Pathology of Prostate Leukemia and Lymphoma
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Prostatic involvement by lymphoma and leukemia is rare in surgical pathology practice. In the 2 largest consecutive series, leukemia/lymphoma was identified in less than 1% of prostates.
Terris et al evaluated 1092 consecutive radical prostatectomy specimens, and pelvic lymph nodes if available, removed for prostatic adenocarcinoma. [1] They found 1.2% of cases were involved by leukemia or lymphoma: 9 chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLLs), 3 Hodgkin lymphomas, and 1 hairy cell leukemia. In total, 0.8% (9 cases) demonstrated prostate and lymph node involvement, while 0.4% (4 cases) showed lymph node involvement only. Five (38.5%) patients had preoperative lymphocytosis.
Similarly, Chu et al evaluated 4831 consecutive prostate specimens (3,405 biopsies, 266 transurethral resections, and 1,160 prostatectomies). [2] They found that 15 (0.3%) cases demonstrated involvement by leukemia or lymphoma: 8 CLL/SLLs, 1 follicular lymphoma, 2 marginal-zone lymphomas, 2 mantle cell lymphomas, and 2 diffuse large B-cell lymphomas (DLBCLs).
Combined, these studies suggest CLL/SLL is the most common type of leukemia/lymphoma to involve the prostate in routine specimens, and it is usually seen in association with involvement at different sites, particularly the pelvic lymph nodes.
Primary prostatic lymphoma has been defined by the criteria of Bostwick and Mann, which include (1) symptoms attributable to prostatic enlargement, (2) prostate as the predominant site of involved, and (3) absence of involvement of liver, spleen, or lymph nodes within 1 month of diagnosis. [3] Primary prostatic lymphoma is probably less common than secondary prostatic involvement, as the largest series to date consists of 22 cases, pulled from the archives of 3 major academic medical centers. [4] The majority in this series (12 cases) were DLBCLs, with smaller numbers of SLL (4 cases), follicular lymphoma (4 cases), and Burkitt lymphoma (2 cases).
Taken as a group, primary and secondary prostatic leukemia/lymphoma most commonly presents in the seventh decade. [1, 4] Primary prostatic lymphomas, which tend to be high grade per the largest series, usually present with symptoms of a large prostatic mass, including obstructive symptoms (eg, hesitancy, urgency) and hematuria. [4] Digital rectal examination findings usually are abnormal, showing a diffusely enlarged or nodular prostate in the majority of cases. Serum prostate-specific antigen (PSA) usually is not elevated (mean 3.5 ng/mL). [4]
Secondary prostatic leukemia/lymphoma is often discovered incidental to a diagnosis of prostatic adenocarcinoma. Symptoms at presentation may thus be intermixed with those of prostate cancer and include elevated serum PSA (mean PSA 10.3 ng/mL). [1] Secondary prostatic leukemia/lymphoma may also present with obstructive symptoms. [4]
As in other sites, chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) of the prostate histologically appears as expanses of monomorphic mature-appearing lymphocytes with round nuclear contours, condensed chromatin, and inconspicuous nucleoli. The infiltrate usually is patchy in distribution. Lymphoma cells may efface the prostate architecture and may extend outside of the prostate. Tumor cells typically infiltrate the prostatic stroma in a nonperiglandular manner, and they may infiltrate between normal prostate glands. The typical immunophenotype is CD20+/CD10–/CD5+/cyclin D1–. Light-chain restriction may be identifiable by immunohistochemistry.
The primary differential diagnosis of CLL/SLL is benign chronic inflammation, which is very common in the prostate. In contrast to the monomorphic, expansive infiltrate of CLL/SLL, benign chronic inflammation is composed of a heterogeneous inflammatory cell population, which tends to be more limited in extent than lymphoma. Benign chronic inflammation is also preferentially periglandular, and thus it does not demonstrate the infiltrative growth in the prostatic stroma frequently observed in CLL/SLL.
See the images below.
Diffuse large B-cell lymphoma (DLBCL) appears as an expansive proliferation of high-grade lymphoid cells with enlarged nuclei with vesicular chromatin. Mitotic activity is increased and apoptotic debris is common. Tumor cells often demonstrate destructive growth and extend beyond the prostate. They may also infiltrate between benign glands. Expression of CD45 and CD20 is seen, consistent with B-cell lineage.
