Wide Local Excision of an Intermediate-Thickness Back Melanoma with a Sentinel Lymph Node Biopsy of Left Axillary Lymph Nodes

Wide local excision (WLE) with sentinel lymph node biopsy (SLNB) remains the cornerstone for treatment of patients with intermediate-thickness and thick melanoma lesions with clinically negative nodes. This procedure involves resection of the melanoma with circumferential margins including all the subcutaneous tissue to the level of the deep fascia. WLE is accompanied by lymphatic mapping in order to localize, resect, and analyze the sentinel node(s) for the presence of lymph node metastases. In this paper with accompanying animation and video, a 40-year-old otherwise healthy patient presents with a new melanoma on his back diagnosed via biopsy. The surgical management of intermediate-thickness melanoma and rationale for treatment are reviewed. We also highlight recent advances in postoperative treatment of those with clinically occult regional disease.

Melanoma; sentinel lymph node biopsy; lymphangiography; surgical oncology.

Invasive cutaneous melanoma is estimated to be the sixth most common cancer in the United States, accounting for approximately 84,000 new cases and 8,200 deaths in 2018.¹ Early identification of suspicious skin lesions is critical. For patients with lesions less than 1 mm in thickness and no nodal involvement, 5-year survival is excellent. In the setting of localized disease with a primary greater than 1 mm in thickness, 5-year survival depends on Breslow depth, ulceration, and mitotic rate but can approach 90%. Prognosis varies widely among patients with locoregional disease (stage III) and primarily depends on tumor burden in draining lymph nodes and resectability of the primary lesion.² Finally, survival was historically poor in patients with distant metastatic sites such as the lung, brain, or bone (stage IV), but recent advances in targeted therapy and immune checkpoint blockade have reshaped the treatment landscape.^3–5 

Wide local excision (WLE) with sentinel lymph node biopsy (SLNB) remains the cornerstone for treatment of melanoma lesions with Breslow thickness greater than 0.8 mm and clinically negative nodes (stage I/II disease). The WLE procedure involves excision of the lesion with 1–2-cm margins and resection of the subcutaneous tissues to the level of the deep fascia. The goal of the SLNB is to accurately stage and assess the draining nodal basin in patients with no clinical evidence of regional disease. This procedure involves intradermal injection of blue dye or radioisotope in the skin surrounding the primary lesion in order to localize, resect, and analyze the draining node(s) for the presence of subclinical metastases. 

The probability of a positive SLN is related to the tumor (T) stage of the primary lesion and associated adverse factors.⁶ The 8th edition of the American Joint Committee on Cancer (AJCC) T staging classification is predominantly based on Breslow thickness and the presence or absence of ulceration. However, a number of additional prognostic factors have been identified and are commonly reported in pathology reports such as tumor cell mitotic rate.^7–10 For lesions with a Breslow depth less than 0.8 mm without adverse features (T1a), the probability of positive SLNB is less than 5%. For lesions with a Breslow thickness less than 0.8 mm with ulceration or 0.8–1 mm with or without ulceration (T1b), the probability is 5–10%. Finally, for lesions with a Breslow depth greater than 1 mm (T2a or greater), the probability is greater 10% and will vary based on additional adverse features. These probabilities can be used to determine the risks and benefits of the SLNB when assessing the utility of this prognostic procedure for an individual patient. The rationale for this practice is based on important data from the Multicenter Selective Lymphadenectomy Trials (MSLT)-I and II.^13-15, 24

