Another problem in the treatment of cutaneous melanoma is centered on the therapeutic efficacy of regional lymphadenectomy. Morton and colleagues investigated whether lymphatic mapping and sentinel node biopsy would lead to the more accurate detection of metastases and reduce the morbidity of lymphadenectomy. They intra-operatively injected blue dye to allow visual identification of the sentinel node. In a series of more than 200 patients, the incidence of false-negative sentinel nodes (negative sentinel nodes in a patient with metastases in other regional nodes) was less than 1%.9
The work of Morton et al led to an explosion of interest in lymphatic mapping. Today, the growing consensus is that lymphatic mapping can identify the sentinel node in 90% to 95% of patients with a variety of solid tumors. In addition, the incidence of false-negative sentinel nodes is low—less than 5% of patients with positive nodes. Although lymphatic mapping has become part of the standard surgical evaluation of patients with breast cancer and melanoma, regional lymphadenectomy continues to be performed. Several large phase III trials in breast cancer and melanoma patients are exploring whether regional lymphadenectomy can be omitted in patients with a negative sentinel node.
Techniques
Preoperative lymphoscintigraphy. When primary tumors occur in locations where the route of lymphatic drainage is ambiguous, preoperative lymphoscintigraphy is a vital element of lymphatic mapping. Such tumors include head and neck primary tumors; melanomas of the head, neck, and trunk; breast cancers in the medial third of the breast, which may have drainage to internal mammary lymph nodes; and, perhaps, periclitoral vulvar tumors, which may have unilateral or bilateral lymphatic drainage.
Intraoperative mapping and node removal. Although there remains some debate over the relative merits of intraoperative lymphoscintigraphy versus lymphatic mapping with blue dye, most experts agree that combining the 2 techniques helps shorten the learning curve for surgeons new to the procedure. Since most radionuclides have a halflife of 6 hours, injections as early as 18 hours prior to surgery are acceptable. Typically, the radionuclide is injected 1 to 6 hours prior to surgery. As for the blue dye, which is visible for only about 30 to 45 minutes in most cases, it is injected just prior to the incision, after the induction of anesthesia. A handheld gamma probe is inserted into the wound to detect radioactivity. High levels of radioactivity and visualization of blue dye are used to identify the sentinel node.
Pathologic examination of sentinel nodes. Standard practice after regional lymphadenectomy is to send the lymph-node-containing fat pad, unoriented, to the surgical pathologist. The nodes are teased from the fat, usually divided in half, and mounted on slides.
Biopsying the sentinel node yields further opportunities for study. Sentinel nodes are subjected to serial-step sectioning, which greatly increases the number of cells actually reviewed by the pathologist. Typically, the sentinel lymph node is cut into 2- or 3-mm sections using a “bread-loaf” technique. Each block is then cut into multiple slices, which are placed on slides for review by a pathologist. Techniques such as immunohistochemical staining also can be performed to search for micrometastases. Immunohistochemical staining has proved especially important in patients with melanoma or breast cancer, because small nests of malignant cells from these tumors are difficult to detect on standard hematoxylin- and eosin-stained slides.
Breast cancer
Although lymphatic mapping and sentinel node biopsy were pioneered in patients with cutaneous melanoma, the techniques are most widely practiced in patients with breast cancer. Along with breast-conserving surgery, sentinel node biopsy is becoming a standard element of the surgical treatment of early breast cancer. Patients with a positive sentinel node receive additional treatment. It has not yet been determined whether patients with negative sentinel nodes can safely be spared further axillary treatment. Several large randomized trials are studying this issue. One of those trials—the American College of Surgeons (ACS) Oncology Group protocol Z-10—will enroll more than 7,000 patients over the next 4 years.
In patients with small primary breast tumors, the risk of lymph node metastases is low, perhaps 20%. This means that if sentinel node biopsy is performed routinely in all such patients, 80% of them will receive no benefit yet will be exposed to the risk of lymphedema, which remains a common and incurable complication of regional lymphadenectomy for breast cancer despite improved surgical techniques, antibiotics, and wound drains. Patient should review their risk of nodal metastases and indications for adjuvant treatments with their physician before deciding on sentinel node biopsy alone or axillary lymphadenectomy.
Vulvar cancer
Because vulvar cancer is the only cutaneous malignancy treated by gynecologic oncologists, it was an obvious first choice for gynecologic lymphatic mapping and sentinel node biopsy. Progress has been slow, in part because of the infrequency of the disease, which has an incidence of fewer than 4,000 cases per year in the United States.10 Several studies have demonstrated the feasibility of lymphatic mapping in patients with vulvar cancer (Table 1).11-18 Results of a validation study of lymphatic mapping and sentinel node biopsy in patients with early squamous carcinoma of the vulva (Gynecologic Oncology Group protocol 173) are probably several years away. At present, the standard of care for patients with vulvar cancer remains inguinal femoral lymphadenectomy, although sentinel node biopsy alone is an option in patients at extreme risk for metastases or in whom prolonged anesthesia is inadvisable.