Ultrastaging Protocol Research Articles

Survival associated with the use of sentinel lymph node in addition to lymphadenectomy in early-stage cervical cancer treated with surgery alone: A sub-analysis of the Surveillance in Cervical CANcer (SCCAN) collaborative study

AimThe aim of this study was to assess whether the use of sentinel lymph node (SLN) in addition to lymphadenectomy was associated with survival benefit in patients with early-stage cervical cancer. MethodsInternational, multicenter, retrospective study. Inclusion criteria: cervical cancer treated between 01/2007 and 12/2016 by surgery only; squamous cell carcinoma, adenocarcinoma, adenosquamous carcinoma, FIGO 2009 stage IB1-IIA2, negative surgical margins, and laparotomy approach. Patients undergoing neo-adjuvant and/or adjuvant treatment and/or with positive para-aortic lymph nodes, were excluded. Women with positive pelvic nodes who refused adjuvant treatment, were included. Lymph node assessment was performed by SLN (with ultrastaging protocol) plus pelvic lymphadenectomy (‘SLN’ group) or pelvic lymphadenectomy alone (‘non-SLN’ group). Results1083 patients were included: 300 (27.7 %) in SLN and 783 (72.3 %) in non-SLN group. 77 (7.1 %) patients had recurrence (N = 11, 3.7 % SLN versus N = 66, 8.4 % non-SLN, p = 0.005) and 34 (3.1 %) (N = 4, 1.3 % SLN versus N = 30, 3.8 % non-SLN, p = 0.033) died. SLN group had better 5-year disease-free survival (DFS) (96.0 %,95 %CI:93.5–98.5 versus 92.0 %,95 %CI:90.0–94.0; p = 0.024). No 5-year overall survival (OS) difference was shown (98.4 %,95 %CI:96.8–99.9 versus 96.8 %,95 %CI:95.4–98.2; p = 0.160). SLN biopsy and lower stage were independent factors associated with improved DFS (HR:0.505,95 %CI:0.266–0.959, p = 0.037 and HR:2.703,95 %CI:1.389–5.261, p = 0.003, respectively). Incidence of pelvic central recurrences was higher in the non-SLN group (1.7 % versus 4.5 %, p = 0.039). ConclusionAdding SLN biopsy to pelvic lymphadenectomy was associated with lower recurrence and death rate and improved 5-year DFS. This might be explained by the lower rate of missed nodal metastasis thanks to the use of SLN ultrastaging. SLN biopsy should be recommended in patients with early-stage cervical cancer.

Sentinel lymph node pathological ultrastaging: Final outcome of the Sentix prospective international study in patients with early-stage cervical cancer

ObjectiveTo report the outcome of SLN staging in the SENTIX international prospective trial of SLN biopsy in patients with cervical cancer with an intensive ultrastaging protocol and central quality control and to evaluate how the intensity of pathological assessment correlates with metastatic detection rate in SLNs. MethodsEligible were patients with stages T1a1/LVSI+ to T1b2 (<4 cm, ≤2 cm for fertility sparing), common tumor types, no suspicious lymph nodes on imaging, and bilateral SLN detection. SLNs were examined intraoperatively and processed by an intensive protocol for ultrastaging (paraffin blocks sectioned completely in 150-μm intervals/levels). SLNs from each site were submitted for central quality control. ResultsIn the SENTIX SLN study, 647 out of 733 enrolled patients underwent SLN ultrastaging, identifying 12.5% (81/647) with node positive, N1 cases. Intraoperative detection revealed metastases in 56.8% (46/81) of these cases, categorized into macrometastases (83.7%), micrometastases (26.3%), and isolated tumor cells (9.1%). Ultrastaging identified additional metastatic involvement in 43.2% (35/81) of patients, with detailed sectioning revealing metastases (MAC/MIC) at first level in 20 cases (24.7%), at levels 2–4 in 9 cases (11.1%), and at level ≥5 in 6 cases (7.4%). ConclusionSLN ultrastaging detects additional 43% of N1 (MAC/MIC) in patients with negative LNs by imaging and intraoperative pathological assessment. The detection rate of positive SLN correlates with the intensity (number of levels) of ultrastaging. Examination of four levels from paraffin blocks, which detects >90% of patients with N1, is a reasonable compromise for an international standard for ultrastaging.Study registration:NCT02494063 (ClinicalTrials.gov).

