Development of an ex vivo model to define the role of the IGF-1 receptor in photocarcinogenesis
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P7851 Cutaneous metastasis from glioblastoma multiforme Sevil Alan, MD, Akdeniz University Department of Dermatology and Venereology, Antalya, Turkey; Cumhur Ibrahim Bassorgun, MD, Akdeniz University School of Medicine Department Of Pathology, Antalya, Turkey; Ethem G€ oksu, MD, Akdeniz University School of Medicine Department of Neurosurgery, Antalya, Turkey Glioblastoma multiforme (GBM) is the most malignant astrocytic tumor. 90% of the patients lose their lives in 2 years after the diagnosis is made. Extracranial metastasis seldomly occurs. It is frequently misdiagnosed as a primary subcutaneous tumor. In literature, the number of declared cases about GBM’s skin metastasis are very few. Here, we presented a case of a high-grade GBM which made an appeal with formations like keloid on the old craniotomy scar and metastasized on the scalp. Pathology result of a patient, who had tumor resection with left frontal craniotomy 3 years ago, was anaplastic astrocytoma grade 3. Later on, adjuvant radiotherapy and simultaneous temozolomide chemotherapy were given. A year after the operation reoperation was made because of an observed relapse lesion, pathology was reported as inactive tumor cells and reactive gliosis. 4 months later, awake surgical operation was performed again because of relapse lesion, this time pathology after gross total resection was reported as glioblastoma multiforme (GBM grade 4). The patient admitted to us because of swollen, hard, skin-colored infiltrated papules on the area that was compatible with incision scar on frontal craniotomy line. The patient was consulted to plastic surgery with keloid and skin metastasis prediag- noses, and patient’s biopsy results, which were taken from 4 ulcer nodular lesions, were reported as undifferential tumor (malign tumor metastasis) that presents neuroendocrine differential. Within 2 months, 3 to 5 papules on the incision scar became a giangantic tumoral mass that covered the whole of the frontal scalp. We present this case because it is a rarely seen mestastasis. Commercial support: None identified. P8217 Development of an ex vivo model to define the role of the IGF-1 receptor in photocarcinogenesis Rachel Ward, Indiana University School of Medicine, Indianapolis, IN, United States; Dan Spandau, PhD, Indiana University School of Medicine, Indianapolis, IN, United States; Jeffrey Travers, MD, PhD, Indiana University School of Medicine, Indianapolis, IN, United States The 2 most important risk factors for developing nonmelanoma skin cancer (NMSC) are exposure to the UVB component in sunlight and aging. The skin of geriatric individuals is susceptible to UVB-induced DNA damage, which could result in initiation of NMSC. Previous in vivo studies have demonstrated that the increased susceptibility to UVB-induced damage with age is caused by the silencing of insulin- like growth factor 1 (IGF-1) expression in dermal fibroblasts and the resulting failure to activate the IGF-1 receptor (IGF-1R) on epidermal keratinocytes. The objective of this study is to develop an in vitro model system using human skin to explicitly delineate the mechanism of how IGF-1 silencing leads to NMSC initiation. Human skin samples obtained from panniculectomy surgeries were grown ex vivo, treated topically with an IGF-1R inhibitor (or vehicle control) and UVB irradiated. The samples were then harvested at various times, formalin-fixed, paraffin-embedded, and 5-M sections were examined via immunofluorescence for the presence of thymine dimers (TD), indicative of DNA damage, and Ki67, a cellular proliferation factor. Basal keratinocytes proliferating with DNA damage are indicative of an inappropriate, procarcinogenic response to UVB light, which is a precursor to NMSC. UVB-irradiated skin treated with the IGF-1R inhibitor (AG538) contained a 10-fold increase in Ki67 + :TD + keratinocytes compared to the vehicle-treated UVB- irradiated tissue. These findings indicate that this model can be used as a surrogate for geriatric skin. Consequently, similar studies have been conducted in immuno- deficient SCID mice, xenografted in the manner described above, which yielded similar results. Long-term UVB studies using this model are currently underway. Commercial support: None identified. P8245 Distal digital keratoacanthoma: Report of 2 cases Maria Pilar P erez Garc ıa, Hospital Doctor Peset, Valencia, Spain; Almudena Mateu Puchades, Hospital Doctor Peset, Valencia, Spain; Amparo Marquina Vila, Hospital Doctor Peset, Valencia, Spain; Celia Sanchis S anchez, Hospital Doctor Peset, Valencia, Spain; Sof ıa De As ıs Cuestas, Hospital Doctor Peset, Valencia, Spain Background: Distal digital keratoacanthoma (DKA) is a rare and destructive variant of keratoacanthoma (KA) that seldom regresses