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Pattern of first recurrence in melanoma patients after radical lymph node dissection1
P450
P452
EVALUATION OF THE REPRODUCIBILITY OF TOTAL DERMOSCOPIC SCORE OF THE STOLZ’S ABCD RULE AS A PREOPERATIVE PREDICTOR OF MELANOMA THICKNESS Patrizia Valeri, MD, Department of Dermatology, University of L’Aquila, L’Aquila, Italy, 67100 L’Aquila, Italy, Maria Concetta Fargnoli, MD, Gian Piero Lozzi, MD, Ketty Peris, MD Several studies demonstrated the usefulness of dermoscopy in the preoperative detection of cutaneous melanoma thickness. Three different approaches, including pattern analysis, the combination of clinical and dermoscopic criteria, and attribution of total dermoscopic score (TDS) according to the Stolz’s ABCD rule may be used. The aim of our study was to evaluate the reproducibility of TDS of the ABCD rule as a preoperative predictor of melanoma thickness, involving dermatologists with different degrees of experience in dermoscopy. Dermoscopic images of 73 melanomas were examined by 7 dermatologists classified in two groups: experts (3) and non experts (4) in dermoscopy. The results of the study showed a 6.2 TDS cut-off point for the detection of melanomas with Breslow thickness ⱖ 0.75 mm with 85.7% of sensitivity, 80.0% of specificity, and 82.2% of diagnostic accuracy (AUC value, 0.848), when the method was applied by the experts. A good agreement between the experts (k value, 0.66) and a poor agreement between the non experts (k value, 0.22) were observed. In conclusion, TDS provides useful information for the preoperative assessment of melanoma thickness ⬎ 0.75 mm, as reported in a previous study. However, this method has been proved to be more accurate when it is applied by dermatologists expert in dermoscopy.
CUTANEOUS MILIARY PATTERN IN METASTASIZING THIN MALIGNANT MELANOMA Joanna E Gach, MD, University Hospitals Coventry and Warwickshire, Coventry, England, Imtiaz Ahmed, University Hospitals Coventry and Warwickshire, Coventry, England, David Snead, University Hospitals Coventry and Warwickshire, Coventry, England, Andrew Ilchyshyn, University Hospitals Coventry and Warwickshire, Coventry, England We report a 60 year old woman with multiple black dot-like lesions on her body representing metastatic melanoma. Four weeks previously the patient noticed rapidly increasing in number small black macules on her skin and regarded them as “blackheads” before deciding to seek medical advice. Three and a half years earlier she had a nonulcerated superficial spreading malignant melanoma arising in a pre-existing naevus. The lesion had Breslow thickness 1 mm, Clark’s level 4 and was excised from her lower back with 1 cm margin of clearance. There was no sign of vascular invasion or regression of the lesion with only a sparse lymphocytic infiltration. She had been under a regular follow-up at 3-monthly intervals and remained well. Her other medical problems included discoid cutaneous lupus with scarring alopecia which was treated with mepacrine 50 mg daily and topical clobetasol propionate. On examination there were multiple 1-2 mm dot-like black macules and papules on her scalp, face, neck, trunk and limbs. The rest of her clinical examination was unremarkable except for a 3 ⫻ 2 cm tender nodule palpable in the lower outer quadrant of her breast. The breast nodule was not detectable a week later. Skin biopsy confirmed metastatic melanoma in the skin. Baseline investigations showed mild hypercalcaemia of 2.69 mmol/L(normal range 2.22-2.58 mmol/L), and raised alkaline phosphatase of 317iu/L (30-120 iu/L), but normal lactic dehydrogenase and serum S-100 protein of 0.37 ug/L (normal ⬍ 0.20ug/L). Her chest radiograph was normal. Abdominal ultrasound did not show any evidence of metastasis in her liver, pancreas or kidneys. Bone scan demonstrated an increased uptake in the skull, ribs, L2 and right femur. Cutaneous metastasis from malignant melanoma usually present as flesh coloured papules or nodules in the skin. Our patient presented with multiple small black cutaneous dot-like metastasis from a primary thin melanoma on the back. The mechanism for developing miliary cutaneous pattern of metastatic disease with widespread multiple pigmented lesions is not known although it has been suggested that distant metastasis result from haematogenic seeding. It has been shown that thin melanomas which exhibit extensive spontaneous regression represent a group at higher risk of developing metastasis, particularly if the primary lesion involved the torso. However, repeated examination of our patient’s lesion failed to show any evidence of regression.