Earlier data from the MSLT-I trial demonstrated the prognostic significance of the sentinel node.^13, 141717 For patients with intermediate-thickness or thick melanoma lesions (> 1.2 mm), the disease-specific survival rate at 10 years was significantly worse in patients with lymph node disease compared with those who had a negative SLNB (62 versus 85%, hazard ratio [HR] 3.09, 95% CI 2.12-4.49). At that time, if a positive SLN was identified, completion lymph node dissection (CLND) was then performed. The MSLT-II trial was then designed to assess the disease-specific survival benefit of CLND procedure in patients with a positive SLN.²⁴ Approximately 2000 patients who had a WLE of intermediate-thickness or thick melanoma lesions with a positive SLNB were randomized to CLND or close observation with nodal basin ultrasounds. While there was improvement in regional control in patients undergoing CLND, there was no improvement in melanoma-specific survival between the two groups at three years (86 vs 86%, adjusted HR 1.08, 95% CI 0.88-1.34). The DeCOG-SLT trial demonstrated similar findings with no difference in distant metastasis-free survival or overall survival at five years.^25, 263030 As a result, patients without clinically evidence locoregional disease now rarely undergo CLND. The SLNB is instead used as a staging procedure, which helps to determine the adjuvant surveillance and treatment plans for patients with melanomas of Breslow depth 0.8 mm or greater. Importantly, MSLT-I and -II largely reflect an era in melanoma surgery prior to the discovery of effective systemic therapies for metastatic melanoma, providing even further rationale to (1) limit morbid surgeries such as the CLND, which has no proven impact on melanoma-specific survival, and (2) encourage the use of the SLNB, which can best stratify a patient's stage and the predicted benefit of adjuvant systemic therapies.

This a 40-year-old, otherwise healthy individual who presented with a changing pigmented lesion on his left upper back. This was biopsied by his dermatologist and demonstrated melanoma with 1.4-mm Breslow depth. He was referred to a surgical oncologist for further management. Review of pathology report showed no ulceration and 2 mitoses. No other worrisome features.

Examination of the patient demonstrates a well-healing biopsy site with no evidence of gross residual melanoma. There is no evidence of either satellite lesions (cutaneous nodules that are < 2 cm in distance from primary tumor and draining lymph node basin) or in-transit metastases (cutaneous nodules > 2 cm between primary tumor and draining lymph node basin). These physical findings would reflect disease in the draining lymphatic channels and are considered locoregional disease. 

A thorough lymph node examination, including palpation of cervical, supraclavicular, axillary, and inguinal nodes, reveals no palpable lymphadenopathy. Approximately 10% of melanoma patients will present with regional disease (lymphatic spread of tumor to nearest nodal basin), and 5% can present with distant metastases (hematogenous spread to distant organs).¹¹ Any clinically suspicious nodes should be biopsied prior to surgical resection. The presence of clinically-evident, biopsy-proven lymph node spread of melanoma signifies clinical stage III disease. In these cases SLNB is unnecessary as the utility of SLNB is in identifying clinically-occult lymph node metastases. 

For this patient, no additional work up or preoperative treatment is necessary. In the absence of physical exam findings suggestive of locoregional disease or neurological symptoms that may reflect distant metastases, routine labs or cross sectional imaging are not recommended by the National Comprehensive Cancer Network (NCCN).¹²

Based on the T stage, the probability of a positive lymph node biopsy is greater than 10% for this patient. The therapeutic value of the SLNB remains controversial. However, SLNB certainly provides prognostic information that guides adjuvant treatment options and surveillance. If the sentinel node is negative, patients are typically followed with physical examination including total body skin exam and nodal basin evaluation. No additional labs or imaging are necessary to screen for asymptomatic reoccurrence. If the sentinel node is positive, treatment varies based on individual patient risk factors and the underlying tumor biology.

Localization of sentinel nodes can be performed with intraoperative dermal injection of a vital blue dye (isosulfan blue (up to 1 ml) or methylene blue (up to 1 ml of 1% solution)) and/or preoperative lymphangiography with a radiotracer. In the latter procedure, a technetium-99m sulfur radiocolloid (0.25 mCi–0.5 mCi) is injected intradermally into the primary lesion, typically on the day of surgery. Static and dynamic images are obtained that highlight the draining lymph node basin. When both blue dye and radiotracer are used for localization, the success rate of identifying the SLN is greater than 95%.^13, 16 When the sentinel node is not identified, it can be secondary to poor technique (i.e. inadequate injection of tracer), prior surgery that disrupted the lymphatic drainage channels, or complete infiltration of the draining lymphatic vessels with metastatic disease.¹⁷ In this procedure, the combination of techniques will be described. 

