Cells In Sentinel Lymph Nodes Research Articles

Albumin-mediated molecular competition of supramolecular photosensitizers for NIR-II imaging-guided phototherapy

Heptamethine cyanines (Cy7) typically exhibit strong near-infrared (NIR) fluorescence signals when in monodisperse states, but their distinctive π-conjugated structure leads to limited solubility in aqueous solutions, ultimately resulting in inherent fluorescence self-quenching. Enhancing the fluorescence quantum yield of these agents within aqueous environments, in order to achieve high-resolution biological imaging, presents a significant challenge. Herein, a benzothiazole-based Cy7-derivative (Cy7-BTH) is developed, exhibiting unique H-aggregation properties in aqueous solutions. Bovine serum albumin (BSA) binds to Cy7-BTH (BSA@Cy7-BTH) to modulate its molecular stacking and energy transfer, boosting its fluorescence accompanied by bright NIR-II tail emission. The competitive binding alters the planarity of Cy7-BTH, restricting its intramolecular rotation, and simutaneously changes the conformation of BSA, leading to BSA@Cy7-BTH aggregation to form hierarchical-structured nanoparticles. Notably, the BSA@Cy7-BTH nanoparticles significantly enhanced photothermal response of Cy7-BTH while maintaining its controlled reactive oxygen species (ROS) generation, offering NIR-II imaging-guided surgical removal of primary tumors, and simultaneously inhibiting cancer cell metastasis by synergistic PDT/PTT dissection of metastatic tumor cells in sentinel lymph nodes (SLNs). This study provides an innovative but facile strategy for their potential clinical applications by precisely regulating the intermolecular competitive interactions of NIR theranostic agents.

Isolated melanoma cells in sentinel lymph node in stage IIIA melanoma correlate with a favorable prognosis similar to stage IB

BackgroundThe American Joint Committee on Cancer 8th edition (AJCC v8) defines sentinel lymph nodes (SLN) containing any tumor cells as positive SLN. Consequently, even thin melanomas with isolated tumor cells (ic) in SLN are classified as stage IIIA, making them candidates for adjuvant therapy. Objectives and endpointsWe aimed to evaluate survival outcomes of melanoma stage IIIA (ic) and compare them with stage IIIA with lymph node (LN) metastases > 0.1 mm. Primary endpoints were relapse-free survival (RFS) and distant metastases-free survival (DMFS). Secondary endpoint was melanoma specific survival (MSS). ResultsThe discovery cohort from the Department of Dermatology, University Hospital Tuebingen, included 237 patients; confirmation cohort included 143 patients from the DeCOG trial. The Tuebingen cohort included 95 patients with stage IIIA (ic) and 142 patients with stage IIIA. The DeCOG trial included 39 patients with stage IIIA (ic) and 104 patients with stage IIIA. In the Tuebingen cohort, 10-year RFS rates for stage IIIA (ic) and IIIA were 84% (95% CI 75–94) and 49% (95% CI 39–59), respectively (p < 0.001). 10-year DMFS rates for stage IIIA (ic) and IIIA were 89% (95% CI 81–97) and 56% (95% CI 45–67), respectively; (p < 0.001). In the DeCOG cohort, 10-year RFS for stage IIIA (ic) and stage IIIA were 88% (95% CI 78–99) and 35% (95% CI 7–62), respectively; (p = 0.009). 10-year DMFS for stage IIIA (ic) and IIIA was 88% (95% CI 77–99) and 60% (95% CI 39–80), respectively (p = 0.061). ConclusionStage IIIA (ic) melanoma exhibits a prognosis similar to stage IB. Recommendation of adjuvant therapy in Stage IIIA (ic) warrants thorough discussion.

Omission of axillary lymph node dissection in breast cancer patients with micrometastasis or isolated tumor cells in sentinel lymph nodes: a 12-year experience in a tertiary breast unit.

