Dedifferentiated adenoid cystic carcinoma: A clinicopa-thologic study of 6 cases
Dedifferentiated adenoid cystic carcinoma: A clinicopa-thologic study of 6 cases
复制标题
DOI：
10.1097/01.mp.0000097366.88165.08
复制
发表时间：
2003-12-01
期刊：
影响因子：
7.5
通讯作者：
Lewis, JE
中科院分区：
文献类型：
--
作者：
Nagao, T;Gaffey, TA;Lewis, JE
去分化腺样囊性癌是最近定义的腺样囊性癌的一种罕见变体，其组织学特征由两个组成部分组成：传统的低级别腺样囊性癌和高级别“去分化”癌。我们检查了 6 例病例并分析了他们的临床病理学特征，包括免疫组织化学特征和 p53 基因改变。这 6 名患者（3 名男性和 3 名女性）的平均年龄为 46.8 岁（范围为 34-70 岁）。肿瘤的平均大小为3.5厘米（范围1.7-6厘米）。颌下腺、上颌窦、鼻腔各受累2例。术后，5 例患者出现局部复发，5 例出现转移。 5 名患者在诊断后平均 33.7 个月（范围为 6-69 个月）死于疾病，另一名患者在 60 个月时仍因疾病存活。在组织学上，肿瘤的传统低级别腺样囊性癌成分由筛状和管状图案的混合组成，实性区域很少。高级别去分化癌成分为低分化腺癌（4例）或未分化癌（2例）。对三种肿瘤进行了免疫组织化学研究。肌上皮标志物在低级别腺样囊性癌中表达，但在去分化成分中不表达。在 2 例中，弥漫性阳性 p53 免疫反应性以及 HER-2/neu 过度表达仅限于去分化成分。 pRb 表达缺失仅在另外 1 例的去分化成分中得到证实。去分化成分中的 Ki-674 标记指数高于低级别腺样囊性癌成分。此外，2例的分子分析显示，仅在1例的去分化癌成分中，p53微卫星位点杂合性丧失，并伴有p53基因点突变，该例的去分化癌成分为p53免疫染色阳性。这些结果表明去分化腺样囊性癌是一种高度侵袭性的肿瘤。由于复发和转移频繁，临床病程短，与腺样囊性癌相似，以实性生长为主。有限的证据表明 p53 异常与 HER-2/neu 过表达或 pRb 表达缺失相结合可能在腺样囊性癌的去分化中发挥作用。
Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoild cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in. low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immuno-reactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-674-labeling index was higher in the dedifferentiated component than in the lowgrade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of I case, which was positive for p53 inummostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.