LACC临床随机对照试验研究的启示

LACC研究结果提示对于早期子宫颈癌患者,接受微创手术相比于开腹手术的患者有更高的复发率和更低的生存率。基于该研究结果,目前包括安德森癌症中心在内的国内外医疗机构均已停止或减少对ⅠA2～ⅠB1期子宫颈癌患者提供微创手术。文章在回顾LACC试验结果的同时,分析了目前妇科肿瘤学界对LACC研究结论存在的疑问及微创手术的改良空间,探讨了随机对照试验的临床价值及中国现状。     

Gene expression profiles in squamous cell cervical carcinoma using array-based comparative genomic hybridization analysis

Our aim was to identify novel genomic regions of interest and provide highly dynamic range information on correlation between squamous cell cervical carcinoma and its related gene expression patterns by a genome-wide array-based comparative genomic hybridization (array-CGH). We analyzed 15 cases of cervical cancer from KangNam St Mary's Hospital of the Catholic University of Korea. Microdissection assay was performed to obtain DNA samples from paraffin-embedded cervical tissues of cancer as well as of the adjacent normal tissues. The bacterial artificial chromosome (BAC) array used in this study consisted of 1440 human BACs and the space among the clones was 2.08 Mb. All the 15 cases of cervical cancer showed the differential changes of the cervical cancer-associated genetic alterations. The analysis limit of average gains and losses was 53%. A significant positive correlation was found in 8q24.3, 1p36.32, 3q27.1, 7p21.1, 11q13.1, and 3p14.2 changes through the cervical carcinogenesis. The regions of high level of gain were 1p36.33-1p36.32, 8q24.3, 16p13.3, 1p36.33, 3q27.1, and 7p21.1. And the regions of homozygous loss were 2q12.1, 22q11.21, 3p14.2, 6q24.3, 7p15.2, and 11q25. In the high level of gain regions, GSDMDC1, RECQL4, TP73, ABCF3, ALG3, HDAC9, ESRRA, and RPS6KA4 were significantly correlated with cervical cancer. The genes encoded by frequently lost clones were PTPRG, GRM7, ZDHHC3, EXOSC7, LRP1B, and NR3C2. Therefore, array-CGH analyses showed that specific genomic alterations were maintained in cervical cancer that were critical to the malignant phenotype and may give a chance to find out possible target genes present in the gained or lost clones.     

Blue rubber bleb nevus syndrome: Report of a patient with hemangiomas of the vaginal portion of the cervix appearing during pregnancy

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder showing venous malformations in the skin and gastrointestinal tract, and other internal organs. We encountered a patient with BRBNS in whom hemangiomas of the uterine cervix appeared during pregnancy. This was apparently the first reported occurrence. To avoid unexpected bleeding from hemangiomas, patients with BRBNS should be examined repeatedly for hemangiomas of the birth canal, and special care should be taken in deciding the mode of delivery.     

Nonneoplastic signet-ring cells in the gallbladder and uterine cervix. A potential source of overdiagnosis

We describe 3 cases of nonneoplastic signet-ring cell change in ulcerated mucosa, 2 of them in the gallbladder and 1 in an endocervical polyp. In the gallbladder cases, there were focal collections of signet-ring cells both on the mucosal surface and within the lumen of tubules, whereas in the endocervical polyp, the signet-ring cell aggregates were entirely confined to the mucosal surface. In all 3 cases, the signet-ring cells were positive for Mayer's mucicarmine and immunoreactive for keratin AE1/AE3. The lack of nuclear atypicality, the arrangement in superficial and intraluminal nests, and the admixture with histiocytes and other inflammatory cells are in keeping with the interpretation that the signet-ring cells are disrupted mucosal goblet cells exhibiting hyperplastic and degenerative changes. A review of the literature disclosed only other 2 previously reported cases of benign signet-ring cell changes in the gallbladder and none--to the best of our knowledge--in an endocervical polyp. Awareness of this phenomenon is of importance to avoid a potential overdiagnosis of signet-ring cell adenocarcinoma.     