After the IBCSG 23-01 trial, our breast center no longer performed axillary lymph node dissection (ALND) after detection of isolated tumor cells (ITC) or micrometastasis in the sentinel lymph nodes (SLN). A recent study suggested that up to half of the patients with micrometastasis in the SLN could benefit from ALND in terms of disease-free survival (DFS) and overall survival (OS). This retrospective, unicentric, study analyzed 261 consecutive cT1-3 cN0 breast cancer patients with ITC or micrometastasis in their SLN. Primary objective was comparison of ALND vs. SLN biopsy (SLNB) with regard to DFS and OS. Secondary objectives included analysis of factors associated with an increased rate of locoregional recurrence (LRR), distant metastasis (DM) and metachronous contralateral breast cancer (MCBC). DFS events occurred in 19 patients (7.3%) and 14 patients died (5.4%). Median follow-up time was 78months. 251 patients (96.2%) had micrometastasis in their SLN. There was no difference in the OS or DFS of ALND vs. SLNB patients. History of previous contralateral breast cancer and WBI were associated with an increased and decreased rate of LRR, respectively. Larger tumor size was associated with an increased rate of DM. Non-ductal histological types were associated with an increased rate of MCBC. Avoiding ALND may be safe in pN1mi/pN0(i+) patients. Besides, we strongly encourage clinicians to develop their own follow-up protocols based on the best available evidence, to rapidly identify and treat breast cancer recurrence.

Prognostic value of isolated tumor cells in sentinel lymph nodes in low risk endometrial cancer: results from an international multi-institutional study

ObjectiveThe prognostic significance of isolated tumor cells (≤0.2 mm) in sentinel lymph nodes (SLNs) of endometrial cancer patients is still unclear. Our aim was to assess the prognostic value of...

Applications and Safety of Sentinel Lymph Node Biopsy in Endometrial Cancer.

Lymph node status is important in predicting the prognosis and guiding adjuvant treatment in endometrial cancer. However, previous studies showed that systematic lymphadenectomy conferred no therapeutic values in clinically early-stage endometrial cancer but might lead to substantial morbidity and impact on the quality of life of the patients. The sentinel lymph node is the first lymph node that tumor cells drain to, and sentinel lymph node biopsy has emerged as an acceptable alternative to full lymphadenectomy in both low-risk and high-risk endometrial cancer. Evidence has demonstrated a high detection rate, sensitivity and negative predictive value of sentinel lymph node biopsy. It can also reduce surgical morbidity and improve the detection of lymph node metastases compared with systematic lymphadenectomy. This review summarizes the current techniques of sentinel lymph node mapping, the applications and oncological outcomes of sentinel lymph node biopsy in low-risk and high-risk endometrial cancer, and the management of isolated tumor cells in sentinel lymph nodes. We also illustrate a revised sentinel lymph node biopsy algorithm and advocate to repeat the tracer injection and explore the presacral and paraaortic areas if sentinel lymph nodes are not found in the hemipelvis.

Mannose and Hyaluronic Acid Dual-Modified Iron Oxide Enhances Neoantigen-Based Peptide Vaccine Therapy by Polarizing Tumor-Associated Macrophages.

