Intraoperative assessment of depth of myometrial invasion in endometrial carcinoma.

OBJECTIVE: To evaluate the adequacy of intraoperative assessment of depth of myometrial invasion in patients with endometrial adenocarcinoma. METHODS: Of the 58 evaluable cases, depth of myometrial invasion was estimated by gross examination of fresh tissue by an experienced surgeon and a pathologist and on the frozen section by the same pathologist. This was compared with the depth of invasion on the final microscopic examination performed by another pathologist. RESULTS: The depth of invasion was accurately predicted by the surgeon in 89.7% of the patients, while the pathologist's accurate prediction rates on fresh tissue and frozen section were 86.2% and 91.4%, respectively. The accurate prediction rate gradually diminished for both the surgeon and the pathologist as the histologic grade increased. Frozen section examination was reliable in grade I cancer (100%), while gross examination of the surgeon and the pathologist had a significant error rate in predicting accurate depth of invasion (7.6%-33%). CONCLUSION: If frozen section shows that myometrial invasion in patients with grade 1 endometrial carcinoma is less than 1/3, lymphadenectomy may be omitted. In all other cases radical surgery and surgical staging is mandatory to avoid undertreatment.     

Difficulties in assessing the depth of myometrial invasion in endometrial carcinoma.

The depth of myometrial invasion (DMI) is one of the most important prognostic indicators and determinants of therapy in endometrial cancer. There are well-documented problems in recognizing DMI. We examined 100 previously diagnosed endometrioid endometrial carcinomas in hysterectomy specimens, reassessed DMI, and explored morphological features that complicated appraisal of myometrial invasion. The DMI was different from the original measurement in 29% of cases. Twelve percent of all cases (40% of cases with measurement discrepancies) involved differences in the assignment of invasion categories (noninvasive, < or =50% myometrial invasion, and >50% myometrial invasion). Nearly all endometrial cancers originally diagnosed as invasive were considered noninvasive on review. We examined whether the distribution of stromal metaplasia, noninvasive patterns (exophytic tumors, irregular endomyometrial junctions, and adenomyosis), and myometrial invasion patterns were different in cases with and without measurement discrepancies. Irregular endomyometrial junctions, exophytic tumors, and adenomyosis tended to coexist and were more common in the cases with DMI discrepancies. Although there seemed to be a relationship between smooth muscle metaplasia and exophytic tumors, it did not appear that smooth muscle metaplasia was significantly more common in cases with measurement difficulties. However, cases with extensive smooth muscle metaplasia posed problems with assessment of myometrial invasion. Patterns of myometrial invasion other than the conventional destructive pattern were sufficiently uncommon as to not impact on DMI measurement in large numbers of cases. Measuring the DMI is usually uncomplicated, but additional scrutiny should be paid to cases involving exophytic tumors, irregular endomyometrial junctions, adenomyosis, and extensive stromal smooth muscle metaplasia.     

Assessment of depth of myometrial invasion in endometrial adenocarcinoma

Depth of myometrial invasion in stage I adenocarcinoma of the endometrium is recognized as a prognostic factor for lymph node metastasis and overall survival. To determine if depth of myometrial invasion estimated by gross examination correlated with final histologic depth of invasion, we retrospectively reviewed all cases of surgical stage I endometrial adenocarcinoma treated at our institution between July 1985 and July 1988. Of the 113 evaluable patients, 63 had grade 1 lesions, 37 grade 2 lesions, and 13 grade 3 lesions. The depth of invasion was accurately determined by gross examination in 55 of 63 (87.3%) grade 1 lesions, 24 of 37 (64.9%) grade 2 lesions, and only 4 of 13 (30.8%) grade 3 lesions. Thus, gross examination of fresh tissue to estimate depth of myometrial invasion in endometrial adenocarcinoma is less reliable as the grade of the tumor increases. Alternative methods, such as frozen section, should be considered when evaluating depth of invasion, especially when this affects intraoperative decisions regarding lymph node sampling.     

Combined use of preoperative transvaginal ultrasonography and intraoperative gross examination in the assessment of myometrial invasion in endometrial carcinoma

Objective

To evaluate the diagnostic performance of gross examination and transvaginal ultrasonography in the assessment of the depth of myometrial infiltration when they are used alone or together as a combined test.

