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Diagnosis of melanocytic lesions using molecular techniques
PD01—MELANOMA, PIGMENTATION, BASIC SCIENCE Underreporting of mitotic rate in cutaneous melanoma: Adhering to the 2009 AJCC guidelines
(Poster reference number 5073)
Rebecca Chibnall, University of Southern California, Department of Dermatology, Los Angeles, CA, United States; Ashley Sutton, MD, University of Southern California, Department of Dermatology, Los Angeles, CA, United States; Myles Cockburn, PhD, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, United States In 2009, the staging system for cutaneous melanoma, instituted by the American Joint Committee on Cancer (AJCC), was significantly altered to include mitotic rate for tumors with less than 1.00 mm thickness. Based on studies from numerous large melanoma databases, which demonstrate that mitotic rate is an independent prognostic factor, this revision represents a significant change from the sixth edition staging system. In light of this recent publication, we sought to determine how frequently and in what manner mitotic rate was reported during the time period from 1988-2008 in Los Angeles County. We theorized that pathologists infrequently recorded mitotic rate before the new guidelines. Also, we suspected that when mitotic rate was reported, it was documented without field of view or in units which could not be generalized, making the information difficult to analyze. To evaluate this hypothesis, we reviewed 7,283 pathology reports for incident melanomas in Los Angeles County from 1988-2008, looking for measurement of mitotic rate and documentation of field of view. We found that before 2006, the frequency of mitotic rate reporting was 3%; however, from 2006 to 2008, mitotic rate has been increasingly reported in Los Angeles County with 28.5% inclusion in 2008. Additionally, when present from 2006-2008, it was documented with units of high powered field (HPF) 50% of the time and square millimeters, the units recommended by the AJCC, the other 50% of the time. Therefore, we concluded that although pathologists still infrequently record mitotic rate, its inclusion in reports has been on the rise since 2006; moreover, when mitotic rate appears in records, it is only conveyed in accordance with the seventh edition staging system 50% of the time. These data from a large urban center highlight the importance of raising awareness regarding regular and consistent reporting of mitotic rate. When considering that 80% of newly diagnosed melanomas measure less than 1 mm in depth, and that one mitotic figure in these tumors changes 10-year survival from 95% to 88%, the need for diligence becomes even more evident. Commercial support: None identified.
Evidence for modification of the ABCDE criteria for pediatric melanoma
(Poster reference number 5407)
Deepti Gupta, MD, UCSF, San Francisco, CA, United States; Ilona Frieden, MD, UCSF, San Francisco, CA, United States; Kelly Cordoro, MD, UCSF, San Francisco, CA, United States; Mohammed Kashani-Sabet, MD, California Pacific Medical Center, San Francisco, CA, United States; Timothy McCalmont, MD, UCSF, San Francisco, CA, United States Background: Melanoma in the pediatric population is understudied, and its incidence is increasing. Childhood melanoma presents with thicker tumors, nodular subtype, and more frequent sentinel lymph node metastases compared to thicknessmatched adults. A low index of suspicion in children combined with atypical clinical and microscopic features leads to diagnostic delays, advanced presentations, and decreased survival. We sought to critically reappraise the utility of the classic ABCDE criteria for children. Methods: We performed a retrospective cohort study of 70 patients less than 20 years old diagnosed with melanoma at UCSF between 1984 and 2009. We stratified our population by age as a proxy for pubertal status into 10 years and younger (‘‘prepubescent’’) and 11 years and