Value of sentinel node ultrastaging and pathologic techniques in tumoral detection.

Sentinel lymph node assessment is an option for patients with clinically early-stage vulvar cancer, endometrial cancer, cervical cancer, and, more recently, ovarian cancer. However, although ultrastaging is mandatory as part of the node evaluation, universally accepted pathology protocols are lacking. This review focuses on the current evidence for the most relevant aspects of sentinel lymph node evaluation, as well as some controversial topics like frozen section or one-step nucleic acid amplification. The diagnostic accuracy of sentinel lymph node detection algorithms for patients with gynecologic neoplasms is high. However, the heterogeneity among the published studies and the absence of clear recommendations from most guidelines make it challenging to recommend one protocol over another. The minimum requirement from ultrastaging protocols (regarding the number of levels to be assessed, among others) to get the highest accuracy with a minor cost is unknown. Sentinel lymph node evaluation is now part of the surgical management for most early-stage gynecologic neoplasms. However, a universally accepted ultrastaging pathology protocol is lacking in literature and clinical practice. This gap requires significant effort from the gynecologic oncology and pathology community to be closed and then to allow advancements in surgical management for early-stage gynecologic tumors to go forward.

Establishing guidelines for sentinel lymph node ultrastaging in endometrial cancer

BackgroundMany sentinel lymph node (SLN) ultrastaging protocols for endometrial cancer exist, but there is no consensus method.ObjectiveThis study aims to develop guidelines for size criteria in SLN evaluation for endometrial...

Consensus on surgical technique for sentinel lymph node dissection in cervical cancer

ObjectiveThe purpose of this study was to establish a consensus on the surgical technique for sentinel lymph node (SLN) dissection in cervical cancer.MethodsA 26 question survey was emailed to international...

Sentinel-node biopsy in apparent early stage ovarian cancer: final results of a prospective multicentre study (SELLY)

AimTo evaluate the sensitivity and specificity of sentinel-lymph-node mapping compared with the gold standard of systematic lymphadenectomy in detecting lymph node metastasis in apparent early stage ovarian cancer. MethodsMulticenter, prospective, phase II trial, conducted in seven centers from March 2018 to July 2022. Patients with presumed stage I-II epithelial ovarian cancer planned for surgical staging were eligible. Patients received injection of indocyanine green in the infundibulo-pelvic and, when feasible, utero-ovarian ligaments and sentinel lymph node biopsy followed by pelvic and para-aortic lymphadenectomy was performed. Histopathological examination of all nodes was performed including ultra-staging protocol for the sentinel lymph node. Results174 patients were enrolled and 169 (97.1 %) received study interventions. 99 (58.6 %) patients had successful mapping of at least one sentinel lymph node and 15 (15.1 %) of them had positive nodes. Of these, 11 of 15 (73.3 %) had a correct identification of the disease in the sentinel lymph node; 7 of 11 (63.6 %) required ultra-staging protocol to detect nodal metastasis. Four (26.7 %) patients with node-positive disease had a negative sentinel-lymph-node (sensitivity 73.3 % and specificity 100.0 %). ConclusionsIn a multicenter setting, identifying sentinel-lymph nodes in apparent early stage epithelial ovarian cancer did not reach the expected sensitivity: 1 of 4 patients might have metastatic lymphatic disease unrecognized by sentinel-lymph-node biopsy. Nevertheless, 35.0 % of node positive patients was identified only thanks to ultra-staging protocol on sentinel-lymph-nodes.

MILACC study: could undetected lymph node micrometastases have impacted recurrence rate in the LACC trial?

ObjectiveThe etiology of inferior oncologic outcomes associated with minimally invasive surgery for early-stage cervical cancer remains unknown. Manipulation of lymph nodes with previously unrecognized low-volume disease might explain this finding....

Diagnostic accuracy of frozen section and patterns of nodal spread in high grade endometrial cancer: A secondary outcome of the SENTOR prospective cohort study

