Evaluation Of Sentinel Lymph Nodes Research Articles

Estrogen Receptor Immunohistochemistry for Confirmation of Sentinel Lymph Node Metastasis in Cases With Equivocal Cytokeratin Positivity

Differentiation of true metastases from cytokeratin (CK)-positive nonepithelial cells by immunohistochemistry occasionally may be difficult in the evaluation of sentinel lymph nodes (SLNs) for occult breast carcinoma metastases. In this study, we evaluated estrogen receptor (ER) immunostaining superimposed on CK as a method for the confirmation of metastasis when CK immunostaining alone was equivocal. We performed sequential ER staining on previously CK-stained slides on 15 axillary SLNs from breast cancer patients: 5 SLNs with known metastatic carcinoma (positive controls), 6 known negative SLNs (negative controls), and 4 test cases (3 SLNs in which CK-positive cells were equivocal for malignancy and 1 SLN in which metastasis was obvious, but contained focal weakly CK-positive signet ring cells). The primary tumor in all cases expressed ER in >50% of cells. Only 3 of 5 positive controls showed metastatic cells with dual CK/ER staining. CK-positive reticulum cells in all negative controls were ER negative. Three test cases showed dual CK/ER staining in the equivocal cells. The case with signet ring cells showed strong ER staining in the nonsignet ring cells and weaker staining in the signet ring cells. We conclude that dual CK/ER staining can be useful in SLNs when CK staining alone is equivocal, particularly when the primary tumor is known to have high expression of ER. Although dual ER/CK positivity helps to confirm metastasis, negative ER staining does not exclude metastatic disease.

A prospective study comparing touch imprint cytology, frozen section analysis, and rapid cytokeratin immunostain for intraoperative evaluation of axillary sentinel lymph nodes in breast cancer

The intraoperative evaluation of axillary sentinel lymph nodes (SLNs) allows the surgeon to complete axillary dissection in 1 setting at the time of the primary breast surgery. However, to the authors' knowledge, there is no consensus regarding the optimal method for intraoperative evaluation of SLNs in breast cancer. The authors of this report prospectively compared touch imprint (TI) cytology with frozen section (FS) analysis and rapid cytokeratin immunostaining (RCI) of SLNs for the intraoperative evaluation of disease and compared the results with final pathologic examination (FP). Patients with invasive breast carcinoma who were diagnosed with lymph node-negative disease (based on preoperative clinical and sonographic evaluation with or without fine-needle aspiration of the indeterminate lymph nodes) and who subsequently were scheduled for lymphatic mapping were eligible to participate in this prospective protocol. TI and FS analysis were performed on all SLNs, and the lymph nodes were stained by the hematoxylin and eosin (H&E) method. RCI was performed using the enhanced polymer 1-step cytokeratin method. The results of TI, FS, RCI, TI plus FS, and FS plus RCI were compared with the results from FP, including 1 H&E stain and cytokeratin immunostain of the third level. One hundred patients with invasive mammary carcinoma were accrued to the study. Eighty-five tumors were the ductal type, 8 tumors were lobular, 5 tumors were mixed ductal and lobular, 1 was an adenoid cystic tumor, and 1 tumor was metaplastic carcinoma. Seventy-two tumors were staged clinically as T1N0M0, 25 tumors were staged as T2N0M0, and 3 tumors were staged as T3N0M0. Metastatic carcinoma was detected in the SLNs by 1 or more methods, including TI, FS, RCI, and FP, in 20 tumors, which included 12 macrometastases and 8 micrometastases. TI detected 8 of 12 macrometastases (67%), FS detected 12 of 12 macrometastases (100%), RCI detected 12 of 12 macrometastases (100%), and FP detected 12 of 12 macrometastases (100%). TI detected 1 of 8 micrometastases (13%), FS detected 3 of 8 micrometastases (38%), RCI detected 4 of 8 micrometastases (50%), and FP detected 6 of 8 micrometastases (75%). The sensitivities of TI, FS, RCI, TI plus FS, and FS plus RCI (with FP as the gold standard) were 50%, 72%, 78%, and 83%, respectively, and the sensitivities of the same intraoperative methods were 45%, 75%, 80%, and 85%, respectively, with detection of metastatic disease by any method as the gold standard. The specificities of the different methods (with FP as the gold standard) were 100% for TI and 97.5% for FS, RCI, TI plus FS, and FS plus RCI. The specificity of each method was 100% when the detection of metastatic disease by any method was regarded as the gold standard. Although the difference in sensitivity between FS and TI was not statistically significant (P = .08), the difference between RCI and TI bordered on significance (P = .046); however, FS analysis plus RCI was significantly superior to TI (P = .03) and produced results comparable to those of FP. The sensitivities of FS, RCI, TI plus FS, and FS plus RCI were better than the sensitivity of TI cytology of axillary SLNs. However, only the combination of FS and RCI was statistically superior to TI and generated results comparable to those of FP in SLNs. RCI can be completed within the time constraints for intraoperative use and, in conjunction with FS, can be useful for generating results closer to those generated by FP. FS analysis plus RCI have a role in the intraoperative evaluation of SLNs.