Simple SummaryCancer vaccine therapy is promising, though its efficacy is compromised in an immunosuppressive tumor microenvironment. Tumor-associated macrophages (TAMs) have the potential to be repolarized to an antitumor subtype, and their antigen-presenting ability might enhance the efficacy of cancer vaccination. Here, we aimed to develop a nanoparticle with adjuvant effect that could be a carrier for neoantigen-based vaccine to target and repolarize TAMs in situ. Therefore, we prepared a hyaluronic acid and mannose dual-modified iron oxide nanoparticle, and the enhanced efficiency of nanoparticle intake of macrophages was confirmed. It could repolarize macrophages and outperformed a commercialized iron oxide nanoparticle, ferumoxytol. Combined with peptides, this nanoparticle strongly inhibited TC1 tumor growth, and 40% of mice reached complete regression. This is the first report using mannose, hyaluronic acid, and iron oxide to target TAMs and achieve ideal outcomes in vivo. This study provides a facile nanoplatform for neoantigen-based vaccine therapy and a reference for repolarizing TAMs to promote immunotherapy.Neoantigen-based cancer vaccine therapy is a breakthrough in the field of immunotherapy. However, it is difficult for vaccines against neoantigens to overcome the immunosuppressive microenvironment, where tumor-associated macrophages (TAMs) play a significant role. Herein, we report an iron oxide nanoparticle modified with hyaluronic acid and mannose to reshape the tumor microenvironment by targeting and repolarizing TAMs from protumor M2 to antitumor M1 phenotype. Mannose decoration could confer the nanoparticle-enhanced TAM targeting ability, while hyaluronic acid and iron oxide could repolarize M2-like macrophages both in vitro and in vivo. Combined with antigenic peptides, this nanovaccine could significantly increase the infiltration of CD8+ T cells into tumor tissue and strongly activate dendritic cells in sentinel lymph nodes. Finally, we used the dual-modified nanoparticles to first convert the tumor microenvironment and then the nanovaccine administration in a TC1 tumor model to further enhance efficacy. This strategy inhibited tumor growth and achieved a 40% cure rate in mice (two of five). In summary, this study provides a potent and rationally designed nanoadjuvant to enhance antitumor efficiency and facilitate delivery of neoantigen vaccines by repolarizing TAMs and harmonizing immune cells.

Lighting up Self-Quenching Nanoaggregates with Protein Corona for Simultaneous Intraoperative Imaging and Photothermal Theranostics of Metastatic Cancer

Near-infrared (NIR) photothermal transduction agents (PTAs) with large rigid π-extended and planar structures are prone to aggregate in a physiological environment where their emission is often quenched due to the strong intermolecular dipole-dipole or π-π interactions. This aggregation-caused quenching effect greatly impedes their applications in image-guided photothermal theranostics. Herein, we made an interesting finding that engineering a bioinspired protein corona (PC), once thermodynamically stabilized in preferred orientations on PTA nanoaggregates, can produce brilliant NIR fluorescence with a high quantum yield (∼6.2%) without compromising their photothermal properties. Both experimental data and computational modeling suggest that the mechanism of fluorescence enhancement is due to the high-affinity binding of nano-sized PTA to albumin, which regulates the molecular conformation and aggregation state of PTA. High spatial and temporal resolution imaging of albumin PC-coated PTA aggregates enables image-guided photothermal therapy for cancer cells in sentinel lymph nodes to remarkably inhibit pulmonary metastasis. Such a treatment combined with the surgical removal of the primary tumor can prolong animal survival, which is a promising candidate for clinical applications in the treatment of advanced metastatic cancers.

Flow Cytometry for Detection and Quantification of Micrometastases in Sentinel Lymph Nodes from Patients with Primary Melanoma

BackgroundDetection of micrometastases in the regional lymph nodes is one of the most important prognostic factors for melanoma patients. Our aim was to evaluate the suitability of flow cytometry for rapid quantification of disseminated melanoma cells in sentinel lymph nodes (SLN). Methods132 SLNs from 104 patients diagnosed with melanoma were analyzed by flow cytometry, utilizing the extracellular marker melanoma-associated chondroitin sulfate proteoglycan, in addition to quantitative immunocytology and conventional histopathology, including immunohistochemistry. For quantification, the number of melanoma-positive cells per million lymph node cells (disseminated cancer cell density, DCCD) detected by flow cytometry was compared to the DCCD obtained by immunocytology. ResultsCompared to histopathology and immunocytology, flow cytometry exhibited a sensitivity of 50% and a specificity of 85%. DCCDs of immunocytology and flow cytometry of the 37 immunocytologically positive SLNs showed a positive correlation (Spearman's ρ = 0.7, P < 0.0001). In 10 SLNs from 9 patients with high tumor load, the flow cytometric DCCD was 8-fold higher on average than the immunocytologic DCCD. ConclusionsAlthough flow cytometry is not yet suitable for early detection of metastatic melanoma, it promises to become a valuable tool for rapidly quantifying tumor load in high-risk patients.

SOX10-positive perivascular cells in sentinel lymph nodes: A reliably intrinsic internal control.