ObjectivesThe study aimed to define the accuracy of intraoperative frozen section (FS) for the detection of metastases in sentinel lymph node biopsy (SLNB) and describe the pattern of lymph node (LN) spread and relation to molecular classifiers in patients with high-grade endometrial cancer (EC). MethodsWe performed a secondary outcome of clinicopathologic data from the Sentinel Lymph Node Biopsy versus Lymphadenectomy for Intermediate- and High-Grade Endometrial Cancer Staging (SENTOR) prospective cohort study evaluating SLNB in patients with clinical stage I high-grade EC (ClinicalTrials.gov ID: NCT01886066). The primary outcome was the sensitivity of FS of the sentinel lymph node (SLN) specimen, compared to a standardized ultrastaging protocol. Secondary outcomes included the pattern and characteristics of LN spread. ResultsThere were 126 patients with high-grade EC with a median age of 66 years (range:44–86) and a median Body Mass Index (BMI) of 26.9 kg/m2 (range:17.6–49.3). FS was performed on surgical specimens from 212 hemipelves; SLNs were identified in 202 specimens (95.7%) and fatty tissue alone was identified in 10 specimens (4.7%). Of the 202 hemipelves in which SLNs were identified, 24 were positive for metastatic disease on final pathology. Initial FS correctly identified only 12, yielding a sensitivity of 50% (12/24, 95% CI 29.6–70.4) and a negative predictive value of 94% (178/190, 95% CI 89–96.5). A total of 24 patients (19%) had LN metastases: 16 (13%) had isolated pelvic metastases, 7 (6%) had both pelvic and para-aortic metastases and 1 (0.8%) had an isolated para-aortic metastasis. ConclusionsIntraoperative FS of SLNs in high-grade EC patients has poor sensitivity. Since isolated para-aortic metastases are rare, para-aortic lymphadenectomy may be omitted in patients in which SLNs were successfully mapped to the pelvis.

Value of routine cytokeratin immunohistochemistry in detecting low volume disease in cervical cancer

ObjectiveIn cervical cancer, sentinel lymph nodes (SLNs) are processed according to the pathological ultrastaging protocol. According to current guidelines, immunohistochemistry with pancytokeratin antibodies is performed in addition to step sectioning with hematoxylin and eosin (H&E), aiding the detection of low volume disease (micrometastasis and isolated tumor cells (ITC)). We studied the added clinical value, and costs, of routine immunohistochemistry (IHC). MethodsWe retrospectively included all FIGO stage IA-IIA1 cervical cancer patients who had undergone SLN procedures at UMC Utrecht from 2008 to 2020. Pathological data were derived from the Dutch Pathology Registry (PALGA) including SLN tumor status and number of slides stained with IHC. ResultsIn total 234 cervical cancer patients were included. In the 516 surgically resected SLN specimens, 630 SLNs were discovered by the pathologist. Hereof, 579 SLNs from 211 patients were routinely processed with IHC. IHC identified three patients with micrometastasis and five patients with ITC undetected with H&E staining. Thereby, IHC significantly increased the number of patients with low volume disease from 11 (5.3%) to 19 patients (9.1%) (p = 0.04). To achieve this, 3791 slides were stained with IHC at an estimated additional cost of €94,775. In 1.4% (95% CI 0.3%–4.3%) of patients routine use of IHC adjusted the adjuvant treatment. ConclusionsRoutine use of IHC increases detection of low volume disease in cervical cancer SLNs compared to step sectioning with H&E alone by nearly 4%, with an impact on therapeutic strategy-decisions in about 1% of patients. In view of the high associated costs, cost-effectiveness of routine IHC is questionable.

Diagnostic accuracy of frozen section and patterns of nodal spread in high grade endometrial cancer: a secondary analysis of the SENTOR prospective cohort study