The main differential diagnosis of DLBCL is poorly differentiated carcinoma. DLBCL is CD45 positive and pan-cytokeratin negative in the great majority of cases, while prostatic adenocarcinoma and urothelial carcinoma are CD45 negative and pan-cytokeratin positive. Granulomatous prostatitis may also be in the differential diagnosis for DLBCL, as it demonstrates an expansive, destructive infiltrate of CD45-positive cells. The cells comprising granulomatous prostatitis are much less atypical than those of DLBCL, and they are CD68-positive histiocytes, while DLBCL is CD68 negative.
See the images below.
Mantle cell lymphoma typically appears as a proliferation of monomorphic small lymphocytes with irregular, angulated nuclei and inconspicuous nucleoli. Tumors cells grow in an expansive, infiltrative manner. The typical immunophenotype is CD20+/CD10–/CD5+/Cyclin D1+.
See the images below.
Marginal-zone lymphoma typically appears as an expansive, infiltrative proliferation of small- to medium-sized lymphocytes with variably smooth to irregular nuclear contours. Enlarged, higher-grade tumor cells resembling centroblasts are frequently seen, with increasing number associated with more aggressive tumor behavior. A subset of tumor cells may have the appearance of plasma cells. Associated benign chronic inflammation, including reactive non-neoplastic germinal cells, is common. As with other lymphomas, marginal-zone lymphomas grow in a destructive manner and may extend beyond the prostate. Lymphoepithelial lesions are a classic (but nonspecific) finding in marginal-zone lymphoma and consist of tumor cells infiltrating altered benign prostate glands. The typical immunophenotype is CD20+/CD10–/CD5–/cyclin D1-. CD43 may be expressed. Light-chain restriction may be seen, particularly when there is a plasmacytic component.
See the images below.
Leukemias and lymphomas are an extraordinarily diverse group of disease, with multiple subtypes with unique molecular findings. To date, no study has shown that leukemias and lymphomas of the prostate differ molecularly from analogous leukemias/lymphomas at other locations.
As in other locations, prognosis in prostatic involvement by leukemia/lymphoma is dependent on the subtype.
The majority of cases are low grade, predominantly chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). As such, prognosis in these cases is generally favorable. In the largest consecutive series to date with follow-up data, which showed predominantly low-grade leukemia/lymphoma, only 1 patient had died from disease at follow-up. [1]
In contrast, diffuse large B-cell lymphoma (DLBCL), which is often primary, carries a considerably less favorable prognosis. In the largest series of primary prostatic lymphomas to date, which notably included numerous high-grade secondary prostatic lymphomas in survival analysis, 5-year lymphoma-specific survival was only 33%. [4]
Benign chronic inflammation
Granulomatous prostatitis
Prostatic adenocarcinoma
Terris MK, Hausdorff J, Freiha FS. Hematolymphoid malignancies diagnosed at the time of radical prostatectomy. J Urol. 1997 Oct. 158(4):1457-9. [Medline].
Chu PG, Huang Q, Weiss LM. Incidental and concurrent malignant lymphomas discovered at the time of prostatectomy and prostate biopsy: a study of 29 cases. Am J Surg Pathol. 2005 May. 29(5):693-9. [Medline].
Bostwick DG, Mann RB. Malignant lymphomas involving the prostate. A study of 13 cases. Cancer. 1985 Dec 15. 56(12):2932-8. [Medline].
Bostwick DG, Iczkowski KA, Amin MB, Discigil G, Osborne B. Malignant lymphoma involving the prostate: report of 62 cases. Cancer. 1998 Aug 15. 83(4):732-8. [Medline].
Joshua I Warrick, MD Fellow in Surgical Pathology, Department of Pathology, University of Michigan Medical School
Joshua I Warrick, MD is a member of the following medical societies: American Society for Clinical Pathology, College of American Pathologists
Disclosure: Nothing to disclose.
Liang Cheng, MD Professor of Pathology and Urology, Department of Pathology and Laboratory Medicine, Indiana University School of Medicine; Chief, Genitourinary Pathology Service, Indiana University Health
Liang Cheng, MD is a member of the following medical societies: American Association for Cancer Research, American Urological Association, College of American Pathologists, United States and Canadian Academy of Pathology, International Society of Urological Pathology, Arthur Purdy Stout Society
Disclosure: Nothing to disclose.
Kenneth A Iczkowski, MD Pathology Laboratory Director, Urology Specialists of America, Columbus, OH
Kenneth A Iczkowski, MD is a member of the following medical societies: College of American Pathologists and United States and Canadian Academy of Pathology
Disclosure: Nothing to disclose.
Acknowledgments
The author would like to acknowledge Scott Owens, MD, Associate Professor, Department of Pathology, University of Michigan Medical School, for his review and feedback on this article.
Pathology of Prostate Leukemia and Lymphoma
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