older (‘‘pubescent’’). Nineteen of 70 patients (27%) were prepubescent and 51of 70 (73%) were pubescent. Results: Prepubescent patients were more likely to have lesions that were amelanotic (76% vs 21%; P \.0001), a single color (87% vs 49%; P ¼.01), bleeding (54% vs 23%; P ¼.04), and diameter \6 mm (72% vs 54%; P ¼.03) compared with pubescent patients. Overall, 91% of melanomas presented with elevation while 9% were flat. Histologically, spitzoid melanomas accounted for 26% of the prepubescent cohort versus 0% of pubescent. Three patients overall had melanoma within a LCMN. Sixtyfive percent of the full cohort had a time to diagnosis of [12 months. Tumor thickness ranged from Breslow depth of 0.17 to 17.5 mm. Primary tumors were thick (Breslow depth [1 mm) in 67% of the overall cohort, 93% of prepubescent and 59% of pubescent children. SLNB was performed in 43/70 (61%) of patients and 16 (27%) were positive. Of positive SLNB, 58% were prepubescent versus 30% pubescent. Fifty-six percent of prepubescent versus 36% of pubescent cohort had metastatic disease. Overall, 7 patients died of melanoma. Three of 7 (43%) deaths occurred in the context of a LCMN. Death occurred in 6% of the prepubescent and 12% of the pubescent cohort. Conclusion: There are distinct differences in clinical presentation of melanoma between younger and older children. Our data suggest that the conventional ABCDE criteria for clinical detection of melanoma should be modified for prepubescent patients to include amelanotic, bleeding, single color, diameter may be \6 mm, and elevation. Our results confirm published data that despite longer time to diagnosis, thicker tumors, and metastatic disease the mortality of childhood melanoma, while still a possible outcome, is low. Commercial support: None identified.
Combination (hydroquinone 5%, tretinoin 0.1%, and hydrocortisone 1%) cream in treating facial hyperpigmentation; a retrospective patient satisfaction study
(Poster reference number 5700) Diagnosis of melanocytic lesions using molecular techniques
(Poster reference number 5109)
Melissa McEnery-Stonelake, University of Massachusetts Medical School, Worcester, MA, United States; April Deng, MD, PhD, Department of Pathology, University of Massachusetts Medical School, Worcester, MA, United States; Keith Tomaszewicz, Laboratory of Diagnostic Molecular Oncology, University of Massachusetts Memorial Medical Center, Worcester, MA, United States; Lloyd Hutchinson, PhD, Laboratory of Diagnostic Molecular Oncology, University of Massachusetts Memorial Medical Center, Worcester, MA, United States Background: Identifying malignant melanoma using histopathologic characteristics can be challenging, because melanoma can share features similar to several benign melanocytic nevi, for example, pediatric Spitz nevi. Additional techniques are needed to aid pathologists in the diagnosis of melanoma. The objective of this study was to identify a genetic signature able to distinguish melanoma from benign melanocytic lesions using multiplex ligation probe-dependent amplification (MLPA) screening method and BRAF quantitative PCR. Methods: Laser capture microdissection was used to isolate target cells from 10 malignant melanoma and 12 benign melanocytic nevi samples. DNA was extracted. MLPA was used to evaluate copy number loss/gain of 120 genes implicated in cancer. BRAF point mutation analyses were also performed. Results: Chromosome abnormalities were observed in benign melanocytic nevi and melanoma. Melanomas showed a greater number of chromosome abnormalities than benign melanocytic nevi (average, 10.8 6 7.3 vs 2.0 6 2.5; median, 9.5 vs 1.0; minimum, 4 vs 0; maximum, 28 vs 6). Some abnormalities were exclusive to melanoma (eg, MYB, TANK, IL1A, BRCA2, and LRMP), whereas a CDKN2A (9p21, p16) deletion was not, in contrast to previous reports. Benign melanocytic nevi tended to have a combination of BRAF mutation and PTEN deletion (;80%), while melanoma did not (\16.7%).