<h3>Objectives:</h3> Recent studies have shown that sentinel lymph node (SLN) biopsy accurately detects nodal metastases in patients with high-grade endometrial cancer (EC). SLN biopsy has the potential to replace complete lymphadenectomy for surgical staging in patients with high-grade EC, provided that an SLN algorithm is followed (side-specific pelvic and para-aortic lymphadenectomy for non-mapped hemipelves). The aim of this study was to define the accuracy of intraoperative frozen section for the detection of metastases in SLN biopsy and describe the pattern of lymph node (LN) spread in patients with high-grade EC. <h3>Methods:</h3> We performed a secondary analysis of clinicopathologic data from the SENTOR prospective cohort study evaluating SLN node biopsy at 3 designated cancer centres in Toronto, Canada (ClinicalTrials.gov ID: NCT01886066). Patients with clinical stage I high-grade EC (grade 3 endometrioid, serous, clear cell, carcinosarcoma, undifferentiated, or mixed tumors) undergoing laparoscopic or robotic primary hysterectomy were enrolled. The primary outcome was sensitivity of frozen section of the SLN specimen, compared to a standardized ultrastaging protocol. Secondary outcomes included the pattern and characteristics of LN spread. <h3>Results:</h3> There were 126 patients with high-grade EC with median age 66 years (range: 44-86) and median BMI 26.9 kg/m² (range: 17.6-49.3). Frozen section was performed on surgical specimens from 212 hemipelves; SLNs were identified in 202 specimens (95.7%) and fatty tissue alone was identified in 10 specimens (4.7%). Of the 202 hemipelves in which SLNs were identified, 24 were positive for metastatic disease. Frozen section correctly identified only 12, yielding a sensitivity of 50% (12/24, 95% CI 29.6-70.4) and negative predictive value of 94% (178/202, 95% CI 89-96.5). A total of 24 patients had LN metastases: 16 (13%) had isolated pelvic metastases, 7 (6%) had both pelvic and para-aortic metastases and 1 (0.8%) had an isolated para-aortic metastasis. All para-aortic metastases (n=8) occurred in non-sentinel LNs, among patients with serous (n=5), carcinosarcoma (n=2), and dedifferentiated (n=1) histology. One patient with isolated para-aortic metastases (carcinosarcoma, p53 abnormal) did not have a mapped SLN, but was identified by the SLN algorithm. Nodal metastases occurred in 10% of patients (3/30) with grade 3 endometrioid histology (all pelvic), compared to 33% of patients (15/46) with serous histology (10 pelvic alone, 5 pelvic and para-aortic). <h3>Conclusions:</h3> Intraoperative frozen section of SLNs in high-grade EC patients has poor sensitivity. However, frozen section may still be beneficial to confirm the presence of nodal tissue and ensure adherence to an SLN algorithm, including complete pelvic and para-aortic lymphadenectomy for non-mapped hemipelves. Because isolated para-aortic metastases are rare, para-aortic lymphadenectomy may be omitted in patients in which SLNs were successfully mapped to the pelvis.

O69: THE SENTINEL LYMPH NODE TECHNIQUE IN THE ENDOMETRIAL CANCER

Abstract Introduction The sentinel lymph node (SLN) concept represents advancement in the management of the endometrial cancer (EC). We aim to assess the performance of the SLN procedure; its positive predictive value (PPV) and negative predictive value (NPV); in stage I of EC (FIGO2009). Method A prospective study is conducted in our institution. We perform a double detection of the SLN (radiolabel Tc 99 microsulfur colloid and a color method using patent blue) followed by pelvic lymphadenectomy with or without paraaortic lymphadenectomy. A pelvic MRI is performed to determine myometrial invasion and nodal status. The injection of Tc 99m colloid occurs the day prior to surgery. The injection into the stroma of the cervix at the 3 and 9 o'clock positions was performed by an oncologist surgeon with the assistance of a nuclear medicine physician. Preoperative lymphoscintigraphy was obtained after 90-120 minutes. We inject into the cervical stroma 2cc of patent blue similar to the Tc99 injection. A gamma detecting probe is used to locate radioactive lymph nodes. The SLNs identified then are labelled as radioactive and/or blue. No frozen-section analysis was performed. Results For the pathological analysis of the SLN, Haematoxylin Eosin is used. If there is no metastasis detected, an ultra staging protocol using different anti-cytokeratines is conducted. Studies have shown that this approach is possible having satisfactory results when conducted by dedicated surgical, radiology and pathology team. We look forward to our outcomes to illustrate those results. Take-home message Sentinel lymph node is a good alternative for gynecological cancer

Ultrastaging protocol in sentinel lymph node for apparent early stage ovarian cancer