SOX10-positive perivascular cells in sentinel lymph nodes: A reliably intrinsic internal control.

Oncologic impact of micrometastases or isolated tumor cells in sentinel lymph nodes of patients with endometrial cancer: a meta-analysis

There is a gap in knowledge regarding the impact of micrometastases (MIC) and isolated tumor cells (ITCs) found in the sentinel lymph nodes of patients with endometrial cancer. Here, we present a meta-analysis of the published literature on the rate of MIC and ITCs after lymphatic mapping and determine trends in postoperative management. Literature search of Medline and PubMed was done using the terms: micrometastases, isolated tumor cells, endometrial cancer, and sentinel lymph node. Inclusion criteria were: English-language manuscripts, retrospectives, or prospective studies published between January 1999 and June 2019. We removed manuscripts on sentinel node mapping that did not specify information on micrometastases or isolated tumor cells, non-English-language articles, no data about oncologic outcomes, and articles limited to ten cases or less. A total of 45 manuscripts were reviewed, and 8 studies met inclusion criteria. We found that the total number of patients with MIC/ITCs was 286 (187 and 99, respectively). The 72% of patients detected with MIC/ITCs in sentinel nodes received adjuvant therapies. The MIC/ITCs group has a higher relative risk of recurrence of 1.34 (1.07, 1.67) than the negative group, even if the adjuvant therapy was given. We noted that there is an increased relative risk of recurrence in patients with low-volume metastases, even after receiving adjuvant therapy. Whether adjuvant therapy is indicated remains a topic of debate because there are other uterine factors implicated in the prognosis. Multi-institutional tumor registries may help shed light on this important question.

FEATURES OF DEFEATS OF SENTINEL LYMPH NODES AT PRIMARY MELANOMA OF SKIN

Introduction. Each tenth tumor of skin is melanoma. Presence of tumor cells in sentinel lymph node influenced the medical tactics.The objective of the research was to study the metastasis of skin melanoma into the clinically negative regional lymph nodes.Material and methods. Histological, immunohistochemical, cytological and immunocytochemical methods were used to study biopsies of regional lymph nodes in 60 patients with skin melanoma.Results. 5 % of patients were diagnosed with melanoma in situ, 15 % – Т1, 28.3 % – Т2, 23.3 % – Т3, 28.3 % – Т4. At outflow of the lymph through 1 collector, the metastases in sentinel lymph node (SLN) was defined in 51 %, through 2 collectors – in 81.8 % of cases. Tumor cells damaged single lymph node in 35.3 % of cases, two and more lymph nodes in 64.7 % of cases. Metastases in SLN with formation of secondary tumor at the T1 melanoma were observed at 11.1 %, T2 – 5.9 %, T3 – 21.4 %, T4 – 47.1 % of studies. Clusters of cells or isolated cells of melanoma in SLN at Т1 were noted in 22.2 %, at Т2 – in 41.2 %, at Т3 – in 42.9 %, at Т4 – in 35.3 % of cases. At outflow of lymph through 1 collector, metastasises of melanoma in non-sentinel lymph nodes (NSLN) were revealed in 24 %, through 2 collectors – in 44.4 % of cases. Secondary changes of NSLN were noted in 16.7 % of cases of defeat of single SLN, in 31.8 % of cases of defeat of two and more SLN. Metastases of melanoma were revealed in 69.2 % of cases of formation of secondary tumor and in 4.8 % of cases of presence of clusters in SLN in removed NSLN.Conclusion. At increase of Тmelanoma of the skin, the quantity of sentinel lymph nodes with reactive changes decreased, and their number with metastases increased. Metastatic defeat of sentinel lymph nodes at outflow of lymph through 2 lymph collectors in two and more SLN and NSLN exceeded the defeat of SLN at outflow of lymph through 1 lymph collector in single lymph nodes. The use of immunocytochemical method of research allowed to expand pathomorphological verification of metastatic defeat of sentinel lymph nodes by 66.7%.