The use of touch prep for the evaluation of sentinel lymph nodes in breast cancer.

Abstract Abstract #1018 Background: Sentinel lymph node (SLN) biopsy has become the standard of care for the evaluation of axillary metastasis in breast cancer. The accurate determination of metastasis in SLNs at the time of surgery is required in order to properly select those patients who should undergo axillary node dissection (AND).
 Methods: We performed a retrospective review of 402 breast cancer patients who underwent SLN biopsy with evaluation of 931 nodes by touch prep from June 2000 through January 2007. Results of touch prep diagnosis at the time of surgery were compared to final pathologic evaluation by permanent H&E. All false negative (FN) results were re-reviewed to determine possible reasons for errors in diagnosis.
 Results: At least one SLN was successfully identified in 379 patients. Of 68 patients with a true positive SLN, all underwent AND and in 46% the SLN was the only node in which metastases were identified. A total of 32 patients (8.44%) had at least one FN result. In 931 nodes evaluated, there were 38 (4.1%) FN results and no false positives. There were no significant differences between FN results in patients with invasive ductal cancer (26 of 284 patients, 4.3% nodes) compared to invasive lobular cancer (5 of 46 patients, 5.6% nodes). The remaining patients had DCIS or other primary diagnosis with two FN SLNs. Of the 38 SLNs with a FN result, 30 (79%) had only micromets on permanent H&E. Of the remaining 8 SLN with a FN touch prep, 3 of 703 SLNs (0.4%) occurred with invasive ductal cancer and 4 of 108 SLNs (3.7%) occurred with invasive lobular cancer, demonstrating a significant difference, p=0.01. In the 32 patients with a FN SLN result, 19 patients underwent completion AND and in 12 patients (63%), the SLNs were the only nodes with cancer. Examining the 19 patients with FN SLN who underwent completion AND, 14 patients had invasive ductal cancer with only 4 (29%) having cancer found in non-SLN compared to 5 patients with invasive lobular cancer with 3 (60%) having cancer in non-SLN. Touch prep evaluation of SLN in breast cancer had an overall sensitivity of 72%, specificity of 100%, positive predictive value of 100% and negative predictive value of 95.4%. The cost for touch prep is $32 less per node compared to frozen section or an average cost reduction of $74 per patient.
 Conclusion: The accuracy of touch prep for the evaluation of SLN in breast cancer compares favorably to the reported results for frozen section with a lower cost. In patients with a FN SLN result, the SLNs are likely to be the only nodes involved with metastases, especially if the SLN is found to have only micromets. However, patients with invasive lobular cancer were more likely to have a FN finding in the setting of marcomets and were more likely to have metastases in non-SLNs. Patients with invasive lobular cancer who have a negative SLN by touch prep should have the SLN evaluated by frozen section to confirm the diagnosis. The data also suggest that patients with invasive lobular cancer and a FN SLN by touch prep may benefit from AND. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1018.