Cervical adenocarcinoma with stromal micropapillary pattern

Adenocarcinoma with a stromal micropapillary pattern (SMP) has been described in various organs, but not in the uterus. We encountered a case of uterine cervical carcinoma with SMP. A54‐year‐old Japanese woman was referred to the hospital with abnormal vaginal bleeding. The cervical cytodiagnosis was adenocarcinoma with features resembling serous adenocarcinoma. Cervical cytology showed many small clusters of tumor cells, present in up to two or three layers, composed of atypical cells with markedly increased nucleus: cytoplasm ratios. A radical hysterectomy with bilateral adnexectomy and retroperitoneal lymph node dissection was performed. Microscopically, the tumor was composed predominantly of adenocarcinoma with SMP. The outer surface of the SMP cell clusters showed membranous expression of mucin‐1 (MUC‐1). Many lymph node metastases were detected. The tumor was diagnosed as a cervical adenocarcinoma with SMP and coexistent squamous cell carcinoma in situ. The pathology was classified as T1b1N1M1, stage IVB. The patient underwent postoperative adjuvant chemotherapy and is without local recurrence or distant metastasis 48 months after the operation. To the best of our knowledge, this is the first reported case of cervical adenocarcinoma with SMP. Diagn. Cytopathol. 2016;44:133–136. © 2015 Wiley Periodicals, Inc.     

子宫颈小细胞癌的临床病理特征和预后分析

目的探讨子宫颈小细胞癌的临床病理特征和影响预后的因素。方法回顾性对比分析18例早期子宫颈小细胞癌和40例鳞状细胞癌的临床病理特征,采用Kaplan-Meier法分析子宫颈小细胞癌的3年总生存率及临床病理特征对生存率的影响,采用Cox回归模型明确独立的预后因素。结果 18例子宫颈小细胞癌中位年龄39岁,40例鳞状细胞癌中位年龄47岁,小细胞癌患者的中位年龄低于鳞状细胞癌(P0.05)。早期子宫颈小细胞癌的淋巴结转移率为44.4%,脉管瘤栓发生率38.9%,复发率33.3%,均明显高于鳞状细胞癌(P0.05)。早期子宫颈小细胞癌术后3年生存率为61.1%,鳞状细胞癌为92.5%,早期子宫颈小细胞癌的生存率明显低于鳞状细胞癌(P0.05)。临床分期、肿块大小、淋巴结转移和脉管瘤栓是影响子宫颈小细胞癌预后的危险因素。Cox回归模型多因素分析表明以上各临床病理特征均不是独立预后因素。结论子宫颈小细胞癌与鳞状细胞癌相比,其早期易发生淋巴结转移和脉管瘤栓,易复发,预后较差。临床分期、肿块大小、淋巴结转移和脉管瘤栓是影响其预后的危险因素,但不是独立预后因素。     

Limiting factors for cytopathological diagnosis of high-grade squamous intraepithelial lesions: a cytohistological correlation between findings in cervical smears and loop electrical excision procedure.

The present study sought possible factors leading to the cytological diagnosis of atypical squamous cells of uncertain significance (ASCUS) in cases of high-grade squamous intraepithelial lesions (HSIL). Based on retrospective histopathological analysis of loop electrical excision procedure (LEEP) products that diagnosed HSIL, two study groups were randomly selected. The first was consisted of cases with two consecutive Papanicolaou (Pap) smears with the diagnosis of ASCUS. The second (control) group was represented by cases diagnosed as HSIL by cytology. From the Pap smears diagnosed as ASCUS, the sampling limitations was different from control group (P < 0.05). The median size of the largest lesion in each case with ASCUS was 2.66 mm (+/- 1.71 mm). In the control group, the median size of the largest lesion was 5.15 mm (+/-2.58 mm) (P < 0.05). The size of the lesion and sample limitations led patients with cervical intraepithelial neoplasms to be diagnosed as ASCUS for two consecutive times, after a 6-mo period.     

Abnormal cervicovaginal smears due to endometriosis: a continuing problem.

