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Malignant melanoma arising in a nevus of Ota
P2810
P2812
Malignant melanoma arising in a nevus of Ota Clare Patterson, Amersham Hospital, Amersham, Buckinghamshire, United Kingdom; Katharine Acland, MD, MBBS, Amersham Hospital, Amersham, Buckinghamshire, United Kingdom Background: A 32-year-old white male presented with a 3-year history of asymptomatic discoloration around his right eye. In the last year, a nodule had developed within it. A clinical examination revealed very subtle slate grey pigmentation in the supraorbital area. Within this was a 3- 3 3-mm pigmented nodule that was pigmented and regular in color and contour. He was seen by a number of dermatologists who felt that it was benign, but the lesion was excised based on the history of change. Histology: This was consistent with an invasive malignant melanoma Breslow thickness 6.0 mm.
Changes in the dermatoscopic appearance of melanocytic nevi after radiation therapy David Swanson, PhD, Mayo Clinic Scottsdale, Scottsdale, AZ, United States; Ronald Tee, MD, Mayo Clinic Scottsdale, Scottsdale, AZ, United States
Ocular findings: More extensive examination of his eye revealed unusual yellow pigment on the upper and lower eyelid of the right eye. On the conjunctiva surrounding the entire circumference of the globe and extending to the fornices was an indurated pigmented ring like structure. Biopsy of this revealed dermal melanocytosis and no atypia. Progress: Staging investigations have shown metastatic nodules in the lung and liver and a metastatic deposit in the supraorbital area of the frontal bone. He is now on a phase 1 clinical trial of an arsenic-based treatment called GSAO. Discussion: There are been 40 reported cases of melanomas occurring within a nevus of Ota (Patel et al). The majority have been in the choroid plexus and the central nervous system. Only 10 have occurred in the cutaneous part of the nevus. In all cases where race was reported, the patient was Caucasian. Each time the melanoma exhibited no suspicious features but was consistent with a benign nevus.
Exposure to therapeutic radiation can lead to a number of clinical and histopathologic changes in the skin. While changes in the dermatoscopic appearance of melanocytic nevi after photochemotherapy or narrow-band ultraviolet B phototherapy have been described, those changes after radiation therapy have not been reported. We describe two patients who were identified as having nevi within projected radiation treatment fields. Their nevi were followed with dermatoscopy before radiation exposure, immediately after completion of radiation, and at subsequent postradiation follow-up. Dermatoscopic changes were clearly identified suggesting that radiation therapy does appear to induce changes in melanocytic nevi. The etiology and long-term significance of these changes remains to be elucidated. Commercial support: None identified.
Commercial support: None identified.
NONMELANOMA SKIN CANCER P2900 Future consequences, health literacy, and perception of risk of developing squamous cell carcinomas in solid organ transplant recipients and their intention to perform skin self-examination Susan L. Boone, MD, Northwestern University, Department of Dermatology, Chicago, IL, United States; Jerod Stapleton, Biobehavioral Health and Prevention Research Center, University Park, PA, United States; June Robinson, MD, Northwestern University, Department of Dermatology, Chicago, IL, United States; Sara Ortiz, Northwestern University, Department of Dermatology, Chicago, IL, United States
P2811 Insulin-like growth factor 1 receptor as the therapeutic target in melanoma Ada Girnita, CAN, Department of Dermatology/Department of OncologyPathology, Stockholm, Sweden; Daiana Vasilcanu, MD, PhD, Department of Oncology-Pathology, Stockholm, Sweden; Leonard Girnita, MD, PhD, St. Eriks Eye Hospital/Department of Oncology-Pathology, Stockholm, Sweden Melanoma is a malignant tumor of melanocytes which are found predominantly in skin but also in the bowel and the eye. Skin melanoma causes a vast number of skin cancererelated deaths. Despite many years of intensive laboratory and clinical research, the sole effective cure is surgical resection of the primary tumor before it achieves a thickness [1 mm. When there is distant metastasis, the cancer is generally considered incurable, and the 5-year survival rate is decreasing dramatically. Insulin-like growth factor 1 receptor (IGF-1R) is crucial for the growth and survival of melanoma cells. IGF-1R down-regulation required expression of the MDM2 E3 ligase, which recently was found to ubiquitinate and cause degradation of the IGF-1R. Here we compare two different approaches of targeting IGF-1R in melanoma cells both, in cell cultures and animal models: inhibition of IGF-1R kinase activity versus IGF-1R down-regulation. We used dominant negative mutants to inhibit IGF-1R kinase activity and RNA interference strategies to down-regulate IGF-1R. As an alternative experimental model of down-regulation, we overexpressed MDM-2, the ubiquitine ligase responsible for IGF-1R degradation. Our results suggest that IGF-1R degradation, although partial, is very important to the final outcome, while the down-regulation of IGF-1R is necessary for induction of apoptosis in melanoma cells. An inhibition of IGF-1R phosphorylation, without accompanying down-regulation, leads only to decreased proliferation but not to apoptosis. Targeting IGF-1R may therefore comprise a strategy to treat ongoing disease (today incurable) and a strategy to prevent development of metastases in patients with primary disease.