High and intermediate grade ductal carcinoma in-situ of the breast: a comparison of pathologic features in core biopsies and excisions and an evaluation of core biopsy features that may predict a close or positive margin in the excision

Low and high-grade ductal carcinoma in-situ (DCIS) are known to be highly disparate by a multitude of parameters, including progression potential, immunophenotype, gene expression profile and DNA ploidy. In this study, we analyzed a group of intermediate and high-grade DCIS cases to determine how well the core biopsy predicts the maximal pathology in the associated excisions, and to determine if there are any core biopsy morphologic features that may predict a close (≤ 0.2 cm) or positive margin in the subsequent excision. Forty-nine consecutive paired specimens [core biopsies with a maximal diagnosis of DCIS, and their corresponding excisions, which included 20 and 29 specimens from mastectomies and breast conserving surgeries respectively] were evaluated in detail. In 5 (10%) of 49 cases, no residual carcinoma was found in the excision. In another 4 cases, the changes were diagnostic only of atypical ductal hyperplasia. There were 4 and 3 respective cases of invasive and microinvasive carcinoma out of the 49 excision specimens, for an overall invasion frequency of 14%. In 28 cases where a sentinel lymph node evaluation was performed, only 1 was found to be positive. Among the 40 cases with at least residual DCIS in the excision, there were 5 cases in which comedo-pattern DCIS was present in the excision but not in the core biopsy, attributed to the lower maximal nuclear grade in the biopsy proliferation in 4 cases and the absence of central necrosis in the 5th. For the other main histologic patterns, in 8 (20%) of 40 cases, there were more patterns identified in the core biopsy than in the corresponding excision. For the other 32 cases, 100%, 66%, 50%, 33% and 25% of the number of histologic patterns in the excisions were captured in 35%, 5%, 17.5%, 15% and 7.5% of the preceding core biopsies respectively. Therefore, the core biopsy reflected at least half of the non-comedo histologic patterns in 77.5% of cases. In 6(15%) of the 40 cases, the maximum nuclear grade of the excision (grade 3) was higher than that seen in the core biopsy (grade 2). Overall, however, the maximum nuclear grade in the excision was significantly predicted by maximum nuclear grade in the core biopsy (p = 0.028), with a Phi of 0.347, indicating a moderately strong association. At a size threshold of 2.7 cm, there was no significant association between lesional size and core biopsy features. Furthermore, the clear margin width of the cases with lesional size ≤ 2.7 cm (mean 0.69 cm) was not significantly different (p = 0.4) from the cases with lesional size > 2.7 cm (mean 0.56 cm). Finally, among a variety of core biopsy features that were evaluated, including maximum nuclear grade, necrosis, cancerization of lobules, number of tissue cores with DCIS, number of DCIS ducts per tissue core, total DCIS ducts, or comedo-pattern, only necrosis was significantly associated with a positive or close (≤ 0.2 cm) margin on multivariate analysis (Phi of 0.350). It is concluded that a significant change [to invasive disease (14%) or to no residual disease (10%)] is seen in approximately 24% of excisions that follow a core biopsy diagnosis of intermediate or high-grade DCIS. Core biopsy features are of limited value in predicting a close or positive margin in these lesions.

Impact and Outcomes of Routine Microstaging of Sentinel Lymph Nodes in Breast Cancer: Significance of the pN0(i+) and pN1mi Categories

In 2003, the American Joint Committee on Cancer (AJCC) initiated the 6th edition staging criteria, including pN0(i+) and pN1mi categories for breast cancer. However, the clinical significance of these categories is debated in the literature. A prospective registry was used to identify patients staged with sentinel lymph node (SLN) biopsy. SLN evaluation included routine serial sectioning and immunohistochemical stains. SLN biopsies performed before January 2003 were restaged according to the AJCC's 6th edition criteria. Of 954 SLN biopsies identified, on review, 491 N0i-, 86 N0i+, 73 N1mi, 146 N1a, 29 N2a, and 11 N3a patients were available for analysis with a median follow-up of 45.4 months. Significant prognostic and therapeutic differences existed between the groups. Differences in overall survival (OS) and recurrence-free survival (RFS) were only noted when the size of the metastases reached the N1a level. There were no statistically significant differences in OS or RFS between N0(i-) and N0(i+) or N1mi disease. Cases that were N0(i+) or N1mi were more likely to have other poor prognostic factors and to receive more aggressive therapy. SLN biopsy allows a more sensitive evaluation of lymph nodes for metastatic cells. This has led to the increased identification of very small axillary metastases. While the new microstaging categories are not yet clearly associated with a significantly decreased OS or DFS in this series, they are associated with other poor prognostic factors and more local/regional and systemic therapy. Further analysis of the microstaging categories is needed.

