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CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 4  |  Page : 977-979

Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations


1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, All India Institute of Medical Sciences, New Delhi, India
3 Department of Urology, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication15-Feb-2016

Correspondence Address:
Aanchal Kakkar
Department of Pathology, All India Institute of Medical Sciences, New Delhi - 110 029
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.176122

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 > Abstract 

Primary prostatic lymphomas are extremely unusual neoplasms. Their rarity and nonspecific symptomatology at presentation usually prompt a clinical diagnosis of benign prostatic hyperplasia or chronic prostatitis, leading to significant delay in diagnosis. Clinical examination, serum prostate-specific antigen levels, and transrectal ultrasonography (TRUS) are not of much utility in differential diagnosis, and histological examination is the gold standard. We report two cases of primary non-Hodgkin lymphoma of prostate, diffuse large B-cell type, diagnosed on TRUS-guided prostatic biopsies. Correct diagnosis is of crucial importance as the therapeutic strategy for lymphoma is radically different from that for carcinoma, and early detection of prostatic lymphoma can be potentially curative. Thus, knowledge of this rare entity, inclusion in differential diagnosis of lower urinary tract obstruction, and application of an appropriate immunohistochemical panel are essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery.

Keywords: Diffuse large B-cell lymphoma, extranodal, non-Hodgkin lymphoma, prostate


How to cite this article:
Kakkar A, Rajeshwari M, Bhethanabhotla S, Kaur K, Jain D, Gogia A, Ray R, Seth A. Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations. J Can Res Ther 2015;11:977-9

How to cite this URL:
Kakkar A, Rajeshwari M, Bhethanabhotla S, Kaur K, Jain D, Gogia A, Ray R, Seth A. Primary diffuse large B-cell lymphoma of the prostate: A report of two cases with diagnostic considerations. J Can Res Ther [serial online] 2015 [cited 2019 Sep 20];11:977-9. Available from: http://www.cancerjournal.net/text.asp?2015/11/4/977/176122


 > Introduction Top


Primary malignant lymphomas of the prostate are extremely rare, representing 0.09% of prostate neoplasms. [1] Due to their rarity, they are seldom considered in differential diagnosis of prostatic enlargement. Histological diagnosis of lymphomas at extranodal sites, including prostate, remains a challenge.


 > Case report Top


A 35-year-old male presented with complaints of postcoital pain, increased frequency of micturition, urgency, poor urinary flow, and incomplete emptying of bladder for 6 months. There was no history of fever, night sweats, dysuria, or weight-loss. On digital rectal examination, prostate was found to be enlarged, firm to hard, and nodular. Ultrasonography confirmed moderate enlargement of prostate, with moderate right and minimal left hydroureteronephrosis. Postvoiding residual urine volume was 30 ml. Serum creatinine was 1.6 mg/dl while serum prostate-specific antigen (PSA) was 0.78 ng/ml.

The second patient, a 65-year-old man, presented with complaints of hematuria for 1 month. He had undergone laser excision of prostate for benign hyperplasia 3 years ago. The urinary bladder mucosa was unremarkable on cystoscopy. Computed tomography abdomen and pelvis revealed a pelvic mass displacing the bladder and rectum, extending to the lateral pelvic wall; the prostate could not be visualized separately from the mass. Bilateral internal iliac lymph nodes were enlarged; no other lymph node group was involved. Serum PSA level was 0.08 ng/ml.