There are limited alternative options for excision of the primary lesion for this patient that would have similar oncologic outcomes. Standard Mohs micrographic surgery is not recommended for invasive melanomas and remains controversial even for in situ disease or in cosmetically sensitive areas.¹⁸ The definitive diagnosis of melanoma depends on the use of immunohistochemistry so surgical procedures that rely on the use of frozen section evaluation may not be sufficient. In cosmetically sensitive cases staged procedures, sometimes referred to as “slow Mohs”, may be considered as these allow tissue fixation and IHC evaluation. With regards to standard surgical resection, several large randomized studies have assessed the margins required for local control.^19-22 Current recommendations are for 1-cm margins for lesions < 1 mm in Breslow depth, 1–2-cm margins for those 1–2 mm in depth, and 2 cm for those > 2 mm.¹² 

There are certain populations that may not benefit from SLNB. For patients with T1a disease and less than 5% chance of positive sentinel node, SLNB is typically deferred. Furthermore, for patients with T1b disease and a 5–10% chance of a positive sentinel node with additional low risk factors such as older age or low mitotic rate,^7, 23 the decision regarding whether to perform SLNB requires an individualized discussion with the patient. A personalized risk and benefits discussion is also appropriate for patients with decreased 10-year survival due other medical conditions, as well as those unable to or unwilling to undergo adjuvant therapy and surveillance.

This case outlines the surgical management of a patient with intermediate-thickness melanoma. 

Preoperatively, same-day dynamic lymphoscintigraphy is obtained which demonstrates mapping of the draining nodal basin to the left axilla. Formal lymphoscintigraphy is most useful in the case of a truncal injection as the lymphatic drainage pattern can be less stereotyped than for the extremities. For example the skin of the mid back could drain to a single or multiple nodal basins in the bilateral axillae or groins. The skin of the upper back could drain to the neck or the axillae. 

Following induction of general anesthesia, the patient is positioned for optimal resection of the primary lesion and the SLNB. It is important to discuss these plans with the anesthesiologist, as it may affect the airway management. Here, the patient is initially positioned in the right lateral decubitus position. The patient is prepped and draped in the normal sterile fashion. 

Vital blue dye (isofulfan blue) is injected intradermally around the primary lesion, creating a wheal. It is important that the dye is injected intradermally, and not subcutaneously, in order to be taken up by the lymphatic vessels. 

The site of the primary melanoma is outlined with a skin marker. It is important to include all areas of color irregularity and any possible satellite lesions. Then, 1–2 cm margins are outlined around the border of the lesion. These margins are sufficient for oncologic resection as discussed in the earlier section. In order to facilitate closure of the resection in a tension-free, linear fashion, an elliptical shape can be used. Skin flaps may also be used. If it appears that the final tissue defect cannot be closed primarily due to tumor size or anatomic constraints, then a rotational flap or skin graft is considered.²⁸

Local anesthetic, typically lidocaine with 1% epinephrine, is injected along the elliptical outline. Using a combination of sharp dissection and electrocautery, the skin and subcutaneous tissues are divided down the deep fascia. For appropriate oncologic resection, it is critical to divide the tissue at a 90-degree angle to avoid skiving toward the tumor and to remove all tissue above the fascia. 

The specimen is removed and oriented appropriately for pathologic analysis. Any method of marking can be appropriate as long as it allows orientation of the specimen in the event that a positive margin would need further surgical treatment.

Hemostasis is achieved and the space is closed in multiple layers. The specific method can vary per surgeon preference. Here, the deep space is closed with a series of interrupted deep dermal sutures using Vicryl to release the tension at the fascial layer. The skin is closed with a running subcuticular stich using Monocryl. The closed wound is then covered with skin glue or Steri-Strips per surgeon preference, followed by a sterile dressing with Tegaderm. 

