Pathologic Ultrastaging Improves Micrometastasis Detection in Sentinel Lymph Nodes During Endometrial Cancer Staging

Abstract

Objective To describe the incidence of low-volume, ultrastage-detected metastases in sentinel lymph nodes (SLNs) identified at surgical staging for endometrial carcinoma and to correlate it with depth of myoinvasion (DMI) and tumor grade. Methods We reviewed all patients who underwent primary surgery for endometrial carcinoma with successful mapping of at least one SLN at our institution from 9/2005-12/2011. All patients underwent a cervical injection for mapping. The SLN ultrastaging protocol involved cutting an additional two adjacent 5-μm sections at each of two levels, 50-μm apart, from each paraffin block lacking metastatic carcinoma on routine H&E. At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anti-cytokeratin AE1:AE3. Micrometastases (tumor deposits <0.2mm and ≤2mm) and isolated tumor cells (≤0.2mm) were classified as low-volume, ultrastage-detected metastases if pathologic ultrastaging was the only method allowing detection of such nodal disease. Results Of 508 patients with successful mapping, 413(81.3%) had endometrioid carcinoma. Sixty-four(12.6%) of 508 patients had positive nodes: routine H&E detected 35 patients(6.9%), ultrastaging detected an additional 23 patients(4.5%) who would have otherwise been missed (4 micrometastases, 19 isolated tumor cells), and 6 patients(1.2%) had metastatic disease in their non-SLNs. The incidence of low-volume, ultrastagedetected nodal metastases in grade 1, 2, and 3 patients was 3.8%, 3.4%, and 6.9%, respectively. The frequency of low-volume, ultrastage-detected metastases in patients with a DMI of 0, <50%, and ≥50% was 0.8%, 8.0%, and 7.4%, respectively. Lymphovascular invasion was present in 20(87%) of the cases containing low-volume, ultrastage-detected metastases in the lymph nodes. Conclusions SLN mapping with pathologic ultrastaging in endometrial carcinoma detects additional low-volume metastases(4.5%) that would otherwise go undetected with routine evaluations. Our data support the incorporation of pathologic ultrastaging of SLNs in endometrial carcinoma with any degree of myoinvasion. The oncologic significance of lowvolume nodal metastases requires long-term follow-up.

Sentinel lymph node mapping and staging in endometrial cancer: A Society of Gynecologic Oncology literature review with consensus recommendations

“…The algorithm proposed by the group at Memorial Sloan Kettering (MSK) consists of an initial evaluation by routine H&E, and if negative, two adjacent 5-μm sections (one H&E and one cytokeratin AE1/AE3) cut from each paraffin block at each of two levels 50 pm apart [38,45]. Holloway et al [67] used a similar approach with H&E-negative nodes sectioned at 50-μm intervals, resulting in three H&E slides and one stained with AE1/AE3.…”

“…Alternatively, endometrial SLNs have been examined by leveling the block at 50-μm intervals with levels 1, 3, and 5 stained with H&E and levels 2 and 4 stained with AE1/AE3 [41]; or by bisecting the node, creating a cytologic smear, and then grossly slicing in 3-mm intervals, which in turn, were sectioned at 200-μm intervals, with H&E-negative nodes stained with AE1/AE3 [68,69]. Likely as a result of differences in patient populations studied, and possibly the surgical and pathologic processing techniques used, identification of low-volume disease (micrometastasis and isolated tumor cells [ITCS]) varies widely between institutions and case series (Table 3) [30,41,45,55,67,69]. Ultrastaging can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion (0.8% metastasis of 242 cases) [45].…”

“…Likely as a result of differences in patient populations studied, and possibly the surgical and pathologic processing techniques used, identification of low-volume disease (micrometastasis and isolated tumor cells [ITCS]) varies widely between institutions and case series (Table 3) [30,41,45,55,67,69]. Ultrastaging can likely be eliminated in endometrioid adenocarcinoma with no myoinvasion (0.8% metastasis of 242 cases) [45]. …”

“…The same investigators described a learning curve with an increase in SLN detection from 77% to 94% ( p =0.03) following a 30-case experience [72]. Enhanced pathologic analysis with serial sectioning and IHC increased the detection of metastasis by approximately two-fold compared to routine H&E findings in patients undergoing SLN mapping, largely through the detection of micrometastases and ITCs that were not identified on the initial H&E examinations [30,45,67,69]. …”

“…However, both the biology and natural history of breast and endometrial cancers are quite different, and the application of breast cancer guidelines to endometrial cancer is untested. For endometrial cancer, low-volume metastases found with ultrastaging make up approximately half of the lymph node metastases identified through SLN assessments (Table 3) [30,41,45,55,67,69]. Occult (IHC positive) lymph node metastases in SLNs or non-SLNs are associated with high-risk uterine features such as lymph-vascular space invasion and deep myometrial invasion, and are associated with a higher rate of recurrence [92,93].…”