Validation of Ex Vivo Lymphatic Mapping in Hematoxylin-Eosin Node-Negative Carcinoma of the Colon and Rectum

Background: Substantial evidence supports that detailed analysis of the regional lymphatics will identify previously unrecognized micrometastatic disease in colorectal cancer. In order to determine whether the sentinel lymph node(s) (SLNs) harvested by ex vivo lymphatic mapping in node-negative colorectal cancer (CRC) are the most likely node(s) to harbor micrometastatic disease, we examined all nodes in CRC specimens in an identical fashion.Methods: One hundred twenty-four specimens from patients with colorectal cancer were delivered to pathology in the fresh state and underwent ex vivo sentinel lymph node mapping. If negative by routine hematoxylin and eosin (H&E) analysis, the SLNs and non-SLNs were subjected to further analysis by level section H&E and immunohistochemical (IHC) analysis.Results: A mean of 30 nodes were harvested (range, 5–111). Fifty-one patients (41%) were found to be node-positive by routine H&E analysis. SLNs were identified in all but three specimens. A total of 2177 nodes were analyzed from the 66 H&E node-negative specimens (1883 non-SLNs and 294 SLNs). Overall, metastases were identified in 13 of 278 SLNs and in only 5 of 1829 non-SLNs (P < .001). Only 5 of 66 patients (7.5%) had evidence of metastatic disease in non-SLNs when the SLNs were negative. Thirteen apparently node-negative patients (19.3%) were upstaged by IHC analysis of the SLNs (P = .04).Conclusions: If the SLN is negative by both H&E and IHC analysis, the probability of finding metastases in a non-SLN is remote. If microstaging is demonstrated to be prognostically relevant, focused examination should be of the SLN(s).     

Microstaging of Breast Cancer Patients Using Cytokeratin Staining of the Sentinel Lymph Node

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of axillary nodal evaluation for metastatic disease. Cytokeratin (CK) immunohistochemical (IHC) staining of the SLN has found micrometastatic disease previously undetected by routine hematoxylin and eosin (H&E) stains. The purpose of this study is to determine the number of patients who were upstaged or microstaged, i.e., detected to have micrometastatic disease only by combined lymphatic mapping with CK IHC.Methods: Two hundred and ten patients with newly diagnosed breast cancer underwent intraoperative lymphatic mapping using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised sentinel lymph nodes were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. SLNs that were only CK positive were confirmed to be malignant by histologic examination.Results: CK IHC staining was performed on 381 SLNs in 210 breast cancer patients. Forty-seven of 210 patients (22.4%) had positive nodes. Thirty of these 47 patients (63.8%) had both H&E- and CK-positive SLNs, and an additional 17 of the 47 positive patients (36.2%) had only CK-positive SLNs. Seventeen of the 180 patients (9.4%) who were negative on H&E staining were upstaged by CK IHC staining of malignant cells in the SLN. Comparison of tumor size with the total number of node-positive patients demonstrated that 16 of 30 node-positive T0 and T1 patients (53.5%) and 22 of 39 nodes (56.4%) were upstaged by CK IHC staining. T2 and T3 patients were less frequently upstaged by cytokeratin analysis of lymph nodes. Only one of 17 node-positive patients (5.9%) and seven of 34 nodes (20.6%) in patients with T2 and T3 tumors were upstaged.Conclusion: CK IHC staining of SLNs shifted 9.4% of patients from stage I to stage II. There was a significant upstaging influence noted in patients with tumor sizes under 2 cm. This microstaging shift or upstaging may account for the significant proportion of stage I breast cancer treatment failures. Microstaging of the SLNs using more sensitive assays may help identify a subgroup of patients with invasive breast cancer who would benefit from systemic adjuvant treatment, while sparing a disease-free subset of patients the additional risks of toxic adjuvant chemotherapy.     