Endometriosis may be challenging when identified on cervicovaginal smears (CVS), leading to an incorrect interpretation of high-grade squamous intraepithelial lesion (HSIL), or atypical glandular cells of undetermined significance (AGUS) including adenocarcinoma in situ (AIS). Awareness of cervical endometriosis, particularly in predisposed patients, is crucial for a correct diagnosis. While cervical endometriosis has been reported to be a diagnostic pitfall of glandular abnormalities, its characteristic features are still not well-established. This may partially be attributed to the varied cytomorphologic features endometriosis shows, depending on menstrual cycle hormonal changes. We describe our experience with three examples where CVS were interpreted as either AGUS or HSIL, which led to a hysterectomy in 2 of 3 patients. Cervical endometriosis needs to be considered with other well-known benign conditions that mimic glandular abnormalities, including cervicitis, tubal metaplasia, lower uterine segment sampling, and microglandular hyperplasia. Published series and our own experience lead us to suggest that these smears will continue to present diagnostic difficulties.     

Diagnostic significance of endocervical glandular cells with "golden-yellow" mucin on pap smear

Endocervical glandular cells rarely show "golden-yellow" mucin staining using the Papanicolaou technique, whereas the cells of adenoma malignum (minimal deviation adenocarcinoma) do. To further evaluate the significance of this finding, we reviewed the Pap smears of six cases in which atypical glandular cells containing golden-yellow mucin was identified. Microscopic examination of the hysterectomy specimens confirmed one case of adenoma malignum, whereas the other five cases were diagnosed as endocervical glandular hyperplasia with pyloric gland metaplasia. Glandular cells observed in all six cases were filled with golden-yellow mucin. In the case of adenoma malignum the nuclei were somewhat more enlarged and the chromatin texture was coarsely granular, although a distinction between adenoma malignum and the five benign lesions was difficult. Special staining performed on tissue sections in all cases demonstrated that the intracytoplasmic mucin of the glandular cells in portion of both pyloric gland metaplasia and adenoma malignum was predominantly PAS-positive and showed immunoreactivity for M-GGMC-1 (HIK1083), which reacts with pyloric gland mucin of the stomach. A review of 1,165 consecutive Pap smears failed to identify cells with golden-yellow mucin. These observations indicate that golden-yellow mucin on Papanicolaou smear seems to represent a gastric phenotype of endocervical glandular cells, which is a unique characteristic shared by adenoma malignum and pyloric gland metaplasia. This finding should therefore be regarded as a warning sign, raising the possibility of adenoma malignum and requiring prompt histopathologic assessment, although not of itself diagnostic of malignancy.     

Human papillomavirus genotyping by oligonucleotide microarray and p16 expression in uterine cervical intraepithelial neoplasm and in invasive carcinoma in Korean women

For evaluating the diagnostic significance of p16(INK4A) over-expression in the uterine cervical intraepithelial neoplasm and in invasive carcinoma, human papillomavirus (HPV) was detected and genotyped by oligonucleotide microarray in archival tissues of 117 cervical specimens, including 47 invasive squamous cell carcinomas (SCC), 30 cases of cervical intraepithelial neoplasia (CIN), 20 adenocarcinomas, and 20 cases of non-neoplastic cervix. The expression of p16(INK4A) protein was immunohistochemically studied in these cases and in five HPV-positive and one HPV-negative cervical cancer cell lines. HPV was detected in 50% of CIN, 61.7% of SCC, and 45.5% of adenocarcinomas. p16(INK4A) expression was seen in all 20 cases of adenocarcinoma, 78.7% (37/47) of SCC, and 96.7% (29/30) of CIN, but not in any cases of the non-neoplastic cervix. There was no difference in p16(INK4A) expression between the HPV-positive and HPV-negative cervical lesions. All HPV-positive and -negative cervical cancer cell lines expressed p16(INK4A) protein. In conclusion, the presence of p16(INK4A) expression in cervical squamous and glandular epithelium indicates the existence of dysplasia or malignancy in the uterine cervix, regardless of HPV infection.