Isolated Tumor Cells in Sentinel Lymph Nodes of Primary Invasive Breast Carcinoma: A Cohort Analysis

BackgroundThe practice of performing routine cytokeratin immunohistochemistry (CK-IHC) on sentinel lymph nodes in early stage invasive breast cancer leads to frequent identification of isolated tumor cells (ITCs), the clinical significance of which remains unclear. After emergence of guidelines that suggested limited clinical utility of ITC detection, routine CK-IHC (rCK-IHC) staining was discontinued at our institution. We studied the rate and clinical utility of ITC detection before and after the discontinuation of rCK-IHC. Patients and MethodsWe retrospectively reviewed 2 cohorts of 250 consecutive early stage invasive breast cancer (IBC) patients with sentinel lymph node biopsies (SLNBs) in 2010 to 2011 (rCK-IHC) and 2015 to 2016 (selective CK-IHC [sCK-IHC]). Variables abstracted included: tumor histology, tumor size, grade, lymphatic-vascular invasion, hormone receptor expression, HER2 status, and nodal status including ITCs. All cases from the 2015 to 2016 cohort for which sCK-IHC was performed underwent pathology review. A clinical review of treatment decision effect and cost analysis was undertaken. Data were analyzed using descriptive statistics and Fisher exact test. ResultsIn the rCK-IHC cohort, all 250 cases underwent CK-IHC staining versus 57 cases in the sCK-IHC cohort. There were 23 ITC cases observed in the rCK-IHC cohort compared with 11 in the sCK-IHC cohort (P = .049). Excluding lobular carcinomas, 19 ITC cases were observed with rCK-IHC versus 7 with sCK-IHC (P = .02). ITC detection did not affect adjuvant treatment decision-making and resulted in savings of at least Can$8000. ConclusionSelective rather than routine use of CK-IHC staining for SLNB evaluation in early-stage IBC results in decreased ITC detection without affecting treatment decisions and leads to cost savings.

Imaging of Metastatic Cancer Cells in Sentinel Lymph Nodes using Affibody Probes and Possibility of a Theranostic Approach.

The accurate detection of lymph node metastases is essential for treatment success in early-stage malignant cancer. Sentinel lymph node (SLN) biopsy is the most effective procedure for detecting small or micrometastases that are undetectable by conventional imaging modalities. To demonstrate a new approach for developing a more efficient SLN biopsy procedure, we reported a two-stage imaging method combining lymphoscintigraphy and near-infrared (NIR) fluorescence imaging to depict metastatic cancer cells in SLNs in vivo. Furthermore, the theranostic potential of the combined procedure was examined by cell culture and xenograft mouse model. Anti-HER2 and anti-epidermal growth factor receptor (EGFR) affibody probes were used for NIR fluorescence imaging. Strong NIR fluorescence signal intensity of the anti-EGFR affibody probe was observed in SAS cells (EGFR positive). Radioactivity in the SLNs was clearly observed in the in vivo studies. High anti-EGFR affibody NIR fluorescence intensity was observed in the metastatic lymph nodes in mice. The addition of the IR700-conjugated anti-EGFR affibody to the culture medium decreased the proliferation of SAS cells. Decreased proliferation was shown in Ki-67 immunohistochemistry in xenograft tumors. Our data suggest that a two-stage combined imaging method using lymphoscintigraphy and affibody probes may offer the direct visualization of metastatic lymph nodes as an easily applied technique in SLN biopsy. Although further animal studies are required to assess the effect of treating lymphatic metastasis in this approach, our study results provide a foundation for the further development of this promising imaging and treatment strategy for earlier lymph node metastasis detection and treatment.

Prognostic value of isolated tumour cells in sentinel lymph nodes in early-stage breast cancer: a prospective study.