John Fleming, MBBS, Dermatology Department, King’s College Hospital, London, United Kingdom; Saqib Bashir, MBBS, MD, Dermatology Department, King’s College Hospital, London, United Kingdom Background: Melasma and postinflammatory hyperpigmentation provide a significant source of psychosocial morbidity, especially in those with Fitzpatrick skin types III-VI. Kligman’s formula was the mainstay of topical depigmenting therapy but occasionally induced skin irritation. Further, it has a short shelf life and high cost, when compounded to order by pharmacists. In Europe, a proprietary product, with a long expiry date, has become available, which may influence treatment effectiveness by: reduced cost of manufacture versus compounding, and increased patient use as a result of the longer shelf life. Its ingredients—hydroquinone 5%, tretinoin 0.1%, and hydrocortisone 1%—are similar to Kligman’s formula. We assessed patient satisfaction with a newly available combination depigmenting preparation. Methods: We studied the effect the proprietary cream had in improving a patient’s quality of life and the symptoms they experienced from their skin. Forty-one subjects, who had all been prescribed a 15-g tube to use sparingly at night for 90 days within the last 12 months, were telephoned to rate the effect the cream had on their quality of life and skin symptom improvement. Each patient also had their Dermatology Life Quality Index (DLQI) score assessed. Results: Data were obtained from 29 subjects (22 with melasma, 7 with postinflammatory hyperpigmentation secondary to acne). Twelve subjects noted a marked improvement in their quality of life, 9 a moderate improvement, 5 a mild improvement with no improvement noted in 3. Skin symptoms were markedly improved in 11, moderately in 12, mildly in 4 with no improvement in 2. The mean posttreatment DLQI was 4.4 (range, 1-10). Patients deriving the most benefit from the treatment were those making a 15-g tube last 2 months or more. Of the 7 patients reporting skin irritation and peeling following use, 5 had finished a 15-g tube of cream in \30 days.
Conclusion: BRAF status in combination with the number of abnormalities (eg, [5) or a specific deletion/amplification pattern may distinguish malignant melanoma from benign melanocytic nevi. Additional studies (more specimens, confirmatory probe sets) are required to validate both the algorithm and potential target genes.
Conclusion: Patients reported improvement in both hyperpigmentation and in quality of life, suggesting a high level of satisfaction with treatment. The advantages of the long shelf life product may also include decreased cost via decreased physician and pharmacist time; however, these data confirm that treatment with the new product effectively improves self-assessed quality of life and hyperpigmentation.
Commercial support: None identified.
Commercial support: None identified.
APRIL 2012
J AM ACAD DERMATOL
AB1
(Poster reference number 5073)
Rebecca Chibnall, University of Southern California, Department of Dermatology, Los Angeles, CA, United States; Ashley Sutton, MD, University of Southern California, Department of Dermatology, Los Angeles, CA, United States; Myles Cockburn, PhD, Department of Preventive Medicine, Keck School of Medicine, Los Angeles, CA, United States In 2009, the staging system for cutaneous melanoma, instituted by the American Joint Committee on Cancer (AJCC), was significantly altered to include mitotic rate for tumors with less than 1.00 mm thickness. Based on studies from numerous large melanoma databases, which demonstrate that mitotic rate is an independent prognostic factor, this revision represents a significant change from the sixth edition staging system. In light of this recent publication, we sought to determine how frequently and in what manner mitotic rate was reported during the time period from 1988-2008 in Los Angeles County. We theorized that pathologists infrequently recorded mitotic rate before the new guidelines. Also, we suspected that when mitotic rate was reported, it was documented without field of view or in units which could not be generalized, making the information difficult to analyze. To evaluate this hypothesis, we reviewed 7,283 pathology reports for incident melanomas in Los Angeles County from 1988-2008, looking for measurement of mitotic rate and documentation of field of view. We found that before 2006, the frequency of mitotic rate reporting was 3%; however, from 2006 to 2008, mitotic rate has been increasingly reported in Los Angeles County with 28.5% inclusion in 2008. Additionally, when present from 2006-2008, it was documented with units of high powered field (HPF) 50% of the time and square millimeters, the units recommended by the AJCC, the other 50% of the time. Therefore, we concluded that although pathologists still infrequently record mitotic rate, its inclusion in reports has been on the rise since 2006; moreover, when mitotic rate appears in records, it is only conveyed in accordance with the seventh edition staging system 50% of the time. These data from a large urban center highlight the importance of raising awareness regarding regular and consistent reporting of mitotic rate. When considering that 80% of newly diagnosed melanomas measure less than 1 mm in depth, and that one mitotic figure in these tumors changes 10-year survival from 95% to 88%, the need for diligence becomes even more evident. Commercial support: None identified.
