Sentinel lymph node: What it is, how it is examined, and how the results change treatment

A sentinel lymph node is the first lymph node to which tumor cells are most likely to reach from the primary tumor via the lymphatic system. Sometimes there is not just one such node, but several. This is why modern oncology seeks not just any nearby node, but the one that is truly the first in the lymphatic drainage pathway from the tumor. [1]

A sentinel lymph node biopsy is a procedure in which the node is first located, then removed, and examined under a microscope. A negative result usually indicates that the tumor has likely not yet spread to nearby lymph nodes. A positive result means that tumor cells have already been detected in the primary drainage node, meaning the risk of further regional spread is higher. [2] [3]

The main value of this method is that it allows for tumor staging without the automatic removal of a large number of lymph nodes. The US National Cancer Institute emphasizes that if the sentinel node is free of tumor cells, the patient can often avoid more extensive lymph node dissection, along with some of the associated complications. This idea has made this method one of the most prominent tools for surgical de-escalation in oncology. [4] [5]

However, this method is not universal for all tumors and all clinical situations. At a general level, the US National Cancer Institute still considers it to be most widely used, primarily for breast cancer and melanoma, but current European guidelines for 2023-2025 have already established its use for a number of gynecological tumors in carefully selected patients. This is a good example of how surgical oncology is moving away from a one-size-fits-all approach and is increasingly basing its tactics on tumor biology and the specific disease scenario. [6] [7] [8] [9]

It's important to understand another principle: a sentinel lymph node is not a treatment in itself, but a diagnostic and staging tool that influences the extent of surgery, the need for additional lymph node dissection, radiation therapy, systemic treatment, and follow-up. Therefore, it's not just the fact of node removal that matters, but also how it was found, how it was examined, and how the results were interpreted in the context of a specific tumor. [10] [11] [12]

The key question	Short answer
What is a sentinel lymph node?	The first node in the lymphatic drainage pathway from the tumor
Could he be more than one?	Yes, sometimes there are several guard nodes
Why is it being removed?	To understand whether there is early lymphatic spread
What gives a negative result?	Often avoids more extensive lymph node dissection
What gives a positive result?	Changes staging and may affect further treatment

Sources for the table: [13] [14]

How is a biopsy performed and what happens to the node after removal?

The procedure begins with identifying the lymphatic drainage pathway from the tumor. To do this, a tracer—a radioactive drug, a blue dye, or both—is injected near the tumor or in an anatomically related area. The surgeon then uses imaging, a radioactive signal detector, or direct staining to locate the node that first accumulated the tracer and remove it through a small incision. [15]

In modern practice, the choice of mapping tools depends on the tumor and current guidelines. For the cervix and endometrium, European guidelines prefer indocyanine green, while for vulvar cancer, they emphasize the necessity of a radioactive tracer and recommend combined detection methods. While the sentinel node concept is uniform, the technical implementation has long ceased to be uniform across all anatomical zones and tumors. [16] [17] [18]

A biopsy is most often performed simultaneously with the removal of the primary tumor. The US National Cancer Institute notes that in some cases, the procedure can be performed before or after tumor removal if the lymphatic vessels have not yet been significantly disrupted. However, in most classic scenarios, the surgeon attempts to combine mapping and the main operation to obtain the most accurate information about the actual lymphatic drainage pathway. [19]

After removal, the node is sent to a pathologist. Standard histological examination is typically performed, but in some tumors, so-called ultrastaging—a more intensive pathological evaluation of the sentinel node—is becoming increasingly important. The 2025 guidelines for endometrial cancer explicitly state that all sentinel nodes should undergo ultrastaging, as this approach improves the accuracy of detecting small tumor deposits. [20]

In the cervix and some other gynecological tumors, not only postoperative examination but also intraoperative assessment is important. The 2023 cervical cancer guidelines state that if lymph node involvement is detected intraoperatively, further pelvic lymph node dissection and radical hysterectomy should be avoided, and the patient should be referred for definitive chemoradiation. This demonstrates how sentinel node findings can change the course of surgery on the very same day. [21]

Stage	What are they doing?
Mapping	A marker is inserted near the tumor
Node search	Find the first node that accepts the label
Removal	A minor surgical removal of the node is performed
Pathomorphology	The node is examined for the presence of tumor cells.
Ultrastaging	Small tumor deposits in individual tumors are being looked for more thoroughly
Changing the treatment plan	Based on the results, a decision is made on additional surgery and other therapy.

