Neoplasms of the fallopian tube and broad ligament: a selective survey including historical perspective and emphasising recent developments

Recent contributions on selected aspects of the pathology of tubal and paratubal neoplasms are reviewed after a brief historical perspective. The most important, considering both frequency and clinical importance, are those pertaining to tubal carcinoma. These can be grouped as follows: (1) recognition that endometrioid carcinoma is the second most common carcinoma of the tube, after serous, and other variants of müllerian carcinoma are rare; (2) expansion of knowledge about the morphological spectrum of tubal endometrioid carcinoma; (3) modifications of the FIGO staging system; (4) heightened appreciation of the occasional origin of tubal carcinomas from the tubal fimbriae; (5) increased awareness of early carcinoma arising in patients with the BRCA mutation; (6) greater recognition of the propensity for non-tuberculous salpingitis with reactive atypia to mimic carcinoma. Brief consideration then follows of certain other tubal and paratubal neoplasms including those of the broad ligament, emphasising issues in differential diagnosis.     

The shifting landscape of genetic alterations separating endometriosis and ovarian endometrioid carcinoma

Ovarian cancer is one of the most common cancers worldwide, and is associated with a prior diagnosis of endometriosis in several cases. Our aim was to correlate genetic and methylation profile of ovarian endometrioid ovarian cancer and endometriosis patients. We evaluated the genetic profile of 50 ovarian endometriosis and 20 ovarian endometrioid carcinoma samples using next generation sequencing technology. In addition, the DNA methylation profile was evaluated for both cohorts of patients. We observed several mutated genes that were common for both types of patients, but we also identified mutated genes that were characteristic for each group: JAK3, KRAS and RB1 for endometriosis; and ATM, BRAF, CDH1, EGFR, NRAS, RET and SMO for ovarian endometrioid cancer. Also we idenfied genes that are highly methylated only in endometriosis samples (PYCARD, RARB, RB1, IL2, CFTR, CD44 and CDH13) and MLH3 gene was methylated only in endometrioid ovarian carcinoma samples. Also, BRCA1, CADM1, PAX6 and PAH genes are mainly methylated in endometrioid ovarian carcinoma patients. We identified a correlation for the cancer group between tumor stage, copy number aberrations and the presence of metastases; more specifically, the presence of BRCA1 pathogenic variants was correlated with tumor differentiation degree, TP53 variants and copy number aberrations. This study was able to demonstrate the presence of similar pathways being altered in both endometriosis and ovarian endometrioid carcinoma, which could mean that a diagnosis of endometriosis could be an early marker for cancer diagnosis. In addition, we showed that GATA2 hypomethylation, ATM hypermethylation, CREM hypomethylation, higher tumor differentiation degree or higher tumor stage is associated with a poor prognosis in patients with ovarian endometrioid carcinoma.     

MELF invasion in endometrial cancer as a risk factor for lymph node metastasis

Pavlakis K, Messini I, Vrekoussis T, Panoskaltsis T, Chrysanthakis D, Yiannou P & Voulgaris Z
(2011) Histopathology  58 , 966–973
MELF invasion in endometrial cancer as a risk factor for lymph node metastasis Aim: To investigate whether the microcystic, elongated and fragmented (MELF) pattern of myometrial invasion encountered in certain endometrioid endometrial carcinomas can be considered as a risk factor for lymph node metastasis. Methods and results: A total of 351 cases of total abdominal hysterectomy and bilateral salpingo‐oophorectomy with/without lymphadenectomy or lymph node sampling, performed for endometrioid endometrial adenocarcinoma, were included in this study. The existence of MELF invasion, vascular invasion, fibromyxoid stromal reaction and lymph node metastasis were recorded. Immunohistochemistry for endothelial and epithelial markers was performed on selected cases. MELF invasion was identified in 20 (10.81%) and 13 cases (13.13%) treated without and with lymphadenectomy, respectively. All these cases were either well or moderately differentiated carcinomas, stages IA–II (without considering lymph node status). Positive lymph nodes were detected in seven of 13 MELF‐positive (53.84%) and six of 86 MELF‐negative cases (6.97%) This observation was statistically significant. Of the seven MELF‐positive tumours with lymph node metastasis, three cases exhibited intravascular tumour emboli while four showed a fibromyxoid stromal reaction. Conclusion: MELF pattern invasion was found to be related statistically to lymph node metastasis. Nevertheless, further studies are needed in order to evaluate the clinical significance of this observation.     