Evidence for modification of the ABCDE criteria for pediatric melanoma
(Poster reference number 5407)
Deepti Gupta, MD, UCSF, San Francisco, CA, United States; Ilona Frieden, MD, UCSF, San Francisco, CA, United States; Kelly Cordoro, MD, UCSF, San Francisco, CA, United States; Mohammed Kashani-Sabet, MD, California Pacific Medical Center, San Francisco, CA, United States; Timothy McCalmont, MD, UCSF, San Francisco, CA, United States Background: Melanoma in the pediatric population is understudied, and its incidence is increasing. Childhood melanoma presents with thicker tumors, nodular subtype, and more frequent sentinel lymph node metastases compared to thicknessmatched adults. A low index of suspicion in children combined with atypical clinical and microscopic features leads to diagnostic delays, advanced presentations, and decreased survival. We sought to critically reappraise the utility of the classic ABCDE criteria for children. Methods: We performed a retrospective cohort study of 70 patients less than 20 years old diagnosed with melanoma at UCSF between 1984 and 2009. We stratified our population by age as a proxy for pubertal status into 10 years and younger (‘‘prepubescent’’) and 11 years and older (‘‘pubescent’’). Nineteen of 70 patients (27%) were prepubescent and 51of 70 (73%) were pubescent. Results: Prepubescent patients were more likely to have lesions that were amelanotic (76% vs 21%; P \.0001), a single color (87% vs 49%; P ¼.01), bleeding (54% vs 23%; P ¼.04), and diameter \6 mm (72% vs 54%; P ¼.03) compared with pubescent patients. Overall, 91% of melanomas presented with elevation while 9% were flat. Histologically, spitzoid melanomas accounted for 26% of the prepubescent cohort versus 0% of pubescent. Three patients overall had melanoma within a LCMN. Sixtyfive percent of the full cohort had a time to diagnosis of [12 months. Tumor thickness ranged from Breslow depth of 0.17 to 17.5 mm. Primary tumors were thick (Breslow depth [1 mm) in 67% of the overall cohort, 93% of prepubescent and 59% of pubescent children. SLNB was performed in 43/70 (61%) of patients and 16 (27%) were positive. Of positive SLNB, 58% were prepubescent versus 30% pubescent. Fifty-six percent of prepubescent versus 36% of pubescent cohort had metastatic disease. Overall, 7 patients died of melanoma. Three of 7 (43%) deaths occurred in the context of a LCMN. Death occurred in 6% of the prepubescent and 12% of the pubescent cohort. Conclusion: There are distinct differences in clinical presentation of melanoma between younger and older children. Our data suggest that the conventional ABCDE criteria for clinical detection of melanoma should be modified for prepubescent patients to include amelanotic, bleeding, single color, diameter may be \6 mm, and elevation. Our results confirm published data that despite longer time to diagnosis, thicker tumors, and metastatic disease the mortality of childhood melanoma, while still a possible outcome, is low. Commercial support: None identified.