BackgroundThe prognostic significance of isolated tumour cells (ITCs) in the sentinel nodes (SNs) is controversial in early breast cancer, and some centres have abandoned immunohistochemistry to detect ITCs.MethodsPatients with unilateral pT1N0 breast cancer, operated between February 2001 and August 2005 at a university hospital were included in this prospective, population-based cohort study. Survival of 936 patients with or without isolated tumour cells (ITC) in their SNs were compared with the log-rank test and Cox regression analysis.ResultsEight hundred sixty one (92.0%) patients were ITC-negative (pN0i−) and 75 (8.0%) ITC-positive (pN0i+). Patients with ITC-positive cancer received more frequently adjuvant systemic therapies than those with ITC-negative cancer. The median follow-up time was 9.5 years. Ten-year distant disease-free survival was 95.3% in the pN0i− group and 88.8% in the pN0i+ group (P = 0.013). ITCs were an independent prognostic factor in a Cox regression model (HR = 2.34, 95% CI 1.09–5.04; P = 0.029), together with tumour Ki-67 proliferation index and diameter. ITCs were associated with unfavourable overall survival (P = 0.005) and breast cancer-specific survival (P = 0.001).ConclusionsWe conclude that presence of ITCs in the SNs is an adverse prognostic factor in early small node-negative breast cancer, and may be considered in the decision-making for adjuvant therapy.

Iatrogenically false positive sentinel lymph nodes in breast cancer: Methods of recognition and evaluation.

With the introduction of sentinel lymph node (SLN) biopsy as a standard procedure for staging clinically node negative breast cancer patients, meticulous pathologic evaluation of SLNs by serial sections and/or immunohistochemistry for cytokeratins has become commonplace in order to detect small volume metastases (isolated tumor cells and micrometastases). This practice has also brought to the fore the concept of iatrogenically false positive sentinel nodes secondary to epithelial displacement produced largely by preoperative needling procedures. While this concept is well described in the clinical and pathologic literature, it is, in our experience, still under-recognized, with such lymph nodes frequently incorrectly diagnosed as harboring true metastases, possibly resulting in unwarranted further surgery and/or chemotherapy. This review discusses the concept of displaced epithelium in the histologic evaluation of breast surgical specimens and provides a stepwise approach to the correct identification of iatrogenically transported displaced epithelial cells in sentinel lymph nodes.

Evaluation of Sentinel Lymph Node Intraoperative Touch Imprint Cytology in Breast Cancer Surgery

Background: One of the strongest prognostic factor for breast cancer is the regional lymph node status, which can be evaluated intraoperatively by sentinel lymph node biopsy. Many methods (e.g. frozen section, touch imprint cytology (TIC) and one-step nucleic-acid amplification) are available to detect metastatic cells in axillary lymph nodes. The aim of this study is to evaluate the feasibility of using TIC to detect metastatic cells in sentinel lymph nodes. Methods: This is a retrospective single center cohort analysis conducted on prospectively recorded data. The study included all patients admitted to the Department of General Surgery of Trieste University Hospital for invasive clinically node-negative breast cancer who underwent sentinel lymph node assessment by means of TIC. Results: Between January 2015 and December 2016, 343 patients (338 females and 5 males) underwent breast surgery and sentinel lymph node TIC. Patient’s median age was 66 (33-92) years. The sensitivity of TIC was 54% (95% C.I. 39% to 69%), whereas its specificity and accuracy were 99% (95% C.I. 98% to 100%) and 90%, respectively. The median time required to obtain the result was 20 (15-45) min. The overall cost per each TIC analysis was about 20.50€. Conclusion: Touch imprint cytology appears to be a fast, cost-effective and reliable technique to intraoperatively detect breast cancer lymph node metastasis.

Could the immune response in the sentinel lymph nodes of gastric cancer patients be the key to tailored surgery?