The authors have no financial interest to disclose.
Disclosure not available at press time.
P453
POSSIBLE USE OF FLAVONOIDS AS CELL GROWTH INHIBITORS IN MALIGNANT MELANOMA Ada Girnita, MD, Karolinska Hospital, Stockholm, Sweden, Leonard Girnita, MD, PhD, Karolinska Hospital, Stockholm, Sweden, Magnus Axelson, MD, PhD, Karolinska Hospital Department of Clinical Chemistry, Stockholm, Sweden, Olle Larsson, MD, PhD, Karolinska Hospital, Stockholm, Sweden Flavonoids are a group of polyphenolic compounds ubiquitously found in fruits and vegetables. They are natural estrogenic compounds chemically related to tamoxifen and have been proposed as chemopreventive and/or curative agents in different types of tumors. The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in transformation, growth and survival of malignant cells, and has emerged as a general and promising target for cancer treatment. IGF-1R belongs to the family of transmembrane tyrosine kinase receptors. Genetic evidence has been presented that IGF-1R is essential for optimal growth in vivo and in vitro of malignant cells but not for normal cells and is involved in tumor cell protection against anti-tumor therapy. For investigating the possible use of these substances on melanoma we used some selected flavonoids and tamoxifen on five human melanoma cell lines FM55, BE, DFB, SK-Mel 28 and SK-Mel 5 in similar concentrations. Our study shows that both some flavonoids and tamoxifen can inhibit the proliferation of melanoma cells by inducing apoptosis in different degrees. The effect was correlated with a decrease in phosphorylation of IGF-1R. These data suggest that tamoxifen analogues could be useful tools in melanoma treatment using IGF-1R as a target.
PATTERN OF FIRST RECURRENCE IN MELANOMA PATIENTS AFTER RADICAL LYMPH NODE DISSECTION Nir Nathansohn, MD, Chaim Sheba Medical Center, Rishon Lezion, Israel, Jackob Schachter, MD, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel, Haim Gutman, MD, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel Introduction: Radical lymph node dissection (RLND) is the current practice treating melanoma patients with isolated regional lymph node metastases. The purpose of this study was to describe the pattern of the first recurrence after RLND, and to identify the factors associated with recurrence and specifically with surgical-field recurrence. Methods: Prospectively collected data of all melanoma patients, undergoing axillary or groin RLND, at a tertiary referral center, by a single surgical oncologist. Chi squared test, logistic regression and Cox regression analyses were applied to identify prognosticator for post-RLND recurrences. Results: RLND was performed on 148 lymph node basins (141 patients). Eighty-six axillae and 62 groins were dissected. Median follow-up was 41 months after the RLND. Eighteen patients (13%) had had previous “tampering” in 20 basins. “Tampering” was defined as any open intervention other than radical complete lymph basin dissection, carried out before the RLND that is the subject of this study. RLND was preformed prophylactically on 36 (24%) basins, for palpable disease in 79 (53%) basins and for positive sentinel node in 33 (23%) basins. 74 patients (52.5%) failed after the RLND during the follow-up period: 52 patients (70%) had systemic disease, 12 patients (16%) had surgical field recurrence, 8 patients (11%) had in-transit metastases and 2 patients (3%) had local recurrence. By multivariate analysis using the logistic regression model, the only significant predictors of recurrence after RLND were Breslow’s thickness ⬎4 mm (p ⫽ 0.015), tampering (p ⫽ 0.011) and lymph node capsular invasion (p ⫽ 0.001). “Tampering” was the only independent prognosticator for surgical field failure: 10 out of 12 patients (83.3%) who had surgical field failure had previous tampering, compared to 5 out of 62 patients with other types of first failures (8.1%) (p ⬍ 0.001). This effect of “tampering” did not translate into survival difference (p ⫽ .96). Surgical field failure was not detected in any of the patients who underwent sentinel lymph node biopsy. Conclusion: “Tampering” the regional basin that drains a melanoma site prior to the definitive surgery, significantly increases the risk of surgical-field melanoma recurrence after RLND. Thus, such procedures should be avoided. Sentinel node biopsy, performed under strict surgical oncology techniques, is safe with regard to surgical field failure.
Disclosure not available at press time.
Disclosure not available at press time.