The drapes are removed, and the patient is repositioned supine with the left arm out at a 90-degree angle. Using the gamma probe, mapping of the draining lymph node basin is confirmed to track to the left axilla. While this technique has a high success rate, the false negative rate (or inability to identify the sentinel node) historically has been noted at approximately 5%.^16, 19 In the modern era of radiographic surveillance and effective salvage systemic therapies a CLND is not indicated in the case of a lymphatic mapping failure. Surveillance nodal ultrasound and physical exam would be a more appropriate alternative, with further treatment as indicated if a recurrence were to occur.

The left axilla is prepped and draped in a sterile fashion. The incision is marked along the inferior aspect of the hairline for cosmetic purposes, and local anesthetic is injected. Using a combination of sharp dissection and electrocautery, the skin and subcutaneous tissues are incised down to the axillary fascia. The gamma probe is then used to aid further dissection and identify the sentinel nodes. Once a node is identified, it can be removed by placing a silk stitch through the node to serve as an anchor and then using electrocautery to perform a circumferential dissection. Care must be taken during dissection near the lymphovascular pedicle in order to maintain hemostasis. 

Once the node is removed, the gamma probe is used to quantify the final count ex vivo. The procedure continues until all the sentinel nodes with gamma counts greater than 10% of highest nodal count are removed. It is also important to remove nodes that otherwise appear suspicious based on the presence of blue dye, abnormal size, or obvious nodal metastases. 

Once the sentinel nodes have been identified and removed, the axillary incision is closed in multiple layers. This can be dictated by surgeon preference. It is typical to close the axillary fascia with interrupted Vicryl stiches, followed by the subcutaneous space and skin as described above. The wound is closed with skin glue or Steri-Strips, and then with a dry sterile dressing and Tegaderm. The patient is extubated and taken to the postoperative recovery area. 

Operating time can vary widely, but can often be 1–3 hours from incision to closure depending on the location of the primary lesion, need for repositioning, and the number of nodal basins that must be explored. Blood loss is typically minimal. Cosmesis can be excellent. Typically, patients are discharged that same day with minimal range of motion restrictions.³⁰ Pain is usually managed without opioids although axillary surgery may require some additional pain control in the first few postoperative days. 

The morbidity of sentinel node dissection is significantly lower compared to CLND.^24, 31, 34 Complications are mostly limited to infection, seromas/hematomas, wound dehiscence, and sensory nerve injuries. The rate of lymphedema depends on the extent of the dissection and the number of nodes that must be removed, in addition to patient factors. Rates of lymphedema after SLNB can vary between 0.5–5%, compared to up to 30% for CLND.^{24, 33, 35}

This patient underwent complete resection of his 1.4-mm melanoma with no evidence of residual melanoma at the primary site and no evidence of lymph node metastases in any of the lymph nodes sampled on final pathologic evaluation. His wounds healed well without complication and he returned to work. Final AJCC 8th edition melanoma stage is determined to be Stage IB. Routine dermatologic follow-up is recommended every 3–6 months for 5 years, and the signs/symptoms of melanoma recurrence that should prompt urgent evaluation were reviewed.

Current guidelines support the use of adjuvant therapy in stage IIB or greater melanoma. Thus patients with melanoma metastases identified in the SLN specimens or with high risk primary features (T3b or greater) are usually completely staged with cross-sectional imaging and brain MRI. A medical oncologist with expertise in melanoma will then discuss adjuvant treatment and surveillance options with the patient, and a multidisciplinary treatment team including a dermatologist, surgical oncologist, and medical oncologist will be established.^36-41

• Vital blue dye (isosulfan blue or methylene blue)
• Nuclear medicine facilities for lymphoscintigraphy
• Intraoperative gamma probe

Nothing to disclose.

The patient referred to in this video article has given their informed consent to be filmed and is aware that information and images will be published online.