Michael S. Sabel
Presentation
A 45-year-old woman presented to her dermatologist after noticing a suspicious lesion on her left thigh. An excisional biopsy performed in the office demonstrated a 1.8-mm superficial spreading melanoma with ulceration. The patient now presents to your office for surgical management. On physical examination, there is a well-healed longitudinal scar on the left thigh and a palpable 1.5-cm, mobile, firm lymph node in the left groin.
Differential Diagnosis
All patients diagnosed with invasive melanoma should undergo a thorough physical examination, paying particular attention to the regional draining lymph node basins. Approximately 5% of patients will present with clinically apparent regional lymph node involvement at the time of diagnosis. Still others develop palpable lymphadenopathy months or years after excision of a primary melanoma, while occasional patients present with nodal metastasis in the absence of a detectable primary tumor. Regional lymph nodes may become enlarged due to infection, inflammation, or reactive hyperplasia, particularly after an excisional biopsy of the primary tumor has been performed. However, any palpable nodes that are larger than 1 to 1.5 cm in size, hard, or fixed to adjacent structures must be considered suspicious for metastatic involvement. Metastatic nodal involvement can be reliably verified in most cases with a fine needle aspiration (FNA) biopsy. Excisional biopsy should be reserved for situations in which the node is clinically suspicious, but the aspiration biopsy is negative or indeterminate because the complications of an open biopsy (including seroma, infection, and scarring) can interfere with the performance of a subsequent lymph node dissection. If an excisional biopsy is performed, it is important to orient the incision so that it can be readily re-excised during the complete node dissection if the node proves to be involved with tumor.
(FNA of the palpable node confirms the presence of metastatic melanoma)
Workup
Unfortunately, once melanoma has spread to the lymph nodes, there is a steep drop-off in survival. However, node-positive melanoma is a potentially curable disease, and an aggressive surgical approach is warranted. Patients, such as this one, with biopsy-proven palpable nodal involvement, should undergo wide local excision of the primary tumor and complete lymph node dissection if there is no radiologic evidence of distant metastases.
A metastatic workup should be performed to evaluate any patients presenting with clinical stage III disease. The most important part of this workup is a detailed history and physical examination. The history should include a thorough review of symptoms, focusing on symptoms consistent with metastatic disease, including any neurologic symptoms from possible brain metastases. In addition to the history and physical examination, all patients with clinically evident stage III disease should have a serum lactate dehydrogenase (LDH) level measurement and at minimum a chest x-ray. Many surgeons, however, would recommend staging of these patients with a CT scan of the chest/abdomen/pelvis, PET scan, or PET/CT. Several retrospective studies have suggested that these studies can lead to a change in surgical management in 15% to 35% of cases, with PET/CT outperforming either PET or CT alone. For patients, such as the present one, with palpable inguinal adenopathy, a CT scan of the abdomen and the pelvis not only may evaluate for intra-abdominal metastasis but can also identify enlarged pelvic lymph nodes that might convert an inguinal node dissection to an inguinal-iliac dissection. CT scan or MRI of the brain is not routinely necessary in asymptomatic patients.
It is important to note that with both CT scans and PET scans, false-positive findings are common; histologic confirmation of an abnormal lesion should be obtained whenever feasible before concluding a patient has stage IV disease and abandoning a potentially curable surgical approach.
The patient is asymptomatic and physical examination shows no evidence of metastatic disease. A serum LDH level and CT scan of the chest, abdomen, and pelvis show no areas suspicious for metastatic disease and no enlarged pelvic lymph nodes. The enlarged inguinal lymph node was visualized (Figure 1).
FIGURE 1
Surgical Approach
For patients with palpable disease in the axilla, a complete axillary lymph node dissection should include levels I, II, and III to provide the best regional control. In a very thin person, anterior retraction of the pectoralis major and minor muscle may allow for adequate dissection of the level III nodes. However, in most individuals, it may be necessary to divide the pectoralis minor. To do so, the pectoralis major is retracted anteriorly and the fascia on either side of the tendon of the pectoralis minor is incised. With a finger behind the muscle to protect the axillary artery and vein, the insertion of the pectoralis minor is divided with electrocautery.
