The prognostic importance of sentinel lymph node biopsy in thin melanoma.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is prognostically useful in patients with cutaneous melanoma with Breslow thickness > 1 mm. The objective of this study was to determine whether sentinel node histology has similar prognostic importance in patients with thin melanomas (< or = 1 mm). METHODS: This was a retrospective study of patients who underwent SLNB for clinically localized melanoma at Indiana University Medical Center between 1994 and 2003. SLNB results and traditional melanoma prognostic indicators were studied in univariate log-rank tests. RESULTS: One hundred eighty-four patients with melanomas < or = 1 mm thick underwent SLNB. SLNB was tumor positive in 12 patients (6.5%). Univariate analysis of SLNB results revealed that Breslow thickness, Clark level of invasion, and mitotic index were associated with SLNB status. Tumor positivity was observed at different rates in tumor thickness subsets: < .75 mm, 2.3%; and .75 to 1.0 mm, 10.2% (P = .0372). Disease-free survival and overall survival were significantly associated with SLNB results in melanomas < or = 1 mm (log-rank test: P < .0001 and P = .0125, respectively) at a median follow-up of 26.3 months. CONCLUSIONS: SLNB histology in melanomas < or = 1.0 mm deep is a significant predictor of outcome. SLNB should be considered for selected patients with melanomas .75 to 1.0 mm.

The association between malignant melanoma and noncutaneous malignancies.

BACKGROUND: Both increases and decreases in the incidence of subsequent malignancies in melanoma patients have been reported. We examined the database of the Indiana University Cancer Center to determine whether there is an association between malignant melanoma and noncutaneous malignancies. OBJECTIVE: We searched for evidence of noncutaneous malignancies in a cohort of melanoma patients. METHODS: Patients with microscopically confirmed malignant melanoma diagnosed between January 1987 and March 2001 were analyzed. This cohort was investigated for noncutaneous malignancies occurring either before or after the diagnosis of melanoma. The standardized incidence ratios (SIR) were calculated as the ratio of the observed to the expected number of patients with second malignancies, and 95% confidence intervals (95% CI) around the SIR were estimated from the cumulative Poisson distribution. RESULTS: A total of 955 patients with melanoma (498 males and 457 females) were documented over the 14-year period. Sixty-nine noncutaneous malignancies were identified in 59 (6.2%) melanoma patients (39 males and 20 females). There was a higher risk of non-Hodgkin's lymphoma (SIR = 1.91; 95% CI, 0.88-3.62) in men and renal cell carcinoma (SIR = 2.41, 95% CI, 0.97-4.97) in men. In female patients, however, there was no higher risk of noncutaneous malignancies. CONCLUSIONS: This study did not show a higher risk of prostate cancer, gastrointestinal cancer, leukemia, endometrial cancer, or cancer of the nerve and neuroendocrine systems in melanoma patients. No female patients incurred a higher risk of noncutaneous cancers. The increased risk of non-Hodgkin's lymphoma and renal cell carcinoma in men might be attributed to a mutual carcinogenic exposure, an aberration of cell-mediated immunity, a shared genetic susceptibility, increased medical surveillance among cancer patients, a post-therapy effect after cancer management, or factors not as yet clear. Close monitoring of melanoma patients for signs of second malignancy is warranted.

Inefficacy of F-18 fluorodeoxy-D-glucose-positron emission tomography scans for initial evaluation in early-stage cutaneous melanoma.