Sources for the table: [22] [23] [24]

Where the method is especially important today

In breast cancer, sentinel lymph node biopsy has long been the standard approach to minimizing axillary surgery. The US National Cancer Institute notes that clinical trials have shown the sufficiency of sentinel node biopsy without the need for complete axillary lymph node dissection in women without clinical evidence of axillary node involvement if they are receiving modern surgical and systemic treatment. This has become one of the strongest arguments for de-escalating axillary surgery. [25]

Moreover, by 2025, de-escalation has gone even further. Updated guidelines from the American Society of Clinical Oncology indicate that routine sentinel node biopsy may be waived in some postmenopausal patients aged 50 years and older with a negative preoperative axillary ultrasound, a small tumor up to 2 centimeters in size, grades 1-2 malignancy, the presence of hormone receptors, and the absence of human epidermal growth factor receptor 2 overexpression, if breast-conserving treatment is planned. This is no longer simply a reduction in the extent of surgery, but rather a waiver for some low-risk patients. [26] [27]

In melanoma, this method retains a very important role as a tool for staging occult regional nodal involvement. In a 2025 professional review, the US National Cancer Institute recommends considering sentinel node biopsy for clinically negative nodes in patients with primary melanoma at least 0.8 millimeters thick, as well as for certain thin but unfavorable variants. It also emphasizes that, when micrometastases are detected, active ultrasound surveillance of the regional lymph node basin has already widely replaced mandatory complete lymph node dissection. [28]

The situation has changed particularly significantly in endometrial cancer. The 2025 guidelines from the European Society of Gynecologic Oncology, the European Society of Radiotherapy, and the European Society of Pathologists recommend that sentinel lymph node biopsy be performed for staging in all patients with suspected uterine-limited disease, with indocyanine green injection into the cervix being the preferred mapping method. If no nodes are detected on one side of the pelvis, the need for additional lymph node dissection is determined based on the risk group. [29]

In cervical and vulvar cancer, the method has also gained a firm foothold, but only under strictly defined conditions. For early cervical cancer, the 2023 guidelines recommend performing sentinel node biopsy before pelvic lymph node dissection, with indocyanine green being the preferred technique. For vulvar cancer, sentinel node biopsy is recommended for unifocal tumors less than 4 centimeters in size without suspicious inguinofemoral nodes, and if mapping is unsuccessful, inguinofemoral lymph node dissection should be performed. In other words, the method works well where the selection criteria and center experience are met. [30] [31] [32]

Tumor	The modern role of the method
Breast cancer	Standard staging of the axillary region, and in some low-risk patients, routine biopsy may be avoided
Melanoma	A key method for identifying hidden lesions of regional nodes
Endometrial cancer	Recommended for staging in suspected uterine-limited disease
Cervical cancer	It is applied at early stages according to clear algorithms
Vulvar cancer	Suitable for unifocal tumors less than 4 cm in size without suspicious inguinal nodes

Sources for the table: [33] [34] [35] [36] [37] [38]

How the results are read and why a small lesion in a node does not always equal a major operation

The simplest interpretation is that if the sentinel node is free of tumor cells, this supports the absence of clinically significant regional lymph node spread at the time of surgery. This finding often allows for the omission of a more extensive lymph node dissection and the transition to observation or treatment based on the properties of the primary tumor itself. However, this conclusion always applies within the boundaries of a specific cancer type and a specific treatment algorithm, and is not a universal rule for all cases. [39] [40]

