Testicular seminoma: a clinicopathologic and immunohistochemical study of 105 cases with special reference to seminomas with atypical features.

In spite of the high curability rates, rare cases of testicular seminoma behave in an unexpectedly aggressive manner. No effective markers are currently available that can predict such uncommon behavior. We studied 105 cases of testicular seminoma on whom the primary resection was performed at the Memorial Sloan-Kettering Cancer Center, New York, to investigate any relationship between morphology, immunohistochemical features, and clinical/pathological stages. Fifty-nine percent of the cases presented with pT stage 1 and 74 percent with American Joint Committee on Cancer (AJCC) stage I. In univariate analysis, tumor size, mitotic count, and presence of necrosis showed significant associations with pT stage (p = 0.0001, 0.0001, and 0.04, respectively), and the presence of vascular invasion (p = 0.0001, 0.0001, and 0.02, respectively). In multivariate analysis, both the tumor size and mitotic counts were independent predictors of pT stage (p = 0.0004 and 0.0001) and vascular invasion (p = 0.0004 and 0.0001). When tumors were separated on the basis of architectural and/or cytological atypia into "usual seminomas" and "seminomas with atypia", these were significantly associated with AJCC stage (p = 0.02), and c-kit protein (p = 0.0005) and CD30 expression (p = 0.02). In addition, "seminomas with atypia" also tended to show a higher proliferation activity as judged by Ki67 reactivity (p = 0.06), as well as express the marker of epithelial differentiation, Cam 5.2 (p = 0.09). In summary, we find that the morphologic features in testicular seminomas are associated with factors of clinical relevance. Also, "seminomas with atypia" differ from "usual seminomas" morphologically, present at a higher AJCC stage, and possibly represent an early step in transformation of seminomas toward a more aggressive phenotype. While not proposing a new entity, we suggest that when these atypical features are encountered in an otherwise classical seminoma, investigations must be performed to exclude an early carcinomatous differentiation or even earlier changes toward such a differentiation, such as lack of c-kit protein expression.