Miller Jeremy S, Lee Thomas K, Epstein Jonathan I, Ulbright Thomas M
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
Am J Surg Pathol. 2009 Sep;33(9):1293-8. doi: 10.1097/PAS.0b013e3181a3166d.
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.
坏死性睾丸肿瘤相对常见,可能带来重大的诊断挑战。由于精原细胞瘤与非精原细胞瘤的治疗方法不同,准确诊断至关重要。从我们的会诊档案中检索出11例完全(n = 9)或几乎完全(n = 2)坏死的睾丸肿瘤。送检病理学家认为4例为良性病变,1例为Leydig细胞瘤,1例为淋巴瘤。对这些病例进行了组织学特征评估,如有可用材料,则用7种抗体进行免疫染色:角蛋白(AE1/AE3)、OCT4、胎盘碱性磷酸酶、甲胎蛋白(AFP)、CD117、CD30和S100。仅坏死区域细胞分布中的明显反应性被视为阳性;OCT4仅对核反应性进行评分,CD117和CD30对膜反应性进行评分。患者平均年龄为35岁(范围16 - 63岁)。肿瘤平均大小为19 mm(范围7 - 53 mm)。所有患者均表现为单侧睾丸肿块(右侧6例,左侧5例);2例还伴有急性疼痛。组织学特征、免疫染色以及1例中的血清AFP相结合,使8例肿瘤得以分类(4例精原细胞瘤、3例胚胎癌、1例卵黄囊瘤)。3例无法分类。坏死性精原细胞瘤缺乏相关的粗大管内钙化,OCT4呈阳性(4/4),CD117呈阳性(3/3),但角蛋白呈阴性(0/4),CD30呈阴性(0/4)。坏死性胚胎癌伴有粗大管内钙化,角蛋白呈阳性(2/3),OCT4呈阳性(2/2),CD30呈阳性(3/3)。OCT4对1例无法分类的肿瘤呈阳性染色,该肿瘤缺乏其他特异性标志物。我们发现胎盘碱性磷酸酶、AFP和S100染色并无帮助,尽管S100在1例中突出显示了肿瘤“幽灵”细胞。大多数病例的其他特征包括管内生殖细胞肿瘤(6/11)、小管萎缩/透明变性(10/11)、肿瘤“幽灵”细胞(10/11)、瘢痕(9/11)和炎症(10/11)。在5例有随访资料的患者中,3例在睾丸切除术后1年、5年和8年无疾病(2例坏死性精原细胞瘤和1例未分类的生殖细胞肿瘤)。1例卵黄囊瘤患者(63岁)在15个月后发生广泛转移并死于该疾病。最后1例最初被误诊为“睾丸梗死,无恶性肿瘤”,16个月后患者出现巨大腹膜后精原细胞瘤。通过评估粗大管内钙化以及角蛋白、OCT4、CD117和CD30的染色反应,大多数完全坏死的睾丸肿瘤可分为具有临床重要意义的组。