Sentinel Node Biopsy in Ductal Carcinoma In Situ Patients

Background: Sentinel lymph node (SLN) mapping is an effective and accurate method of evaluating the regional lymph nodes in breast cancer patients. The SLN is the first node that receives lymphatic drainage from the primary tumor. Patients with micrometastatic disease, previously undetected by routine hematoxylin and eosin (H&E) stains, are now being detected with the new technology of SLN biopsy, followed by a more detailed examination of the SLN that includes serial sectioning and cytokeratin immunohistochemical (CK IHC) staining of the nodes.Methods: At Moffitt Cancer Center, 87 patients with newly diagnosed pure ductal carcinoma in situ (DCIS) lesions were evaluated by using CK IHC staining of the SLN. Patients with any focus of microinvasive disease, detected on diagnostic breast biopsy by routine H&E, were excluded from this study. DCIS patients, with biopsy-proven in situ tumor by routine H&E stains, underwent intraoperative lymphatic mapping, using a combination of vital blue dye and technetium-labeled sulfur colloid. The excised SLNs were examined grossly, by imprint cytology, by standard H&E histology, and by IHC stains for CK. All SLNs that had only CK-positive cells were subsequently confirmed malignant by a more detailed histological examination of the nodes.Results: CK IHC staining was performed on 177 SLNs in 87 DCIS breast cancer patients. Five of the 87 DCIS patients (6%) had positive SLNs. Three of these patients were only CK positive and two were both H&E and CK positive. Therefore, routine H&E staining missed microinvasive disease in three of five DCIS patients with positive SLNs. In addition, DCIS patients with occult micrometastatic disease to the SLN underwent a complete axillary lymph node dissection, and the SLNs were the only nodes found to have metastatic disease. Of interest, four of the five nodepositive patients had comedo carcinoma associated with the DCIS lesion, and one patient had a large 9.5-cm low grade cribriform and micropapillary type of DCIS.Conclusions: This study confirms that lymphatic mapping in breast cancer patients with DCIS lesions is a technically feasible and a highly accurate method of staging patients with undetected micrometastatic disease to the regional lymphatic basin. This procedure can be performed with minimal morbidity, because only one or two SLNs, which are at highest risk for containing metastatic disease, are removed. This allows the pathologist to examine the one or two lymph nodes with greater detail by using serial sectioning and CK IHC staining of the SLNs. Because most patients with DCIS lesions detected by routine H&E stains do not have regional lymph node metastases, these patients can safely avoid the complications associated with a complete axillary lymph node dissection and systemic chemotherapy. However, DCIS patients with occult micrometastases of the regional lymphatic basin can be staged with higher accuracy and treated in a more selective fashion.Presented at the 52nd Annual Meeting of Society of Surgical Oncology, Orlando, Florida, March 4–7, 1999.     

Ex Vivo Sentinel Lymph Node Study For Rectal Adenocarcinoma: Preliminary Study

Intraoperative sentinel lymph node (SLN) detection has been reported for colon cancer, but no study has focused on rectal cancer. Only an ex vivo technique can be performed easily in this location. We evaluated SLN detection using blue dye injection in patients with rectal adenocarcinoma. This prospective study included 31 patients. Preoperative radiotherapy (45 Gy) was done in 15 cases. After proctectomy the surgical specimen was examined in the operating room. Submucosal peritumoral injections were done. One to three SLNs were retrieved. The SLNs were sectioned at three levels and examined histologically and then, if negative by hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC). There were 7 abdominoperineal resections, 12 colorectal anastomoses, 11 coloanal anastomoses, and 1 Hartmann procedure. The median number of lymph nodes harvested was 21 (7–38). A SLN was identified in 30 cases (feasibility 97%). The mean number of SLNs was 2 (0–3). A micrometastasis was discovered in 3 of 23 pNO cases when H&E was used on multisection levels, thus changing the stage to pN1. Each time the only positive lymph node was the SLN. IHC evaluation did not change the result, as only isolated tumor cells were discovered in one case. Only four of seven N+ patients had a positive SLN, resulting in a false-negative rate of 43%. Ex vivo detection of SLNs is possible for rectal cancer and is a simple technique. Classic analysis using H&E remains the gold standard. However, SLNs detection can change the tumor stage by upstaging nearly 15% of the tumors from T2-3N0 to T2-3 N+.     