BACKGROUND: The purpose of the current study was to determine the sensitivity and specificity of initial F-18 fluorodeoxy-D-glucose-positron emission tomography (FDG-PET) scanning for detection of occult lymph node and distant metastases in patients with early-stage cutaneous melanoma. METHODS: The authors conducted a prospective nonrandomized clinical trial. Inclusion criteria were patients with cutaneous melanoma tumors > 1.0 mm Breslow thickness, local disease recurrence, or solitary intransit metastases without regional lymph or distant metastases by standard clinical evaluation. All patients underwent whole-body FDG-PET scanning before surgical therapy. Abnormal PET findings were studied by targeted conventional imaging and/or biopsy. FDG-PET scans were interpreted in a blinded fashion. Regional lymph node basins were staged by sentinel lymph node biopsy (SLNB). PET scan findings in regional lymph nodes were compared with histology of SLNB specimens. Abnormal distant PET scan findings were studied with repeat conventional scan imaging at 3-6 months and were correlated with the first site(s) of clinical disease recurrence. Blinded PET scan findings were correlated with all information to determine sensitivity and specificity. RESULTS: There were 144 assessable patients with a mean tumor depth of 2.8 mm. The median follow-up for these patients was 41.4 months. Blinded interpretations of FDG-PET scan images showed that 31 patients (21%) had signs of metastatic disease, 13 patients had probable regional lymph node metastases, and 18 patients had 23 sites of possible distant metastases. SLNB and/or follow-up demonstrated regional lymph node metastases in 43 of 184 lymph node basins in 40 patients (27.8%). Compared with all clinical information, FDG-PET scan sensitivity for detection of regional lymph node metastases was 0.21 (95% confidence [CI], 0.10-0.36) and specificity was 0.97 (95% CI, 0.93-0.99). No distant sites were confirmed to be true positive by targeted conventional imaging/biopsy at the time of presentation. Thirty-four patients (23.6%) presented with 54 foci of metastatic disease at initial disease recurrence. FDG-PET scan sensitivity for prediction of the first site(s) of clinical disease recurrence was 0.11 (95% CI, 0.04-0.23). Excluding patients with brain metastases, FDG-PET scan sensitivity for detection of occult Stage IV disease in patients was 0.04 (95% CI, 0.001-0.20) and specificity was 0.86 (95% CI, 0.79-0.92). CONCLUSIONS: FDG-PET scanning did not impact the care of patients with early-stage melanoma already staged by standard techniques. Routine FDG-PET scanning was not recommended for the initial staging evaluation in this population.

Lack of prognostic importance of reverse-transcriptase polymerase chain reaction detection of circulating messenger RNA in patients with melanoma.

BACKGROUND: Molecular serologic markers for detecting early melanoma metastases have been described. The objective of this study was to determine whether reverse-transcriptase polymerase chain reaction detection of circulating tyrosinase messenger RNA (mRNA) can identify the presence of subclinical metastases and predict subsequent clinical recurrence in surgically treated melanoma patients who are at significant risk for relapse. METHODS: Preoperative peripheral blood samples of disease-free melanoma patients, disease stage ranging from I to IV, were analyzed for the presence of tyrosinase mRNA by semiquantitative reverse-transcriptase polymerase chain reaction as a putative marker for circulating melanoma cells. Multivariate analysis was performed to evaluate the prognostic value of tyrosinase mRNA in the blood and in the correlating pathologic stage of disease with recurrence and survival. RESULTS: The study group consisted of 96 patients. The mean age was 54 years (range, 24 to 83 years). The mean Breslow thickness was 3 mm (range, 0.9 to 21 mm). Circulating melanoma cells were detected in 66 patients (69 percent). Blood polymerase chain reaction positivity by American Joint Committee on Cancer stage was as follows: stage I, 19 of 28 patients (68 percent); stage II, 17 of 25 patients (68 percent); stage III, 28 of 41 patients (68 percent); and stage IV, two of two patients (100 percent). Tyrosinase detection was not associated with stage of disease (p = 0.77). At a median follow-up of 30 months, disease recurred in 21 patients (22 percent), and 15 patients (16 percent) died. Disease stage of the patients correlated with recurrence (p < 0.0001) and death (p < 0.0001). The finding of mRNA tyrosinase in peripheral blood samples was not associated with recurrence (p = 0.1) or death (p = 0.77). CONCLUSIONS: The use of polymerase chain reaction to detect circulating tyrosinase mRNA in peripheral blood does not correlate with traditional prognostic indicators in patients with cutaneous melanoma and does not appear to be an effective prognostic tool.

Sentinel node biopsy for high-risk nonmelanoma cutaneous malignancy.