Approximately 3 to 7 years after the onset of immunosuppression, solid organ transplant recipients (OTRs) have an increased incidence of squamous cell carcinoma (SCC). SCC is responsible for a mortality rate of 5% to 8% in OTRs. The recommended frequency of skin examinations by a health care provider is dependent on the risk level of the patient; however, patients frequently do not seek health care for routine skin checks. While regular skin self-examination (SSE) is an important secondary prevention method for early detection of skin cancer, OTRs do not routinely perform SSE. This study validates a written educational intervention to help patients comprehend their risk factors, determines optimal time to deliver the intervention, and evaluates change in OTRs’ risk perception, anxiety, selfefficacy, intention to perform SSE, and performance of SSE. A convenience sample of 60 OTRs was accrued from the approximately 820 solid OTRs performed per year at Northwestern Memorial Hospital. The 20 OTRs at each of 3 time points—3 to 6 months, 1 to 2 years, and 3 to 7 years after the transplantation—responded to cognitive qualitative interviews and quantitative questionnaires that assess the patients’ consideration for future consequences, health literacy, sense of the best time to receive this information, how it is best conveyed, and who is the best person to convey this information. Change in knowledge, risk perception, the importance of skin checks, confidence in performance, and intention to perform SSE are measured pre- and postintervention and are compared across three time points. One month after the intervention, the patient is asked if they performed SSE and if they sought the care of a dermatologist. Our hypothesis is that an educational intervention designed to increase OTRs’ awareness of their risk of developing SCC and teach SSE has greater relevance when delivered in proximity to the time at which SCC might develop rather than at the time of organ transplantation. This written educational brochure motivates OTRs to seek care with a dermatologist and can be widely disseminated by physicians who provide continuing care to OTRs after the patients cease receiving care from the surgical transplantation team (eg, kidney transplant recipients from nephrologists).
Commercial support: None identified.
Commercial support: None identified.
AB134
J AM ACAD DERMATOL
MARCH 2009
P2812
Malignant melanoma arising in a nevus of Ota Clare Patterson, Amersham Hospital, Amersham, Buckinghamshire, United Kingdom; Katharine Acland, MD, MBBS, Amersham Hospital, Amersham, Buckinghamshire, United Kingdom Background: A 32-year-old white male presented with a 3-year history of asymptomatic discoloration around his right eye. In the last year, a nodule had developed within it. A clinical examination revealed very subtle slate grey pigmentation in the supraorbital area. Within this was a 3- 3 3-mm pigmented nodule that was pigmented and regular in color and contour. He was seen by a number of dermatologists who felt that it was benign, but the lesion was excised based on the history of change. Histology: This was consistent with an invasive malignant melanoma Breslow thickness 6.0 mm.
Changes in the dermatoscopic appearance of melanocytic nevi after radiation therapy David Swanson, PhD, Mayo Clinic Scottsdale, Scottsdale, AZ, United States; Ronald Tee, MD, Mayo Clinic Scottsdale, Scottsdale, AZ, United States
Ocular findings: More extensive examination of his eye revealed unusual yellow pigment on the upper and lower eyelid of the right eye. On the conjunctiva surrounding the entire circumference of the globe and extending to the fornices was an indurated pigmented ring like structure. Biopsy of this revealed dermal melanocytosis and no atypia. Progress: Staging investigations have shown metastatic nodules in the lung and liver and a metastatic deposit in the supraorbital area of the frontal bone. He is now on a phase 1 clinical trial of an arsenic-based treatment called GSAO. Discussion: There are been 40 reported cases of melanomas occurring within a nevus of Ota (Patel et al). The majority have been in the choroid plexus and the central nervous system. Only 10 have occurred in the cutaneous part of the nevus. In all cases where race was reported, the patient was Caucasian. Each time the melanoma exhibited no suspicious features but was consistent with a benign nevus.
Exposure to therapeutic radiation can lead to a number of clinical and histopathologic changes in the skin. While changes in the dermatoscopic appearance of melanocytic nevi after photochemotherapy or narrow-band ultraviolet B phototherapy have been described, those changes after radiation therapy have not been reported. We describe two patients who were identified as having nevi within projected radiation treatment fields. Their nevi were followed with dermatoscopy before radiation exposure, immediately after completion of radiation, and at subsequent postradiation follow-up. Dermatoscopic changes were clearly identified suggesting that radiation therapy does appear to induce changes in melanocytic nevi. The etiology and long-term significance of these changes remains to be elucidated. Commercial support: None identified.