Frequency of nonsentinel lymph node metastasis in melanoma

Background Completion lymph node dissection (CLND) may not be necessary for some patients because nodal metastasis is rarely detected beyond the sentinel lymph nodes (SLNs). This analysis was performed to determine, among patients with positive SLNs, the rate of nodal metastasis found in nonsentinel nodes (NSNs). Methods This analysis includes patients with positive sentinel nodes, detected by hematoxylin and eosin (H&E) staining or immunohistochemistry (IHC), who then underwent CLND. Results This analysis included 274 patients with at least one positive SLN who underwent CLND of 282 involved regional nodal basins. Of the 282 SLN-positive nodal basins, 45 (16%) were found to have positive NSNs in the CLND specimen. Breslow thickness. Clark level, presence of ulceration, histological subtype, presence of vertical growth phase, evidence of regression, presence of lymphovascular invasion, number of positive SLNs, age, sex, and presence of multiple draining nodal basins were not predictive of positive nodes in the CLND specimen. Patients with SLN metastases detected only by IHC had an equal likelihood of having positive NSNs as those patients with positive SLNs on H&E examination. Conclusions No patient population could be identified with minimal risk of non-SLN metastasis. When a positive SLN is identified on either H&E staining or IHC, CLND should be performed routinely. Presented at the 54th Annual Cancer Symposium of the Society of Surgical Oncology, Washington, DC, March 15–18, 2001.     

Ex vivo sentinel lymph node mapping in colon cancer: improving the accuracy of pathologic staging?

BACKGROUND: A subset of patients with colon cancer staged by conventional methods have occult micrometastases and do not receive adjuvant chemotherapy. Sentinel lymph node (SLN) mapping and staining by immunohistochemistry is a technique that may identify such occult micrometastases, thereby upstaging patients with positive findings. The purpose of this study was to determine whether ex vivo SLN mapping in colon cancer could be applied successfully to patients at our institution. METHODS: Seventeen patients with intraperitoneal colon tumors undergoing resection were studied prospectively. SLNs were identified as the first blue stained node(s) after ex vivo peritumoral injection of isosulfan blue dye. Additional lymph nodes were harvested and processed in accordance with standard pathologic evaluation for colon cancer. All nodes were examined after routine hematoxylin and eosin (H&E) staining. SLNs that were negative on H&E were analyzed further by multilevel sectioning and immunohistochemistry staining using anticytokeratin monoclonal antibody. RESULTS: Of the 17 study patients, SLNs were identified in 16 (94%) cases. The SLN was the only positive node in 3 patients. An identified SLN was positive (by H&E) in all patients with associated positive non-SLN nodes. The average number of nodes retrieved per patient was 16 (range, 4-54). Overall, SLNs accurately reflected the status of the entire lymph node basin in 16 (94%) patients. Two (12%) patients with negative nodes by H&E potentially were upstaged after further SLN analysis. The negative predictive value for SLN mapping was 89%. CONCLUSIONS: The ex vivo technique of SLN mapping for colon cancer is feasible. In the current study, SLN results were concordant with non-SLNs in the majority of patients. Furthermore, this technique may have upstaged 2 (12%) patients. Whether this ultimately will affect overall survival has yet to be determined.     

The use of cytokeratin staining in sentinel lymph node biopsy for breast cancer.

