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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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Malignant of melanoma

and .

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Background

In 1907,Handley described his findings from an autopsy on a young woman with disseminated melanoma and multiple cutaneous nodules. He stated, that “permeation of the lymphatics is the principal agent in this local centrifugal spread” of melanoma. He recommended a circular incision about one inch from the edge of the tumor, and another two inches in the subcutaneous fat. This one report became the standard of care throughout most of the twentieth century. Results of recent randomized studies have addressed the issue of resection margins. As a result, we now know that less extensive surgery can result in local control with better cosmetic results.

The other major controversy has dealt with the merits of lymph node dissection for the purpose of removing and staging melanoma. In the past, retrospective studies suggested a benefit from electively removing the lymph nodes before the disease was clinically detectable by lymph node enlargement. Randomized studies showed that this did not appear to be beneficial to these patients. The current interest in lymphatic mapping and sentinel node biopsy has replaced this controversy by what seems to be a logical method of managing the regional nodes in these patients.

Microstaging

Before one can understand how to manage patients with melanoma, it is important to know the concept of microstaging. Basically, the prognosis of a patient with melanoma can be predicted by the thickness of the tumor.Clark described five levels of dermal invasion, Clark levels I to V, that correlated with the patient's five year survival (Clark et al. 1969). Subsequently,Breslow showed that by measuring the tumor thickness in millimeters with an optical micrometer, one could more consistently predict long term survival (Breslow 1970). There tends to be less variation by pathologists interpreting slides in this manner. Unlike Clark's approach, the Breslow technique is not affected by the variations in skin thickness from one portion of the body to another. Thus, two different melanomas with the same Clark's level, may differ in thickness based on where they are located. A Clark's III of the eyelid will be thinner and more favorable than a Clark's III on the back where the skin tends to be thicker.

There are other histologic features of the primary melanoma that have independent prognostic value (Clark et al. 1989). These include: mitotic rate per square millimeter, tumor-infiltrating lymphocytes, anatomic site of primary melanoma (extremity more favorable than truncal), sex of the patient (female better prognosis than male), or evidence of histologic regression in the lesion itself (worse prognosis).

Biopsy

When a melanocytic nevus develops certain clinical features, a biopsy is warranted. The “ABCD rules” should be followed: A = asymmetric appearance, B = border that is irregular, C = color that is black, blue, red, brown, tan or changing, D = diameter of the nevus that is growing. In order to accurately microstage the melanoma, the biopsy must be a full thickness sample of the lesion that includes subcutaneous fat. If a lesion is less than about 2 cm in width, either a punch biopsy or excisional biopsy can be performed. Lesions that are too large to excise completely without leaving a significant cosmetic defect, should be sampled by either a punch or incisional biopsy. It is critical in these latter situations to include the thickest part of the lesion in addition to a portion of adjacent normal skin.

Ideally, one should never perform a shave biopsy on a pigmented lesion to rule out melanoma. If the melanoma extends to the deep surface of the shave (which is common), then melanoma may still be left in the tumor bed. Thus, one can not be certain of the actual thickness of the lesion. As noted below, this information is critical to determining the margin of excision or need for lymph node biopsy. Despite this, shave biopsies can still provide a diagnosis and the minimal depth of invasion. Many knowledgeable and experienced physicians have shaved off both benign appearing pigmented and nonpigmented skin lesions to discover melanoma on the pathology report.

Margins

Studies have shown that the ten year survival for patients who recur locally after excision of melanoma is only 20%. One reason for this is that deposits of melanoma cells tend to occur outside the borders of the lesion. One needs to go widely enough around the lesion to prevent this from happening.

When discussing margins, one is talking about the distance from the edge of the melanoma in centimeters. Thus, if the goal is to obtain a 2 cm margin for a 2 mm thick melanoma, then the diameter of the specimen is at least 4 cm. If the width of the melanoma is 1 cm, then the total diameter is 5 cm. Although large, if one followed Hanley's original description, then the defect would be at least 11 cm. This lead to studies the past two decades with the goal of decreasing the resection margins but achieving the same local control.

A number of prospective randomized studies have conclusively shown that a more conservative approach to local therapy is reasonable (Baron 1996). Since the depth of invasion correlates with the risk of local recurrence and metastases, one can base the extent of surgery on the thickness of the lesion.Veronesi reported that thin melanomas (less than 1 mm thick) can be adequately treated with a 1 cm margin of excision (Veronesi et al. 1988, Veronesi et al 1991). He showed that this method had the same long term survival and local control as a 3 cm margin.

Balch published a multi-institutional trial of patients with intermediate thickness melanomas (between 1 and 4 mm) who were randomized to either a 2 cm or 4 cm margin of excision (Balch et al. 1993). This study demonstrated that the 2 cm margin was adequate since the survival and local control rates were comparable to those for patients who had a 4 cm excision. In addition, the patients with the 2 cm margin had a less frequent need for skin grafts and a shorter hospital stay when compared to the wider margin patients.

At this point in time, it is not clear how wide a margin is needed for patients with thick melanomas (over 4 mm). These patients have a 70% risk of distant metastases. As a result, it is reasonable to excise these with either a 2 or 3 cm margin (table I).

Table I. Recommended margin of excision based on thickness of primary melanoma.

Table I

Recommended margin of excision based on thickness of primary melanoma.