OBJECTIVE: To evaluate the feasibility of sentinel node staging for detection of occult regional lymph node metastasis in high-risk cutaneous nonmelanoma malignancies. DESIGN: Consecutive clinical case series. SETTING: Referral university medical center. PATIENTS: A consecutive sample of patients with a variety of high-risk nonmelanoma cutaneous malignancies without evidence of regional lymph node metastases. INTERVENTION: Sentinel node biopsies were performed using preoperative lymphoscintigraphy, blue dye, and intraoperative radiolocalization. MAIN OUTCOME MEASURE: Sensitivity, determined by comparing the results of biopsy specimen evaluation with those of completion lymphadenectomy and/or clinical follow-up. RESULTS: Twenty-four patients underwent sentinel node biopsy for the staging of 29 nodal basins identified by lymphoscintigraphy. Primary diagnoses were squamous cell carcinoma (n = 17), Merkel cell carcinoma (n = 5), and adenocarcinoma (n = 2). Seven patients (29%) had a tumor-positive sentinel node. Sentinel node biopsy followed by complete lymphadenectomy was performed in 12 patients and sentinel node biopsy alone in 12 patients. Tumor-positive lymph nodes were noted in 8 patients, 7 of whom also had positive sentinel nodes. There was 1 false-positive result (1/8 [12%]), in a patient with recurrent squamous cell carcinoma of the scalp. At a median follow-up of 10 months, no recurrences in a sentinel node-negative basin have been noted. Compared with all information, the sensitivity of sentinel node staging was 88% and the negative predictive value was 0.94. CONCLUSIONS: Sentinel node biopsy is a minimally invasive staging procedure useful in identifying occult regional lymph node disease in selected patients with nonmelanoma cutaneous malignancies. Further studies to verify these findings and develop formal guidelines are indicated.

Patterns of initial recurrence and prognosis after sentinel lymph node biopsy and selective lymphadenectomy for melanoma.

The histologic status of the sentinel lymph node is a highly significant prognostic factor for patients with clinically localized cutaneous melanoma. The patterns of initial treatment failure of patients with positive sentinel lymph node biopsy versus those with negative results have not been well described. The purpose of this study was to determine the relative prognostic importance of sentinel lymph node status and to compare patterns of initial treatment failure and prognosis of node-positive versus node-negative cutaneous melanoma patients staged by sentinel lymph node biopsy and selective lymphadenectomy. The authors reviewed the pertinent demographic and surgical data in a consecutive series of patients with cutaneous melanoma who underwent sentinel lymph node staging of nonpalpable regional nodes. Sentinel lymph node biopsy was performed using a combination of blue dye and radiolocalization. Patients with positive biopsy results underwent selective lymphadenectomy, whereas those with negative results were observed. Site(s) and date(s) of initial recurrence and death were determined, and disease-free and overall survival probabilities were compared between positive and negative groups using the log-rank test and multivariable Cox regression analysis. Between February of 1994 and August of 2000, 408 patients with melanoma underwent sentinel lymph node biopsy to stage 518 regional lymph node basins. Mean Breslow tumor thickness was 2.27 mm (range, 0.2 to 14.0 mm). Eighty-five patients (20.8 percent) had at least one histologically positive sentinel lymph node, and selective lymphadenectomy yielded additional positive lymph nodes in 18 of 84 patients (21.4 percent). Recurrences were noted in 70 patients (17 percent) at a median follow-up period of 31.4 months. Recurrences were more frequent in patients with positive biopsy results (36.5 percent) than in those with negative results (12.1 percent, p < 0.0001). Distant sites of initial recurrence were more likely in the positive group than in the negative group (71 percent versus 49 percent of recurrences, respectively; p = 0.06). The false-negative rate for sentinel lymph node staging was 4.5 percent and overall accuracy was 99 percent compared with clinical follow-up. Disease-free and overall survival correlated significantly with tumor thickness, ulceration, sentinel lymph node status, and the number of tumor-positive lymph nodes (two-sided p < 0.0001 for all comparisons). Multivariable analysis revealed that sentinel lymph node status (p = 0.003), tumor thickness (p = 0.016), ulceration (p = 0.006), and age (p = 0.003) were significant independent predictors of survival for the entire group. Tumor thickness and ulceration were significant predictors of recurrence and survival in sentinel node-negative patients but not in sentinel node-positive patients. Sentinel lymph node histology is possibly the most important negative predictor of early recurrence and survival in patients with American Joint Committee on Cancer stage I and II melanoma. The number of positive lymph nodes provides additional prognostic information. Although sentinel node-negative patients are a prognostically favorable group, various combinations of local and regional recurrences comprise the most common pattern of initial relapse after a negative sentinel lymph node biopsy result.

Sentinel lymph node biopsy in children and adolescents with malignant melanoma.

