Pathology of Prostate Leukemia and Lymphoma

Prostatic involvement by lymphoma and leukemia is rare in surgical pathology practice, identified in less than 1% of prostate specimens.[1, 2, 3] ​

Terris et al evaluated 1,092 consecutive radical prostatectomy specimens, and pelvic lymph nodes, if available, removed for prostatic adenocarcinoma.[1] They found 1.2% of cases involved leukemia or lymphoma: nine chronic lymphocytic leukemia/small lymphocytic lymphomas (CLL/SLLs), three Hodgkin lymphomas, and one hairy cell leukemia. In total, 0.8% (nine cases) demonstrated prostate and lymph node involvement, whereas 0.4% (four cases) showed lymph node involvement only. Five (38.5%) patients had preoperative lymphocytosis.[1]

Similarly, Chu et al evaluated 4,831 consecutive prostate specimens (3,405 biopsies, 266 transurethral resections, and 1,160 prostatectomies).[2] They found that 29 (0.6%) cases demonstrated involvement by leukemia or lymphoma: 17 CLL/SLLs, three marginal-zone lymphomas, three mantle cell lymphomas, one diffuse large B-cell lymphoma (DLBCL), and four follicular lymphomas.[2]

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.

Relatively recent case reports exist of an elderly Indian male with synchronous bladder urothelial carcinoma and prostatic carcinoma with CLL (triple cancer),[4] a senior Serbian patient with synchronous mantle cell lymphoma and prostate adenocarcinoma,[5] and an elderly Czech patient with mantle cell lymphoma and prostate adenocarcinoma.[6] Non-Hodgkin lymphoma of the prostate, albeit rare, also occurs; Galante et al described the longitudinal clinical course of a case that was refractory to treatment.[7]  Thomas et al reported the case of an elderly man with prostate and bladder wall CLL.[8]

The criteria of Bostwick and Mann defines primary prostatic lymphoma to include (1) symptoms attributable to prostatic enlargement; (2) the prostate as the predominant site of involvement; and (3) the absence of involvement of the liver, spleen, or lymph nodes within 1 month of diagnosis.[9] One of the largest series contains 62 prostatic lymphomas based on the archives of three major academic medical centers, of which 22 (35%) were primary to the prostate.[10] The majority of primary cases in this series (12 cases) were DLBCLs, with smaller numbers of SLL (4 cases), follicular lymphoma (4 cases), and Burkitt lymphoma (2 cases).[10] In another series, 8 of 29 (28%) were primary prostatic lymphomas.[2]

Taken as a group, primary and secondary prostatic leukemia/lymphoma most commonly presents in the seventh decade.[1, 10] Primary prostatic lymphomas, which tend to be high grade on the basis of a large series, usually present with symptoms of a large prostatic mass, including obstructive symptoms (eg, hesitancy, urgency) and hematuria.[10] 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).[10]

Secondary prostatic leukemia/lymphoma is often discovered incidental to a diagnosis of prostatic adenocarcinoma.[11] 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.[10, 12]

The differential diagnosis for prostatic tumors that have the appearance of diffuse large B-cell lymphomas (DLBCL) is wide, including the following[3] :

• High-grade neoplasms (eg, prostatic adenocarcinoma, urothelial carcinoma)
• Small cell carcinoma
• Sarcoma

The differential diagnosis for prostate leukemia/lymphoma also includes the following non-neoplastic processes:

• Benign chronic inflammation with follicular hyperplasia
• Granulomatous prostatitis

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) of the prostate

As in other sites, 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 is usually 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)

DLBCL appears as an expansive proliferation of high-grade lymphoid cells that have 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, whereas 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, whereas DLBCL is CD68 negative.

See the following images.

Mantle cell lymphoma

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

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; increasing number is 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 lymphomas, and they 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 diseases, with multiple subtypes and 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, the prognosis in these cases is generally favorable. In a large consecutive series with follow-up data, which showed predominantly low-grade leukemia/lymphoma, only one 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 a large series of primary prostatic lymphomas, which notably included numerous high-grade secondary prostatic lymphomas in survival analysis, 5-year lymphoma-specific survival was only 33%.[10]