Melanoma can arise from skin virtually any place on the body. This sometimes leads to management problems when for anatomic or cosmetic reasons, it would be preferable to limit the extent of excision. Irregardless of tumor thickness, melanoma on the face can be treated by a 1 cm margin of excision. Those on the ear should have a wedge resection. Melanoma on the skin of the breast was treated by mastectomy in the past. Simple excision based on tumor depth is sufficient. Subungual lesions on the toes or fingers will usually need some form of amputation of the digit (table II).Recently, there has been interest in the use of Mohs micrographic surgery to treat melanoma with a minimal margin (Zitelli et al. 1997). This study used fresh-tissue Mohs micrographic surgery with frozen-section examination of the margins. The results were compared to historical controls and concluded that most melanomas can be excised with this technique and result in rare local recurrences. The authors concluded that this method may be especially useful when tissue conservation is important such as with melanomas on the head, neck, hands or feet. This is despite the NIH consensus panel conclusion that Mohs is not recommended for treating melanoma (1992). More data will be needed to confirm these reports.

Table II. Recommended margin of excision for melanoma at special sites.

Table II

Recommended margin of excision for melanoma at special sites.

In all cases, the goal is to cover the excision bed. Ideally, this is by primary closure. Split or full thickness skin grafts are often the easiest and best tissue coverage. If the defect is in an important area because of frequent usage (such as sole of foot) or cosmesis (face), a local skin flap or even a free flap may be appropriate.

Lymph node dissection

In addition to managing the local disease, the other goal of treatment is to evaluate the patients who may be at risk of spread to regional lymph nodes. For the past few decades, this lead to a great deal of controversy between those proposing patients undergo either an elective lymph node dissection (ELND) or a therapeutic node dissection (TLND). In an ELND, patients at increased risk for nodal metastases, undergo removal of the nodes before they are clinically positive. The theoretic benefit of this was that the disease would be early, and more likely curable. Retrospective studies supported this argument (Das Gupta 1977,Balch 1981). The obvious downside to this approach, is that as many as 80% of patients had their nodes removed and found to have no metastatic disease. Lymph node dissections can carry a significant risk of wound complications and long term risk of lymphedema of the extremity.

The other approach has been to follow the patient for evidence of changes in the lymph nodes. If they become clinically positive, then the patient should undergo a TLND. The theoretical argument against this approach is that by the time the disease is large enough to be palpable, the patient is at higher risk for distant metastases. A number of prospective randomized studies have failed to show any survival benefit of ELND over observation alone (Veronesi et al. 1977,Sim et al. 1986). Recently,Balch and colleagues published their study in which patients with intermediate thickness melanoma were randomized to ELND vs. observation (Balch et al. 1996). The data has shown that there is no benefit for patients undergoing ELND. They also performed subgroup analysis suggesting that patients benefited from ELND if they were under the age of 60, had tumors between 1.0 and 2.0 mm thick and/or were free of tumor ulceration. This approach of going back to the data and reanalyzing for features not included in the randomization, has met with a great deal of criticism about its statistical validity.

Sentinel node biopsy

The whole controversy about lymph node dissections has changed dramatically the past few years. While the data suggests that some patients may benefit from a lymph node dissection, certainly those without metastatic disease to their nodes will not be helped from a node dissection. If one can identify which patients clearly have microscopic metastases to nodes, and those nodes are dissected out, then there may be a survival benefit.

In 1992, Morton described a procedure in which isosulfan blue dye was injected into the dermis around the skin at a melanoma site (Morton et al. 1992). An incision was then made over the nodal basin likely to have metastatic disease. The tissue was dissected until a lymphatic channel containing blue dye was identified, and traced forward to the first blue stained node. This node was removed, and then the rest of the nodes in the basin were dissected out. Morton showed that if this “sentinel node” was negative for melanoma, then 99% of the time, all the remaining nodes were also negative. As a result, patients with a negative sentinel node can avoid the morbidity of an ELND.

This technique was further refined byKrag and coworkers (Krag 1995). They injected technetium sulfur colloid intradermally around the primary tumor site. Planar gamma camera images were taken to confirm the draining lymph node basin. The patient was taken to the operating room where isosulfan blue dye was also injected circumferentially in the skin surrounding the melanoma in some patients. An incision was placed over the lymph node basin and a handheld gamma detector guided the dissection to the radiolabeled node. The sentinel node was detected in 118 of 121 (98%) patients. This approach, when combined with the blue dye technique described byMorton, increases the likelihood of successfully finding the sentinel node in patients with melanoma.

The current trend is to offer sentinel node biopsy to patients at an increased risk for nodal disease. Those patients likely to benefit have tumors 1.0 mm or greater, ulcerated or regressed primary lesions, and/or Clark's level IV or greater. Most centers performing this procedure will also obtain immunohistochemical staining for S-100 and HMB 45. If the sentinel node is positive for melanoma, which occurs about 20% of the time, then the patient needs to be returned to the operating room for an ELND. It is interesting to note that about 80% of the time, the sentinel node is the only positive node in the dissected basin (Leong et al. 1997). There are currently a number of prospective studies looking at the impact of sentinel node biopsy on long term outcome for patients with melanoma.

Conclusion

The surgical management of melanoma is dictated by the depth of invasion of the tumor. Prospective randomized studies have shown the acceptable width for margins of resection to decrease the likelihood of local recurrence. Lymphatic mapping with sentinel node biopsy has replaced the need for elective node dissections in patients with high risk melanomas. Ongoing prospective studies will determine the impact of this new technique on melanoma patients.

References

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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK6877

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