Study design

The data of 219 consecutive patients with a diagnosis of endometrial cancer were evaluated retrospectively. Transvaginal ultrasound was carried out as a part of the routine preoperative work-up within three days of surgical intervention in all cases. All patients underwent hysterectomy with bilateral salpingo-oophorectomy and routine surgical staging and all uterine specimens were examined immediately after hysterectomy. The depth of myometrial invasion was classified into two groups: no or <50% invasion and ≥50% invasion. The findings of ultrasound and intraoperative gross examination were compared with the final histopathological results. The data of these two methods were integrated to evaluate the diagnostic performance of the combined test. If the results of myometrial invasion evaluation were different for the same patient, the deeper one (the depth of invasion ≥50%) was accepted.

Results

Sensitivity, specificity, PPV, NPV and accuracy of preoperative ultrasonography in predicting myometrial infiltration ≥50% were 62%, 81%, 60%, 82%, and 75% respectively. The corresponding rates for intraoperative gross examination were 61%, 88%, 70%, 83% and 79%, respectively. For the combined test they were 78%, 76%, 60%, 88% and 70% respectively. There was no statistically significant difference in sensitivity and specificity between ultrasound and gross examination. The sensitivity of the combined test was significantly higher than that of ultrasound and gross examination (p = 0.001 and p < 0.0001, respectively). The specificity of the combined test was significantly lower than that of TVS and gross examination (p = 0.008 and p < 0.0001, respectively).

Conclusion

Combining ultrasonography and intraoperative gross examination may be a good option to assess the depth of myometrial invasion, as it has a higher sensitivity and negative predictive value in comparison to using these methods alone.     

子宫内膜癌肌层浸润深度的评估

目的　探讨术前B超、术中肉眼观察、术后大体标本测量和血清CA12 5测定 ,对判断子宫内膜癌肌层浸润深度的价值。方法　采用术前B超、术中肉眼观察和术后大体标本测量对 13 3例手术病理分期Ⅰ期子宫内膜癌患者的肌层浸润深度的判断进行评估 ,并分析 91例 (79例为Ⅰ期 ,12例为同期的Ⅱ～Ⅳ期患者 )子宫内膜癌患者血清CA12 5水平与子宫内膜癌的关系。结果　术前B超判断子宫内膜癌肌层浸润和深肌层浸润的敏感性分别为 62 6%和 47 8% ,特异性分别为 67 7%和90 0 % ;术中肉眼观察判断子宫内膜癌肌层浸润和深肌层浸润的敏感性分别为 5 9 6%和 73 9% ,特异性分别为 76 5 %和 94 6% ;术后大体标本测量判断子宫内膜癌肌层浸润和深肌层浸润的敏感性分别为 70 0 %和 94 4% ,特异性分别 92 0 %和 97 7%。子宫内膜癌手术病理分期Ⅰ期患者血清CA12 5水平异常 (≥ 3 5kU/L)的发生率为 8% (6/79) ,Ⅱ～Ⅳ期患者的发生率为 5 8% (7/12 ) ,血清CA12 5水平异常的发生率与手术病理分期的期别有极显著相关性 (P <0 0 0 1) ,而与子宫内膜癌肌层浸润深度无显著相关性 (P >0 0 5 )。结论　术前B超、术中肉眼观察和术后大体标本测量对判断Ⅰ期子宫内膜癌肌层浸润深度有一定帮助 ,其中术后大体标本测量的准确性相对较好。血     

Intraoperative frozen section examination of myometrial invasion depth in patients with endometrial carcinoma

The objective of this study was to evaluate the accuracy of frozen sections (FS) as a method for estimation of the depth of myometrial invasion in patients with stage I endometrial carcinoma. During a 3-year period (1989–1992), 46 consecutive patients with FIGO stage I endometrial carcinoma were included in this study. The depth of myometrial invasion was estimated by FS examination performed during surgery. The final histologic findings of the surgical specimen were compared to the FS evaluation. The results of this study demonstrate that deep or superficial myometrial invasions were correctly diagnosed by FS in 42 out of 46 cases (91.3%). Three cases (6.6%) with deep myometrial invasion were falsely diagnosed as superficially invasive. One case with superficial invasion (2.1%) was falsely diagnosed as deeply invasive. In conclusion, intraoperative FS examination of depth of myometrial invasion by endometrial carcinoma is a simple and accurate method, providing a good correlation with the final histologic report of the surgical specimen.     

