Sentinel Lymph Node in Breast Cancer: Review Article from a Pathologist's Point of View

Breast cancer staging, in particular N-stage changed most significantly due to the advanced technique of sentinel lymph node biopsy two decades ago. Pathologists have more thoroughly examined and scrutinized sentinel lymph node and found increased number of small volume metastases. While pathologists use the strict criteria from the Tumor Lymph Node Metastasis (TNM) Classification, studies have shown poor reproducibility in the application of American Joint Committee on Cancer and International Union Against Cancer/TNM guidelines for sentinel lymph node classification in breast cancer. In this review article, a brief history of TNM with a focus on N-stage is described, followed by innate problems with the guidelines, and why pathologists may have difficulties in assessing lymph node metastases uniformly. Finally, clinical significance of isolated tumor cells, micrometastasis, and macrometastasis is described by reviewing historical retrospective data and significant prospective clinical trials.

Impact on Prognosis of Lymph Node Micrometastasis and Isolated Tumor Cells in Stage II Colorectal Cancer

PURPOSE: Even though the importance of micrometastases (MMS) and isolated tumor cells (ITC) has been brought up by many physicians, its impact on the prognosis in stage II colorectal cancer is uncertain. In this research, we tried to investigate the clinical features of MMS and ITC and to prove any correlation with prognosis. METHODS: The research pool was 124 colorectal cancer patients who underwent a curative resection from April 2005 to November 2009. A total of 2,379 lymph nodes (LNs) were examined, and all retrieved LNs were evaluated by immunohistochemical staining with anti-cytokeratin antibody panel. Clinicopathologic parameters and survival rates were compared based on the presence of MMS or ITC and on the micrometastatic lymph node ratio (mmLNR), which is defined as the number of micrometastatic LNs divided by the number of retrieved LNs. RESULTS: Out of 124 patients (26.6%) 33 were found to have MMS or ITC. There were no significant differences in clinicopathologic features, such as gender, tumor location and size, depth of invasion, histologic grade, except for age (P = 0.04). The three-year disease-free survival rate for the MMS or ITC positive group was 85.7%, and that for MMS and ITC negative group was 92.8% (P = 0.209). The three-year disease-free survival rate for the mmLNR > 0.25 group was 73.3%, and that for the mmLNR < or = 0.25 group was 92.9% (P = 0.03). CONCLUSION: The presence of MMS or ITC was not closely correlated to the prognosis. However, mmLNR is thought to be a valuable marker of prognosis in cases of stage II colorectal cancer.

Fatores clínico-patológicos de predição do acometimento axilar em pacientes com metástases de câncer de mama no linfonodo sentinela / Clinicopathological predictor factors of axillary involvement in patients with metastatic breast cancer in the sentinel lymph node

Objetivos: avaliar os fatores clínicos, patológicos e imunoistoquímicos podem ser indicativos de comprometimento metastático de outros linfonodos em pacientes com carcinoma de mama submetidas à biópsia do linfonodo sentinela (BLNS). Métodos: estudo retrospectivo de 1.000 pacientes sucessivas com biópsia do LS, de 1998 a 2008. Foram avaliados: idade, tamanho do tumor, grau histológico, invasão angiolinfática, o status de receptores hormonais e HER-2, o tamanho da metástase e número de LS positivos. As associações entre as características dos tumores e os tipos de metástases foram avaliadas com testes de razão de verossimilhança corrigida com χ2 para amostras insuficientes. Resultados: a idade média foi 57,6 anos, e o tamanho médio do tumor foi de 1,85 cm. Um total de 72,2 por cento LS foram negativos e 27,8 por cento foram positivos, mas em 61,9 por cento dos casos, o LS foi o único positivo; com 78,4 por cento de macrometástases, 17,3 por cento de micrometástases e 4,3 por cento de células tumorais isoladas (CTI). O tamanho do tumor foi fator preditivo de metástases em linfonodos não-sentinela. Após 54 meses de acompanhamento, não houve recidivas em pacientes com CTI, no grupo de micrometástases houve uma recorrência local e duas sistêmicas, e no grupo de macrometástases ocorreram quatro locais e 30 a distância. Conclusões: dos parâmetros clínicos estudados, apenas o tamanho do tumor foi correlacionado com comprometimento metastático de linfonodos axilares. O tamanho das metástases e do número de LS positivos também aumenta diretamente a possibilidade de recidiva sistêmica. As diferentes taxas de recidiva indicam que o significado biológico desses tipos de metástases é diferente e que os pacientes com metástases nos LS também podem ter diferentes riscos de comprometimento metastático de outros linfonodos axilares.

