Department of Pathology, National Cancer Institute, Bethesda, MD, USA.
Int J Gynecol Pathol. 2010 Mar;29(2):146-56. doi: 10.1097/PGP.0b013e3181b8e951.
The majority of endometrial endometrioid adenocarcinomas involving the cervix have tumor morphology that is similar in the endometrium and the endocervix. There are, however, some cases in which the morphology of the tumor in the endocervix is different from the endometrial carcinoma, in which it is more invasive than the endometrial carcinoma, or in which invasion only occurs in the endocervix while there is no or only minimal myometrial invasion. The goal of this study was to investigate whether tumors involving the endometrium and the endocervix are similar or 2 independent primaries by hematoxylin and eosin stain, immunohistochemistry (IHC), human papillomavirus (HPV) DNA in situ hybridization, RNA reverse transcriptase in situ polymerase chain reaction (PCR) analyses to reveal HPV, and DNA clonality studies. We selected 14 cases of endometrial endometrioid adenocarcinomas involving the cervix with complete pathology material available from the years between 1968 and 2004. Immunohistochemical studies for vimentin, carcinoembryonic antigen, estrogen receptor, progesterone receptor, and p16 were performed in 12 cases; HPV DNA/RNA analyses in 4 cases; and clonality studies in 9 cases. The patients' ages ranged from 42 to 81 years (mean: 62 y). Follow-up information was obtained in 11 patients. Histologic features varied between the tumors in the endometrium and the endocervix in 8 cases, and 5 of these cases had uniform, dilated glands having a microcystic appearance in the cervix. In 6 cases, the tumors in the endometrium and the endocervix had similar histologic features. The immunohistochemical studies showed some differences between the endometrial and endocervical adenocarcinomas in 8 of the 12 cases, independent of differing or similar histologic features. HPV testing in 4 of the cases (3 with similar and 1 with different histology) yielded similar results in the endometrium and endocervix: 2 cases were negative, 1 was positive and 1 was equivocal for HPV DNA/RNA analyses. Clonality studies showed differences between the adenocarcinoma in the endometrium and the endocervix in 7 cases, including 5 cases with different histologic appearances; 2 cases had similar loss of heterozygosity patterns. In conclusion, as suggested by clonality studies, coexisting endometrial and endocervical carcinomas with different histologic features are most likely independent neoplasms. Endometrial and endocervical carcinomas that have similar appearances can represent either the same neoplasm or independent primaries. Clonality tests may help determine their relationship. IHC studies may not be helpful for synchronous endometrial and endocervical tumors, especially those of endometrioid type. It is possible that IHC identifies cell differentiation, rather than site of origin. HPV studies are important to identify endocervical tumors associated with high-risk HPV. However, endometrial tumors involving the cervix and endocervical tumors unrelated to HPV are both negative for high-risk HPV.
大多数累及宫颈的子宫内膜样腺癌在子宫内膜和宫颈内具有相似的肿瘤形态。然而,有些病例中,宫颈内肿瘤的形态与子宫内膜癌不同,其侵袭性比子宫内膜癌更强,或者仅发生在宫颈内而无或仅有最小的子宫肌层浸润。本研究的目的是通过苏木精和伊红染色、免疫组织化学(IHC)、人乳头瘤病毒(HPV)原位杂交、RNA 逆转录原位聚合酶链反应(PCR)分析来揭示 HPV 以及 DNA 克隆性研究,探讨累及子宫内膜和宫颈的肿瘤是否相似或 2 个独立的原发性肿瘤。我们选择了 14 例累及宫颈的子宫内膜样腺癌,这些病例在 1968 年至 2004 年间均有完整的病理材料。对 12 例进行了波形蛋白、癌胚抗原、雌激素受体、孕激素受体和 p16 的免疫组织化学研究;4 例进行了 HPV DNA/RNA 分析;9 例进行了克隆性研究。患者年龄 42 岁至 81 岁(平均:62 岁)。11 例患者获得随访信息。8 例肿瘤在子宫内膜和宫颈内存在组织学特征差异,其中 5 例宫颈内有均匀扩张的腺体,呈微囊状外观。6 例肿瘤在子宫内膜和宫颈内具有相似的组织学特征。在 12 例中的 8 例中,免疫组织化学研究显示子宫内膜和宫颈腺癌之间存在一些差异,而组织学特征或相似或不同。4 例 HPV 检测(3 例组织学特征相似,1 例不同)显示,在子宫内膜和宫颈内的结果相似:2 例为阴性,1 例 HPV DNA/RNA 分析阳性,1 例 HPV DNA/RNA 分析不确定。克隆性研究显示,7 例中腺癌在子宫内膜和宫颈内存在差异,包括 5 例组织学外观不同;2 例具有相似的杂合性丢失模式。总之,正如克隆性研究表明的那样,具有不同组织学特征的共存子宫内膜和宫颈腺癌很可能是独立的肿瘤。具有相似外观的子宫内膜和宫颈腺癌可以代表同一肿瘤或独立的原发性肿瘤。克隆性检测可能有助于确定它们之间的关系。免疫组织化学研究对于同步的子宫内膜和宫颈肿瘤可能没有帮助,尤其是子宫内膜样型。免疫组织化学可能识别的是细胞分化,而不是起源部位。HPV 研究对于识别与高危 HPV 相关的宫颈肿瘤很重要。然而,累及宫颈的子宫内膜肿瘤和与 HPV 无关的宫颈肿瘤均为高危 HPV 阴性。