PATHOLOGY

The utility of microscopic findings and immunohistochemistry in the classification of necrotic testicular tumors: a study of 11 cases
Miller JS, Lee TK, Epstein JI, Ulbright TM
Departments of Pathology Urology Oncology, The Johns Hopkins Hospital, Baltimore, MD, Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA
Am J Surg Pathol. 2009; 20 [Epub ahead of print]

• Necrotic testicular tumors are relatively frequent and can present a significant diagnostic challenge. Because of differing treatments for seminomas versus nonseminomas, accurate diagnosis is critical. Eleven totally (n = 9) or almost totally (n = 2) necrotic testicular tumors were retrieved from our consult files. The submitting pathologists favored benign processes in 4 cases, Leydig cell tumor in 1, and lymphoma in 1. The cases were evaluated for histologic features and, when material was available, by immunostaining with 7 antibodies: keratin (AE1/AE3), OCT4, placental alkaline phosphatase, alpha-fetoprotein (AFP), CD117, CD30, and S100. Only distinct reactivity in a cellular distribution in the necrotic zone was considered positive; nuclear reactivity alone was scored for OCT4 and membrane reactivity for CD117 and CD30. Mean patient age was 35 years (range 16-63). Mean tumor size was 19 mm (range 7-53). All patients presented with unilateral testicular masses (6 right, 5 left); 2 also had acute pain. The combination of histologic features, immunostains and, in 1 case, serum AFP permitted classification of 8 tumors (4 seminomas, 3 embryonal carcinomas, 1 yolk sac tumor). Three were not classifiable. The necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 (4/4) and CD117 (3/3) but negative for keratin (0/4) and CD30 (0/4). The necrotic embryonal carcinomas had associated coarse intratubular calcifications and were positive for keratin (2/3), OCT4 (2/2), and CD30 (3/3). OCT4 stained 1 unclassifiable tumor, which lacked other specific markers. We did not find placental alkaline phosphatase, AFP, and S100 stains useful, although S100 did highlight tumor “ghost” cells in 1 case. Other features in most cases included intratubular germ cell neoplasia (6/11), tubular atrophy/hyalinization (10/11), tumor “ghost” cells (10/11), scar (9/11), and inflammation (10/11). Of the 5 patients with available follow-up, 3 were free of disease at 1, 5, and 8 years after orchiectomy (2 necrotic seminomas and 1 germ cell tumor, unclassified). One patient with yolk sac tumor (age 63 y) developed widespread metastases after 15 months and died of disease. The final case was initially misinterpreted as “testicular infarction, no malignancy” and 16 months later the patient developed a large retroperitoneal seminoma. Most totally necrotic testicular tumors can be placed into clinically important groups by assessment for coarse intratubular calcifications and staining reactions for keratin, OCT4, CD117, and CD30.

• Editorial Comment
  For a proper treatment, testicular tumors must be classified as seminomatous and non-seminomatous. In order to consider a tumor purely seminoma the neoplasia must be adequately processed. At least one section per centimeter of greatest diameter of the tumor is optimal. Each histological type has peculiar microscopic findings that allow a proper diagnosis. In some cases, the diagnosis is difficult. One example is the differential diagnosis in cases of solid embryonal carcinoma. Characteristically this tumor shows tubular arrangement. In cases it is solid it must be differentiated from seminoma. Some nuclear characteristics help in this distinction but immunohistochemistry is also very helpful (1).
  In cases of necrotic tumors or totally necrotic the diagnosis is a challenge for the pathologist. The study by Miller et al. shows that immunohistochemistry and some other additional microscopic findings may be very helpful in the recognition of the type of tumor. As an example: necrotic seminomas lacked associated coarse intratubular calcifications and were positive for OCT4 and CD117 but negative for keratin and CD30, and necrotic embryonal carcinomas had associated coarse calcifications and were positive for keratin, OCT4, and CD30. The study showed that in spite of necrosis, most tumors could be placed into clinically important groups for treatment.

Reference

1. Ulbright TM, Amin MB, Young RH: Tumors of the Testis, Adnexa, Spermatic Cord, and Scrotum. Atlas of Tumor Pathology. Washington, Armed Forces Institute of Pathology. 3rd Series, Fascicle 25. 1999; pp. 385.

Dr. Athanase Billis
Full-Professor of Pathology
State University of Campinas, Unicamp
Campinas, São Paulo, Brazil
E-mail: athanase@fcm.unicamp.br