spontaneously. Distinguishing features of DKA include pain, rapid growth, and early underlying bone destruction. Its importance lies in its similarity to squamous cell carcinoma. We report 2 cases of this entity attended in our service. Case 1: A 57-year-old female presented with a painful subungual keratotic lesion in the distal phalanx of the right first finger. The tumor had been developing for 2 years with no history of previous trauma or inflammation. Radiographic results showed an osteolytic area in the distal phalanx. Biopsy confirmed the diagnosis. We carried out a complete excision of the lesion, adopting a conservative approach. Case 2: A 64-year-old man presented with a hyperkeratotic nodular lesion, with a characteristic central keratin-filled crater, under the distal portion of the nail of the first finger of the right hand, of three months of evolution. The histologic study was compatible with KA, with later resection of the whole tumor. Conclusion: DKA should be considered in the differential diagnosis of painful lesions of the distal phalanx. It consists of a keratotic or verrucous nodule in the nail bed at the distal nail border, often in association with partial onycholysis. The hallmark of DKA is its rapid growth, within a period of weeks; because of this, often causes bone erosion, which at radiographic examination appears as a cup-shaped defect of the terminal phalanx. The diagnosis of DKA should be based on the correlation of clinical, radiologic, and pathologic findings. It is essential to recognize KA and separate it from squamous cell carcinoma both for prognostic and therapeutic reasons. Conservative surgery is the first choice of treatment. Commercial support: None identified. P8532 Effectiveness of a 595-nm pulsed dye laser for the treatment of basal cell carcinoma using 1 stacked-pulse session Sasima Eimpunth, MD, Department of Dermatology, Faculty of Medicine Siriraj Hospital, Bangkok, Thailand; Gagik Oganesyan, MD, PhD, Division of Dermatology, University of California, San Diego, San Diego, CA, United States; Michael Shane Hamman, MD, Division of Dermatology, University of California, San Diego, San Diego, CA, United States; Robert A. Lee, MD, PhD, Division of Dermatology, University of California, San Diego, San Diego, CA, United States; Shang I. Brian Jiang, MD, Division of Dermatology, University of California, San Diego, San Diego, CA, United States; Soohyun Silvia Kim, University of California, San Diego School of Medicine, San Diego, CA, United States Background: Treatment of basal cell carcinomas (BCCs) with pulsed-dye laser (PDL) has shown cure rates ranging from 62% to 91% when using multiple single pass treatments. Given the inconvenience of multiple visits, we conducted a pilot study to investigate if nonmelanoma skin cancers could be treated with just a single PDL session. The results from this small pilot study showed clearance rates of 71% (5/7). This study aims to conduct a larger scale study to determine statistical significance and to validate the treatment of BCCs with a single PDL session using stacked-pulsed setting. Objective: To study the effectiveness and safety of a single stacked-pulse session on BCC treatment. Methods: This was a prospective randomized study where 24 patients with biopsy- proven, superficial or nodular BCCs located on trunk or extremities were random- ized into 2 groups: laser-treatment group and control. Control group received no treatment and treatment group received one session of double stacked-pulses of PDL treatment using 10 mm spot size, 3-ms pulse width, and a fluence of 7.5 J/cm 2 at the office visit. Lesions were treated with 1 single session and included a 6-mm margin of normal skin around the clinically apparent tumor. Lesions were subsequently excised and histologically evaluated. Adverse reactions were evaluated immediately after the laser treatment and at the surgical excision visit. Results: Twenty-four patients, 16 males and 8 females aged between 29-88 years old with a total of 24 tumors, participated in the study. There was a significant difference in the clearance rated for the BCCs between the control and treatment groups. The treatment group showed 71.4% (10/14) clearance whereas control group had 20% (2/10) clearance rate (P ¼ .01). Adverse events found immediately after the laser treatment was purpura (100%) and at the surgical excision visit were blister (21.4%), dyspigmentation (21.4%), and 1 case of hypertrophic scar (7.14%). Conclusion: These results show that single PDL session using double stacked-pulsed setting may be a viable alternative to surgical and other nonsurgical modalities with similar clearance rates and adverse effects. Commercial support: None identified. AB134 JAM ACAD DERMATOL MAY 2014
Transcript of Development of an ex vivo model to define the role of the IGF-1 receptor in photocarcinogenesis
P7851Cutaneous metastasis from glioblastoma multiforme