P451
MARCH 2004
J AM ACAD DERMATOL
P117
P452
EVALUATION OF THE REPRODUCIBILITY OF TOTAL DERMOSCOPIC SCORE OF THE STOLZ’S ABCD RULE AS A PREOPERATIVE PREDICTOR OF MELANOMA THICKNESS Patrizia Valeri, MD, Department of Dermatology, University of L’Aquila, L’Aquila, Italy, 67100 L’Aquila, Italy, Maria Concetta Fargnoli, MD, Gian Piero Lozzi, MD, Ketty Peris, MD Several studies demonstrated the usefulness of dermoscopy in the preoperative detection of cutaneous melanoma thickness. Three different approaches, including pattern analysis, the combination of clinical and dermoscopic criteria, and attribution of total dermoscopic score (TDS) according to the Stolz’s ABCD rule may be used. The aim of our study was to evaluate the reproducibility of TDS of the ABCD rule as a preoperative predictor of melanoma thickness, involving dermatologists with different degrees of experience in dermoscopy. Dermoscopic images of 73 melanomas were examined by 7 dermatologists classified in two groups: experts (3) and non experts (4) in dermoscopy. The results of the study showed a 6.2 TDS cut-off point for the detection of melanomas with Breslow thickness ⱖ 0.75 mm with 85.7% of sensitivity, 80.0% of specificity, and 82.2% of diagnostic accuracy (AUC value, 0.848), when the method was applied by the experts. A good agreement between the experts (k value, 0.66) and a poor agreement between the non experts (k value, 0.22) were observed. In conclusion, TDS provides useful information for the preoperative assessment of melanoma thickness ⬎ 0.75 mm, as reported in a previous study. However, this method has been proved to be more accurate when it is applied by dermatologists expert in dermoscopy.
CUTANEOUS MILIARY PATTERN IN METASTASIZING THIN MALIGNANT MELANOMA Joanna E Gach, MD, University Hospitals Coventry and Warwickshire, Coventry, England, Imtiaz Ahmed, University Hospitals Coventry and Warwickshire, Coventry, England, David Snead, University Hospitals Coventry and Warwickshire, Coventry, England, Andrew Ilchyshyn, University Hospitals Coventry and Warwickshire, Coventry, England We report a 60 year old woman with multiple black dot-like lesions on her body representing metastatic melanoma. Four weeks previously the patient noticed rapidly increasing in number small black macules on her skin and regarded them as “blackheads” before deciding to seek medical advice. Three and a half years earlier she had a nonulcerated superficial spreading malignant melanoma arising in a pre-existing naevus. The lesion had Breslow thickness 1 mm, Clark’s level 4 and was excised from her lower back with 1 cm margin of clearance. There was no sign of vascular invasion or regression of the lesion with only a sparse lymphocytic infiltration. She had been under a regular follow-up at 3-monthly intervals and remained well. Her other medical problems included discoid cutaneous lupus with scarring alopecia which was treated with mepacrine 50 mg daily and topical clobetasol propionate. On examination there were multiple 1-2 mm dot-like black macules and papules on her scalp, face, neck, trunk and limbs. The rest of her clinical examination was unremarkable except for a 3 ⫻ 2 cm tender nodule palpable in the lower outer quadrant of her breast. The breast nodule was not detectable a week later. Skin biopsy confirmed metastatic melanoma in the skin. Baseline investigations showed mild hypercalcaemia of 2.69 mmol/L(normal range 2.22-2.58 mmol/L), and raised alkaline phosphatase of 317iu/L (30-120 iu/L), but normal lactic dehydrogenase and serum S-100 protein of 0.37 ug/L (normal ⬍ 0.20ug/L). Her chest radiograph was normal. Abdominal ultrasound did not show any evidence of metastasis in her liver, pancreas or kidneys. Bone scan demonstrated an increased uptake in the skull, ribs, L2 and right femur. Cutaneous metastasis from malignant melanoma usually present as flesh coloured papules or nodules in the skin. Our patient presented with multiple small black cutaneous dot-like metastasis from a primary thin melanoma on the back. The mechanism for developing miliary cutaneous pattern of metastatic disease with widespread multiple pigmented lesions is not known although it has been suggested that distant metastasis result from haematogenic seeding. It has been shown that thin melanomas which exhibit extensive spontaneous regression represent a group at higher risk of developing metastasis, particularly if the primary lesion involved the torso. However, repeated examination of our patient’s lesion failed to show any evidence of regression.
The authors have no financial interest to disclose.
