In-transit lymph node metastases in breast cancer: a possible source of local recurrence after Sentinel Node procedure
ABSTRACT In-transit lymph node metastases are a common phenomenon in melanoma patients and have been increasingly recognised since the introduction of the Sentinel Node (SN) procedure. To which extent this also occurs in patients with breast cancer has not been studied yet. The aim of this study was therefore to explore the occurrence of in-transit lymph node metastases in patients with breast cancer.
Afferent lymph vessels to the SN identified by blue dye were removed from 17 patients with breast cancer during a regular SN procedure.
Three out of 17 patients showed a lymph node associated with the afferent lymph vessel. One of these lymph nodes showed a breast cancer macrometastasis, to be regarded as an in-transit metastasis. This metastasis would normally have been left in situ.
In-transit lymph nodes associated with the afferent SN lymph vessels seem to occur in a significant proportion of patients with breast cancer. These lymph nodes may contain metastases, which are a potential source of local recurrence when left in situ. This finding generates the hypothesis that there may be an indication to remove these lymph vessels during the SN procedure.
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ABSTRACT: Lymphatic vessels are thought to contribute to metastasis primarily by serving as a transportation system. It is widely believed that tumor cells enter lymph nodes passively by the flow of lymph. We demonstrate that lymph node lymphatic sinuses control tumor cell entry into the lymph node, which requires active tumor cell migration. In human and mouse tissues, CCL1 protein is detected in lymph node lymphatic sinuses but not in the peripheral lymphatics. CCR8, the receptor for CCL1, is strongly expressed by human malignant melanoma. Tumor cell migration to lymphatic endothelial cells (LECs) in vitro is inhibited by blocking CCR8 or CCL1, and recombinant CCL1 promotes migration of CCR8(+) tumor cells. The proinflammatory mediators TNF, IL-1β, and LPS increase CCL1 production by LECs and tumor cell migration to LECs. In a mouse model, blocking CCR8 with the soluble antagonist or knockdown with shRNA significantly decreased lymph node metastasis. Notably, inhibition of CCR8 led to the arrest of tumor cells in the collecting lymphatic vessels at the junction with the lymph node subcapsular sinus. These data identify a novel function for CCL1-CCR8 in metastasis and lymph node LECs as a critical checkpoint for the entry of metastases into the lymph nodes.Journal of Experimental Medicine 07/2013; 210(8). DOI:10.1084/jem.20111627 · 13.91 Impact Factor
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ABSTRACT: Sentinel node mapping is widely applied in patients with melanoma. Although this type of skin cancer usually drains to the standard regional nodal basins, some patients have drainage to an unpredicted site. Nodes lying along a lymphatic channel, between the primary melanoma site and a common basin, are often called interval, in-transit, ectopic, intercalated, or aberrant nodes. They must be considered sentinel lymph nodes because they receive direct lymphatic drainage from a primary tumor site. Most investigators agree that interval sentinel nodes should be harvested; however, the management of melanoma patients with an involved interval sentinel node without established metastasis in the regional basin downstream is controversial. New and innovating technologies have improved nuclear medicine images, including single-photon emission computed tomography/computed tomography (SPECT/CT), a multimodal technique that fuses the radioactivity distribution detected by SPECT with the anatomic information harvested by CT. SPECT/CT does not replace the conventional planar images; it should be considered as a complementary modality for the search of sentinel lymph nodes. We report three illustrative cases that underline the decisive role of SPECT/CT with two-dimensional and three-dimensional reconstruction images to localize the uncommon periscapular sentinel nodes in patients with melanoma of the posterior trunk. The use of this image fusion technique on these patients leads to improved preoperative visualization of the sentinel nodes, may help identify additional periscapular interval sentinel nodes, and enables precise localization of the nodes with their surrounding anatomic structures. The cases are discussed together with a review of the literature.Melanoma research 03/2012; 22(3):278-83. DOI:10.1097/CMR.0b013e32835312b1 · 2.10 Impact Factor
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ABSTRACT: In transit metastases in melanoma are intralymphatic metastases located between primary tumour site and the regional lymph nodes. Such metastases have not been recognised in breast cancer, although intralymphatic metastases do exist in this organ too. Recently, "in transit lymph nodes" have also been reported as lymph nodes associated with the afferent lymphatic vessel of lymph nodes identified as sentinel lymph nodes during dye guided lymphatic mapping. It has been suggested that such in transit lymph nodes are not rare, and may be the source of locoregional recurrence of breast cancer. Although this is an attractive hypothesis and a previously unrecognized phenomenon, it is related to false-negative sentinel node biopsies, and its frequency and contribution to recurrent breast cancer will require prospective investigation.Journal of clinical pathology 11/2008; 61(12):1233-5. DOI:10.1136/jcp.2008.060848 · 2.55 Impact Factor