Sevil Alan, MD, Akdeniz University Department of Dermatology and Venereology,Antalya, Turkey; Cumhur Ibrahim Bassorgun, MD, Akdeniz University School ofMedicine Department Of Pathology, Antalya, Turkey; Ethem G€oksu, MD, AkdenizUniversity School of Medicine Department of Neurosurgery, Antalya, Turkey
Glioblastoma multiforme (GBM) is the most malignant astrocytic tumor. 90% of thepatients lose their lives in 2 years after the diagnosis is made. Extracranial metastasisseldomly occurs. It is frequently misdiagnosed as a primary subcutaneous tumor. Inliterature, the number of declared cases about GBM’s skin metastasis are very few.Here, we presented a case of a high-grade GBM which made an appeal withformations like keloid on the old craniotomy scar and metastasized on the scalp.Pathology result of a patient, who had tumor resection with left frontal craniotomy 3years ago, was anaplastic astrocytoma grade 3. Later on, adjuvant radiotherapy andsimultaneous temozolomide chemotherapy were given. A year after the operationreoperation was made because of an observed relapse lesion, pathology wasreported as inactive tumor cells and reactive gliosis. 4 months later, awake surgicaloperation was performed again because of relapse lesion, this time pathology aftergross total resection was reported as glioblastoma multiforme (GBM grade 4). Thepatient admitted to us because of swollen, hard, skin-colored infiltrated papules onthe area that was compatible with incision scar on frontal craniotomy line. Thepatient was consulted to plastic surgery with keloid and skin metastasis prediag-noses, and patient’s biopsy results, which were taken from 4 ulcer nodular lesions,were reported as undifferential tumor (malign tumor metastasis) that presentsneuroendocrine differential. Within 2 months, 3 to 5 papules on the incision scarbecame a giangantic tumoral mass that covered the whole of the frontal scalp. Wepresent this case because it is a rarely seen mestastasis.
AB134
cial support: None identified.
CommerP8217Development of an ex vivo model to define the role of the IGF-1 receptorin photocarcinogenesis
Rachel Ward, Indiana University School of Medicine, Indianapolis, IN, UnitedStates; Dan Spandau, PhD, Indiana University School of Medicine, Indianapolis,IN, United States; Jeffrey Travers, MD, PhD, Indiana University School ofMedicine, Indianapolis, IN, United States
The 2 most important risk factors for developing nonmelanoma skin cancer (NMSC)are exposure to the UVB component in sunlight and aging. The skin of geriatricindividuals is susceptible to UVB-induced DNA damage, which could result ininitiation of NMSC. Previous in vivo studies have demonstrated that the increasedsusceptibility to UVB-induced damage with age is caused by the silencing of insulin-like growth factor 1 (IGF-1) expression in dermal fibroblasts and the resulting failureto activate the IGF-1 receptor (IGF-1R) on epidermal keratinocytes. The objective ofthis study is to develop an in vitro model system using human skin to explicitlydelineate the mechanism of how IGF-1 silencing leads to NMSC initiation. Humanskin samples obtained from panniculectomy surgeries were grown ex vivo, treatedtopically with an IGF-1R inhibitor (or vehicle control) and UVB irradiated. Thesamples were then harvested at various times, formalin-fixed, paraffin-embedded,and 5-�M sections were examined via immunofluorescence for the presence ofthymine dimers (TD), indicative of DNA damage, and Ki67, a cellular proliferationfactor. Basal keratinocytes proliferating with DNA damage are indicative of aninappropriate, procarcinogenic response to UVB light, which is a precursor toNMSC. UVB-irradiated skin treated with the IGF-1R inhibitor (AG538) contained a10-fold increase in Ki67+:TD+ keratinocytes compared to the vehicle-treated UVB-irradiated tissue. These findings indicate that this model can be used as a surrogatefor geriatric skin. Consequently, similar studies have been conducted in immuno-deficient SCID mice, xenografted in the manner described above, which yieldedsimilar results. Long-term UVB studies using this model are currently underway.
cial support: None identified.
CommerJ AM ACAD DERMATOL
P8245Distal digital keratoacanthoma: Report of 2 cases
Maria Pilar P�erez Garc�ıa, Hospital Doctor Peset, Valencia, Spain; Almudena MateuPuchades, Hospital Doctor Peset, Valencia, Spain; Amparo Marquina Vila,Hospital Doctor Peset, Valencia, Spain; Celia Sanchis S�anchez, Hospital DoctorPeset, Valencia, Spain; Sof�ıa De As�ıs Cuestas, Hospital Doctor Peset, Valencia,Spain
Background: Distal digital keratoacanthoma (DKA) is a rare and destructive variantof keratoacanthoma (KA) that seldom regresses spontaneously. Distinguishingfeatures of DKA include pain, rapid growth, and early underlying bone destruction.Its importance lies in its similarity to squamous cell carcinoma. We report 2 cases ofthis entity attended in our service.
