specific bleeds in the genitourinary tract. However, there was significant prostatomegaly, which was unexpected owing to the recent TURP performed. An emergency cystoscopy confirmed multiple bladder clots with prostatomegaly. Clot evacuation with re-resection of the prostate was performed, and chips were sent for histopathological examination.
The specimen was evaluated in our laboratory, and a provisional diagnosis of high-grade round cell neoplasm, most likely lymphoma, was given [Figure 1]. On immunohistochemistry (IHC), tumor cells expressed CD20 [Figure 2], BCL2 [Figure 3], multiple myeloma 1 (MUM1) (70%) [Figure 4], BCL6 (40%) [Figure 5], and c-Myc (60–70%) [Figure 6]. The proliferative index (Ki-67) was 80% [Figure 7]. Tumor cells were immunonegative for CD10, CD5, and CD3. A final diagnosis of diffuse large B-cell lymphoma (DLBCL) of non-germinal center type of double-expressor was given.
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Figure 1: H and E of the biopsy (40X)
Figure 2: IHC showing immunoreactivity for CD20 (40X)
Figure 3: IHC showing immunoreactivity for BCL2 (40X)
Figure 4: IHC showing immunoreactivity for MUM1 (40X)
Figure 5: IHC showing immunoreactivity for BCL6 (40X)
Figure 6: IHC showing immunoreactivity for C-Myc (40X)
Figure 7: IHC showing Ki-67 (20X)
Other systemic investigations were performed, including positron emission tomography (PET) scan and bone marrow examination. A bone marrow examination showed cellular marrow with all marrow components, showing normal hematopoiesis. On a PET scan, the residual prostate gland was hypermetabolic, most likely mitotic in nature. No other lesion was noted.
The patient was started on rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) chemotherapy with radiotherapy. He responded well, and his follow-up scan revealed that the response to the therapy was complete remission.
DISCUSSION
A total of 165 cases of primary and secondary lymphomas involving the prostate have been reported[4-6] Prostatic lymphoma usually occurs in elderly men (mean age: 60–63 years).[4,7]
In determining which cases are acceptable as primary lymphoma of the prostate, we apply the criteria of Bostwick and Mann[1]: 1) presenting symptoms attributable to prostatic enlargement; 2) involvement of the prostate predominantly, with or without involvement of adjacent tissue; and 3) absence of involvement of the liver, spleen, or lymph nodes within 1 month of diagnosis of prostatic involvement.[8]
The symptoms are similar to those of other prostate diseases, with the vast majority of patients coming to the hospital for nonspecific symptoms such as urgency, frequency, painful urination, hematuria, nocturia, dysuria, and acute urinary retention, while specific symptoms associated with lymphomas such as fever, night sweats, and weight loss rarely appear in the early stages.[1]
In this case study, our patient presented with hematuria. On cystoscopy, generalized oozing was seen from the prostate. Thus, a decision to perform TURP was made to stop the bleeding, which gave us an opportunity for tissue diagnosis. We would like to highlight that lymphoma was not clinically suspected until the histopathological examination was performed.
Similar to our case, other authors have also reported presentation with hematuria.[9,10]
PSA is typically within or near normal limits in cases of prostatic lymphoma, with patients presenting with a mean PSA of 3.5–5.3 μg/L[11] Our case also showed similar findings. However, some case reports have shown an elevated PSA as a presenting feature.[12]
Almost all the cases in the literature were not diagnosed until a tissue biopsy was performed for prostate lymphoma. For a pathologist, the most difficult situation to obtain an accurate histological diagnosis is highly undifferentiated NHL occurring only in the prostate, without any other evidence, or any other tissue involved in another part of the body.[1,13]
Differential diagnosis includes prostatitis,[14] prostate cyst or abscess, small cell carcinoma, lymphoepithelioma-like carcinoma, and Hodgkin lymphoma (HL). Sometimes doctors must be aware of existing neoplasms originating from seminal vesicles and Mullerian duct relics.[15] Other two important differentials to be kept in mind are leukemic infiltration of prostate[14,16] and coexisting lymphoma and adenocarcinoma.[17] IHC can help in the further workup of these differentials. In our case, a thorough IHC workup helped in the holistic and timely evaluation of the patient. Large B-cell lymphoma is the main pathologic type of primary prostate lymphoma (PPL).[1,18-20]
In the World Health Organization (WHO) classification of tumors of hematopoietic and lymphoid tissues,[21] DLBCL consists of DLBCL, not otherwise specified (DLBCL NOS), and various specific variants. Typical IHC results of DLBCL NOS are characterized by large, atypical CD3-negative and CD20-positive lymphocytes with a Ki-67 labeling index greater than 80%. Furthermore, the cell of origin (COO) classification is performed by staining for CD10 (cutoff: 30%), BCL-6 (cutoff: 30%), and MUM1 (cutoff: 30%) through the Hans algorithm.[22] Their double-expressor phenotype is verified by staining for BCL-2 (cutoff: 50%) and c-Myc (cutoff: 40%).[23]
At present, there is no established consensus on the management of primary lymphoma of the prostate. Chemotherapy and radiotherapy are widely used modalities, with surgery being used for relieving obstructive symptoms.[24-26]
It is said, “what the mind doesn’t know, the eyes cannot see.” So, we would like to reiterate that lymphoma of the prostate is a very rare entity. It tends to get missed if there is an absence of a high index of suspicion. Including this entity in differentials will ensure that the condition is not underdiagnosed. Ancillary tools such as IHC can help a pathologist reach a diagnosis. It is important to remember that it is essentially a histopathological diagnosis. It is relevant to make the distinction between lymphoma and other carcinomas of the prostate because their clinical management differs vastly.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
Acknowledgement
We would like to acknowledge Dr S N Sharma, chief of pathology and owner of Haroti Diagnostic Centre, Kota, for his support and encouragement.
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