12-core trans-rectal ultrasonography-guided prostatic biopsies performed for both patients displayed similar features. Microscopic examination [Figure 1] showed a neoplasm composed of medium- to large-sized discohesive cells with scant cytoplasm and hyperchromatic nuclei. Occasional cells had vesicular nuclei with prominent nucleoli. Scattered eosinophils were identified. Perineural infiltration by tumor cells was present. Single file pattern was common at places, while other areas showed marked crushing of the tumor cells. All 12 cores were involved in both cases, indicating the diffuse involvement of both prostatic lobes. In Case 1, tumor cells were seen to infiltrate in between normal prostatic glands. However, in Case 2, the prostatic parenchyma was completely replaced by the tumor. Morphological diagnoses considered were non-Hodgkin lymphoma (NHL) and small cell carcinoma (SCC). Immunohistochemically [Figure 2], tumor cells from both cases were strongly positive for leukocyte common antigen and CD20 (B-cell marker), while they were negative for cytokeratin, chromogranin, synaptophysin, CD3, and Tdt. A final diagnosis of prostatic diffuse large B-cell lymphoma (DLBCL) was made in both cases. Case 1 was immunopositive for CD10 and bcl6, but negative for MUM1 that is, germinal center type DLBCL; Case 2 showed immunopositivity for MUM1, while CD10 and bcl6 were negative, indicating postgerminal center type DLBCL. Positron emission tomography scan performed in Case 1 showed increased uptake in prostate and pararectal, obturator, and bilateral internal iliac lymph nodes. Serum lactic acid dehydrogenase was 259 U/L. Peripheral blood and bone marrow examinations were normal, that is, stage IIE. The patient was started on cyclophosphamide, doxorubicin, vincristine, prednisone, rituximab (R-CHOP) regimen. His renal parameters improved after the first cycle. Six cycles were administered, followed by involved-field radiotherapy (45 Gy in 25 fractions). Interim imaging was suggestive of complete response. After completion of treatment, he was clinically in remission and is currently under follow-up for the last 8 months. Case 2 is presently being worked up and is scheduled to start R-CHOP chemotherapy.
Figure 1: Microscopic examination: Case 1 showing prostate infiltrated by a tumor (a; H and E, ×200) composed of large cells with scant cytoplasm and hyperchromatic nuclei (b; H and E, ×400), single file pattern and interspersed eosinophils (c; H and E, ×400); perineural infiltration (d; H and E, ×400), marked crushing, and stromal hyalinization present (e; H and E, ×400). Case 2 shows diffuse infiltration by tumor, with no residual prostatic glands (f; H and E, ×200)

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Figure 2: Immunohistochemistry: Tumor cells are immunopositive for leukocyte common antigen (a) but negative for cytokeratin (b); CD20 (c) is positive while CD3 (d) is negative; CD10 (e) and bcl6 (f) are positive while MUM1 (g) and Tdt (h) are negative (IHC, ×400)

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 > Discussion Top


Although the secondary extranodal involvement of prostate can occur in advanced lymphomas, primary prostatic lymphomas are exceedingly rare, constituting about 0.2-0.8% of extranodal lymphomas. [1],[2],[3],[4] Definition of primary extranodal lymphoma is controversial. Some authors use stringent criteria, excluding cases with nodal/hepatosplenic involvement at presentation; others include disseminated cases if the extranodal component is clinically dominant. One of the largest series of prostatic lymphomas, in which 35% were primary, used the following criteria to identify primary prostatic lymphomas: (i) Presenting symptoms attributable to prostatic enlargement; (ii) involvement of prostate predominantly, with or without involvement of adjacent tissue; and (iii) absence of involvement of liver, spleen, or lymph nodes within 1 month of diagnosis of prostatic involvement. [5] The two cases under discussion had bulk of disease in the prostate and involved only draining lymph nodes, thus falling into the category of primary prostatic NHL.

Prostatic lymphoma usually occurs in elderly men (mean age: 60-63 years). [6],[7] Our first patient was three decades younger; however, primary prostatic lymphoma has been reported in patients as young as 29 years. [3] Clinical presentation is variable, with most patients displaying symptoms of lower urinary tract obstruction, such as urinary frequency, urgency, hematuria, or acute retention, sometimes leading to renal failure. [1],[7] Due to the nonspecificity of symptoms, this condition is often mistaken for benign hyperplasia or chronic prostatitis, causing a delay in treatment. Systemic symptoms such as fever and weight loss are usually absent, [7] while serum PSA levels are normal. [8]

