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The use of 7 days of topical 5-fluorouracil to diagnose subclinical actinic keratosis that remain 3 months after 3 different actinic keratosis treatment protocols
P7099
P7066
Spleen tyrosine kinase expression is a marker for ultraviolet light damage and nonmelanoma skin cancer Andres Kriete, PhD, Drexel University, Philadelphia, PA, United States; Chetana Sunkari, PhD, Drexel University, Philadelphia, PA, United States; David Alfego, MS, Drexel University, Philadelphia, PA, United States; Jouni Uitto, MD, PhD, Thomas Jefferson University, Philadelphia, PA, United States
Subcutaneous dermatofibrosarcoma protuberans of the head: An uncommon histologic subtype in an uncommon location Beatriz Llombart, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos Guillen, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos Serra, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Celia Requena, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Eduardo Nagore, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Onofre Sanmartin, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Victor Traves, Instituto Valenciano de Oncologıa, Valencia, Spain
Spleen tyrosine kinase (Syk) is a 72-kDa protein thought to be mainly expressed in hematopoietic cells and is implicated in several instances of malignancies. In the absence of an early marker of UV damage, we investigated the role of Syk in cell lines and mice in response to UV radiation. In addition, we studied protein expression in pathways potentially interacting with Syk. The presence of Syk was also determined in clinical samples from nonmelanoma skin cancer (NMSC) patients. A solar radiator was developed to expose fibroblasts and SKH1 hairless mice with UVA and UVB spectrum. Human dermal fibroblasts (HDFs) were transfected with Syk cDNA to overexpress Syk. SKH1 mice were UV radiated at 4 dorsal skin locations at a 5 mJ/cm2 for 5 and 10 weeks. Skin samples were then tested for changes in Syk expression along with other relevant protein markers in comparison nonradiated animals. Fibroblast and animal experiments showed that Syk is overexpressed in response to UV exposure. Changes in Syk protein correlated with JNK and MMP-1 in vitro, and MMP-13 in mice in vivo. However, Syk appeared to be an earlier indicator of UV damage than MMP-1. The results further demonstrate that Syk changes MMP1 expression by affecting JNK activity but not through p38 or Erk1/2 phosphorylation. The effect of Syk on MMP-1 was further confirmed by applying either Syk siRNA or a selective Syk inhibitor, in which cases MMP-1 expression was reduced. To determine the role of Syk in nonmelanoma skin cancers, we screened human SCC, BCC and actinic keratosis samples and control tissue biopsies. Samples and controls were stained with Syk antibody and DAPI as well as immunohistochemistry. Results from human biopsies indicated significantly higher levels of Syk in BCC, SCC and AK samples if compared to control tissue samples from the same patients. Our results indicate that Syk has merit as a novel early marker of UV damage and is a potential target to slow photocarcinogenesis.
Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumor of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence. DFSP is preferentially located on the trunk, generally on the chest and shoulders, and in the proximal portion of the limbs; only 10% to 15% of DFSP affects the head and neck, generally the scalp, cheek, and supraclavicular area. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. DFSP has been typically considered to be a tumor of the dermis rather than the subcutis and rarely presents as a purely subcutaneous mass showing no connection with the dermis. In this regard, \20 cases of subcutaneous DFSP have been described in the literature and only 1 case was located in the head. The purpose of this study is to characterize the clinicopathologic features of a series of DFSP located in the head, showing exclusive or near-exclusive involvement of the subcutaneous fat and to compare with the dermal DFSP in the same location. Our study presents a total of 22 cases located in the head (12 face and 10 scalp). The subcutaneous DFSP of the head is in our study a common type of presentation. The principal significance lies in its potential to be confused with other spindle cell neoplasms. Clinically, the DFSP located in head are usually deeper than at other locations and, as the skin in not affected, there is probably a delay in the diagnosis and the treatment becomes more difficult. Commercial support: None identified.
Commercial support: None identified.