Combination (hydroquinone 5%, tretinoin 0.1%, and hydrocortisone 1%) cream in treating facial hyperpigmentation; a retrospective patient satisfaction study
(Poster reference number 5700) Diagnosis of melanocytic lesions using molecular techniques
(Poster reference number 5109)
Melissa McEnery-Stonelake, University of Massachusetts Medical School, Worcester, MA, United States; April Deng, MD, PhD, Department of Pathology, University of Massachusetts Medical School, Worcester, MA, United States; Keith Tomaszewicz, Laboratory of Diagnostic Molecular Oncology, University of Massachusetts Memorial Medical Center, Worcester, MA, United States; Lloyd Hutchinson, PhD, Laboratory of Diagnostic Molecular Oncology, University of Massachusetts Memorial Medical Center, Worcester, MA, United States Background: Identifying malignant melanoma using histopathologic characteristics can be challenging, because melanoma can share features similar to several benign melanocytic nevi, for example, pediatric Spitz nevi. Additional techniques are needed to aid pathologists in the diagnosis of melanoma. The objective of this study was to identify a genetic signature able to distinguish melanoma from benign melanocytic lesions using multiplex ligation probe-dependent amplification (MLPA) screening method and BRAF quantitative PCR. Methods: Laser capture microdissection was used to isolate target cells from 10 malignant melanoma and 12 benign melanocytic nevi samples. DNA was extracted. MLPA was used to evaluate copy number loss/gain of 120 genes implicated in cancer. BRAF point mutation analyses were also performed. Results: Chromosome abnormalities were observed in benign melanocytic nevi and melanoma. Melanomas showed a greater number of chromosome abnormalities than benign melanocytic nevi (average, 10.8 6 7.3 vs 2.0 6 2.5; median, 9.5 vs 1.0; minimum, 4 vs 0; maximum, 28 vs 6). Some abnormalities were exclusive to melanoma (eg, MYB, TANK, IL1A, BRCA2, and LRMP), whereas a CDKN2A (9p21, p16) deletion was not, in contrast to previous reports. Benign melanocytic nevi tended to have a combination of BRAF mutation and PTEN deletion (;80%), while melanoma did not (\16.7%).
John Fleming, MBBS, Dermatology Department, King’s College Hospital, London, United Kingdom; Saqib Bashir, MBBS, MD, Dermatology Department, King’s College Hospital, London, United Kingdom Background: Melasma and postinflammatory hyperpigmentation provide a significant source of psychosocial morbidity, especially in those with Fitzpatrick skin types III-VI. Kligman’s formula was the mainstay of topical depigmenting therapy but occasionally induced skin irritation. Further, it has a short shelf life and high cost, when compounded to order by pharmacists. In Europe, a proprietary product, with a long expiry date, has become available, which may influence treatment effectiveness by: reduced cost of manufacture versus compounding, and increased patient use as a result of the longer shelf life. Its ingredients—hydroquinone 5%, tretinoin 0.1%, and hydrocortisone 1%—are similar to Kligman’s formula. We assessed patient satisfaction with a newly available combination depigmenting preparation. Methods: We studied the effect the proprietary cream had in improving a patient’s quality of life and the symptoms they experienced from their skin. Forty-one subjects, who had all been prescribed a 15-g tube to use sparingly at night for 90 days within the last 12 months, were telephoned to rate the effect the cream had on their quality of life and skin symptom improvement. Each patient also had their Dermatology Life Quality Index (DLQI) score assessed. Results: Data were obtained from 29 subjects (22 with melasma, 7 with postinflammatory hyperpigmentation secondary to acne). Twelve subjects noted a marked improvement in their quality of life, 9 a moderate improvement, 5 a mild improvement with no improvement noted in 3. Skin symptoms were markedly improved in 11, moderately in 12, mildly in 4 with no improvement in 2. The mean posttreatment DLQI was 4.4 (range, 1-10). Patients deriving the most benefit from the treatment were those making a 15-g tube last 2 months or more. Of the 7 patients reporting skin irritation and peeling following use, 5 had finished a 15-g tube of cream in \30 days.
Conclusion: BRAF status in combination with the number of abnormalities (eg, [5) or a specific deletion/amplification pattern may distinguish malignant melanoma from benign melanocytic nevi. Additional studies (more specimens, confirmatory probe sets) are required to validate both the algorithm and potential target genes.
Conclusion: Patients reported improvement in both hyperpigmentation and in quality of life, suggesting a high level of satisfaction with treatment. The advantages of the long shelf life product may also include decreased cost via decreased physician and pharmacist time; however, these data confirm that treatment with the new product effectively improves self-assessed quality of life and hyperpigmentation.
Commercial support: None identified.
Commercial support: None identified.
APRIL 2012
J AM ACAD DERMATOL
AB1