Intraoperative cytologic evaluation of sentinel lymph nodes in patients with breast carcinoma by scrape preparation

Intraoperative evaluation of sentinel lymph nodes (SLNs) in patients with breast carcinoma allows surgeons to complete axillary lymph node dissection in one procedure if any SLN shows metastasis. The accuracy of intraoperative pathological diagnosis is critical for decision-making. The purpose of this study was to evaluate our rapid intraoperative cytologic diagnosis of SLN through comparing with the final surgical pathologic diagnosis of the corresponding lymph nodes. A total of 454 SLNs from 159 consecutive female patients with a preoperative diagnosis of breast carcinoma over 3-year period were included in this study. After gross examination of each bisected lymph node, a scrape preparation was prepared for each submitted lymph node and was stained by the rapid Papanicolaou method. The intraoperative cytologic diagnosis was compared with the final surgical pathologic diagnoses. The overall sensitivity of intraoperative cytology was 52.5% with specificity of 100%. There were 17 false-negative cases. Of them, six nodes had isolated tumor cells, seven nodes had micrometastasis (0.2-2 mm), and four nodes had macrometastasis (>2 mm). There were no interpretive errors identified. The size of metastasis and tumor grade appeared to be significant factors in detecting metastasis by cytology. In addition, subsequent non-SLN involvement was 9% in patients with micrometastasis versus 50% in patients with macrometastasis (P < 0.05). Our study shows that the intraoperative cytologic evaluation of SLNs in breast carcinoma is a reasonably accurate method. The majority of false-negative cases were due to micrometastasis and isolated tumor cells.

Current concepts of metastasis in melanoma

The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development.

Patterns of DNA copy number changes in sentinel lymph node breast cancer metastases

The sentinel lymph node (SLN) is considered to be the first axillary node that contains malignant cells in metastatic breast tumors, and its positivity is currently used in clinical practice as an indication for axillary lymph node dissection. Therefore, accurate evaluation of the SLN for the presence of breast metastatic cells is essential. The main aim of our study is to characterize the genomic changes present in the SLN metastatic samples with the ultimate goal of improving the predictive value of SLN evaluation. Twenty paired samples of SLN metastases and their corresponding primary breast tumors (PBT) were investigated for DNA copy number changes using comparative genomic hybridization (CGH). Non-random DNA copy number changes were observed in all the lesions analyzed, with gains being more common than losses. In 75% of the cases there was at least one change common to both PBT and SLN. The most frequent changes detected in both lesions were gains of 1pter→p32, 16, 17, 19, and 20 and losses of 6q13→q23 and 13q13→q32. In the PBT group, alterations on chromosomes 1, 16, and 20 were the most frequent, whereas chromosomes 1, 6, and 19 were the ones with the highest number of changes in the SLN metastatic group. A positive correlation was found between the DNA copy number changes per chromosome in each of the groups. Our findings indicate the presence of significant DNA copy number changes in the SLN metastatic lesions that could be used in the future as additional markers to improve the predictive value of SLN biopsy procedure.

Sentinel Lymph Node Biopsy for Melanoma: Aspects of Pathologic Assessment

Sentinel lymph node (SLN) biopsy affords an accurate, minimally invasive means of staging and determining prognosis in patients with melanoma and for identifying those patients who may benefit from complete regional lymph node dissection. Careful and accurate histopathologic assessment of SLNs is critical to achieving optimal reliability of the technique. Micromorphometric parameters of melanoma deposits in SLNs have been shown to be predictive of regional non-SLN involvement and of clinical outcomes. Several non-histopathologic methods of SLN evaluation have been investigated, and while some of them show promise for the future, excision and histopathologic examination currently remains the gold standard for the evaluation of SLNs.

