Kuo T T, Chan J K
Department of Pathology, Chang Gung University and Chang Gung Memorial Hospital, Kwei San, Tao Yuan, Taiwan.
Am J Surg Pathol. 1998 Dec;22(12):1474-81. doi: 10.1097/00000478-199812000-00004.
Thymic carcinoma is an uncommon tumor. Most cases appear to arise de novo, but in rare instances they can arise in thymomas. We report the clinicopathologic features and immunohistochemical profile of five cases of thymic carcinoma accompanied by a component of thymoma. Immunohistochemical studies were performed with the avidin-biotin-peroxidase complex method using monoclonal antibodies to p53(DO7), CD99(O13), epithelial membrane antigen, CD5(NCL-CD5-4C7), vimentin (V9), and cytokeratins 7, 8, 18, and 19. The patients consisted of three men and two women with a median age of 57 years. One patient had myasthenia gravis, and the other four presented with chest symptoms. One patient had concurrent adenocarcinoma of the lung with metastasis. Four of the patients died within 15 months. The thymomas consisted of two large polygonal cell thymomas, two squamoid thymomas, and one spindle cell thymoma. The malignant components included two undifferentiated carcinomas, one spindle cell carcinoma, one squamous cell carcinoma, and one clear cell carcinoma with squamous differentiation. There was no correlation between the histologic types of the thymoma and the thymic carcinoma. In three cases, excluding the two squamoid thymomas, the thymic carcinomas occurred in the necrotic areas of the thymoma. They showed upregulated expression of epithelial membrane antigen and cytokeratins 7, 8, 18, and 19, similar to the so-called "interface phenomenon" described in the invasion front of other types of carcinoma. Increased p53 protein expression was observed in all five carcinomas, and there was loss of CD99+ immature T lymphocytes. Among the thymic carcinomas, only the squamous component of the clear-cell carcinoma stained for CD5, a marker commonly expressed in thymic carcinomas. Paradoxically, a squamoid thymoma, but not its associated spindle cell carcinoma, expressed CD5, suggesting the acquisition of an "aggressive" phenotype by the squamoid thymoma, but with loss of the marker on malignant transformation. One undifferentiated carcinoma acquired vimentin immunoreactivity, whereas four other carcinomas and all five thymomas were negative. In conclusion, thymic carcinoma can arise in any histologic type of thymoma, including spindle cell thymoma, which is generally regarded as a benign neoplasm. The prognosis appears to be poor. Tumor necrosis in a thymoma should alert the pathologist to search for malignant change. The malignant change is commonly associated with increased expression of epithelial membrane antigen, cytokeratin subtypes, or p53 protein, and loss of CD99+ immature T lymphocytes, and is occasionally associated with a change in the expression of CD5 or vimentin.
胸腺癌是一种罕见的肿瘤。大多数病例似乎是新发的，但在极少数情况下可起源于胸腺瘤。我们报告了5例伴有胸腺瘤成分的胸腺癌的临床病理特征和免疫组化谱。采用抗生物素蛋白-生物素-过氧化物酶复合物法，使用针对p53（DO7）、CD99（O13）、上皮膜抗原、CD5（NCL-CD5-4C7）、波形蛋白（V9）以及细胞角蛋白7、8、18和19的单克隆抗体进行免疫组化研究。患者包括3名男性和2名女性，中位年龄为57岁。1例患者患有重症肌无力，其他4例表现为胸部症状。1例患者同时患有肺腺癌并伴有转移。4例患者在15个月内死亡。胸腺瘤包括2例大细胞多边形胸腺瘤、2例鳞状胸腺瘤和1例梭形细胞胸腺瘤。恶性成分包括2例未分化癌、1例梭形细胞癌、1例鳞状细胞癌和1例伴有鳞状分化的透明细胞癌。胸腺瘤的组织学类型与胸腺癌之间无相关性。在3例病例中，不包括2例鳞状胸腺瘤，胸腺癌发生在胸腺瘤的坏死区域。它们表现出上皮膜抗原以及细胞角蛋白7、8、18和19的表达上调，类似于在其他类型癌的浸润前沿所描述的所谓“界面现象”。在所有5例癌中均观察到p53蛋白表达增加，且CD99 +未成熟T淋巴细胞缺失。在胸腺癌中，只有透明细胞癌的鳞状成分对CD5染色阳性，CD5是胸腺癌中常见表达的一种标志物。矛盾的是，1例鳞状胸腺瘤而非其相关的梭形细胞癌表达CD5，提示鳞状胸腺瘤获得了“侵袭性”表型，但在恶性转化时该标志物丢失。1例未分化癌获得波形蛋白免疫反应性，而其他4例癌和所有5例胸腺瘤均为阴性。总之，胸腺癌可起源于任何组织学类型的胸腺瘤，包括通常被视为良性肿瘤的梭形细胞胸腺瘤。预后似乎较差。胸腺瘤中的肿瘤坏死应提醒病理学家寻找恶性改变。恶性改变通常与上皮膜抗原、细胞角蛋白亚型或p53蛋白表达增加以及CD99 +未成熟T淋巴细胞缺失有关，偶尔也与CD5或波形蛋白表达的改变有关。