Sentinel lymph node mapping with pathologic ultrastaging: A valuable tool for assessing nodal metastasis in low-grade endometrial cancer with superficial myoinvasion

Objective

To report the incidence of nodal metastases in patients presenting with presumed low-grade endometrioid adenocarcinomas using a sentinel lymph node (SLN) mapping protocol including pathologic ultrastaging.

Methods

All patients from 9/2005 to 12/2011 who underwent endometrial cancer staging surgery with attempted SLN mapping for preoperative grade 1 (G1) or grade 2 (G2) tumors with < 50% invasion on final pathology, were included. All lymph nodes were examined with hematoxylin and eosin (H&E). Negative SLNs were further examined using an ultrastaging protocol to detect micrometastases and isolated tumor cells.

Results

Of 425 patients, lymph node metastasis was found in 25 patients (5.9%) on final pathology—13 cases on routine H&E, 12 cases after ultrastaging. Patients whose tumors had a DMI < 50% were more likely to have positive SLNs on routine H&E (p < 0.005) or after ultrastaging (p = 0.01) compared to those without myoinvasion.

Conclusions

Applying a standardized SLN mapping algorithm with ultrastaging allows for the detection of nodal disease in a presumably low-risk group of patients who in some practices may not undergo any nodal evaluation. Ultrastaging of SLNs can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion. The long-term clinical significance of ultrastage-detected nodal disease requires further investigation as recurrences were noted in some of these cases.     

子宫内膜样腺癌血管内皮生长因子的表达情况及临床意义

目的 探讨子宫内膜样腺癌血管内皮生长因子(VEGF)的表达情况及临床意义.方法 采用免疫组织化学方法检测49例子宫内膜样腺癌、10例不典型增生子宫内膜及10例正常子宫内膜标本中的VEGF表达情况,同时检测子宫内膜样腺癌组织中雌激素受体(ER)及孕激素受体(PR)的表达情况,分析VEGF阳性表达率与各临床病理参数的关系.结果 子宫内膜样腺癌组织、不典型增生子宫内膜组织和正常子宫内膜组织的VEGF阳性表达率比较,差异有统计学意义(P﹤0.05);子宫内膜样腺癌组织的VEGF阳性表达率高于正常子宫内膜组织(P﹤0.05).病理分级和临床病理分期是子宫内膜样腺癌组织VEGF阳性表达的独立因素(P﹤0.05).结论VEGF在子宫内膜的恶性转变和细胞分化中发挥重要作用,在判断子宫内膜样腺癌的恶性程度和患者预后评价方面具有一定的价值.     

NF-κB和eIF4E在子宫内膜上皮内瘤变和子宫内膜样癌中的表达及意义

目的 :探讨NF-κB和eIF4E在子宫内膜上皮内瘤变（EIN）和子宫内膜样癌（EC）中的表达规律及意义。 方法:免疫组织化学SP法检测NF-κB和eIF4E在增殖期子宫内膜、子宫内膜增生、EIN及EC中的表达,应用Mann－WhitneyU检验及Wilcoxon检验进行数据统计分析。结果:（1）NF-κB在5组中呈递增性表达,EIN组与EC组间无显著差异性（P＞0. 05）,与其余两组组间表达均有统计学意义（P < 0. 05）。（2）eIF4E在EC中的表达明显高于增殖期子宫内膜、子宫内膜增生及EIN,且EIN组与各组间差异有统计学意义（P < 0. 05）。（3）NF-κB和eIF4E在EIN及相关病变中的表达有显著相关性（r = - 0.949,P＜0. 05）。结论:NF-κB和eIF4E在EIN及EC中高表达,在EIN发展为EC的过程中逐渐被激活,进而加速转录、翻译,增大EIN进展为子宫内膜样癌的可能性。     

高分化子宫内膜癌或非典型子宫内膜增生患者保守治疗后妊娠结局影响因素分析

目的 探讨对于高分化子宫内膜癌(EC)或非典型子宫内膜增生(AEH)患者醋酸甲羟孕酮(MPA)保守治疗后妊娠建立的影响因素。方法 回顾性研究65例EC/AEH患者,分为妊娠组(34例)和非妊娠组(31例),统计学分析妊娠建立的影响因素。结果 妊娠组和非妊娠组相比临床基本特征均无统计学差异(P＞0.05);妊娠组的MPA治疗的持续时间、病变消失时间、妊娠允许年龄、复发、行刮宫术次数和排卵期间子宫内膜厚度与非妊娠组相比存在统计学差异(P＜0.05);Logistic回归分析显示复发(OR=2.323,P=0.015)、排卵期间子宫内膜厚度(OR=0.283,P＜0.001)和允许妊娠年龄(OR=2.524,P=0.039)是影响妊娠结局的显著性因素。结论 复发、排卵期子宫内膜厚度和怀孕时年龄是MPA保守治疗后妊娠建立的影响因素;MPA治疗肿瘤消失后即采用辅助生殖技术(ART)保育治疗可能有助于肿瘤复发、薄型子宫内膜或高妊娠年龄的患者保留生育力。     

