David L. Krasne

OBJECTIVE: The authors evaluated the effect of intraoperative lymphatic mapping and sentinel lymphadenectomy (SLND) on the axillary staging of patients with carcinoma of the breast. SUMMARY BACKGROUND DATA: The accurate staging of patients with breast cancer is essential to guide management and determine prognosis. The authors previously reported the feasibility and accuracy of SLND in breast carcinoma. Sentinel lymphadenectomy identifies the first ("sentinel") axillary lymph node draining the site of a primary tumor; because this node is the most likely site of axillary metastasis, histopathologic examination of the sentinel node correlates well with examination of the entire axillary contents. The current study compares SLND with standard axillary lymphadenectomy (ALND) for the staging of breast carcinoma. METHODS: The incidence of axillary node metastasis and micrometastasis in SLND and ALND specimens from patients undergoing operative treatment of a primary breast carcinoma was compared prospectively. Multiple sections of each sentinel lymph node in SLND specimens were examined by hematoxylin and eosin (H&E) staining and by immunohistochemical techniques using antibodies to cytokeratin. One or two sections of each nonsentinel lymph node in ALND specimens were examined by routine H&E staining. RESULTS: One hundred thirty-four patients underwent ALND (ALND group), and 162 underwent successful SLND followed by completion ALND (SLND group). Both groups were similar with respect to age (median, 55 and 54 years, respectively), palpable primary tumors (54.5% and 59.3%, respectively), palpable axillary nodes (5.2% and 7.4%, respectively), size of primary tumor (median, 1.5 cm in each group), and total number of axillary lymph nodes examined (median, 19 and 21, respectively). The number of patients with axillary metastasis was 39 (29.1%) in the ALND group and 68 (42.0%) in the SLND group (p < 0.03). Of these, 4 of 39 (10.3%) ALND patients (3.0% of all ALND patients) and 26 of 68 (38.2%) SLND patients (16.0% of all SLND patients) had micrometastasis (< or = 2 mm), a highly significant difference (p < 0.0005) CONCLUSIONS: Sentinel lymphadenectomy with multiple sectioning and immunohistochemical staining of sentinel nodes increases the accuracy of axillary staging in breast cancer and can identify significantly more patients with lymph nodes metastases, especially micrometastases, than can ALND with routine histopathologic processing of lymph nodes.

BACKGROUND AND OBJECTIVE: The sentinel node hypothesis assumes that a primary tumor drains to a specific lymph node in the regional lymphatic basin. To determine whether the sentinel node is indeed the node most likely to harbor an axillary metastasis from breast carcinoma, the authors used cytokeratin immunohistochemical staining (IHC) to examine both sentinel and nonsentinel lymph nodes. METHODS: From February 1994 through October 1995, patients with breast cancer were staged with sentinel lymphadenectomy followed by completion level I and II axillary dissection. If the sentinel node was free of metastasis by hematoxylin and eosin staining (H&E), then sentinel and nonsentinel nodes were examined with IHC. RESULTS: The 103 patients had a median age of 55 years and a median tumor size of 1.8 cm (58.3% T1, 39.8% T2, and 1.9% T3). A mean of 2 sentinel (range, 1-8) and 18.9 nonsentinel (range, 7-37) nodes were excised per patient. The H&E identified 33 patients (32%) with a sentinel lymph node metastasis and 70 patients (68%) with tumor-free sentinel nodes. Applying IHC to the 157 tumor-free sentinel nodes in these 70 patients showed an additional 10 tumor-involved nodes, each in a different patient. Thus, 10 (14.3%) of 70 patients who were tumor-free by H&E actually were sentinel node-positive, and the IHC lymph node conversion rate from sentinel node-negative to sentinel node-positive was 6.4% (10/157). Overall, sentinel node metastases were detected in 43 (41.8%) of 103 patients. In the 60 patients whose sentinel nodes were metastasis-free by H&E and IHC, 1087 nonsentinel nodes were examined at 2 levels by IHC and only 1 additional tumor-positive lymph node was identified. Therefore, one H&E sentinel node-negative patient (1.7%) was actually node-positive (p < 0.0001), and the nonsentinel IHC lymph node conversion rate was 0.09% (1/1087; p < 0.0001). CONCLUSIONS: If the sentinel node is tumor-free by both H&E and IHC, then the probability of nonsentinel node involvement is <0.1%. The true false-negative rate of this technique using multiple sections and IHC to examine all nonsentinel nodes for metastasis is 0.97% (1/103) in the authors' hands. The sentinel lymph node is indeed the most likely axillary node to harbor metastatic breast carcinoma.

