Testicular natural killer/T-cell lymphoma, nasal type, of true natural killer-cell origin

Archives of Pathology & Laboratory Medicine, Dec 2002 by Totonchi, Kameel F, Engel, George, Weisenberg, Elliot, Rhone, Douglas P, Macon, William R

* The majority of primary testicular lymphomas are of Bcell type. Other primary lymphomas are rarely encountered in the testes. Natural killer (NK)/T-cell lymphomas of nasal type are aggressive extranodal lymphomas associated with Epstein-Barr virus infection that are usually encountered in the upper aerodigestive tract. They also occur in the skin, soft tissue, and colon. Primary testicular NK/Tcell lymphomas are rarely reported. We describe the case of a 66-year-old Korean man who presented with rightsided painless testicular enlargement and underwent radical orchiectomy. Histologic examination revealed an angiocentric and angioinvasive infiltrate of medium to large tumor cells with moderately abundant pale pink cytoplasm and folded and indented pleomorphic nuclei. Paraffin immunohistochemical studies showed positivity of the tumor cells for CD45, TIA-1, granzyme B, CD56, and CD3E. In situ hybridization showed diffuse positivity for Epstein-Barr virus-encoding RNA. The results of gene rearrangement studies for the y chain of the T-cell receptor were negative. The results of paraffin immunohistochemical studies for CD20, CDB, CD45RO, beta fl, and ALK-1 were negative. An extensive workup showed no evidence of lymphoma outside the testes. We report a rare case of primary testicular NK/T-cell lymphoma of the nasal type of true NK-cell origin. (Arch Pathol Lab Med. 2002;126:1527-1529)

66-year-old Korean man presented with painless right testicular enlargement. He was otherwise in good health with no significant findings on a medical history. The results of a physical examination were unremarkable except for nontender right testicular enlargement. Routine preoperative laboratory testing showed no abnormalities. He underwent right radical orchiectomy.

The specimen consisted of a testis and attached spermatic cord, together weighing 81 g. The testis within the intact tunica vaginalis measured 6.0 x 3.3 x 3.2 cm. The testis alone measured 5.5 x 3.0 x 3.0 cm. Sagittal sectioning showed an ill-defined 3.0 x 2.5-cm pale tan homogenous nodule in the inferior pole.

Histologic sections revealed expansion of the interstitium by medium to large cells that had a moderate amount of pink cytoplasm. The infiltrate surrounded atrophic seminiferous tubules and had an angiocentric and angiodestructive growth pattern (Figure 1). Higher magnification showed granular cytoplasm with folded and indented pleomorphic nuclei, fine and diffuse chromatin, and inconspicuous nucleoli (Figure 2). Brisk mitotic activity was present; the mitotic count averaged 52 per 10 highpower fields. Karyorrhexis and apoptotic cells were present.

Immunohistochemical staining of paraffin-embedded sections showed reactivity for LCA, CD3e (cytoplasmic staining pattern), TIA-1, granzyme B, and CD56 (Figure 3). The results of staining for cytokeratin, CD20, CDB, CD45RO, beta fl, and ALK-1 were negative. Weak focal cytoplasmic staining for CD30 was present; however, membranous and perinuclear staining was lacking. Staining for CD4 was not performed.

We performed T-cell receptor (TCR) gene rearrangement studies on formalin-fixed, paraffin-embedded tumor tissue using primers for the y chain gene of the TCR and the polymerase chain reaction as previously described.' These studies did not reveal a clonal population. In situ hybridization studies with probes for Epstein-Barr virus (EBV) genome (Dako Corporation, Carpinteria, Calif) showed distinct nuclear positivity in the neoplastic cells diffusely throughout the tumor.

The patient underwent a staging workup that included computed tomography scans of the chest and abdomen and bilateral bone marrow biopsies and aspirates. The resuits of this workup were negative. COMMENT We have described a testicular natural killer (NK)/T-cell lymphoma, nasal type, of true NK-cell origin. The NK-cell lineage of the lymphoma cells was established by the cytoplasmic CD3e , CD56 , TIA-1-positive, and granzyme B-positive phenotype coupled with a "silent" TCR (beta fl negative and germ line configuration of TCR genes).2

Testicular lymphomas comprise approximately 5% of testicular neoplasms, affecting men with a mean age of 56 years.3 The majority are of B-cell type.3 In a single case report, Sun et a14 provided the initial description of a testicular NK/T-cell lymphoma of true NK-cell origin occurring in a 32-year-old man. In 1996, Chan et a15 described 3 cases of aggressive NK/T-cell testicular lymphoma in Asian men over the age of 60. All 4 of these cases had diffuse interstitial infiltrates of medium to large cells with irregular folded nuclei and clumped/granular chromatin. Karyorrhexis with angiocentric and angioinvasive growth was observed in the 3 cases reported by Chan et al. The neoplastic cells were positive for CD2, CD3(epsilon), and CD56 in all cases, whereas cells in one case also expressed CD7.(4) The tumor cells lacked other T-cell, as well as B-cell, markers. The tumors reported by Chan et al were positive for EBV by in situ hybridization, whereas the tumor in the case described by Sun et al was not tested. The results of studies for TCR gene rearrangement were negative in all cases. The 4 patients died within 6 months of diagnosis; 3 had received combination chemotherapy.