Lymphatic mapping and sentinel lymphadenectomy can be successfully learned and applied in a standardized fashion with high accuracy by centers worldwide. Successful SN identification rates of 97% can be achieved, and the incidence of nodal metastases approaches that of the organizing center. A multidisciplinary approach (surgery, nuclear medicine, and pathology) and a learning phase of > or =30 consecutive cases per center are sufficient for mastery of LM/SL in cutaneous melanoma. Lymphatic mapping performed using blue dye plus radiocolloid is superior to LM using blue dye alone.

Background For stage IV melanoma, systemic medical therapy (SMT) is used most frequently; surgery is considered an adjunct in selected patients. We retrospectively compared survival after surgery±SMT versus SMT alone for melanoma patients developing distant metastases while enrolled in the first Multicenter Selective Lymphadenectomy Trial. Methods Patients were randomized to wide excision and sentinel node biopsy, or wide excision and nodal observation. We evaluated recurrence site, therapy (selected by treating clinician), and survival after stage IV diagnosis. Results Of 291 patients with complete data for stage IV recurrence, 161 (55%) underwent surgery±SMT. Median survival was 15.8 vs. 6.9 months and 4-year survival was 20.8% vs. 7.0% for patients receiving surgery±SMT vs. SMT alone (p<0.0001; HR 0.406). Surgery±SMT conferred a survival advantage for patients with M1a (median >60 months vs. 12.4 months; 4-year 69.3% vs. 0; p=0.0106), M1b (median 17.9 vs. 9.1 months; 4-year 24.1% vs. 14.3%; p=0.1143), and M1c (median 15.0 vs. 6.3 months; 4-year 10.5% vs. 4.6%; p=0.0001) disease. Patients with multiple metastases treated surgically had a survival advantage, and number of operations did not reduce survival in the 67 patients (42%) who had multiple surgeries for distant melanoma. Conclusions Our findings suggest that over half of stage IV patients are candidates for resection and exhibit improved survival over patients receiving SMT alone, regardless of site(s) and number(s) of metastases. We have begun a multicenter randomized phase III trial comparing surgery versus SMT as initial treatment for resectable distant melanoma.

Prolonged survival was observed in patients who received postoperative active immunotherapy with Canvaxin therapeutic cancer vaccine. The correlation of survival with vaccine-DTH responses but not PPD-DTH indicates a treatment-specific effect. These findings suggest that adjuvant active specific immunotherapy should be considered after cytoreductive surgery for advanced melanoma.

Sentinel lymph node dissection is a minimally invasive surgical technique for staging of breast carcinoma. The optimal pathologic examination of the sentinel node (SN) has not yet been determined. Our standard protocol for evaluation of the SN in patients with breast cancer included frozen section at one level, plus paraffin sections at two levels, separated by 40 microm, and stained with hematoxylin and eosin and cytokeratin immunohistochemistry (IHC) at each paraffin section level. In the current study, we evaluated the use of step sections and cytokeratin IHC in 60 SNs (42 consecutive patients) that were tumor-negative on frozen section and hematoxylin and eosin staining at permanent section levels 1 and 2. The SN were reexamined with cytokeratin IHC at eight additional levels (levels 3-10) of the paraffin block, each separated by 40 microm. Previous IHC sections from levels 1 and 2 had shown micrometastases in nine SNs (eight patients) and no tumor cells in the remaining 51 SNs (34 patients). Of the 51 previously negative SNs, only two (4%) SNs from one (3%) patient had metastatic carcinoma cells in levels 3-10. Thus, the additional step sections with cytokeratin IHC did not significantly increase the number of patients with tumor-positive SNs. We currently recommend that the SN be examined with cytokeratin IHC at two levels of the paraffin block. This should optimize sentinel lymph node dissection as a staging technique and minimize the labor and financial burden associated with multiple step sections and IHC stains.

No abstract

The sentinel lymph node (SN) is the first node on the direct lymphatic drainage pathway from a tumor. Melanoma-associated SNs are the most likely site of early metastases and their immune functions are strikingly down-modulated. We evaluated histologic and cytologic characteristics of 21 SNs and 21 nonsentinel nodes (NSNs) from melanoma patients who had clinically localized (AJCC Stage I-II) primary cutaneous melanoma. SNs showed highly significant reductions in total paracortical area and in the area of the paracortical subsector occupied by dendritic cells. The frequency of paracortical interdigitating dendritic cells (IDCs) was dramatically reduced in SNs, and most IDCs (~99%) lacked the complex dendrites associated with active antigen presentation. The release of immunosuppressive factors from the primary melanoma may induce a localized and specific paralysis in the SN, which prevents the recognition of otherwise immunogenic melanoma antigens by IDCs. This immune paralysis may facilitate the implantation and growth of melanoma cells in the SN. Cytokine therapy may be able to reverse this immune paralysis. These findings have an important practical application in the histopathologic confirmation that a node is truly sentinel. They also offer an hypothesis to explain the failure of the immune surveillance mechanisms to identify and respond to a small primary melanoma that expresses immunogenic tumor antigens.

For patients with primary melanomas of the scalp, auricle, or face, sentinel lymphadenectomy can be performed accurately in the parotid region and offers a low-morbidity alternative to routine elective superficial parotidectomy.

A b s t r a c t; conversely, when the SLN contains metastatic carcinoma, 30% to 70% of patients also will have positive nonsentinel axillary nodes. If SLN biopsy and ALND are planned as a single procedure, patients who have a tumor-involved SLN (approximately 25%-30%) may be spared the anxiety, inconvenience, and cost of a separate anesthetic and surgical operation. A positive SLN result from the pathologist's intraoperative examination may direct the surgeon to perform complete ALND. Intraoperative examination of the SLN for tumor cells commonly uses imprint cytology (touch preps), frozen section, or both. Imprint cytology (IC) has the advantage of excellent cytologic detail, whereas frozen section (FS) permits visualization of nodal architecture and can sample more cells. The reported accuracy of these techniques for rapid diagnosis of the SLN ranges from 83% to 98%, with falsely negative results in 3% to 24%. 51113 We reviewed our institution's experience with protocols that combine IC and FS examination for rapid intraoperative assessment of the SLN for breast carcinoma staging. Materials and Methods Case Selection and Data CollectionAll patients enrolled in our institute's trial of SLN biopsy for invasive breast carcinoma between October 1995 and March 1998 were eligible for study. We included 278 consecutive patients with an intraoperative IC and FS diagnosis of the