Clinical validation of a molecular assay for intra-operative detection of metastases in breast sentinel lymph nodes

Background In breast cancer patients, the status of the sentinel lymph nodes (SLNs) has been shown to accurately reflect the presence of metastases in the axillary lymph nodes (ALNs). Intra-operative SLN evaluation by frozen section histology may miss positive cases, leading to a second surgery for complete ALN dissection. Permanent section histology itself has tissue sampling limitations and is partially dependent on pathologist expertise. Methods A prospective study ( N = 78) was conducted in our institution to validate a new intra-operative molecular assay, the GeneSearch™ breast lymph node (BLN) assay. This assay quantifies the expression of mammaglobin and cytokeratin-19 genes using quantitative RT-PCR technology to determine SLN status. Fresh SLN sections (2 mm thick) were analyzed alternatively by BLN assay or post-operative histology (haematoxylin–eosin and immunohistochemistry). The subject was considered positive when histology revealed a focus >0.2 mm. Results BLN assay results corroborated with histologic results in 75 out of 78 patients for an overall agreement of 96%, a sensitivity of 92%, and a specificity of 97%. The positive and negative predictive values of the BLN assay were of 86% (12/14) and 98% (63/64), respectively. Interestingly, a statistically significant correlation was observed between the metastases' histologic size and both assay markers' expression levels as represented by cycle time to positivity ( ρ ≥ 0.71, all p < 0.0001). Conclusions The performance of the BLN assay in identifying nodal metastases >0.2 mm was similar to that of permanent section histology, with the added advantages of an objective and rapid output that could be used for intra-operative decision to remove additional ALN.

Simplified Technique of Radioguided Occult Lesion Localization (ROLL) Plus Sentinel Lymph Node Biopsy (SNOLL) in Breast Carcinoma

Radioguided occult lesion localization (ROLL) is a new technique to detect nonpalpable breast tumors. We report our experience using injection of a single radiotracer to localize occult lesions together with sentinel lymph node (SLN) biopsy (SNOLL). The aim of this series was to evaluate the feasibility of the technique, its efficacy, and the rate of reoperation. Under sonographic guidance, a nanocolloidal tracer was injected peritumorally above and below the lesion. A handheld gamma probe detector was used to locate and to guide its surgical removal. An intraoperative (IO) macroscopic examination of the specimen with margins evaluation and IO imprint cytology of SLN was always performed. The targeted lesion was localized and removed in all cases. Final pathological diagnosis identified invasive in 70 patients and ductal carcinoma in situ (DCIS) in 2 patients. The average size of the resected lesion was 11 mm (4-50 mm). In 61 out of the 72 patients (85%), the breast specimen had clear and large margins. Sentinel lymph node (SLN) biopsy was performed in 70 patients with an identification rate of 90%. Final pathological SLN metastasis rate approached 25% (pN1 14%, pN1(mi) 11%). Despite intraoperative examination of the specimen, a total of 29% (21 out of 72) patients had to be reoperated (8 patients for involved margins, 10 patients for an involved SLN, and 3 for both). This technique with a single nanocolloid tracer used both for ROLL and SLN detection is reliable for removing nonpalpable lesions. The use of this technique may have implications for further reducing reoperation rates.

Sentinel lymph node evaluation in endometrial cancer and the importance of micrometastases

The presence of lymph node (LN) metastases has a major impact on the prognosis of women with endometrial cancer and compromises recurrence-free time. LN assessment has become the standard of care in the surgical staging of patients and plays a crucial role in decision making. Sentinel lymph node (SLN) detection improves the accuracy of lymphatic drainage mapping compared to pelvic node dissection used alone. Serial sectioning of SLNs followed by immunohistochemical examination with conventional histology improves accuracy of micrometastatic identification. In this review, we found a high incidence of micrometastases in endometrial cancer, reaching 25% depending on the stage and the techniques used for the node examination. Current data are insufficient to evaluate the prognostic impact of the presence of micrometastases, but it seems that more accurate detection of lymphatic spread will allow better stratification of intermediate risk patients. Ultimately, this will assist in tailoring adjuvant treatment.