经阴道三维超声诊断子宫内膜癌肌层浸润的价值

目的　探讨经阴道三维超声诊断子宫内膜癌肌层浸润的价值。方法　收集 2 0 0 2年1月至 2 0 0 3年 3月经诊刮确诊并首选手术治疗的子宫内膜癌患者 53例 ,术前 1周内行经阴道二维超声 ,并应用三维超声的多平面成像技术和体积测量功能对肌层浸润深度作出评估 ;同时记录其临床病理指标。结果　 (1)患者年龄 3 8～ 77岁 ;肌层浸润深度 :无、浅、深肌层浸润者分别为 4、3 1、18例 ;病理类型 :子宫内膜样腺癌、非子宫内膜样腺癌分别为 43、10例 ;病理分化程度 :高、中、低分化分别为2 8、13、12例 ;手术病理分期 :Ⅰ、Ⅱ、Ⅲ、Ⅳ期分别为 3 3、10、8、2例。 (2 )三维超声的多平面成像技术和二维超声诊断浅肌层浸润的敏感度、特异度、阳性预测值、阴性预测值分别 92 %、10 0 %、10 0 %、67%和 44%、10 0 %、10 0 %、2 1% ,两者分别比较 ,差异均有极显著性 (χ2 =13 2 0 11,P =0 0 0 5) ;三维超声的多平面成像技术和二维超声诊断深肌层浸润的敏感度、特异度、阳性预测值、阴性预测值分别为 72 %、86%、72 %、86%和 75%、84%、67%、89% ,两者分别比较 ,差异均无显著性 (χ2 =0 0 0 0 0 ,P>0 0 5)。(3 )三维超声的体积测量功能测量的浅、深肌层浸润肿瘤的体积分别为 1 12cm3(Q2 5 75 =1 12～ 4 49)和 9 16cm3(     

Preoperative assessment of myometrial and cervical invasion in endometrial carcinoma by transvaginal ultrasound

Objective

To evaluate the diagnostic accuracy of transvaginal ultrasound (TVS) in preoperative assessment of the depth of myometrial infiltration and the presence of cervical invasion in endometrial carcinoma.

Methods

298 consecutive patients with a diagnosis of endometrial cancer were evaluated by TVS within 3 days of surgical intervention. The depth of myometrial invasion was classified into two groups: no or < 50% invasion and ≥ 50% invasion. Invasion of cervix was diagnosed when the neoplastic tissue distended the cervix and showed ill-defined borders with the cervical stroma.

Results

The sensitivity, specifity, positive predictive value (PPV), negative predictive value (NPV) and overall diagnostic accuracy of TVS in evaluation of the depth of myometrial infiltration were 68.4%, 82%, 65.1%, 84.1% and 77.5%, respectively. While the sensitivity and PPV were significantly higher among grade 3 tumors, the specifity, NPV and accuracy were significantly higher among grade 1 tumors.The sensitivity, specifity, PPV, NPV, and overall diagnostic accuracy of TVS in assessment of the presence or absence of neoplastic tissue in cervix were 76.5%, 99.3%, 86.7%, 98.2% and 98%, respectively. While the sensitivity and PPV were significantly higher among grade 1 tumors, the NPV and accuracy were significantly lower among grade 3 tumors.

Conclusion

TVS can be considered as a feasible, economical and simple imaging modality with a high diagnostic accuracy for the prediction of cervical involvement. However, it is not a reliable method in estimating the depth of myometrial infiltration.     

Transvaginal ultrasound evaluation of myometrial invasion in endometrial carcinoma

In 20 cases of histologically proved endometrial cancer the depth of myometrial invasion was ascertained by means of transvaginal ultrasound, using a high-frequency endocavitary probe. The sonographic findings were confirmed by histologic examination in 18 of the 20 patients evaluated (90.0%). Transvaginal ultrasound provides a fuller preoperative clinical picture and supplies additional diagnostic information which is invaluable in the choice of therapeutic approach.     

经阴道三维超声诊断子宫内膜癌的探讨

目的探讨经阴道三维超声（3-DTVS）诊断子宫内膜癌及肌层浸润的价值。方法收集2003年4月-2005年4月在我院经手术治疗的子宫内膜癌患者72例。其中，术前64例（3-DTVS组）应用3-DTV多平面和血管成像技术以及体积测量功能诊断子宫内膜癌及肌层浸润深度进行评估；25例（MRI组）经核磁共振（MRI）检查为对照组，以手术后病理结果判断符合率，对比两组诊断子宫内膜癌及其肌层浸润情况。结果经3-DTVS诊断子宫内膜癌的符合率为89．1％，判断肌层浸润的符合率为77．1％。应用3-DTVS与MRI诊断子宫内膜癌及肌层浸润准确率两组间无显著性差异（P〉0．05）。结论3-DTVS在诊断子宫内膜癌及肌层浸润深度有诊断价值。     