BACKGROUND: Controversy exists regarding the routine use of cytokeratin immunohistochemistry (IHC) in the histopathologic examination of breast cancer sentinel lymph nodes (SLN) because the clinical significance of micrometastases detected by IHC is unclear. This analysis was performed to determine the frequency of IHC-detected micrometastases. METHODS: All patients underwent SLN biopsy, followed by completion axillary dissection. This analysis included patients who had SLN evaluated by IHC. SLN were examined by hematoxylin and eosin (H&E) stain at 2-mm intervals, with IHC in 2 sections. The axillary dissection specimen was evaluated by routine H&E staining. RESULTS: IHC was performed in SLNs from 973 patients. Of the 869 patients with negative nodes by H&E, 58 (6.7%) were "upstaged" by IHC. In 6 of 58 patients (10.3%) who had IHC-only positive SLN, nodal metastases were found in the axillary dissection specimen. CONCLUSIONS: IHC resulted in upstaging of 6.7% of patients who had negative SLN on H&E staining. These patients had a 10.3% risk of residual axillary nodal metastases. However, the clinical significance of IHC-only positive SLN requires further study.     

Optimal sentinel node examination and a new strategy for axillary control in breast cancer

The sentinel lymph nodes (SLNs) have been reported to reflect the other nodal status in breast cancer, and it is thought that axillary dissection can be avoided in SLN-negative patients, whereas an additional axillary dissection must be performed for SLN-positive patients. To avoid any unnecessary dissection, non–SLN-negative patients should be distinguished among SLN-positive patients. In this study, an optimal histological examination of SLNs was investigated for a precise indication of additional axillary clearance. A modified radical mastectomy with an axillary dissection was performed for 61 patients. Technetium-labeled tin colloids were used to identify the SLNs. In all lymph nodes that were diagnosed as negative at one section by hematoxylin and eosin (H&E) examination, another additional slice was produced for each lymph node. We evaluated how minute areas of cancer in the SLNs can indicate the non-SLNs to be negative. Among 1,092 lymph nodes previously diagnosed by H&E examination as negative at one section, 3 nodes were revealed to be positive in 46 SLNs (6.52%), whereas in additional slices, only 3 nodes out of 1,046 non-SLNs were positive (0.29%). The mean ratio of the cancer cell area to the whole area of SLN on the slice was 15.6% (10–18%) in 12 non–SLN-negative patients and 45.6% (30–83%) in 16 non–SLN-positive patients. It is possible that additional axillary clearance is not needed for patients with a cancer area of less than approximately 20% in the SLN slice, based on an H&E staining evaluation of two slices. SLNs identified with radiolabeled tin colloids could reflect the other nodal status in breast cancer. There is a possibility that additional axillary clearance is not needed for patients with a cancer area of less than approximately 20% in the SLN slice.     

Sentinel lymph node positivity of patients with ductal carcinoma in situ or microinvasive breast cancer

PURPOSE: The purpose of this study was to determine the rates of sentinel lymph node (SLN) positivity in patients with a final diagnosis of ductal carcinoma in situ (DCIS) or microinvasive breast cancer (MIC). METHODS: One hundred thirty patients underwent SLN mapping from 1998 to 2003 for DCIS or MIC. RESULTS: One hundred nine patients with DCIS and 21 with MIC underwent SLN mapping. One patient with bilateral DCIS underwent 2 SLN procedures; therefore, the results of 131 SLN procedures are included. On hematoxylin and eosin (H&E) staining, 4 of 110 patients (3.6%) with DCIS had positive SLNs. Four additional patients had positive SLNs by IHC staining only (3.6%). Two of 8 patients underwent completion axillary dissection, and neither had additional involved nodes on completion axillary dissection. One of the 21 patients with MIC had positive SLNs by hematoxylin and eosin (H&E) (4.8%), and another had an involved SLN by IHC staining (4.8%). The patient with the positive SLN by H&E had 1 additional node on completion axillary dissection. CONCLUSION: Rates of SLN positivity for patients with DCIS are modest, even in a high-risk population, and there is continuing uncertainty about its clinical importance.     

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.     