BACKGROUND/PURPOSE: Sentinel lymph node biopsy (SLNB) provides valuable staging information for adult patients presenting with clinically localized cutaneous melanoma. There are little data pertaining to the use of SLNB in the pediatric melanoma population. The objective of this study is to investigate the use of SLNB in the pediatric population, focusing on its diagnostic and therapeutic implications. METHODS: Retrospective identification was made of patients 18 years or younger who underwent sentinel lymph node biopsy for clinically localized melanoma at Indiana University Medical Center between 1994 and 2001. Patient demographics, primary tumor thickness, location of primary tumor, presence of tumor ulceration, number of lymph nodes removed, pathology of examined nodes, and number of lymph nodes involved with tumor were recorded. Disease status and dates of last clinical contact were determined. RESULTS: Twelve patients, 18 years or younger, were identified. Mean age of the study population was 14.1 years (range, 4 to 18). Mean tumor thickness was 1.65 mm (range, 0.36 to 4.7 mm). Three patients (25%) had positive sentinel lymph node biopsies. All 3 patients underwent completion lymph node dissection (CLND). One patient had micrometastatic disease detected on CLND; he had recurrence 6.1 months later and died 7.5 months after his SLND/CLND. At a median follow-up of 11.7 months, the remaining 11 patients had not experienced recurrence. There were no complications related to the SLNB procedure. CONCLUSIONS: The minimally invasive surgical approach and limited complications associated with SLNB make this procedure a useful aid in assisting the physician in making therapeutic decisions in the pediatric melanoma patient.

Primary cutaneous melanoma: surgical management and other treatment options.

The incidence of primary cutaneous melanoma continues to increase and is a growing public health problem. By virtue of its metastatic potential, melanoma accounts for most of the deaths from cutaneous malignancies. Management of cutaneous melanoma has undergone a paradigm shift in recent years. Clinical studies have furthered our understanding of the biology of this disease and have changed the standards of care. Specifically, sentinel node biopsy and interferon as the first effective postsurgical therapy have had a significant impact on the treatment of patients with melanoma. Surgery remains the primary treatment modality for cutaneous melanoma. An adequate excision of the primary lesion accomplishes durable local control and is curative for patients without micrometastatic disease. Although the extent of surgical resection has decreased in recent years, the standard treatment for primary cutaneous melanoma remains wide surgical excision with histologically negative margins. The extent of excision is based on the theory that the incidence and radial extent of local recurrences can be predicted by specific primary tumor histopathologic characteristics. Tumor thickness and ulceration are the most important histologic features associated with prognosis and are the basis for the current recommendations for surgical treatment of the primary tumor. The extent of surgical therapy for primary melanoma is an area of ongoing debate. No clinical trial has shown a survival disadvantage for narrow versus wide excision regimens for melanoma of any thickness. Ongoing clinical trials will determine the relationship between the extent of surgical therapy for the primary tumor and the outcomes of recurrence and survival in patients with melanoma.

Prognostic importance of lymph node tumor burden in melanoma patients staged by sentinel node biopsy.

BACKGROUND: The objective of this study was to investigate the relationship between nodal tumor burden and the outcomes of recurrence and survival in sentinel node-positive melanoma patients. METHODS: We reviewed a series of sentinel node-positive patients with primary cutaneous melanoma treated with completion lymph node dissection (CLND). Microscopic nodal tumor deposits were counted and measured with an ocular micrometer. Various measures of tumor burden and traditional melanoma prognostic indicators were studied in multivariate Cox regression models. RESULTS: Sentinel lymph node and CLND specimens were evaluated in 90 node-positive patients. The diameter of the largest lymph node tumor nodule and the total lymph node tumor volume were significant predictors of recurrence (two-sided P <.0001 for both) and survival (two-sided P =.0018 and P =.0002, respectively). A tumor deposit diameter of 3 mm was identified as the most significant cut point predictive of recurrence (P <.0001; hazard ratio, 5.18) and survival (P <.0001; hazard ratio, 5.43). The 3-year survival probability was.86 for patients with largest tumor deposit diameters of 3 mm (P <.0001). CONCLUSIONS: Microstaging of melanoma sentinel lymph node/CLND specimens by using the diameter of the largest tumor deposit is a highly significant predictor of early relapse and survival.