ObjectiveThe objective of the present study is to determine the role of sentinel lymph node (SLN) ultrastaging in apparent early-stage ovarian cancer. MethodsWe previously demonstrated the feasibility of SLN in early-stage ovarian cancer in a pilot study and in a clinical trial (NCT03452982). The SLN of the 30 patients involved in both were processed following an ultrastaging protocol. The cost of ultrastaging processing was also reported. ResultsA SLN was detected in up to 91.3% and 90% in the pelvic and para-aortic region, respectively. In all cases, a SLN was detected at least in one field, pelvic or para-aortic. The mean time from injection to SLN resection was 53.3 ± 20.3 min. Two of 30 (6.6%) patients had a contralateral SLN in the para-aortic field, but no patients had contralateral SLN within the pelvic field after injection. The mean number of harvested SLN was 2.1 ± 1.4 (range: 0–5) and 2.7 ± 1.5 (range: 0–7) in the pelvic and para-aortic region, respectively.Two patients were upgraded to stage IIIA1 because of lymph node metastasis. In the first case, based on single sections and haematoxylin and eosin (H&E) examination, a pelvic SLN micrometastasis (1 mm) was found on the first H&E section. By using the ultrastaging protocol, the size of the metastasis was increased to 2.1 mm (macrometastasis). In the same patient, the ultrastaging study of the inframesenteric para-cava SLNs found isolated tumour cells in the subcapsular and interfollicular lymph nodes sinus in one of the two SLN harvested (in one of the sections at the fourth and fifth ultrastage levels). The other upstaged case was a para-aortic macrometastasis in a patient in whom the SLN was not identified in the para-aortic field because of the absence of migration from the infundibulo-pelvic stump injection.The cost of ultrastaging in each patient depended on the total number of SLN retrieved, averaging 96.8 € (range: 0–230.5) and 124.5 € (range: 0–322.7€) for pelvic and para-aortic SLN, respectively. ConclusionsA uniform protocol for ultrastaging is essential for lower-volume metastasis detection and to provide reproducible information between upcoming studies, as evidence about SLN in ovarian cancer is growing.

Standard ultrastaging compared to one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node metastases in early stage cervical cancer

ObjectiveWe compared ultrastaging and one-step nucleic acid amplification (OSNA) examination of sentinel lymph nodes in two homogeneous patient populations diagnosed with early stage cervical cancer. The primary aim of our...

Two ultrastaging protocols for the detection of lymph node metastases in early-stage cervical and endometrial cancers

ObjectiveTo date, there is no universal consensus on which is the optimal ultrastaging protocol for sentinel lymph node (SLN) evaluation in gynecologic malignancies. To estimate the impact of different ultrastaging...

Pathologic Protocols for Sentinel Lymph Nodes Ultrastaging in Cervical Cancer.

Ultrastaging of sentinel lymph nodes (SLNs) is a crucial aspect in the approach to SLN processing. No consensual protocol for pathologic ultrastaging has been approved by international societies to date. To provide a review of the ultrastaging protocol and all its aspects related to the processing of SLNs in patients with cervical cancer. In total, 127 publications reporting data from 9085 cases were identified in the literature. In 24% of studies, the information about SLN processing is entirely missing. No ultrastaging protocol was used in 7% of publications. When described, the differences in all aspects of SLN processing among the studies and institutions are substantial. This includes grossing of the SLN, which is not completely sliced and processed in almost 20% of studies. The reported protocols varied in all aspects of SLN processing, including the thickness of slices (range, 1-5 mm), the number of levels (range, 0-cut out until no tissue left), distance between the levels (range, 40-1000 μm), and number of sections per level (range, 1-5). We found substantial differences in protocols used for SLN pathologic ultrastaging, which can impact sensitivity for detection of micrometastases and even small macrometastases. Since the involvement of pelvic lymph nodes is the most important negative prognostic factor, such profound discrepancies influence the referral of patients to adjuvant radiotherapy and could potentially cause treatment failure. It is urgent that international societies agree on a consensual protocol before SLN biopsy without pelvic lymphadenectomy is introduced into routine clinical practice.

Risk of micrometastases in non-sentinel pelvic lymph nodes in cervical cancer

ObjectiveA high sensitivity of sentinel lymph nodes (SLN) for pelvic lymph node (LN) staging has been repeatedly shown in patients with cervical cancer. However, since only SLN are evaluated by pathologic ultrastaging, the risk of small metastases, including small macrometastases (MAC) and micrometastases (MIC), in non-SLN is unknown. This can be a critical limitation for the oncological safety of abandoning a pelvic lymphadenectomy. MethodsThe patients selected for the study had cervical cancer and were at high risk for LN positivity (stage IB–IIA, biggest diameter≥3cm). The patients had no enlarged or suspicious LN on pre-operative imaging; SLNs were detected bilaterally and were negative on intra-operative pathologic evaluation. All SLNs and all other pelvic LNs were examined using an ultrastaging protocol and processed completely in intervals of 150μm. ResultsIn all, 17 patients were enrolled into the study. The mean number of removed pelvic LNs was 30. A total of 573 pelvic LNs were examined through ultrastaging protocol (5762 slides). Metastatic involvement was detected in SLNs of 8 patients (1× MAC; 4× MIC; 3× ITC) and in non-SLNs in 2 patients (2× MIC). In both cases with positive pelvic non-SLNs, there were found MIC in ipsilateral SLNs. No metastasis in pelvic non-SLNs was found by pathologic ultrastaging in any of the patients with negative SLN Side-specific sensitivity was 100% for MAC and MIC. There was one case of ITC detected in non-SLN, negative ipsilateral SLN, but MIC in SLN on the other pelvic side. ConclusionsAfter processing all pelvic LNs by pathologic ultrastaging, there were found no false-negative cases of positive non-SLN (MAC or MIC) and negative SLN. SLN ultrastaging reached 100% sensitivity for the presence of both MAC and MIC in pelvic LNs.