If the node is positive, this is no longer a one-size-fits-all scenario. Modern pathology distinguishes between isolated tumor cells, micrometastases, and macrometastases. The American Cancer Society defines isolated tumor cells as a lesion smaller than 0.2 millimeters and containing fewer than 200 cells, a micrometastasis as a lesion between 0.2 and 2 millimeters, and anything larger than 2 millimeters is considered a larger metastatic deposit. This distinction is important because the scope of treatment after such a result varies. [41] [42]

In breast cancer, biopsy results are increasingly being interpreted in terms of de-escalation. The US National Cancer Institute notes that in some patients with 1-2 positive sentinel nodes, automatic complete axillary lymph node dissection has not been shown to have any benefit in terms of long-term survival or regional recurrence rates. Therefore, a positive sentinel node today does not always mean that the next mandatory step is removal of all remaining nodes. [43]

In melanoma, a positive sentinel node no longer automatically means immediate complete lymph node dissection for everyone. According to the US National Cancer Institute, the MSLT-II trial showed no benefit from immediate complete lymph node dissection in terms of specific survival when compared with active ultrasound surveillance after a positive sentinel node. Therefore, biopsy results in melanoma today primarily clarify the stage and help determine the need for adjuvant therapy and the frequency of surveillance. [44] [45]

In gynecologic oncology, the interpretation is even more nuanced. Cervical cancer guidelines state that macrometastases and micrometastases in the pelvic nodes require adjuvant chemoradiation, and that adjuvant treatment may be considered for isolated tumor cells, but their prognostic value remains uncertain. For endometrial cancer, the 2025 guidelines specifically emphasize the need for ultrastaging, precisely because the search for small tumor deposits changes the accuracy of staging, although the clinical interpretation of very small findings remains more complex than a simple yes or no answer. [46] [47]

Research result	What does this usually mean?
Negative sentinel node	The likelihood of significant regional lymphatic spread is lower
Isolated tumor cells	Very small lesion, clinical significance depends on tumor type
Micrometastasis	A small but already proven metastatic focus
Macrometastasis	A larger lesion of the node often has a greater impact on the stage and tactics
Positive node	It does not always mean mandatory complete lymph node dissection, the decision depends on the tumor and recommendations

Sources for the table: [48] [49] [50] [51] [52] [53]

Limitations, risks and what has changed in recent years

Although sentinel lymph node biopsy is much less invasive than wide lymph node dissection, it is still a surgical procedure with its own risks. The National Cancer Institute lists lymphedema, seroma, pain, numbness, tingling, bruising, limited motion, and allergic reactions to blue dye as potential complications. The American Cancer Society specifically emphasizes that the risk of lymphedema increases with the number of nodes removed, so sentinel node biopsy is generally safer than wide lymph node dissection precisely because of its smaller invasive nature. [54] [55]

The method also has diagnostic limitations. The US National Cancer Institute warns of the possibility of a false-negative result, when a tumor is not found in the sentinel node, even though it is present in other regional nodes. Therefore, the value of the procedure depends on the quality of mapping, the surgeon's experience, the accuracy of the pathological examination, and proper patient selection. Sentinel node biopsy is not a magic test without errors, but a very useful, but not infallible, tool. [56]

On the other hand, modern data show that in a number of tumors, this method has helped to significantly reduce the extent of surgery without compromising oncological safety. In breast cancer and melanoma, large studies have changed practice so that many patients with a negative sentinel node, and some with a limited positive result, no longer require automatic complete removal of regional nodes. This, in essence, is the main trend of recent years: less unnecessary surgery while maintaining the quality of staging and disease control. [57] [58] [59]

At the same time, the technical role of fluorescence mapping and pathological ultrastaging has grown. Indocyanine green has already become the preferred detection method for endometrial and cervical cancer, and more intensive node examination increases the likelihood of detecting small tumor deposits. This is not just a technological detail: the more accurately a sentinel node is identified and analyzed, the more confidently more invasive interventions can be avoided where they are unnecessary. [60] [61] [62]

But there is a downside to this progress: the more surgery is de-escalated, the higher the demands on the quality of selection and interdisciplinary discussion. The decision to forego a biopsy, limit the extent of surgery after a positive result, or switch to ultrasound monitoring alone is permissible only where supported by data for a specific tumor and a specific risk group. Therefore, the sentinel lymph node is not just a technique today, but part of a broader movement toward personalized oncosurgery. [63] [64] [65]

