Accurate diagnosis of mediastinal
seminoma is critical because of its favorable response to
radiation therapy and/or
cisplatin-based
chemotherapy. Immunohistochemical staining for OCT4 has recently been validated as a powerful tool for detecting gonadal
seminoma. However, discrepancies between the genetic alterations and immunoprofiles of mediastinal and testicular
seminomas have been reported, raising the question of whether techniques that are useful in the diagnosis of gonadal
seminoma are applicable to its mediastinal counterpart. The present study was conducted to evaluate the morphologic and immunohistochemical characteristics and
chromosomal abnormalities of 12p in 23 primary mediastinal
seminomas and to compare their applicability as diagnostic tools. Dual-color fluorescence in situ hybridization (FISH) analyses for chromosome 12p and immunostains for OCT4, c-kit,
placental-like alkaline phosphatase, CD30, and a panel of cytokeratins, including
cytokeratin AE1/AE3 (AE1/3), high molecular weight
cytokeratin (34betaE12, HMWCK),
CAM5.2,
cytokeratin 7 (CK7),
cytokeratin 20 (CK20), and
epithelial membrane antigen were performed. Lymphocytic infiltration was found in all 23 cases (100%). The incidence of other histologic characteristics were as follows: fibrous septa/stroma (21 cases, 91%), prominent
tumor cell nucleoli (21 cases, 91%), clear
tumor cell cytoplasm (20 cases, 87%), distinct
tumor cell borders (20 cases, 87%), granulomatous
inflammation (17 cases, 74%), cellular pleomorphism (10 cases, 43%),
necrosis (8 cases, 35%), prominent cystic change (2 cases, 8%), intercellular
edema (1 case, 4%), and syncytiotrophoblasts (1 case, 4%). The mean mitotic count was 4.4 (range 0 to 16) per 10 high-power fields. Moderate to strong nuclear OCT4 staining was identified in all 23 cases (100%). Seventeen
tumors (74%) showed membranous expression of c-kit, with variable staining intensity and percentages. Weakly to moderately intense immunostaining for
placental-like alkaline phosphatase was identified in 10 cases (43%) with occasional background staining artifact. The incidences of positive staining were 43% for AE1/3, 39% for HMWCK, 48% for
CAM5.2, 39% for CK7, and 9% for
epithelial membrane antigen, respectively. In most cases, these epithelial markers highlighted only a small proportion of
tumor cells with variable intensities. Immunostaining for CD30 and CK20 was completely negative in all
seminomas. Twenty-two
seminomas (96%) revealed chromosome 12p abnormalities, including 12p amplification in 20 cases (87%) or i(12p) in 15 cases (65%). Lymphocytic infiltration is the most common histologic feature observed in primary mediastinal
seminoma and both OCT4 immunostain and FISH for 12p abnormalities can be very helpful in diagnosing mediastinal
seminoma. The intense staining pattern of OCT4 and the high sensitivity of FISH make them superior to other auxiliary diagnostic utilities for detecting
seminoma. In addition, the incidences of
cytokeratin expression of primary mediastinal
seminoma are similar to those of its gonadal counterpart and pathologists must exercise caution in the interpretation of epithelial markers in
mediastinal neoplasms.