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

ObjectiveTo 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. MethodsAll 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. ResultsOf 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. ConclusionsApplying 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.

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

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 and tumor grade. We reviewed all patients who underwent primary surgery for endometrial carcinoma with successful mapping of at least one SLN at our institution from September 2005 to December 2011. All patients underwent a cervical injection for mapping. The SLN ultrastaging protocol involved cutting an additional 2 adjacent 5-μm sections at each of 2 levels, 50-μm apart, from each paraffin block lacking metastatic carcinoma on routine hematoxylin and eosin (H&E) staining. At each level, one slide was stained with H&E and with immunohistochemistry (IHC) using anticytokeratin AE1:AE3.Micrometastases (tumor deposits >0.2 mm and ≤2 mm) and isolated tumor cells (≤0.2 mm) were classified as low-volume ultrastage-detected metastases if pathologic ultrastaging was the only method allowing detection of such nodal disease. Of 508 patients with successful mapping, 413 patients (81.3%) had endometrioid carcinoma. Sixty-four (12.6%) of the 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 and 19 isolated tumor cells), and 6 patients (1.2%) had metastatic disease in their non-SLNs. The incidence rates of low-volume ultrastage-detected nodal metastases in patients with grades 1, 2, and 3 tumors were 3.8%, 3.4%, and 6.9%, respectively. The frequency rates of low-volume ultrastage-detected metastases in patients with a depth of myoinvasion of 0, less than 50%, and 50% or more were 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. Sentinel lymph node 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 low-volume nodal metastases requires long-term follow-up.

Ultrastaging Improves Detection of Metastases in Sentinel Lymph Nodes of Uterine Cervix Squamous Cell Carcinoma

The technique of sentinel lymph node (SLN) detection is increasingly being applied in patients with uterine cervix carcinoma. This study presents the pathologic findings of SLNs in 48 such patients. The institutional pathology files were searched for all patients with a diagnosis of cervical squamous cell carcinoma who had SLNs reported. Patient age, follow-up, tumor size, presence/absence of lymphatic invasion, number and status of SLNs and non-SLNs, location of SLNs, and size of metastases in SLNs were recorded. All SLNs were sectioned in 2-mm slices perpendicular to the long axis and submitted entirely for microscopic examination. For all SLNs negative on the initial hematoxylin and eosin (H&E) stained slides, an ultrastaging protocol was performed consisting of 5 sets of slides at 40-mum intervals (1 H&E slide+2 unstained slides), representing an additional 5 intervals. Lymph nodes negative by the additional H&E intervals had immunohistochemistry for cytokeratin performed on 1 unstained slide. Forty-eight patients ranging from 25 to 62 years of age had a total of 208 SLNs removed. Fifteen (31%) patients had positive SLNs with 1 to 5 positive SLNs per case. The metastasis size ranged from a single cell to 27 mm. Twelve patients had metastasis detected by routine processing in 23 SLNs, whereas ultrastaging detected metastases in 3 SLNs of 3 additional patients. In 2 patients with metastasis detected by ultrastaging, the metastasis was detected by wide H&E intervals (level 2 for 1 patient; level 3 for 1 patient); in 1 patient, the metastasis was detected only by immunohistochemistry and consisted of a single cell. Of the 15 patients with positive SLNs, 3 patients had a total of 6 positive non-SLNs. All of the patients with a positive SLN are currently living. Thirty-three (69%) patients had negative SLNs. Of these, 1 patient had a single positive non-SLN for a false negative rate of 6.25%. Negative SLN predicts negative non-SLN. For most patients with a positive SLN, the SLN will be the only metastasis detected; a minority of patients with a positive SLN may have a positive non-SLN.