Technical Details of Sentinel Lymph Node Mapping in Colorectal Cancer and Its Impact on Staging

Background: Sentinel lymph node (SLN) mapping for melanoma and breast cancer has greatly enhanced the identification of micrometastases in many patients, thereby upstaging a subset of these patients. The purpose of this study was to see if SLN mapping technique could be used to identify SLNs in colorectal cancer and to assess its impact on pathological staging and treatment.Methods: At the time of surgery, 1 ml of Lymphazurin 1% was injected subserosally around the tumor without injecting into the lumen. The first to fourth blue nodes identified were considered the SLNs, which have the highest probability to contain metastases. A standard oncological resection of the bowel was then performed. Multilevel microsections of the SLNs, including a detailed pathological examination of the entire specimen, was performed.Results: SLN was successfully identified in 85 (98.8%) of 86 patients. In 85 patients, there were 1367 (16 per patient) lymph nodes examined, of which 140 (1.6 per patient) were identified as SLNs. In 53 (95%) of 56, of whom the SLNs were without metastases (negative), all other non-SLNs also were negative. In 29 (34% of 85) patients, SLNs were positive for metastases; in 14 of the 29 patients, other non-SLNs also were positive in addition to the SLNs. In the other 15 of the 29 patients (18% of 85 patients), SLNs were the only site of metastases, and all other non-SLNs were negative. In 7 patients (8.2% of 85 patients), micrometastases were identified only in 1 or 2 of the 10 sections of a single SLN. In five of seven patients, such micrometastases were detected by hematoxylin and eosin staining and immunohistochemistry; in the other two patients, it was detected only by immunohistochemistry. In patients with negative SLNs, the rate of occurrence of micrometastases in non-SLNs was 5 (0.4%) of 1184 lymph nodes.Conclusions: SLN mapping can be performed easily in colorectal cancer patients, with an accuracy of more than 95%. The identification of submicroscopic lymph node metastases by this technique may have upstaged these patients (18%) from stage I/II to stage III disease, who may then benefit from further adjuvant chemotherapy.     

Completion axillary lymph node dissection minimizes the likelihood of false negatives for patients with invasive breast carcinoma and cytokeratin positive only sentinel lymph nodes

OBJECTIVE: To document the incidence of metastatic disease in complete axillary lymph node dissections (CALND) of patients with invasive carcinoma after a sentinel lymph node (SLN) biopsy, positive only by immunohistochemical staining for cytokeratin (CK-IHC). METHODS: Sections of all SLNs, negative by routine histology, were immunostained and examined for cytokeratin positive cells. Sections of lymph nodes from CALND specimens were interpreted using routine hematoxylin and eosin (H&E) staining. RESULTS: A total of 409 patients (29.6%) had metastatic disease in at least one sentinel lymph node on H&E examination. Of 971 H&E negative patients, 78 (8.0%) were positive only by CK-IHC. Sixty-two of the CK-IHC positive only patients underwent CALND. Nine of these 62 patients (14.5%) had metastases identified in the CALND specimen. CONCLUSIONS: Because 14.5% of patients with invasive breast cancer and SLNs positive only by CK-IHC were found to have H&E positive lymph nodes on CALND, we conclude first, that CK-IHC should be used to evaluate SLNs, and second, that CALND should be considered when SLNs are positive by CK-IHC only. This approach will result in an absolute reduction of the false negative rate (absolute false negative rate reduced by 2.6% in our series).     

Sentinel Lymph Node Metastases Detected by Immunohistochemistry Only Do Not Mandate Complete Axillary Lymph Node Dissection in Breast Cancer

Background: The significance of breast cancer sentinel lymph node (SLN) metastases detected only by immunohistochemistry staining (IHC) remains poorly understood. This study attempted to quantify the risk of non-SLN metastases.Methods: A prospectively collected database of 750 consecutive SLN biopsy procedures in breast cancer patients was reviewed. Medical records were reviewed to supplement the database.Results: SLNs were identified in 738 (98.4%) of these procedures in 723 patients. Of these, 151 patients (20.5%) had metastases detected by hematoxylin and eosin staining (H&E), and 33 (4.6%) of the 718 with known IHC staining results had metastases detected by IHC only. Twenty-eight (84.8%) of 33 patients with IHC-detected metastases underwent complete axillary lymph node dissection (CALND). The median primary tumor size was 2.0 cm among those undergoing CALND and 0.9 cm among the five patients treated without CALND (P = .10). Two of the 28 patients (7.1%) had additional metastases detected with CALND. These patients had a T3 or T4 invasive lobular primary tumor. Of 24 patients with T1 or T2 primary tumors and IHC-detected metastases who underwent CALND, none had additional metastases detected. Median follow-up was 14.5 months. All patients with IHC-detected SLN metastases were treated with adjuvant systemic therapy. None of the five patients with IHC-detected metastases not undergoing CALND has subsequently manifested clinical axillary disease.Conclusions: CALND could have been or was safely omitted in 29 of 29 patients with T1 or T2 primary tumors and metastases detected by IHC. Such patients should be counseled about this low risk before CALND is recommended.     