P7015 The use of 7 days of topical 5-fluorouracil to diagnose subclinical actinic keratosis that remain 3 months after 3 different actinic keratosis treatment protocols Emil Tanghetti, MD, Center for Dermatology and Laser Surgery, Sacramento, CA, United States
P6953 StewarteTreves syndrome: A rare complication of lymphedema Imane Tirhazouine, University Hospital Ibn Rushd, Casablanca, Morocco; Farida Marnissi, University Hospital Ibn Rushd, Casablanca, Morocco; Hakima Benchikhi, University Hospital Ibn Rushd, Casablanca, Morocco; Soumia Chiheb, University Hospital Ibn Rushd, Casablanca, Morocco Background: StewarteTreves syndrome (SST) represents a rare and very serious complication of the chronic lymphedema as a cutaneous angiosarcoma; formerly called lymphangiosarcoma. We report a new case. Case report: An 85-year-old woman has a history of infiltrating canalaire carcinoma of the right breast treated in 2000 by Patey with axillar ganglionar cleaning out, then radiotherapy and chemotherapy. Two years later, the patient presented a chronic lymphedema of the right upper limb, on which appeared a nodular angiomatous lesions 9 years later on 2011. The clinical examination found maculous and erythematous lesions associated with nodular and angiomatous measuring 6 cm 3 3 cm, localized on the right upper limb which was totally tumefied. The rest of the somatic examination was without particularity. The histologic study had ended in a well differentiated angiosarcoma retaining a SST. The abdominopelvic echography was normal. The thoracic radiography showed a right mediastinal opacity in favor of a metastasis. The thoracoabdominopelvien tomodensitometry was not able to be made because the patient died before. Discussion: The diagnosis of SST was retained in this case front of the association of a cutaneous angiosarcoma with a chronic lymphedema, what corresponds to its definition in the literature. This syndrome is mainly related to the breast cancer (90% of cases). It occurs in 0.03% of patients surviving 10 or more years after radical mastectomy. The prognosis is very poor with a 5-year survival close to 10% despite the various treatment modalities. The treatment of choice is a large resection, but some authors recommend radical resection in the form of shoulder disarticulation or forequarter amputation. Surgical treatment can be preceded or followed by radiation therapy. Commercial support: None identified.
AB166
J AM ACAD DERMATOL
Background:We have documented previously the utility of topical 5-FU in highlighting and treating both clinical and subclinical actinic keratosis. In a head to head study of imiquimod and 5% topical 5-FU, there was a striking difference in the AK counts before and after 4 weeks of therapy with topical 5-FU. There were 43% more lesions than at baseline. In his investigation, Dr George Martin has described a method to rechallenge patients who have been treated with different actinic keratosis treatment protocols that included adjunctive 5-FU pretreatment with ALAPDT versus ALA PDT alone. He rechallenged patients with topical 5-FU 3 to 7 months after treatment. This method identified subclinical and questionable clinical lesions that remained. Methods: The study has 3 arms with 30 patients randomized 1:1:1. The first arm subjects’s entire face and lateral neck pretreated for 6 days with 5% 5-FU. On the seventh day, ALA applied and incubate for 2 hours and then illuminate the face and lateral neck with the Blu-U 10 J/cm2. The second arm subjects apply 5% 5-FU for 6 to 7 days with no ALA/PDT treatment. The third arm subjects with no pretreatment have ALA applied to the face and lateral neck and incubate for 2 hours to be followed by illuminatation with the Blu-U 10 J/cm2. We felt that a diagnostic rechallenge is a novel method to document efficacy after completion of a course of treatment for actinic keratosis. We are in the process of conducting a study demonstrating the outcomes of combination topical 5% 5-FU and ALA PDT for actinic keratosis. Both of these agents are currently FDA approved for the treatment of actinic keratoses and successfully used. Our presumption is that topical 5-FU enhances the generation of PpIX by prompting cellular differentiation. We will document numbers of actinic keratosis and the appearance of new lesions at baseline, after 6 days of pretreatment with topical 5-FU, 1 day, 6 days and 3 months after completion of treatment. After this last 3-month count, all arms will be treated with 1 week of BID 5% topical 5-FU. Lesion counts will then be taken upon completion of this rechallenge. Conclusions: We will present photography and lesion counts, demonstrating the utility of this approach as a method to assess subclinical lesions that remain after the completion of a therapeutic course of medication and PDT treatment. We feel that acknowledging the presence or absence of subclinical lesions will ultimately be the best guide in assessing remaining actinic keratosis or subclinical precursor lesions. DUSA Pharmaceuticals Grant for Study, Valeant drug for study.