BACKGROUND: False-negative results from lymphatic mapping and sentinel lymphadenectomy (LM/SL) are associated with technical failures in nuclear medicine and surgery or with erroneous histologic evaluation. Any method that can confirm sentinel lymph node (SN) identity might decrease the false-negative rate. Carbon dye has been used as an adjunct to assist lymphadenectomy for some tumors, and the authors hypothesized that it could be used for the histologic verification of SNs removed during LM/SL. The current study assessed the clinical utility of carbon dye as a histopathologic adjunct for the identification of SNs in patients with melanoma and correlated the presence of carbon particles with the histopathologic status of the SNs. METHODS: LM/SL was performed using carbon dye (India ink) combined with isosulfan blue dye and sulfur colloid. Blue-stained and/or radioactive lymph nodes (two times background) were defined as SNs. Lymph nodes were evaluated for the presence of carbon particles and melanoma cells. If an SN lacked carbon dye in the initial histologic sections, four additional levels were obtained with S-100 protein and HMB-45 immunohistochemistry. Completion lymph node dissection (CLND) was performed if any SN contained melanoma cells. RESULTS: One hundred patients underwent successful LM/SL in 120 lymph node regions. Carbon particles were identified in 199 SNs from 111 lymph node regions of 96 patients. Sixteen patients had tumor-positive SNs, all of which contained carbon particles. The anatomic location of the carbon particles within these tumor-positive SNs was found to be correlated with the location of tumor cells in the SNs. The presence of carbon particles appeared to be correlated with blue-black staining (P = 0.0001) and with tumor foci (P = 0.028). All 35 non-SNs that were removed during LM/SL were tumor-negative, and only 2 contained carbon particles. Of the 272 non-SNs removed during CLND, 5 contained metastases; 3 of these 5 were the only non-SNs that had carbon particles. The use of carbon particles during LM/SL was found to be safe and nontoxic. CONCLUSIONS: Carbon dye used in LM/SL for melanoma permits the histologic confirmation of SNs. Carbon particles facilitate histologic evaluation by directing the pathologist to the SNs most likely to contain tumor. The location of carbon particles within SNs may assist the pathologist in the detection of metastases, thereby decreasing the histopathologic false-negative rate of LM/SL and subsequently reducing the same-basin recurrence rate.

PURPOSE: Sensitive detection methods and accurate reporting are necessary to determine the prognostic significance of micrometastases (MM) and isolated tumor cells (ITCs) in lymph nodes that drain colorectal cancers (CRCs). This study examined the role of lymphatic mapping (LM) in the application of the new tumor-node-metastasis (TNM) classification for MM and ITC. PATIENTS AND METHODS: All patients at the John Wayne Cancer Institute underwent LM immediately before standard resection of primary CRC between 1996 and 2001. Sentinel nodes (SNs) were identified using blue dye and/or radiotracer and were examined by hematoxylin-eosin (H&E) staining, cytokeratin immunohistochemistry, and multilevel sectioning. The comparison group comprised 370 patients whose primary CRCs were resected without LM during the same period at the same institution. RESULTS: LM was successfully performed in 115 of 120 (96%) patients and correctly predicted the tumor status of the nodal basin in 110 of 115 (96%) patients. Thirty-seven patients (32%) were lymph node-positive by H&E, ITC and MM were found in 23 patients (29.4%) whose lymph nodes were negative by H&E. Tumor deposits were found in the SN only in 29 patients (50%). Nodal involvement was identified for 14.3%, 30%, 74.6%, and 83.3% of T1, T2, T3, and T4 tumors, respectively, in the study group, and for 6.8%, 8.5%, 49.3%, and 41.8% of T1, T2, T3, and T4 tumors, respectively, in the comparison group. The study group had a higher percentage of nodal metastases (53% v 36%; P <.01) and a higher incidence of MM and ITC (29.4% v 1.9%; P <.0001). The mean number of lymph nodes found in the study group (14) was also significantly more than the number found in the comparison group (10; P <.00001). CONCLUSION: Conventional examination of lymph nodes for CRC is inadequate for the detection of MM and ITC as described in the new TNM classification. Thus, LM and focused SN analysis should be considered to fully stage CRC.

Comprehensive pathologic evaluation of the sentinel lymph node using step sections and cytokeratin immunohistochemistry enhances detection of micrometastases and optimizes the staging of breast carcinoma. This review discusses our current understanding of the pathologic and molecular techniques for sentinel node examination.