Intraoperative evaluation of depth of myometrial invasion in stage I endometrial adenocarcinoma

In patients with stage I endometrial adenocarcinoma, the incidence of pelvic and para-aortic lymph node metastasis is related to the grade of the tumor and the depth of myometrial invasion. Although the grade of the tumor may be predicted preoperatively by endometrial sampling, the depth of myometrial invasion cannot be determined until after the uterus has been removed. Although complications have been attributed to lymph node sampling, failure to perform the procedure in patients at risk for nodal metastasis may result in underdiagnosis of extrauterine disease, leading to inadequate therapy. Gross visual examination of the cut surface of the tumor at the time of hysterectomy accurately determined the depth of myometrial invasion in 135 of 148 prospectively studied patients (91%) (P less than .001). The sensitivity of the test was 0.71, the specificity was 0.96, and the positive predictive value was 0.80. Intraoperative assessment of the depth of myometrial invasion is a simple, inexpensive, and useful technique for selecting those patients with stage I endometrial adenocarcinoma who might benefit from selective para-aortic lymphadenectomy.     

Intraoperative frozen section diagnosis of depth of myometrial invasion in endometrial adenocarcinoma

From January 1981 to December 1988, a prospective trial was conducted on 216 consecutive patients undergoing hysterectomy for FIGO stage I endometrial adenocarcinoma to determine the accuracy of intraoperative frozen section (IFS) diagnosis of depth of myometrial invasion. IFS and D&C diagnoses were compared to the permanent section diagnosis to determine their accuracy. Patients with an IFS or D&C diagnosis of grade 3 carcinoma, deep myometrial invasion, cervical invasion, or adnexal involvement were considered high risk for paraaortic nodal metastasis, and paraaortic lymphadenectomy was performed. IFS correctly diagnosed the depth of myometrial invasion in 194 of 204 cases (95%). The sensitivity of IFS diagnosis of deep invasion was 87%, the specificity was 99%, the positive predictive value was 98%, and the negative predictive value was 94%. Grade, subtype, cervical invasion, and adnexal involvement were also accurately diagnosed. Based on IFS and D&C diagnosis, paraaortic lymphadenectomy was performed in 32% of patients, while 68% were considered low risk and were spared paraaortic lymphadenectomy. Eight patients (5%) were incorrectly diagnosed as low risk and did not have paraaortic lymphadenectomy performed. Sixty-five of seventy-three (90%) patients considered high risk on permanent section had paraaortic lymphadenectomies performed on the basis of IFS and D&C diagnosis. Inaccurate IFS diagnosis of depth of myometrial invasion can occur when tumor involves the uterine isthmus or cornua and when tumor invades areas of adenomyosis.     

Magnetic resonance imaging determination of myometrial invasion in endometrial carcinoma

Fifteen patients with FIGO stage I biopsy confirmed endometrial adenocarcinoma underwent preoperative pelvic magnetic resonance imaging (MRI) to evaluate the presence and depth of myometrial invasion. Imaging was performed with a Diasonics superconducting imaging system operating at 0.35 T (15 MHz); multislice multi-spin-echo pulse sequences were used exclusively, with 5-mm contiguous sections. All patients then received primary therapy consisting of abdominal hysterectomy and bilateral salpingo-oophorectomy. Imaging findings were then compared with the uterine specimen histopathology. MRI was accurate in predicting the presence or absence of invasion in 13 of 15 cases (87%) and was able to discriminate superficial from deep invasion in 9 of 11 cases (82%). Based on our findings, we conclude that MRI appears to be an excellent technique for determining myometrial invasion, and that it may play a significant role in the preoperative planning of a thorough search for lymphatic spread in those patients considered to be at high risk by virtue of myometrial invasion.     

Preoperative endovaginal ultrasound in the assessment of myometrial invasion of endometrial adenocarcinoma

OBJECTIVE: To determine, according to histological tumor grade, the reliability of preoperative endovaginal ultrasound in the detection of myometrial invasion in patients with stage I endometrial cancer. PATIENTS AND METHODS: Sixty-one patients with stage I endometrial carcinoma were evaluated with preoperative endovaginal ultrasound compared to postoperative results of pathologic examination, in a six-year retrospective study. RESULTS: Twenty-nine patients had a deep myometrial invasion (stage IC). The mean endometrial thickness was 9.5 mm in stage IA, 17.0 mm in stage IB and 20.0 mm in stage IC disease (P = 0.01). The sensitivity and the specificity of the ultrasound in the assessment of myometrial invasion in grade 1 tumors were 100% and 93.7%, respectively. They fell to 69.2% and 88.9% for high-grade tumors. The global accuracy of ultrasound was 82%. DISCUSSION AND CONCLUSIONS: The performance of preoperative ultrasound varies according to the literature. The association of morphological and morphometric criteria enables an increase in the sensitivity of the exam. In grade 1 tumors, the preoperative endovaginal ultrasound could help in identifying a group of patients at low risk of lymph node metastasis for which a pelvic lymphadenectomy would be avoidable.     