KBA.62: a useful marker for primary and metastatic melanomas

We previously described a novel antimelanoma antibody, designated KBA.62. However, review of the literature showed that only a few studies have reported on this antibody. We report our experience in the diagnosis of melanoma using KBA.62 and its value in both primary and metastatic conditions. In addition to conventional melanomas, we included desmoplastic and spindle cell melanomas, whose diagnosis can be challenging. We also focus on identification of malignant cells in sentinel lymph node biopsies using KBA.62, by comparison with anti-S-100 protein and HMB-45 antibodies, because discrepancies in sensitivity and specificity of melanoma markers have given rise to numerous studies aiming to determine the best panel for the evaluation of sentinel lymph node from patients with melanoma. Overall, KBA.62 was positive in 93% of primary and metastatic melanomas. Interestingly, the 12 cases of desmoplastic and spindle cell melanomas had strongly positive results. In addition, the results of our study performed on a series of 215 sentinel lymph nodes showed that the sensitivity of anti-S-100 protein and KBA.62 antibodies in detecting occult metastasis was similar. Moreover, KBA.62 identified 6 patients (3%) who had confirmed sentinel lymph node metastasis but were negative for HMB-45. The resolution was higher with KBA.62 than that observed with anti-S-100 protein antibody, as the nonmelanocytic positive cells for KBA.62 in lymph nodes were only represented by endothelial cells, which therefore constituted an intrinsic positive control. We conclude that KBA.62 antibody is a useful additional marker for melanoma, specifically in desmoplastic/spindle cell cases and in the context of micrometastasis in sentinel lymph node.

Quality control: Surgical management of breast cancer—Opportunities and challenges

6521 Background: Intermountain Healthcare is a system of 9 major community hospitals based in Salt Lake City, Utah. The system has a long history of quality improvement and previously has standardized the use of breast preservation and the surgical management of ductal carcinoma in situ (DCIS). This project was undertaken to standardize evaluation of the axilla; specifically the incorporation and utilization of sentinel lymph node biopsy as the standard of care. Methods: Baseline data for sentinel node evaluation was obtained from 9 hospitals showing substantial variation between facilities and among surgeons. A physician-based surgical quality improvement team with system wide representation defined a 75% sentinel node biopsy rate as a minimally achievable goal. This allowed for legitimate omissions of sentinel node evaluation in a minority of patients. Processes put in place to increase compliance included: improved infrastructure, physician mentoring and increased accountability. The project was presented at each facility and surgeons were provided with data on their personal performance. Results were confirmed by individual chart review on a quarterly basis. Results: Sentinel node utilization was tracked in 265 patients treated by 67 surgeons from January 1, 2007 to June 30, 2007. Utilization increased from 69.1% to 82.6% system wide and in one facility increased from 39.1% to 90.9%. Utilization of sentinel node evaluation increased the axillary evaluation of patients with DCIS; an unexpected consequence of this project. Conclusions: Variation in surgical management can be decreased in a large hospital system through validated organizational processes. This process requires constant monitoring to assure gains are maintained and other quality indicators are not adversely affected. No significant financial relationships to disclose.

Lymphatic mapping and sentinel node biopsy in gynecological cancers: a critical review of the literature

Although it does not have a long history of sentinel node evaluation (SLN) in female genital system cancers, there is a growing number of promising study results, despite the presence of some aspects that need to be considered and developed. It has been most commonly used in vulvar and uterine cervivcal cancer in gynecological oncology. According to these studies, almost all of which are prospective, particularly in cases where Technetium-labeled nanocolloid is used, sentinel node detection rate sensitivity and specificity has been reported to be 100%, except for a few cases. In the studies on cervical cancer, sentinel node detection rates have been reported around 80–86%, a little lower than those in vulva cancer, and negative predictive value has been reported about 99%. It is relatively new in endometrial cancer, where its detection rate varies between 50 and 80%. Studies about vulvar melanoma and vaginal cancers are generally case reports. Although it has not been supported with multicenter randomized and controlled studies including larger case series, study results reported by various centers around the world are harmonious and mutually supportive particularly in vulva cancer, and cervix cancer. Even though it does not seem possible to replace the traditional approaches in these two cancers, it is still a serious alternative for the future. We believe that it is important to increase and support the studies that will strengthen the weaknesses of the method, among which there are detection of micrometastases and increasing detection rates, and render it usable in routine clinical practice.

