Answer: Mediastinal Seminoma

Histology: The tumor consists of sheets, nests and clusters of large atypical cells with prominent nucleoli and a moderate amount of pale cytoplasm. Associated with the large atypical cells are numerous admixed small lymphocytes as well as individual and small collections of epithelioid histiocytes. There is a somewhat thickened capsule surrounding the tumor as well as some areas of fibrosis. The large atypical cells usually have one large nucleus but occasionally one sees binucleated and/or trinucleated cells. Mitotic activity is observed within the large atypical cells.

Discussion: The major differential diagnosis in this case rests between a large cell lymphoma or Hodgkin’s disease versus a metastatic carcinoma or a mediastinal germ cell tumor such as a seminoma. Mediastinal germ cell tumors usually do not occur in females but this is a male, so this diagnosis would certainly be in the differential diagnosis. The association of the large atypical cells with both lymphocytes as well as epithelioid histiocytes can be seen in both Hodgkin’s disease and mediastinal seminioma. The focal clustering of the cells would be more typical of a seminoma rather than a large B-cell lymphoma or Hodgkin’s disease. The lack of true lacunar type Reed Sternberg cells would also be helpful in excluding the diagnosis of Hodgkin’s disease. Furthermore, immunohistochemical testing can be extremely helpful in establishing a definitive diagnosis and/or ruling out some of the other diagnoses. In this case, the neoplastic cells were positive for PLAP and C-Kit and negative for cytokeratin, EMA, CD30, and CD15 as well as CD20 and CLA. These stains are consistent with the diagnosis of a mediastinal seminoma. The lack of staining for CD30 or CD15 rules out the possibility of Hodgkin’s disease. The lack of staining for cytokeratin also rules out the possibility of a metastatic undifferentiated carcinoma. The prominent association of the large atypical cells with normal lymphocytes as well as clusters of epithelioid histiocytes is typical in seminomas whether it is seen in the mediastinum or in the more common location in the testicle. The diagnosis of diffuse large B-cell lymphoma which could be entertained in this case is ruled out by the lack of staining of the cells with the usual antibodies directed against B-cell antigens. Also, although large B-cell lymphoma may occur in the mediastinum of both sexes, it is more common in young adult females.