APRIL 2013
P7066
Spleen tyrosine kinase expression is a marker for ultraviolet light damage and nonmelanoma skin cancer Andres Kriete, PhD, Drexel University, Philadelphia, PA, United States; Chetana Sunkari, PhD, Drexel University, Philadelphia, PA, United States; David Alfego, MS, Drexel University, Philadelphia, PA, United States; Jouni Uitto, MD, PhD, Thomas Jefferson University, Philadelphia, PA, United States
Subcutaneous dermatofibrosarcoma protuberans of the head: An uncommon histologic subtype in an uncommon location Beatriz Llombart, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos Guillen, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Carlos Serra, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Celia Requena, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Eduardo Nagore, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Onofre Sanmartin, PhD, Instituto Valenciano de Oncologıa, Valencia, Spain; Victor Traves, Instituto Valenciano de Oncologıa, Valencia, Spain
Spleen tyrosine kinase (Syk) is a 72-kDa protein thought to be mainly expressed in hematopoietic cells and is implicated in several instances of malignancies. In the absence of an early marker of UV damage, we investigated the role of Syk in cell lines and mice in response to UV radiation. In addition, we studied protein expression in pathways potentially interacting with Syk. The presence of Syk was also determined in clinical samples from nonmelanoma skin cancer (NMSC) patients. A solar radiator was developed to expose fibroblasts and SKH1 hairless mice with UVA and UVB spectrum. Human dermal fibroblasts (HDFs) were transfected with Syk cDNA to overexpress Syk. SKH1 mice were UV radiated at 4 dorsal skin locations at a 5 mJ/cm2 for 5 and 10 weeks. Skin samples were then tested for changes in Syk expression along with other relevant protein markers in comparison nonradiated animals. Fibroblast and animal experiments showed that Syk is overexpressed in response to UV exposure. Changes in Syk protein correlated with JNK and MMP-1 in vitro, and MMP-13 in mice in vivo. However, Syk appeared to be an earlier indicator of UV damage than MMP-1. The results further demonstrate that Syk changes MMP1 expression by affecting JNK activity but not through p38 or Erk1/2 phosphorylation. The effect of Syk on MMP-1 was further confirmed by applying either Syk siRNA or a selective Syk inhibitor, in which cases MMP-1 expression was reduced. To determine the role of Syk in nonmelanoma skin cancers, we screened human SCC, BCC and actinic keratosis samples and control tissue biopsies. Samples and controls were stained with Syk antibody and DAPI as well as immunohistochemistry. Results from human biopsies indicated significantly higher levels of Syk in BCC, SCC and AK samples if compared to control tissue samples from the same patients. Our results indicate that Syk has merit as a novel early marker of UV damage and is a potential target to slow photocarcinogenesis.
Dermatofibrosarcoma protuberans (DFSP) is a rare, infiltrative skin tumor of intermediate malignancy, with a limited potential for metastasis but a high rate of recurrence. DFSP is preferentially located on the trunk, generally on the chest and shoulders, and in the proximal portion of the limbs; only 10% to 15% of DFSP affects the head and neck, generally the scalp, cheek, and supraclavicular area. Histologically, several variants of DFSP have been described and should be well characterized to avoid misdiagnosis with other tumors. DFSP has been typically considered to be a tumor of the dermis rather than the subcutis and rarely presents as a purely subcutaneous mass showing no connection with the dermis. In this regard, \20 cases of subcutaneous DFSP have been described in the literature and only 1 case was located in the head. The purpose of this study is to characterize the clinicopathologic features of a series of DFSP located in the head, showing exclusive or near-exclusive involvement of the subcutaneous fat and to compare with the dermal DFSP in the same location. Our study presents a total of 22 cases located in the head (12 face and 10 scalp). The subcutaneous DFSP of the head is in our study a common type of presentation. The principal significance lies in its potential to be confused with other spindle cell neoplasms. Clinically, the DFSP located in head are usually deeper than at other locations and, as the skin in not affected, there is probably a delay in the diagnosis and the treatment becomes more difficult. Commercial support: None identified.
Commercial support: None identified.