Advantages of the method	Limitations and risks
Less volume of surgery	A false negative result is possible
Lower risk of lymphedema compared with wide lymph node dissection	There remains a risk of pain, seroma, numbness and infection.
More accurate staging than clinical examination	Not suitable for all tumors and all patients
Possibility of de-escalation of treatment	It strongly depends on the experience of the center and the quality of pathomorphology
Helps make decisions about adjuvant therapy	A positive result is not always interpreted the same way in different tumors.

Sources for the table: [66] [67] [68] [69] [70]

FAQ

Are sentinel lymph nodes and sentinel lymph node biopsy the same thing?
No. A sentinel lymph node is the first node in the lymphatic drainage pathway away from a tumor. A sentinel lymph node biopsy is a procedure to locate, remove, and examine the sentinel lymph node. [71]

If the sentinel node is negative, does that mean the tumor has definitely not spread?
Not quite. A negative result greatly reduces the likelihood of regional lymph node spread, but it doesn't eliminate it. The National Cancer Institute specifically notes the possibility of false-negative results, so clinical presentation and other data still play a role. [72]

Does a positive sentinel node always mean complete lymph node dissection?
No. In breast cancer and melanoma, modern practice has largely abandoned automatic complete lymph node dissection after limited sentinel node involvement. The decision depends on the tumor type, lesion size, additional risk factors, and current guidelines. [73] [74] [75]

Where is this method used most often?
At a general level, it is still most widely used for breast cancer and melanoma. However, current European guidelines have now firmly included it in the treatment of certain forms of endometrial cancer, cervical cancer, and vulvar cancer in properly selected patients. [76] [77] [78] [79]

Why has this method been so controversial in recent years?
Because the discussion is now not only about the benefits of the biopsy itself, but also about the possibility of safely forgoing it in some patients or foregoing subsequent wide lymph node dissection after a limited positive result. This is one of the central examples of the de-escalation of oncologic surgery in recent years. [80] [81]

What most often frightens patients about this procedure?
They are usually afraid of lymphedema, complications, and the very fact of lymph node removal. However, the risk of lymphedema is directly related to the extent of removal, which is why sentinel node biopsy is considered a more gentle option compared to wide lymph node dissection. [82] [83]

Key points from experts

Armando E. Giuliano, MD, Chief of Surgical Breast Oncology at Cedars-Sinai, is recognized for his development of the sentinel lymph node technique in breast cancer surgery. The major practical impact of his school is that the sentinel node technique has enabled surgical staging to be transformed from the traumatic routine lymph node dissection to a more precise and gentle procedure, and has subsequently paved the way for further de-escalation in some patients. [84] [85] [86]

Mark B. Faris, MD, is a surgical oncologist at Cedars-Sinai, specializing in cutaneous oncology, melanoma surgery, lymphatic biology, and tumor biology. His focus is particularly important for understanding modern melanoma: sentinel node biopsy is needed primarily as an accurate staging method and to guide further therapy, rather than as a mandatory step toward automatic complete lymph node dissection. [87] [88] [89]

David Cibula, MD, PhD, is the head of the Gynecologic Oncology Center at the General University Hospital in Prague, a professor at the First Faculty of Medicine, Charles University, and a former president of the European Society of Gynecologic Oncology. His clinical school emphasizes that sentinel lymph node profiling in gynecologic oncology is only meaningful with strict adherence to the algorithm, high-quality mapping, and thorough pathological analysis, especially in early cervical and endometrial cancer. [90] [91] [92] [93]

Ko Un Park, MD, associate professor of surgery at Harvard Medical School, a breast surgeon at Brigham and Women's Hospital, and a researcher on the implementation of modern surgical approaches in breast oncology. The practical thesis here is this: the future of the method lies not only in high-quality biopsy performance but also in accurately determining who no longer needs it, without compromising tumor control or depriving the patient of important treatment data. [94] [95]