Among prostatic lymphomas, NHL predominates, with DLBCL being the most common. [1],[5],[8] The differential diagnosis includes rarer prostatic carcinoma variants, such as SCC and lymphoepithelioma-like carcinoma. SCC shows single cells with scant cytoplasm and hyperchromatic nuclei. Similar to prostatic NHL, it may show extensive crushing. However, subtle features like single file pattern of infiltration favor lymphoma, while nuclear molding is indicative of SCC. Lymphoepithelioma-like carcinoma shows a predominant population of lymphocytes, with scant interspersed large atypical cells, thus mimicking lymphoma. A basic immunohistochemical panel is helpful in differential diagnosis [Table 1]; a more extensive panel is required for further classification of NHL. As primary prostatic DLBCL can be of germinal center or postgerminal center type, it is likely that prognostic subgroups exist within this entity. However, a large number of patients would need to be evaluated to comment definitively on the same.
Table 1: Immunohistochemical panel for differential diagnosis of prostatic lymphoma


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As for most early-stage nodal DLBCL, R-CHOP is the mainstay of therapy. Although earlier series report a poor prognosis for primary and secondary prostatic lymphomas, recent case reports have shown better progression-free survival with combined chemotherapy (R-CHOP). [9],[10]

Thus, although prostatic lymphomas are extremely rare, their diagnosis is of crucial importance. Therapeutic strategy for lymphoma is radically different from that for carcinoma, and early diagnosis of prostatic lymphoma can be potentially curative. Thus, inclusion of this entity in differential diagnosis of lower urinary tract obstruction with diffuse prostatic enlargement, recognition of morphological clues, and application of an appropriate immunohistochemical panel is essential so as not to miss this unusual diagnosis and to avoid unnecessary surgery, especially when presenting as a primary lesion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 > References Top

1.
Sarris A, Dimopoulos M, Pugh W, Cabanillas F. Primary lymphoma of the prostate: Good outcome with doxorubicin-based combination chemotherapy. J Urol 1995;153:1852-4.  Back to cited text no. 1
    
2.
Iczkowski KA, Lopez-Beltran A, Sakr WA. Haematolymphoid tumours. In: Eble JN, Sauter G, Epstein JI, Sesterhenn IA, editors. Pathology and Genetics of Tumours of the Urinary System and Male Genital Organs. Lyon: IARC Press; 2004. p. 212.  Back to cited text no. 2
    
3.
Alvarez CA, Rodriguez BI, Perez LA. Primary diffuse large B-cell lymphoma of the prostate in a young patient. Int Braz J Urol 2006;32:64-5.  Back to cited text no. 3
    
4.
Taleb A, Ismaili N, Belbaraka R, Bensouda A, Elghissassi I, Elmesbahi O, et al. Primary lymphoma of the prostate treated with rituximab-based chemotherapy: A case report and review of the literature. Cases J 2009;2:8875.  Back to cited text no. 4
    
5.
Bostwick DG, Iczkowski KA, Amin MB, Discigil G, Osborne B. Malignant lymphoma involving the prostate: Report of 62 cases. Cancer 1998;83:732-8.  Back to cited text no. 5
    
6.
Bostwick DG, Mann RB. Malignant lymphomas involving the prostate. A study of 13 cases. Cancer 1985;56:2932-8.  Back to cited text no. 6
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7.
Antunes AA, Dall'Oglio M, Srougi M. Primary lymphoma of the prostate: A rare cause of urinary obstruction. Int Braz J Urol 2004;30:410-2.  Back to cited text no. 7
    
8.
Pan B, Han JK, Wang SC, Xu A. Positron emission tomography/computerized tomography in the evaluation of primary non-Hodgkin's lymphoma of prostate. World J Gastroenterol 2013;19:6699-702.  Back to cited text no. 8
    
9.
Rajnics P, Demeter J, Csomor J, Krenács L, Pajor L, Kollár B, et al. Rare primary extranodal lymphomas: Diffuse large B-cell lymphomas of the genital tract. Ann Hematol 2009;88:1223-8.  Back to cited text no. 9
    
10.
Manabe M, Hayashi Y, Yoshii Y, Mukai S, Sakamoto E, Kanashima H, et al. Primary diffuse large B-Cell lymphoma of the prostate presenting with urinary retention and dyschezia for which rituximab-combined CHOP therapy was effective-a case presentation. Gan To Kagaku Ryoho 2012;39:1733-5.  Back to cited text no. 10
    


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