Disclosure not available at press time.
P453
POSSIBLE USE OF FLAVONOIDS AS CELL GROWTH INHIBITORS IN MALIGNANT MELANOMA Ada Girnita, MD, Karolinska Hospital, Stockholm, Sweden, Leonard Girnita, MD, PhD, Karolinska Hospital, Stockholm, Sweden, Magnus Axelson, MD, PhD, Karolinska Hospital Department of Clinical Chemistry, Stockholm, Sweden, Olle Larsson, MD, PhD, Karolinska Hospital, Stockholm, Sweden Flavonoids are a group of polyphenolic compounds ubiquitously found in fruits and vegetables. They are natural estrogenic compounds chemically related to tamoxifen and have been proposed as chemopreventive and/or curative agents in different types of tumors. The insulin-like growth factor-1 receptor (IGF-1R) plays a pivotal role in transformation, growth and survival of malignant cells, and has emerged as a general and promising target for cancer treatment. IGF-1R belongs to the family of transmembrane tyrosine kinase receptors. Genetic evidence has been presented that IGF-1R is essential for optimal growth in vivo and in vitro of malignant cells but not for normal cells and is involved in tumor cell protection against anti-tumor therapy. For investigating the possible use of these substances on melanoma we used some selected flavonoids and tamoxifen on five human melanoma cell lines FM55, BE, DFB, SK-Mel 28 and SK-Mel 5 in similar concentrations. Our study shows that both some flavonoids and tamoxifen can inhibit the proliferation of melanoma cells by inducing apoptosis in different degrees. The effect was correlated with a decrease in phosphorylation of IGF-1R. These data suggest that tamoxifen analogues could be useful tools in melanoma treatment using IGF-1R as a target.
PATTERN OF FIRST RECURRENCE IN MELANOMA PATIENTS AFTER RADICAL LYMPH NODE DISSECTION Nir Nathansohn, MD, Chaim Sheba Medical Center, Rishon Lezion, Israel, Jackob Schachter, MD, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel, Haim Gutman, MD, Rabin Medical Center, Beilinson Campus, Petah Tiqva, Israel Introduction: Radical lymph node dissection (RLND) is the current practice treating melanoma patients with isolated regional lymph node metastases. The purpose of this study was to describe the pattern of the first recurrence after RLND, and to identify the factors associated with recurrence and specifically with surgical-field recurrence. Methods: Prospectively collected data of all melanoma patients, undergoing axillary or groin RLND, at a tertiary referral center, by a single surgical oncologist. Chi squared test, logistic regression and Cox regression analyses were applied to identify prognosticator for post-RLND recurrences. Results: RLND was performed on 148 lymph node basins (141 patients). Eighty-six axillae and 62 groins were dissected. Median follow-up was 41 months after the RLND. Eighteen patients (13%) had had previous “tampering” in 20 basins. “Tampering” was defined as any open intervention other than radical complete lymph basin dissection, carried out before the RLND that is the subject of this study. RLND was preformed prophylactically on 36 (24%) basins, for palpable disease in 79 (53%) basins and for positive sentinel node in 33 (23%) basins. 74 patients (52.5%) failed after the RLND during the follow-up period: 52 patients (70%) had systemic disease, 12 patients (16%) had surgical field recurrence, 8 patients (11%) had in-transit metastases and 2 patients (3%) had local recurrence. By multivariate analysis using the logistic regression model, the only significant predictors of recurrence after RLND were Breslow’s thickness ⬎4 mm (p ⫽ 0.015), tampering (p ⫽ 0.011) and lymph node capsular invasion (p ⫽ 0.001). “Tampering” was the only independent prognosticator for surgical field failure: 10 out of 12 patients (83.3%) who had surgical field failure had previous tampering, compared to 5 out of 62 patients with other types of first failures (8.1%) (p ⬍ 0.001). This effect of “tampering” did not translate into survival difference (p ⫽ .96). Surgical field failure was not detected in any of the patients who underwent sentinel lymph node biopsy. Conclusion: “Tampering” the regional basin that drains a melanoma site prior to the definitive surgery, significantly increases the risk of surgical-field melanoma recurrence after RLND. Thus, such procedures should be avoided. Sentinel node biopsy, performed under strict surgical oncology techniques, is safe with regard to surgical field failure.
Disclosure not available at press time.
Disclosure not available at press time.
P451
MARCH 2004
J AM ACAD DERMATOL
P117