大肠癌前哨淋巴结微转移的检测及其临床意义

为探讨大肠癌前哨淋巴结（SLN）微转移（MM）的检测方法及其临床意义,我们对64例行根治性手术的DukesB期大肠癌患者SLN进行定位;应用常规HE染色联合免疫组化SIP法染色,对定位成功的122枚SLN中细胞角蛋白20（CK20）及端粒酶进行检测,并分析其表达与I临床病理因素的相关性。结果显示：（1）SLN定位成功61例（95．3％）,共获取SLN122枚。（2）定位成功的61例中,有6例9枚SLN常规HE染色阳性;余55例113枚SLNHE染色阴性,其中免疫组化染色CK20阳性15例（27．3％）,端粒酶阳性12例（21．8％）,两者联合检测SLNMM阳性21例（38．2％）。（3）DukesB期大肠癌患者SLNMM（＋）组癌的复发转移率明显高于同期SLNMM（-）组（P〈0．05）,生存率明显降低（P〈0．05）;而与DukesC期复发转移率及生存率比较,差异无统计学意义（P〉0．05）。（4）SLNMM（-）组患者的复发转移率、生存率与同期DukesC期患者比较,差异有统计学意义（P〈0．05）。（5）DukesB期大肠癌患者SLNMM的发生与患者年龄、性别及肿瘤侵犯肠管周径、生长方式、生长部位均无显著相关,而与肿瘤分化程度及大小、外周血癌胚抗原（CEA）值显著相关。结果表明,应用免疫组化法联合检测CK20和端粒酶,可提高大肠癌SLNMM的检出率;大肠癌SLNMM的检出能精确大肠癌的Dukes分期,有助于指导术后的辅助治疗和预后判断。     

Accuracy of Pathologic Techniques for the Diagnosis of Metastatic Melanoma in Sentinel Lymph Nodes

Background: Sentinel lymph node (SLN) biopsy can accurately predict the presence of metastatic melanoma (MM) and has been used to identify patients with occult metastases. We present an analysis of the sensitivity and specificity of standard pathological techniques including intraoperative frozen section, permanent section, and immunohistochemistry in diagnosing MM within the SLN.Methods: Sixty-nine consecutive patients with primary malignant melanoma thickness of .1.0 mm or thinner lesions invading the reticular dermis (Clark level IV) who underwent SLN biopsy were reviewed. Lymph nodes were examined intraoperatively by frozen section (FS), permanent section (H&E), and by immunohistochemistry (IH) for S-100 protein and HMB45.Results: MM was found in 14 of 69 cases (20%). Permanent section H&E was performed in all cases, FS in 64 cases, and IH in 65 cases. FS analysis diagnosed MM in 4 of 14 cases (29%), was suspicious in 2 of 14 (14%), and falsely negative (FN) in 8 of 14 (57%) ultimately found to be positive with further workup. Within the FN group, MM was identified on review of the original FS slides in 3 of 8 cases (38%). Furthermore, within the FN group, the remaining 5 cases were identified as positive for MM by either permanent and/or deeper H&E sections and IH. IH alone with permanent H&E sections would have diagnosed MM in only 8 of 10 cases (80%) that were FS negative or suspicious. In no cases was MM identified by IH alone with the permanent and deeper H&E sections being negative. It is noteworthy that no false-positive cases were identified.Conclusions: Intraoperative FS has low sensitivity in identifying MM within the SLN. IH alone does not increase the diagnostic yield. A combination of permanent H&E sections with deeper levels and S-100 and HMB45 IH dramatically increases the overall diagnostic sensitivity of SLN biopsy. Definitive diagnosis should await permanent H&E sections and IH staining.     