A Prospective, Blinded Trial of Touch Prep Analysis versus Frozen Section for Intraoperative Evaluation of Sentinel Lymph Nodes in Breast Cancer

Sentinel lymph node biopsy (SLNB) has largely replaced axillary dissection (ALND) for axillary staging in early breast cancer. However, intense pathologic evaluation is not routinely available intraoperatively; therefore, patients with SLN metastasis may require a second surgery for completion ALND. We hypothesized that a single-section approach (by either frozen section [FS] or touch preparation analysis [TPA]) could be accurate for intraoperative SLN evaluation. We performed a prospective, blinded study of patients undergoing SLNB for breast cancer from September 2004 to July 2006. SLNs were bivalved along the long axis, underwent FS and TPA of the facing halves, followed by routine sentinel node processing (serial sectioning with hematoxylin/eosin staining). A single pathologist reviewed all study slides and was blinded to the permanent section interpretation. We analyzed 233 nodes from 118 patients. Overall, 21% of patients (N = 25) had SLN metastasis by serial-section histopathology. Single-section FS and TPA had similar sensitivities (0.67 and 0.66, P = .82) and specificities (0.995 and 0.995, P = 1.0) for detection of SLN metastasis, yielding equivalent accuracies (95%). All micrometastases (<2 mm; N = 4) were missed by both techniques. False positives were rare-only one in each group (2% overall). Single-section TPA and FS have similar accuracies and can be safely used to identify the majority of patients with SLN metastasis, sparing these patients a delayed ALND. False-negative results from TPA or FS occur in patients with micrometastatic disease, for which the role of completion ALND remains controversial.

Sentinel Lymph Nodes

Sentinel Lymph Nodes

Sentinel lymph node micrometastasis may predict non‐sentinel involvement in cutaneous melanoma patients

Cutaneous melanoma patients with positive sentinel lymph node biopsy (SLNB) are being treated with completion lymph node dissection (CLND). The aim of our study was to determine the predictive value of sentinel lymph node (SLN) micrometastases (metastases less than 2 mm in diameter) in assessing further lymph node involvement in CLND. Between 2001 and 2005, we performed 476 SLNB in patients with stages I and II melanoma; 74 had metastases in SLN. We evaluated retrospectively the metastases in SLN according to their size and number. The presence of additional metastases in non-sentinel lymph nodes after CLND was evaluated. Thirty-nine patients had micrometastases, 22 of them were solitary, 3 were double, and 14 patients had multiple micrometastases in SLN. Out of 22 solitary micrometastases, no patient had additional metastases in non-sentinel lymph nodes. From 3 patients with double micrometastases, 1 patient had further metastases in non-sentinel lymph nodes after CLND. Out of 14 patients with multiple micrometastases, 2 had additional metastases in CLND. No patient with a single SLN micrometastasis had further metastases after CLND in our series. CLND may not be beneficial after detecting a single micrometastasis in SLN.

No Role for Sentinel Lymph Node Evaluation in Colon Cancer

Sentinel lymph-node (SLN) evaluation is a valuable diagnostic tool in breast cancer and melanoma; however, the role for SLN evaluation in colon cancer

Keratin immunohistochemistry does not contribute to correct lymph node staging in patients with invasive lobular carcinoma

Studies suggest that immunohistochemistry improves rate of detecting sentinel lymph node metastases and is needed for adequate staging in invasive lobular carcinoma. Our study evaluates the use of cytokeratin immunohistochemistry in detecting sentinel lymph node metastases and its effect on staging patients with invasive lobular carcinoma. Material from 76 patients with invasive lobular carcinoma was reviewed. Cytokeratin immunostaining was performed on negative nodes, and deposits were classified as macrometastasis (>2.0 mm), micrometastasis (>0.2-2 mm), or isolated tumor cells (<or=0.2 mm). Of 76 cases, 24 (21 macro- and 3 micrometastases, 32%) were positive for metastasis and 14 (18%) for isolated tumor cells. Immunohistochemistry was needed for all cases with isolated tumor cells and 1 case of micrometastasis. Criteria to distinguish isolated tumor cells and micrometastasis need to be better defined. In our study, immunostaining changed nodal status and stage in 1 of 52 (2%) node-negative patients. Immunohistochemistry is essential to detect isolated tumor cells in sentinel lymph nodes. However, for detecting micro- or macrometastases, it does not provide any significant advantage over detailed histopathological evaluation of sentinel lymph node.