Precise detection of downstream, nonsentinel lymph node metastases is the key to implementation of the sentinel lymph node concept in gastric cancer. To overcome the problem of complex lymphatic drainage, micrometastases, and skip metastases, we investigated the feasibility of tumor cell detection in sentinel lymph nodes, using flow cytometry as well as studied immune suppression in the sentinel lymph node as a potential marker of downstream lymph node metastases. In 21 patients with gastric cancer, the sentinel lymph nodes extracted during operation subjected to frozen sections and flow cytometry. The tumor cells were defined with the cell surface markers CEACAM and EpCAM. Simultaneously, the cell densities of different subsets of Tcells were determined. The sensitivity and specificity of the determination of nodal status with flow cytometry for tumor cell detection was 100% and 63%, respectively, as seen in frozen sections. Correlations with nonsentinel lymph node metastases were seen for CD127(low)CD25(high) and CD45(neg)CD127(low)CD25(high) cell densities, relative proportion of CD45RA(neg)CD127(low)CD25(high) cells, frozen sections results, lymphangial invasion, and tumor size (P≤.043 each). Multivariate analysis identified the relative proportions of CD45RA(neg)CD127(low)CD25(high) cells as the only significant predictor for downstream nonsentinel lymph node metastases (P=.028; 95% confidence interval, 1.107-5.780). The predictive value of combined detection of flow cytometry tumor cells and the relative proportion of CD45RA(neg)CD127(low)CD25(high) cells for nodal stage determination was 91%. Combined detection of tumor cells and CD45RA(neg)CD127(low)CD25(high) cells in sentinel lymph nodes with flow cytometry predicts accurately nonsentinel lymph node metastases.

P342 A ten year review on macro-, micro-metastasis and isolated tumor cells in sentinel lymph nodes

P342 A ten year review on macro-, micro-metastasis and isolated tumor cells in sentinel lymph nodes

Histological examination of sentinel lymph nodes: significance of macrometastasis, micrometastasis, and isolated tumor cells

Sentinel lymph node biopsy has been started in 1990s and has become one of the standard diagnostic procedures used to treat patients with early breast cancer in this century. In Japan, for the microscopic diagnosis of metastasis to sentinel lymph nodes, intraoperative frozen section diagnosis is widely used in combination with subsequent permanent section diagnosis of the residual specimens. Metastatic foci to sentinel lymph nodes have been classified into macrometastasis, micrometastasis, and isolated tumor cells in 2002, and the definition of isolated tumor cells was modified in 2010. Clinical significance of occult sentinel lymph node metastases, being mostly composed of micrometastasis and isolated tumor cells, has been clarified in terms of predictive factors for non-sentinel lymph node metastasis and patient prognosis by large-scale retrospective studies and prospective randomized clinical trials. In the present review, clinical implications of micrometastases and isolated tumor cells in sentinel lymph nodes and the methods for pathological examination of SLN metastases employed in these studies were overviewed.

Macrometastasis, micrometastasis, and isolated tumor cells in sentinel lymph nodes of early breast cancers: a 10-year histopathological and survival analysis of 537 Asian patients.

In patients with negative sentinel lymph node biopsy (SLNB), axillary dissection (AD) can be avoided to reduce morbidities. However, there is only limited data on the rate of positive non-SLN (NSLN) in those who have micrometastasis and isolated tumor cells (ITC) in the literature. We did a retrospective review of all clinically node-negative breast cancer patients with SLNB done at our unit from January 2001 to June 2011. Multivariate analysis was adopted to evaluate the risk factors for NSLN metastasis. Difference in 5-year disease-free survival (DFS) was evaluated with log-rank test. Five-hundred and thirty-seven patients underwent SLNB; 161 (30%) had positive SLN on frozen section (FS), 50 of these patients (31%) had NSLN metastasis, 25 patients had negative SLN on FS but were found to have micrometastasis on histopathology, and only 1 (4%) of them had NSLN metastasis, while 14 patients were found to have ITC in SLN; none of them had NSLN metastasis. Multivariate analysis found that the number of SLN harboring micrometastasis is the only independent risk factor for NSLN metastasis in patients with micrometastasis (p value = 0.008). On the contrary; tumor size, grade, and biology were not associated with NSLN metastasis. 5-year DFS in patients with macrometastasis in SLN was 94.2%, while that in patients with micrometastasis and ITC was 100% (p value <0.001). NSLN metastasis in those who only have micrometastasis and ITC is rare, and 5-year DFS is significantly better in this group of patients as well. It is therefore a routine practice in our unit to omit AD in patients with micrometastasis and ITC on SLN.