Commercial support: None identified.
NONMELANOMA SKIN CANCER P2900 Future consequences, health literacy, and perception of risk of developing squamous cell carcinomas in solid organ transplant recipients and their intention to perform skin self-examination Susan L. Boone, MD, Northwestern University, Department of Dermatology, Chicago, IL, United States; Jerod Stapleton, Biobehavioral Health and Prevention Research Center, University Park, PA, United States; June Robinson, MD, Northwestern University, Department of Dermatology, Chicago, IL, United States; Sara Ortiz, Northwestern University, Department of Dermatology, Chicago, IL, United States
P2811 Insulin-like growth factor 1 receptor as the therapeutic target in melanoma Ada Girnita, CAN, Department of Dermatology/Department of OncologyPathology, Stockholm, Sweden; Daiana Vasilcanu, MD, PhD, Department of Oncology-Pathology, Stockholm, Sweden; Leonard Girnita, MD, PhD, St. Eriks Eye Hospital/Department of Oncology-Pathology, Stockholm, Sweden Melanoma is a malignant tumor of melanocytes which are found predominantly in skin but also in the bowel and the eye. Skin melanoma causes a vast number of skin cancererelated deaths. Despite many years of intensive laboratory and clinical research, the sole effective cure is surgical resection of the primary tumor before it achieves a thickness [1 mm. When there is distant metastasis, the cancer is generally considered incurable, and the 5-year survival rate is decreasing dramatically. Insulin-like growth factor 1 receptor (IGF-1R) is crucial for the growth and survival of melanoma cells. IGF-1R down-regulation required expression of the MDM2 E3 ligase, which recently was found to ubiquitinate and cause degradation of the IGF-1R. Here we compare two different approaches of targeting IGF-1R in melanoma cells both, in cell cultures and animal models: inhibition of IGF-1R kinase activity versus IGF-1R down-regulation. We used dominant negative mutants to inhibit IGF-1R kinase activity and RNA interference strategies to down-regulate IGF-1R. As an alternative experimental model of down-regulation, we overexpressed MDM-2, the ubiquitine ligase responsible for IGF-1R degradation. Our results suggest that IGF-1R degradation, although partial, is very important to the final outcome, while the down-regulation of IGF-1R is necessary for induction of apoptosis in melanoma cells. An inhibition of IGF-1R phosphorylation, without accompanying down-regulation, leads only to decreased proliferation but not to apoptosis. Targeting IGF-1R may therefore comprise a strategy to treat ongoing disease (today incurable) and a strategy to prevent development of metastases in patients with primary disease.
Approximately 3 to 7 years after the onset of immunosuppression, solid organ transplant recipients (OTRs) have an increased incidence of squamous cell carcinoma (SCC). SCC is responsible for a mortality rate of 5% to 8% in OTRs. The recommended frequency of skin examinations by a health care provider is dependent on the risk level of the patient; however, patients frequently do not seek health care for routine skin checks. While regular skin self-examination (SSE) is an important secondary prevention method for early detection of skin cancer, OTRs do not routinely perform SSE. This study validates a written educational intervention to help patients comprehend their risk factors, determines optimal time to deliver the intervention, and evaluates change in OTRs’ risk perception, anxiety, selfefficacy, intention to perform SSE, and performance of SSE. A convenience sample of 60 OTRs was accrued from the approximately 820 solid OTRs performed per year at Northwestern Memorial Hospital. The 20 OTRs at each of 3 time points—3 to 6 months, 1 to 2 years, and 3 to 7 years after the transplantation—responded to cognitive qualitative interviews and quantitative questionnaires that assess the patients’ consideration for future consequences, health literacy, sense of the best time to receive this information, how it is best conveyed, and who is the best person to convey this information. Change in knowledge, risk perception, the importance of skin checks, confidence in performance, and intention to perform SSE are measured pre- and postintervention and are compared across three time points. One month after the intervention, the patient is asked if they performed SSE and if they sought the care of a dermatologist. Our hypothesis is that an educational intervention designed to increase OTRs’ awareness of their risk of developing SCC and teach SSE has greater relevance when delivered in proximity to the time at which SCC might develop rather than at the time of organ transplantation. This written educational brochure motivates OTRs to seek care with a dermatologist and can be widely disseminated by physicians who provide continuing care to OTRs after the patients cease receiving care from the surgical transplantation team (eg, kidney transplant recipients from nephrologists).
Commercial support: None identified.
Commercial support: None identified.
AB134
J AM ACAD DERMATOL
MARCH 2009