子宫内膜异位症与卵巢癌相关性临床分析

目的:探讨子宫内膜异位症(内异症)与卵巢癌的相关性。方法:收集199例卵巢癌患者,分内异症组(n=32),非内异症组（n=167）,回顾性分析两组患者一般情况、临床表现、病理特征、实验室检查及预后。结果:内异症组平均年龄明显小于非内异症组(P＜0.05),年龄<50岁、未生育患者构成比明显高于非内异症组;内异症组患者临床症状以月经改变和下腹痛、腹胀为主（P＜0.05）;内异症组肿瘤直径通常小于20cm,且主要在10-20cm之间,非内异症组肿瘤直径大部分为10-20cm;内异症组患者血CA125主要在200-1000kU/L之间,非内异症组大部分在200kU/L以下;内异症组患者以透明细胞癌、宫内膜样癌为主,非内异症组以浆液性囊腺癌为主(P＜0.05);内异症组患者分期较早,I期 、Ⅱ期占合并卵巢癌患者68.8%,非内异症组分期多处于Ⅱ期、Ⅲ期,占原发卵巢癌患者70.1%（P＜0.05）;内异症组患者病灶部位多位于左侧卵巢,非内异症组病灶部位在左侧、右侧、双侧分布较接近 (P＜0.05);内异症组5年生存率为59.4%,非内异症组5年生存率为34.7%,两组差异具有统计学意义(P＜0.05)。结论:应充分了解内异症恶变的临床症状及病理特征,提高早期诊断率。     

卵巢上皮性癌合并卵巢子宫内膜异位症67例临床病理分析

目的 探讨合并卵巢子宫内膜异位症(内异症)的卵巢上皮性癌(卵巢癌)的临床病理特点.方法 选取1996年1月至2006年12月在复旦大学附属妇产科医院就诊并经手术确诊的卵巢癌共727例,对其中合并卵巢内异症的67例患者(其中由卵巢内异症恶变的卵巢癌患者34例,为A组;其他仅合并卵巢内异症的卵巢癌患者33例,为B组)的临床病理资料进行回顾性分析,并与660例未合并卵巢内异症的卵巢癌患者(C组)进行对照分析.同期本院经手术病理确诊的卵巢内异症患者共3890例.结果 卵巢内异症恶变为卵巢癌的发生率为0.87%(34/3890).卵巢癌合并卵巢内异症的发生率为9.2%(67/727).A、B、C组患者的平均年龄分别为(47.2±1.3)、(47.8±1.2)、(51.2±0.4)岁,3组问比较,差异有统计学意义(P=0.013).A、B组病理类型多为透明细胞癌(分别为67.6%、69.7%),其所占比例均明显高于C组的18.8%(P=0.000);而C组以浆液性腺癌(50.3%)为主,其所占比例明显高于A组的8.8%和B组的12.1%(P=0.000).A、B组手术病理分期多为Ⅰ期(分别为73.5%、63.6%),其所占比例均明显高于C组的31.4%(P=0.000);而C组多为Ⅲ期(47.7%),其所占比例明显高于A组的23.5%和B组的15.2%(P=0.001).A、B、C组高分化(分别为11.8%、6.1%、10.5%)、中～低分化(分别为88.2%、93.9%、89.5%)所占比例分别比较,差异均无统计学意义(P=0.602).A、B、C组雌激素受体(ER)阳性率分别为22.2%(6/27)、31.6%(6/19)、43.9%(136/310),3组间比较,差异有统计学意义(P=0.018);A、B、C组孕激素受体(PR)阳性率分别为22.2%(6/27)、15.8%(3/19)、35.5%(110/310),3组间比较,差异无统计学意义(P=0.082).患者总的5年累积生存率为55.6%,A、B、C组患者的5年累积生存率分别为78.9%、92.8%、51.9%,3组间比较,差异有统计学意义(P=0.000).结论 合并卵巢内异症的卵巢癌患者,具有年轻(尤其是内异症恶变患者)、多为卵巢透明细胞癌、期别早、ER表达水平低、预后好的特点.