Leydig cell tumor of the testis: A clinicopathologic, DNA content, and MIB-1 comparison of nonmetastasizing and metastasizing tumors

Leydig cell tumors of the testis are rare and account for a small proportion of testicular neoplasms. The objective of this study was to identify clinical and morphologic features predictive of metastasis in a large series of Leydig cell tumors, and to determine whether ploidy or proliferative activity were predictive of malignancy. Thirty cases of Leydig cell tumor of the testis (23 tumors that had not metastasized and 7 that had metastasized) were studied. Clinical history and follow-up were collected in all cases. The morphologic features examined included tumor size, mitotic index (mitotic figures/10 high-power fields), necrosis, angiolymphatic invasion, cell type, tumor-testicle interface, presence of extension beyond the testicular parenchyma, and presence of lipochrome and Reinke crystals. Most patients (93%) had a testicular mass. Patients with Leydig cell tumors that metastasized were diagnosed at a mean age of 62 years (range, 39-70 years) compared with 48 years (range, 9-79 years) in patients with nonmetastasizing tumors (p = 0.25). Leydig cell tumors that metastasized were significantly larger than nonmetastasizing tumors (mean, 4.7 versus 2.6 cm, respectively; p = 0.008), and had a significantly higher mitotic index (mean, 13.9 versus 1.9, respectively; p < 0.0001). Metastasizing Leydig cell tumors were significantly associated with atypical mitotic figures (p < 0.0001), nuclear variation (p = 0.0025), necrosis (p < 0.0001), angiolymphatic invasion (p = 0.009), infiltrative margins (p < 0.0001), high grade (p = 0.0004), and invasion into rete testis, epididymis, or tunica (p = 0.001) when compared with nonmetastasizing tumors. There was no significant difference between metastasizing and nonmetastasizing tumors in regard to cell type, lipochrome content, presence of Reinke crystals, or nuclear inclusions. All Leydig cell tumors that metastasized and 7 of 18 (38.9%) nonmetastasizing tumors were DNA aneuploid by static image analysis (p = 0.02). Metastasizing Leydig cell tumors had a significantly higher mean MIB- 1 activity of 18.6% (range, 5.8-33.6) compared with 1.2% (range, 0.04-8.2) in nonmetastasizing tumors (p = 0.001). In this study, the presence of cytologic atypia, necrosis, angiolymphatic invasion, increased mitotic activity, atypical mitotic figures, infiltrative margins, extension beyond the testicular parenchyma, DNA aneuploidy, and increased MIB-1 activity were significantly associated with metastatic behavior in Leydig cell tumors.