Focused examination of sentinel lymph nodes upstages early colorectal carcinoma

Approximately 30 per cent of patients with early colorectal carcinoma (CRC) develop systemic disease. A subgroup of these patients may harbor occult micrometastatic disease and might benefit from adjuvant chemotherapy. We investigated sentinel lymph node (SLN) mapping and focused pathologic examination of the SLN as a means of detecting nodal micrometastases. Between 1996 and 2000 SLN mapping was performed in 50 consecutive patients undergoing colectomy for CRC. All lymph nodes in the resection specimen were examined via routine hematoxylin and eosin (H&E) staining. In addition multiple sections of each SLN were examined via both H&E and cytokeratin immunohistochemistry. At least one SLN was identified in 47 patients (94%). In seven patients (14%) SLN mapping identified aberrant drainage that altered the planned resection. The SLN(s) correctly predicted nodal basin status in 44 of 47 (94%) cases; there were three falsely negative SLNs. Sixteen cases had positive SLNs by conventional H&E staining. An additional 10 (20%) cases were upstaged by a focused examination of the SLNs. Micrometastases were identified in three cases by H&E staining of multiple sections of the SLN and in seven only by cytokeratin immunohistochemistry. In nine cases the SLN was the only node containing tumor cells. In this study, SLN mapping demonstrated aberrant nodal drainage patterns that altered the surgical resection in patients with CRC. Focused examination of SLNs may detect micrometastases missed by conventional techniques and thereby identify patients who might benefit from adjuvant therapy.     

Criteria in Sentinel Lymph Nodes of Melanoma Patients that Predict Involvement of Nonsentinel Lymph Nodes

Background Previous studies described various criteria in sentinel lymph nodes (SLN) of melanoma patients that predict the involvement of further, nonsentinel lymph nodes (NSLN). Such criteria may facilitate the selection of patients who might benefit from a completion lymph node dissection (CLND). However, it is currently unclear which parameters are most important. Methods A total of 180 melanoma patients with positive SLNB and subsequent CLND were investigated. Histopathologic parameters in the SLN were systematically evaluated and compared with regard to NSLN positivity. Twenty-eight of these patients (16.0%) had positive NSLN. Results By univariate analysis several criteria with regard to tumor burden and location of melanoma cells in the SLN correlated with NSLN involvement, such as positivity by hematoxylin-eosin (H&E) staining (P < .001), largest diameter of clusters (P < .001), capsular involvement (P = .001), extranodal extension (P < .001), and tumor penetrative depth (P < .001). Multivariate analysis revealed three independent parameters: (1) positivity of the SLN by H&E staining (versus by immunohistochemistry alone), (2) relative tumor burden >10% of total lymph node tissue, and (3) perinodal intralymphatic tumor. In 23 of 28 patients with positive NSLN the SLN was positive by H&E staining, in 15 of 28 patients the relative tumor burden was >10%, and 13 of 28 showed perinodal intralymphatic tumor. In 5 of 28 patients with NSLN involvement, these three parameters were negative. Conclusions Histopathologic examination of the SLN can identify patients at risk for NSLN positivity.     