P7015 The use of 7 days of topical 5-fluorouracil to diagnose subclinical actinic keratosis that remain 3 months after 3 different actinic keratosis treatment protocols Emil Tanghetti, MD, Center for Dermatology and Laser Surgery, Sacramento, CA, United States
P6953 StewarteTreves syndrome: A rare complication of lymphedema Imane Tirhazouine, University Hospital Ibn Rushd, Casablanca, Morocco; Farida Marnissi, University Hospital Ibn Rushd, Casablanca, Morocco; Hakima Benchikhi, University Hospital Ibn Rushd, Casablanca, Morocco; Soumia Chiheb, University Hospital Ibn Rushd, Casablanca, Morocco Background: StewarteTreves syndrome (SST) represents a rare and very serious complication of the chronic lymphedema as a cutaneous angiosarcoma; formerly called lymphangiosarcoma. We report a new case. Case report: An 85-year-old woman has a history of infiltrating canalaire carcinoma of the right breast treated in 2000 by Patey with axillar ganglionar cleaning out, then radiotherapy and chemotherapy. Two years later, the patient presented a chronic lymphedema of the right upper limb, on which appeared a nodular angiomatous lesions 9 years later on 2011. The clinical examination found maculous and erythematous lesions associated with nodular and angiomatous measuring 6 cm 3 3 cm, localized on the right upper limb which was totally tumefied. The rest of the somatic examination was without particularity. The histologic study had ended in a well differentiated angiosarcoma retaining a SST. The abdominopelvic echography was normal. The thoracic radiography showed a right mediastinal opacity in favor of a metastasis. The thoracoabdominopelvien tomodensitometry was not able to be made because the patient died before. Discussion: The diagnosis of SST was retained in this case front of the association of a cutaneous angiosarcoma with a chronic lymphedema, what corresponds to its definition in the literature. This syndrome is mainly related to the breast cancer (90% of cases). It occurs in 0.03% of patients surviving 10 or more years after radical mastectomy. The prognosis is very poor with a 5-year survival close to 10% despite the various treatment modalities. The treatment of choice is a large resection, but some authors recommend radical resection in the form of shoulder disarticulation or forequarter amputation. Surgical treatment can be preceded or followed by radiation therapy. Commercial support: None identified.
AB166
J AM ACAD DERMATOL
Background:We have documented previously the utility of topical 5-FU in highlighting and treating both clinical and subclinical actinic keratosis. In a head to head study of imiquimod and 5% topical 5-FU, there was a striking difference in the AK counts before and after 4 weeks of therapy with topical 5-FU. There were 43% more lesions than at baseline. In his investigation, Dr George Martin has described a method to rechallenge patients who have been treated with different actinic keratosis treatment protocols that included adjunctive 5-FU pretreatment with ALAPDT versus ALA PDT alone. He rechallenged patients with topical 5-FU 3 to 7 months after treatment. This method identified subclinical and questionable clinical lesions that remained. Methods: The study has 3 arms with 30 patients randomized 1:1:1. The first arm subjects’s entire face and lateral neck pretreated for 6 days with 5% 5-FU. On the seventh day, ALA applied and incubate for 2 hours and then illuminate the face and lateral neck with the Blu-U 10 J/cm2. The second arm subjects apply 5% 5-FU for 6 to 7 days with no ALA/PDT treatment. The third arm subjects with no pretreatment have ALA applied to the face and lateral neck and incubate for 2 hours to be followed by illuminatation with the Blu-U 10 J/cm2. We felt that a diagnostic rechallenge is a novel method to document efficacy after completion of a course of treatment for actinic keratosis. We are in the process of conducting a study demonstrating the outcomes of combination topical 5% 5-FU and ALA PDT for actinic keratosis. Both of these agents are currently FDA approved for the treatment of actinic keratoses and successfully used. Our presumption is that topical 5-FU enhances the generation of PpIX by prompting cellular differentiation. We will document numbers of actinic keratosis and the appearance of new lesions at baseline, after 6 days of pretreatment with topical 5-FU, 1 day, 6 days and 3 months after completion of treatment. After this last 3-month count, all arms will be treated with 1 week of BID 5% topical 5-FU. Lesion counts will then be taken upon completion of this rechallenge. Conclusions: We will present photography and lesion counts, demonstrating the utility of this approach as a method to assess subclinical lesions that remain after the completion of a therapeutic course of medication and PDT treatment. We feel that acknowledging the presence or absence of subclinical lesions will ultimately be the best guide in assessing remaining actinic keratosis or subclinical precursor lesions. DUSA Pharmaceuticals Grant for Study, Valeant drug for study.
APRIL 2013