Sentinel Lymph Node Mapping in Melanoma: The Issue of False-Negative Findings.
ABSTRACT Management of cutaneous melanoma has changed after introduction in the clinical routine of sentinel lymph node biopsy (SLNB) for nodal staging. By defining the nodal basin status, SLNB provides a powerful prognostic information. Nevertheless, some debate still surrounds the accuracy of this procedure in terms of false-negative rate. Several large-scale studies have reported a relatively high false-negative rate (5.6%-21%), correctly defined as the proportion of false-negative results with respect to the total number of "actual" positive lymph nodes. In this review, we identified all the technical aspects that the nuclear medicine physician, the surgeon, and the pathologist should take into account to improve accuracy of the procedure and minimize the false-negative rate. In particular, SPECT/CT imaging detects more SLNs than those found by planar lymphoscintigraphy. Furthermore, the nuclear medicine community should reach a consensus on the radioactive counting rate threshold to better guide the surgeon in identifying the lymph nodes with the highest likelihood of housing metastases ("true biologic SLNs"). Analysis of the harvested SLNs by conventional techniques is also a further potential source for error. More accurate SLN analysis (eg, molecular analysis by reverse transcriptase-polymerase chain reaction) and more extensive SLN sampling identify more positive nodes, thus reducing the false-negative rate.The clinical factors identifying patients at higher-risk local recurrence after a negative SLNB include older age at diagnosis, deeper lesions, histological ulceration, and head-neck anatomic location of the primary lesion.The clinical impact of a false-negative SLNB on the prognosis of melanoma patients remains controversial, because the majority of studies have failed to demonstrate overall statistically significant disadvantage in melanoma-specific survival for false-negative SLNB patients compared with true-positive SLNB patients.When new more effective drugs will be available in the adjuvant setting for stage III melanoma patients, the implication of an accurate staging procedure for the sentinel lymph nodes will be crucial for both patients and clinicians. Standardization and accuracy of SLN identification, removal, and analysis are required.
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ABSTRACT: Immunohistochemical localization of S-100 protein alpha and beta subunits in the cells of melanocytic nevi and malignant melanomas was studied by using monoclonal antibodies directed against each subunit. Although polyclonal anti-S-100 reactivities have been demonstrated uniformly in all nevus cells and melanoma cells, monoclonal anti-S-100 alpha and anti-S-100 beta reactivities were either absent or rarely found in ordinary junctional nevi or junctional nests of ordinary compound nevi. However, in the junctional nests of dysplastic junctional nevi and junctional components of dysplastic compound nevi, monoclonal anti-S-100 alpha reactivity become more frequent, whereas monoclonal anti-S-100 beta reactivity remains negative. In the superficial variety of melanomas such as superficial spreading melanoma and lentigo maligna melanoma, monoclonal anti-S-100 beta is nonreactive until vertical growth or invasiveness begins. Most nodular melanomas are positively stained with both monoclonal anti-S-100 alpha and anti-S-100 beta. It is suggested that monoclonal anti-S-100 alpha can be an indicator of active junctional nevus of melanocytic nevi and the reactivity with monoclonal anti-S-100 beta may be related to vertical progression of superficial spreading melanomas and lentigo maligna melanomas.Cancer 09/1990; 66(4):765-71. DOI:10.1002/1097-0142(19900815)66:43.0.CO;2-M · 4.90 Impact Factor
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ABSTRACT: The specificity and sensitivity of HMB-45, an antimelanoma monoclonal antibody, was evaluated in cytologic specimens from extracutaneous melanomas. Melanoma cells in 23 of 25 (92%) cases stained with this antibody. Staining was intense and diffuse in 22 of these melanomas and focal in 1. Amelanotic tumors and tumors with scanty pigment were included. Neither degree of pigmentation, site of primary, cytologic characteristics of tumor, nor source of specimen predicted the immunostaining pattern. Cytopreparations containing benign (6 cases) and malignant (16 cases) cells with which melanoma may be confused constituted the nonmelanoma group. None of the 22 cases in this group stained. Undifferentiated carcinomas, adenocarcinomas, large cell lymphomas, sarcomas, mesothelial hyperplasias, and a benign nerve sheath tumor were included. Effusions, fine-needle aspirates, bronchial material, and imprints were studied. All smears had been fixed and stained by Papanicolaou's method before immunostaining. Excellent cytomorphologic characteristics were preserved, and immunostaining was not affected. HMB-45 antibody is a highly specific and sensitive marker for malignant melanoma in cytologic material.American Journal of Clinical Pathology 08/1988; 90(1):77-80. · 3.01 Impact Factor
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ABSTRACT: Some patients presenting with cutaneous malignant melanoma without palpable adenopathy have regional metastatic disease. The results of a prospective clinical study of gamma probe-directed sentinel lymph node (SLN) biopsy are presented. Over a 3-year period, 103 patients with a diagnosis of invasive primary cutaneous malignant melanoma (Breslow > 0.12 mm or > Clark level II) underwent preoperative lymphoscintigraphy with technetium sulfur colloid followed by gamma-probe-guided sentinel lymphadenectomy. There were 46 women and 57 men with a mean age of 55.7 years (range, 19-91). Mean Breslow thickness was 2.3 mm (range, 0.12-10 mm). Primary locations were head and neck in 12, trunk 46, upper extremity 19, and lower extremity in 26. One hundred sixteen lymph node basins were mapped in 103 patients. Axillary, inguinal, and cervical nodal basins comprised 55, 34, and 11% of the total basins evaluated, respectively. Sixty-eight patients (66%) underwent lymphatic mapping of one regional nodal basin, 27 patients (26%) underwent synchronous lymphatic mapping of 2 regional nodal basins, 6 patients (6%) underwent synchronous lymphatic mapping of 3 regional nodal basins, and 2 patients (2%) underwent synchronous lymphatic mapping of 4 regional nodal basins. Seroma or infection did not occur in any patients. Micrometastatic disease was identified in 15 sentinel lymph node biopsy sites in 13 (10%) patients. Of 10 patients undergoing lymph node dissection, 9(90%) had no additional pathological lymph node involvement. We achieved 99% success rate, 1% rate of failed sentinel node procedure, and 8% false-negative rate after median follow-up for 2 years. We concluded that gamma probe-directed sentinel lymph node biopsy is a straightforward procedure which can be done in the outpatient setting and facilitates management of patients with cutaneous malignant melanoma. It allows the surgeon to identify all basins at risk for metastatic disease and the location of the sentinel node(s) in relation to the basin.Journal of Surgical Oncology 07/2001; 77(3):157-64. DOI:10.1002/jso.1088 · 2.84 Impact Factor