Purpose: to evaluate which clinical, pathological or immunohistochemical factors may be predictive of metastatic involvement of other lymph nodes in patients with breast carcinoma undergoing sentinel lymph node biopsy (SLNB). Methods: a retrospective study carried out with 1,000 successive patients with SLNB from 1998 to 2008. Age, tumor size, histological grade, lymphovascular invasion, hormone receptor status and HER-2, size of metastasis and number of positive SLN were evaluated. The associations between the characteristics of the tumors and the types of metastases were evaluated through χ2 corrected likelihood ratio tests for insufficient samples. Results: mean age was 57.6 years and mean tumor size was 1.85 cm. A total of 72.2 percent SLN were negative and 27.8 percent were positive, but in 61.9 percent of the cases, the SLN was the only positive one, with 78.4 percent having macrometastases, 17.3 percent micrometastases and 4.3 percent isolated tumor cells (CTI). Tumor size was predictive of metastases in non-sentinel lymph nodes. After 54 months of follow-up, there were no recurrences in patients with CTI, but one local recurrence and two systemic recurrences were observed in the micrometastasis group, as well as four local and 30 distant metastases in the macrometastasis group. Conclusion: among the clinical parameters studied, only tumor size was correlated with metastatic involvement in axillary lymph nodes. The size of the metastases and the number of positive SLN also directly increased the possibility of systemic recurrence. The different rates of recurrence indicate that the biological significance of these types of metastases is different and that patients with SLN metastases may also have different risks of metastatic involvement of other axillary lymph nodes.

Implications of Isolated Tumor Cells in Sentinel Lymph Nodes of Breast Cancer Patients

PURPOSE: Sentinel lymph node (SLN) biopsy has replaced unnecessary axillary dissection in breast cancer surgery except when the nodes are positive for macrometastasis. But guidelines for isolated tumor cells (ITCs) found in SLNs has not yet been established and further study is ongoing. The goal of this study was to consider the implication of the isolated tumor cells found in the SLNs of Korean breast cancer patients. METHODS: Between September 2003 and March 2008, 985 primary breast cancer patients underwent SLN biopsy. On reviewing the medical records, 81 patients were found to have ITCs in SLNs without macrometastasis or micrometastasis. ITCs were detected by serial sectioning and immunohistochemistry. RESULTS: The mean number of detected SLNs was 3.5+/-1.7. Thirty three patients had multifocally distributed ITCs and 9 had ITCs in multiple SLNs whose N stage was N0 (i+). Completion axillary dissection has been performed in 9 patients and 3 of them (33.3%) finally were found to be N1 or N1mi. CONCLUSION: The characteristics of ITCs are not clear yet and their prognostic value is still under investigation. Until the significance of ITCs found in SLNs become definite, axillary dissection should be more aggressively considered.

Cytokeratin-positive Cells in the Bone Marrow of Patients with Gastric Cancer

PURPOSE: Controversy still exists over in the prognostic significance of microscopic tumor cell dissemination in patients with cancer. This study evaluated the prognostic implication of isolated tumor cells in the bone marrow of patients with gastric cancer. MATERIALS AND METHODS: Four hundred nineteen (419) patients who underwent surgery for gastric cancer between June 1998 and July 2000 were enrolled in the study. Bone marrow aspirate was obtained from the iliac crest before removal of the primary tumor. Mononuclear cells were isolated and stained with AE-1/AE-3 PAN-CYTOKERATIN. RESULTS: Cytokeratin-positive cells were found in the bone marrow of 219 patients (52.3%). The incidence varied significantly with the depth of invasion (P=0.021) and the stage (P=0.026). The five-year survival rate of patients with cytokeratin-positive cells was 74.1% and that of patients without cytokeratin-positive cells was 81.1% (P=0.2481). There were no significant differences in the recurrence rate and the site of recurrence according to whether or not cytokeratin-positive cells were present in the bone marrow. CONCLUSION: The presence of cytokeratin-positive cells in the bone marrow of patients with gastric cancer did not predict outcome and recurrence. Therefore, it cannot be used as a prognostic factor.