Encyclopedia of Cancer, 2015
First-echelon node; First-tier node
A sentinel lymph node is a lymph node upon which the primary tumor drains directly.
General anatomy and physiology of the lymphatic system
Lymphatic capillaries are 10–50 mm in diameter, consist of a single endothelial layer with a discontinuous membrane, and are supported by collagen ﬁlaments. They are ﬁlled with lymph ﬂuid originating from the interstitial space due to an osmotic pressure gradient and ﬂuctuating intraluminal pressures. These intraluminal pressures are caused by lymphatic ﬂow that is generated by lymph formation, contractions of the vessel wall, and external pressure. Lymph ﬂuid absorbed by lymphatic capillaries drains into larger collecting lymphatic vessels. Such lymphatic vessels drain into marginal and medullar sinuses located between germinal centers within a lymph node. These centers contain large numbers of phagocytic cells.
A plexus within the lymph node drains to the efferent lymphatic vessel adjacent to the artery and vein in the hilum. Direct drainage of the marginal sinus into the efferent vessel also exists (Fig. 1).
The sentinel node
The sentinel node is the lymph node upon which the primary tumor drains directly. Lymph ﬂuid moves subsequently to second-tier and third-tier lymph nodes (Fig. 2).
The sentinel node concept implies orderly progression of metastases from a primary lesion through the lymphatic system. The concept is only relevant in cancers with predominant lymphatic dissemina- tion, such as melanoma and cancer of the breast, penis, or colon. If the ﬁrst node contains a metastasis, there is a chance of tumor spreading downstream. In case of a tumor-negative sentinel node, second-tier and third-tier nodes are generally without metastases.
The lymphatic drainage pattern can be visualized by lymphoscintigraphy after injection of a radio-labeled tracer in or near the site of the tumor. The radio-labeled tracer is cleared from the lymphatic channels and accumulated by the phagocytic cells in the lymph node. Lymphoscintigraphic images depict the lymph channels and the lymph node or nodes that contain the injected tracer. Dynamic scintigraphy demonstrates in the lymphatic drainage pattern, which enables identiﬁcation of the sentinel node(s). Single-photon emission computed tomography combined with radiographic computed tomography (SPECT/CT) improves the identiﬁcation of the correct number of sentinel nodes and visualizes the anatomy of their location.
Fig. 1. The different relations between lymphatic vessels and lymph nodes. Afferent lymphatic ducts on the left discharge their contents into the marginal sinus. One lymphatic duct runs through the node on the right and another over its surface, bypassing the germinal centers (Illustration made by Tanis PJ; Reprinted from Tanis et al. (2001), with permission from “The American College of Surgeons”)
Fig. 2. A sentinel node is node upon which lymph ﬂuid from the tumor drains directly
Sentinel node biopsy
A sentinel node biopsy is the minimally invasive technique to identify the sentinel lymph node. A vital blue dye is administered at the lesion site. An incision is made over the lymph node region and the blue lymphatic channel is identiﬁed. This channel is dissected and followed to the ﬁrst draining lymph node. Alternatively, a gamma ray detection probe can be used to track the radioactive sentinel node. Afferent and efferent lymph vessels and blood vessels are ligated and divided, and the node is submitted for pathology evaluation. The pathologist obtains multiple sections of the node and uses sensitive and speciﬁc staining techniques in his search for malignant cells.
Fig. 3. A tumor (black area) with lymphatic channels to nodes in the axilla (a) and to lymph nodes below (b) and above (c) the clavicula. A metastasis may be found along this lymphatic pathway
Fig. 4. Patient with a left breast cancer. The radiopharmaceutical was injected in the tumor, and the sentinel node in the left axilla is depicted
The sentinel node procedure provides staging and prognostic information. It identiﬁes patients who may beneﬁt from early regional therapy ( locoregional therapy) and/or adjuvant systemic treatment ( adjuvant therapy). In some cancers, this leads to an improved survival rate.
The predominant lymphatic drainage pathway from the breast is toward the axilla. Metastases are usually situated in the lower axilla ﬁrst and then may travel higher up the chain to the subclavicular and the supraclavicular basins. Occasionally, they travel directly to the more cranial glands (Figs. 3 and 4).
In the past, axillary lymph node dissection is used to be performed in almost every breast cancer patient. This operation has several potential side effects, such as lymph edema, pain, and decreased mobility of the arm, while often no metastases were found. With the introduction of sentinel node biopsy, axillary lymph node dissection is more selectively performed. As a result, many patients are spared an unnecessary operation.
Large observational studies revealed excellent results in patients who did not receive axillary node dissection because of a tumor-negative sentinel node. Recurrence rates vary between 0.12% and 0.6% in these patients.
The sentinel node can be identiﬁed in almost all patients. Unfortunately, the false-negative rates are often between 10% and 20%. False negative means that the sentinel node is disease-free, while there are metastases in the lymph node basin. A large randomized study showed that early regional node dissection based on a positive sentinel node improves survival in patients with an intermediate-thickness melanoma.
The development of the sentinel node concept is a milestone in the understanding of dissemination of solid malignancies. It is now well integrated in the clinical management of a variety of cancers. Many patients are now spared unnecessary surgery without compromising regional control and the accuracy of staging. Important prognostic information is obtained, and survival is improved in patients with mela- noma and penile cancer. The application in patients with other cancer types is being explored.
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