MRI in evaluation of myometrial invasion and staging of endometrial carcinoma

Recently, nuclear magnetic resonance (NMR)-CT has become available for clinical use. A number of reports have stressed its diagnostic usefulness for gynecologic diseases. In the present report, we studied the clinical usefulness of magnetic resonance imaging (MRI) in diagnosing endometrial carcinoma. 1. Determination of the extent of myometrial invasion. We applied following five parameters: 1) transverse area ratio of occupying tumor in the uterine body (TAR), 2) sagittal area ratio of occupying tumor in the uterine body (SAR), 3) volume ratio of occupying tumor in the uterine body (VR), 4) minimal thickness of normal myometrium (MT) and 5) ratio of the maximal thickness to the minimal thickness of normal myometrium (Min./Max.ratio). We compared the NMR-CT findings with those for the surgically removed uterus. The Min./Max.ratio showed a statistically significant difference (p less than 0.05) between cases with myometrial invasion less than 1/3 of the whole thickness and those with invasion from 1/3 to 2/3. VR showed a significant difference (p less than 0.01) between cases with invasion from 1/3 to 2/3 and those with invasion more than 2/3. Thus, we suggest that the Max./Min.-ratio may be useful in detecting invasion less than 1/3, and that VR might be useful in detecting invasion more than 2/3. 2. Determining the clinical stages (FIGO) Correct staging rates by MRI were 100% for stage Ia, 83.3% for stage Ib, 50% for stage II and 100% for stage III. We could completely differentiate stage III cases from those of the lower stages. These results indicate that MRI is quite useful in diagnosing endometrial carcinoma.     

Molecular assessment of depth of myometrial invasion in stage I endometrial cancer: a model based on K-ras mutation analysis

INTRODUCTION: Overall nearly 20% of endometrial cancer (EC) patients die of the disease and over half of these had initially presented with clinical stage I disease. There is a strong correlation between disease mortality and depth of myometrial invasion. Current assessment of depth of invasion relies on light microscopy. Tumor cells can evade detection by light microscopy if they are vastly outnumbered by myometrial cells. Molecular techniques have a great potential in the detection of such isolated cells. OBJECTIVE: The objective was to develop a model for the application of molecular techniques to advance the assessment of risk status in patients with clinical stage I EC. METHODS:The study sample included 21 stage I ECs with a documented K-ras mutation from two series of 96 and 106 ECs from the United Kingdom and Norway, respectively. K-ras was documented using heteroduplex mobility analysis and amplified created restriction site, followed by sequencing to identify the specific base substitution at codon 12 and 13 of K-ras oncogene. For each case with a K-ras mutation, a modified mutant allele-specific amplification technique was carried out on a series of tissue strips microdissected at increasing depths from the myometrium underlying tumor. The microdissected myometrium had been previously examined histologically for absence of infiltrating tumor cells on light microscopy. Presence of K-ras mutations was used to identify the tumor cells within the histologically normal myometrium. Correlations between submicroscopic myometrial tumor cell infiltration and clinicopathological factors were studied. RESULTS: Of 21 cases with K-ras mutation, 6 cases (28%) showed molecular evidence of tumor cell infiltration beyond the histological boundary. The depth of submicroscopic myometrial infiltration was found to be variable. The staging of the tumors would have changed in 3 cases (14%) if tumor cells been detected histologically. A borderline significant correlation between presence of submicroscopic myometrial invasion and depth of myometrial invasion was noted (P = 0.053). The recurrence rate and survival of patients without submicroscopic invasion were better than those with, although it did not reach statistical significance (recurrence rate P = 0.13, recurrence free survival P = 0.14, cause-specific survival P = 0.12, and total survival P = 0.2). CONCLUSIONS: Molecular assessment of depth of myometrial invasion using K-ras mutation is feasible and may add information to conventional light microscopy. Further prospective studies are required to define the clinical significance of this technology.