For patients with palpable disease in the groin, the extent of lymphadenectomy (“superficial” vs. “superficial and deep”) is controversial. Some surgeons advocate complete superficial and deep inguinal lymph node dissections in all patients with palpable adenopathy. Others reserve deep dissection to those patients with a positive Cloquet’s node, or three or more involved nodes. Still others only perform deep groin dissections when there is radiographic evidence of pelvic adenopathy. If a deep groin dissection is to be performed together with a superficial dissection, this can be accomplished through one skin incision by obliquely dividing the external and internal oblique muscles to expose the pelvic retroperitoneum, or alternatively by dividing the inguinal ligament. Dividing the ligament is particularly useful in cases of extensive disease low in the pelvis along the distal external iliac vessels. Although it is simpler to divide the ligament over the femoral vessels, wound healing may be improved if the inguinal ligament is detached from the anterior superior iliac spine (Table 1).
TABLE 1. Key Technical Steps and Potential Pitfalls in Superficial and Deep Inguinal Lymph Node Dissection
The patient undergoes a wide excision of the melanoma with 2-cm margins and a superficial and deep inguinal lymph node dissection. Three of eleven inguinal nodes and zero of five deep nodes are positive for lymph node metastases. There is no evidence of extra-capsular extension.
Postoperative Management
After a complete node dissection, there is a risk of recurrence in and around the dissected bed. The risk of regional recurrence increases with the size and number of involved nodes, and the presence of extracapsular extension. Some have advocated the use of adjuvant radiation to the dissected nodal basin. A recently completed prospective randomized trial demonstrated that radiation to the basin after radical lymph node dissection does decrease regional recurrence rates, although this does not appear to impact overall survival. Therefore, it is reasonable to consider postoperative radiation in patients with extracapsular extension, multiple involved lymph nodes (≥2 cervical or axillary nodes or ≥3 inguinal nodes), or large nodes (≥3 cm in the neck or axilla or ≥4 cm in the groin), but the risks and benefits of adjuvant radiation must be carefully weighed. Given the higher risk of recurrence and lower morbidity of radiation after a neck dissection, the threshold for adjuvant radiation for cervical metastases is lower. On the other hand, adjuvant radiation after an inguinal node dissection is associated with significant morbidity and should be reserved for patients with a very high risk of relapse.
Patients with clinically evident regional metastases are also at a high risk of distant metastases, and most patients in this situation will ultimately die of their disease. Therefore, adjuvant therapy should be considered. Although multiple systemic therapies have been studied, none had demonstrated a benefit in reducing the risk of relapse or death for high-risk melanoma patients until the introduction of high-dose interferon alpha-2b (IFNα-2b). Three randomized studies have demonstrated an improvement in disease-free survival with high-dose interferon (HDI), while two of the three demonstrated an improvement in overall survival. However, significant toxicities of HDI and the equivocal results of some of the trials have made the use of IFNα-2b controversial. Serious side effects include flu-like symptoms (malaise, fevers, chills, arthralgias), fatigue, depression, liver function abnormalities, nausea and vomiting, and neutropenia and infectious complications. Based on the available data, all patients with high-risk melanoma should have a balanced discussion concerning the potential risks and benefits of adjuvant HDI. Participation in clinical trials is strongly encouraged for patients who opt not to be treated with IFNα-2b.
TAKE HOME POINTS
· Approximately 5% of melanoma patients will present with clinically involved regional nodes.
· FNA of suspicious nodes is recommended to document regional involvement. Excisional biopsy can interfere with the subsequent node dissection.
· Workup should include a thorough history and physical examination, serum LDH level and staging, which can be accomplished by CT, PET scan, or CT/PET.
· Patients without definitive evidence of distant disease should undergo complete lymph node dissection. In the axilla, this typically involves levels I, II, and III. In the groin, some surgeons routinely perform a superficial and deep dissection, while other surgeons limit the deep dissection to patients with evidence of iliac or pelvic disease.
· Adjuvant radiation to the regional basin may be considered for patients at high risk of regional recurrence (multiple nodes, extracapsular extension); however, the risks (lymphedema, wound complications) must be carefully weighed against the benefits (decreased regional recurrence, no improvement in overall survival).
· All stage III melanoma patients should be referred to a medical oncologist for consideration of adjuvant therapy with HDI. Patients who opt not to be treated with interferon should be encouraged to participate in clinical trials.