Nonsentinel node metastases in breast cancer patients with isolated tumor cells in the sentinel node: implications for completion axillary node dissection

BACKGROUND: Controversy exists regarding axillary dissection (ALND) for sentinel node (SLN) metastases detected as isolated tumor cells (ITC). We hypothesized that the number of positive non-SLNs is low and ALND is unnecessary for most patients with ITC. METHODS: From 1995 to 1999, 634 breast cancer patients underwent SLND. SLNs were examined using immunohistochemistry if hematoxylin and eosin was negative. ALND was recommended for ITC-positive SLNs. RESULTS: Seventy-eight patients (12.3%) with ITC-positive SLNs were offered ALND. Sixty-one consented, whereas 17 refused. Fifty-eight (95.1%) had negative non-SLNs. Three (4.9%) had non-SLN metastases. One patient (1.6%) had macrometastatic disease, whereas 2 (3.3%) had micrometastases. No ITC-only-positive SLN patient experienced axillary recurrence. CONCLUSIONS: When ALND was performed for ITC, 1.6% of non-SLNs harbored macrometastases and 3.3% had micrometastases. When ALND was not performed, axillary recurrence was not seen. The low risk of non-SLN disease in this study fails to support the routine use of ALND for ITC-positive SLNs.     

Sentinel Lymph Node Evaluation Does Not Improve Staging Accuracy in Colon Cancer

BACKGROUND: Lymph node involvement is an important prognostic factor in colorectal cancer. Sentinel lymph node (SLN) evaluation for assessing lymph node status in colorectal cancer remains controversial. Here we evaluated the sensitivity, predictive value, and accuracy of SLN evaluation for determining lymph node status in resectable colon cancer. METHODS: A prospective phase 2 cohort study of SLN evaluation in colon cancer was conducted from September 1998 to April 2006. Patients underwent resection and SLN mapping with 1% isosulfan blue and (m99)Tc sulfur colloid injection. SLNs were evaluated by hematoxylin and eosin (HE) staining and, if findings were negative, by additional thin HE sections and immunohistochemical (IHC) staining for pancytokeratin and MOC31. Overall survival for patients with IHC-positive disease was evaluated by Kaplan-Meier analysis and the log rank test. RESULTS: SLNs were identified in 119 (99%) of the 120 patients eligible for the study. Median number of SLNs identified was 4 (range, 0-13). Forty-nine patients (40%) had nodal metastases on HE. The SLN accurately identified nodal metastases in 29 (59%) of these 49 patients and was negative for metastases in 22 patients (41%). SLNs in eight patients (7%) were negative by HE but positive by IHC staining. Positive IHC status did not affect survival after a median follow-up of 33 months (P = .41). CONCLUSIONS: The low sensitivity and high false-negative rate of SLN evaluation does not support this technique for improving the accuracy of nodal staging for patients with colon cancer. The significance of IHC-positive SLNs remains uncertain.     

Ex vivo sentinel lymph node mapping in laparoscopic resection of colon cancer

Aim The study examined the feasibility and potential benefit of ex vivo sentinel lymph node (SLN) mapping, including multilevel sectioning (MLS) and immunohistochemistry (IHC) in colon cancer patients undergoing laparoscopic colectomy. The secondary goals were (i) to identify patient and tumour characteristics that might influence the success of the SLN technique, (ii) to investigate the extent of lymphadenectomy required to encompass tumour‐positive nonsentinel lymph nodes (NSLN) and (iii) to ascertain the association of SLN status with oncological outcomes. Method SLN mapping was performed after specimen extraction using 1% Isosulfan blue. The SLNs were analysed with H&E staining after MLS, and if negative, IHC was performed. NSLNs were grouped by distance either greater than or less than 4 cm from the tumour. Results Seventy‐one patients completed the study between 2003 and 2007. Using H&E with MLS, the accuracy of SLN mapping was 76%, sensitivity was 52% and the false‐negative rate was 48%. Excluding patients with clinically positive lymph nodes resulted in a significant improvement in accuracy to 81% and decreased the false‐negative rate to 30%. Furthermore, as the only positive NSLN > 4 cm from the tumour was grossly positive, SLN mapping with a 4‐cm mesenteric cuff would have given 100% sensitivity in patients without macroscopically involved nodes. Conclusions SLN mapping may be of value in selected patients. It may be possible to accurately stage patients with a 4‐cm cuff of mesentery, although further validation of this proposal is required.