Case 1: A 57-year-old female presented with a painful subungual keratotic lesion inthe distal phalanx of the right first finger. The tumor had been developing for 2 yearswith no history of previous trauma or inflammation. Radiographic results showed anosteolytic area in the distal phalanx. Biopsy confirmed the diagnosis. We carried outa complete excision of the lesion, adopting a conservative approach.
Case 2: A 64-year-old man presented with a hyperkeratotic nodular lesion, with acharacteristic central keratin-filled crater, under the distal portion of the nail of thefirst finger of the right hand, of three months of evolution. The histologic study wascompatible with KA, with later resection of the whole tumor.
Conclusion: DKA should be considered in the differential diagnosis of painful lesionsof the distal phalanx. It consists of a keratotic or verrucous nodule in the nail bed atthe distal nail border, often in association with partial onycholysis. The hallmark ofDKA is its rapid growth, within a period of weeks; because of this, often causes boneerosion, which at radiographic examination appears as a cup-shaped defect of theterminal phalanx. The diagnosis of DKA should be based on the correlation ofclinical, radiologic, and pathologic findings. It is essential to recognize KA andseparate it from squamous cell carcinoma both for prognostic and therapeuticreasons. Conservative surgery is the first choice of treatment.
cial support: None identified.
CommerP8532Effectiveness of a 595-nm pulsed dye laser for the treatment of basal cellcarcinoma using 1 stacked-pulse session
Sasima Eimpunth, MD, Department of Dermatology, Faculty of Medicine SirirajHospital, Bangkok, Thailand; Gagik Oganesyan, MD, PhD, Division ofDermatology, University of California, San Diego, San Diego, CA, United States;Michael Shane Hamman, MD, Division of Dermatology, University of California,San Diego, San Diego, CA, United States; Robert A. Lee, MD, PhD, Division ofDermatology, University of California, San Diego, San Diego, CA, United States;Shang I. Brian Jiang, MD, Division of Dermatology, University of California, SanDiego, San Diego, CA, United States; Soohyun Silvia Kim, University of California,San Diego School of Medicine, San Diego, CA, United States
Background: Treatment of basal cell carcinomas (BCCs) with pulsed-dye laser (PDL)has shown cure rates ranging from 62% to 91% when using multiple single passtreatments. Given the inconvenience of multiple visits, we conducted a pilot studyto investigate if nonmelanoma skin cancers could be treated with just a single PDLsession. The results from this small pilot study showed clearance rates of 71% (5/7).This study aims to conduct a larger scale study to determine statistical significanceand to validate the treatment of BCCswith a single PDL session using stacked-pulsedsetting.
Objective: To study the effectiveness and safety of a single stacked-pulse session onBCC treatment.
Methods: This was a prospective randomized study where 24 patients with biopsy-proven, superficial or nodular BCCs located on trunk or extremities were random-ized into 2 groups: laser-treatment group and control. Control group received notreatment and treatment group received one session of double stacked-pulses of PDLtreatment using 10 mm spot size, 3-ms pulse width, and a fluence of 7.5 J/cm2 at theoffice visit. Lesionswere treated with 1 single session and included a 6-mmmargin ofnormal skin around the clinically apparent tumor. Lesions were subsequentlyexcised and histologically evaluated. Adverse reactions were evaluated immediatelyafter the laser treatment and at the surgical excision visit.
Results: Twenty-four patients, 16 males and 8 females aged between 29-88 years oldwith a total of 24 tumors, participated in the study. There was a significant differencein the clearance rated for the BCCs between the control and treatment groups. Thetreatment group showed 71.4% (10/14) clearance whereas control group had 20%(2/10) clearance rate (P ¼ .01). Adverse events found immediately after the lasertreatment was purpura (100%) and at the surgical excision visit were blister (21.4%),dyspigmentation (21.4%), and 1 case of hypertrophic scar (7.14%).
Conclusion: These results show that single PDL session using double stacked-pulsedsetting may be a viable alternative to surgical and other nonsurgical modalities withsimilar clearance rates and adverse effects.
cial support: None identified.
CommerMAY 2014
