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Successful treatment of vulvar bowen’s disease with topical imiquimod 5% cream1
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P484
SUCCESSFUL TREATMENT OF VULVAR BOWEN’S DISEASE WITH TOPICAL IMIQUIMOD 5% CREAM Bo Kyung Koh, MD, Uijungbu St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Uijungbu, Korea, Yeon Jeong Kim, Kyung Ho Lee, Jin Woo Kim Bowen’s disease (BD) is a form of intraepithelial (in situ) squamous cell carcinoma. Typical BD presents as a gradually enlarging well demarcated erythematous plaque with an irregular border and scaly surface. But in the vulvar BD, there are more frequent erosion, ulceration and pigmentation. Possible treatments of BD include physical destruction of the lesion, e.g. cryotherapy, curettage, laser therapy or excision. Also, as a non-invasive options, there are photodynamic therapy (PDT) and topical 5-fluorouracil. Especially, in case of vulvar BD we need more non-invasive and tolerable method. So, we think imiquimod is the most suitable method to treat vulvar BD. Patients just apply cream to the lesion by themselves three times a week. Imiquimod’s activity comes through its ability to induce the production of cytokines, which in turn stimulate T cells, thereby enhancing innate and acquired cellular immunity. A 72-year-old female visited our department of dermatology for further evaluation of painful erosive patches on the vulva for 15 years. Based on the history, at first, there were some vesicles on the vulva and the lesion grew erosive with yellowish discharge. Skin biopsy specimen showed, throughout the epidermis, the cells lay in complete disorder, resulting in a “windblown appearance”. Many cells appeared highly atypical, showing large, hyperchromatic nuclei. But, the border between the epidermis and dermis everywhere appeared sharp and the basement membrane remained intact. So, we diagnosed vulvar Bowen’s disease and started the every other day treatment with topical imiquimod 5% cream for 16 weeks. At the bedtime, she applied it on the vulva by herself and the next morning washed it off. After treatment later, the vulvar lesion almost cleared and the skin biopsy showed no atypical cells in the epidermis. Until now there is no recurrence. We believe imiquimod is an effective, tolerated, safe and new tool for the treatment of vulvar BD. We report a case of vulvar BD successfully treated with topical imiquimod 5% cream.
A CASE OF CUTANEOUS METASTASIS FROM HEPATIC LEIOMYOSARCOMA Jeong-Soo Kim, MD, Hanyang University Guri Hospital, Seoul, Korea, Hee-Joon Yu, MD, PhD, Hanyang University Guri Hospital, Seoul, Korea, Kwang-Yeoll Yeo, MD, Hanyang University Guri Hospital, Seoul, Korea Cutaneous leiomyosarcoma is a rare malignant neoplasm. It constitutes about 2-3% of all superficial soft tissue malignancies. On the biologic behavior, these neoplasms can be divided into three types: cutaneous (intradermal), subcutaneous and secondary (metastatic) leiomyosarcomas. Clinically, secondary type of leiomyosarcoma usually presents as multiple nodules of varying sizes. In the literature review, metastasis to the skin from leiomyosarcoma of extracutaneous organs has been reported in 12 cases. Of these, metastasis from the liver was identified in only one case. A 48-year-old man was referred to the dermatology department from the gastroenterology department for three subcutaneous nodules on the forehead and scalp. Cutaneous examination revealed three, well-defined, hard, movable, subcutaneous nodules. Six months ago, he visited a local clinic and computed tomography showed a hepatic mass in segment I. On admission, 7 days ago, computed tomography showed variable sized multiple hepatic masses in the both lobe, suggesting liver to liver metastasis. A fine needle aspiration biopsy specimen of hepatic mass showed irregular arranged spindle cells possessed elongated nuclei with blunt ends and many mitoses. Biopsy specimens from skin nodules showed spindle cells of same histologic features. The patient was diagnosed as cutaneous metastasis from hepatic leiomyosarcoma. Disclosure not available at press time.
Disclosure not available at press time.
P485
P483 DETECTION AND CLEARANCE OF SUBCLINICAL ACTINIC KERATOSIS (AK) WITH IMIQUIMOD (5%) TREATMENT Eggert Stockfleth, MD, University of Berlin, Berlin, Germany, Jens Bichel, MD, University of Berlin, Berlin, Germany, Claas Ulrich, MD, University of Berlin, Berlin, Germany, Wolfram Sterry, MD, University of Berlin, Berlin, Germany Background: Actinic keratosis is a crucial element in the multistage process of carcinogenesis leading to invasive squamous cell carcinoma (SCC). AK usually develops on sun-damaged skin and frequently involves an extensive area, identified as an ultravioletinduced “field of cancerization.” This area is characterized by the coexistence of early “subclinical” AK lesions and cumulates in multifocal SCC. Most ablative procedures do not target all lesions in a dysplastic area but focus on clearly visible lesions. Yet, untreated subclinical lesions might explain the high recurrence rate of AK after treatment. Thus, simultaneous treatment of clinical and subclinical AK lesions may mitigate disease recurrence. Recent case studies have demonstrated that imiquimod cream (5%) is a safe and effective treatment for AK. We examined the potential efficacy of topical imiquimod (5%) in treating clinical and subclinical AK lesions. Methods: A randomized, double-blind study was conducted in patients with biopsyproven AK (3-10 lesions/patient). Patients applied imiquimod cream (5%) or vehicle 3 times/week for up to 12 weeks. A rest period of up to 3 weeks, followed by resumption at a decreased application frequency (1-2 times/week), was permitted to manage adverse events. The number, size, and appearance of AK lesions were evaluated during each clinic visit. Complete or partial clearance was verified by histologic analysis. Results: Thirty-six patients (treatment group ⫽ 25, vehicle-control group ⫽ 11) completed the 12-week study. After 2-3 weeks of imiquimod (5%) treatment, AK lesion counts were elevated over baseline as subclinical lesions became clinically visible. The treatment area was characterized by mild erythema, and subclinical lesions appeared red and inflamed. On histologic examination, these lesions displayed signs of early AK. With the detection of subclinical lesions, the total number of AK lesions during treatment increased by ⬃300%. At the end of the 12-week study, complete clearance of clinical and subclinical AK lesions was observed in 21 of 25 (84%) patients, and an additional 2 of 25 (8%) patients exhibited partial clearance. The control group had no reductions in the number or size of AK lesions. Conclusions: Imiquimod cream (5%) was effective in clearing baseline AK lesions and early subclinical AK lesions. These findings suggest imiquimod therapy may lead to a lower recurrence rate relative to therapies that only treat visible lesions. Dr Stockfleth is a 3M consultant and Dr. Bichel is a employee of 3M Medica. Approximately 10% is supported by 3M Pharmaceuticals for poster production.
MARCH 2004
MORPHOLOGIC CHARACTERISTICS OF SKIN CANCER AS STUDIED THROUGH ECHOGRAPHY Jose M. Fernandez-Vozmediano, MD, University Hospital Puerto Real, Puerto Real, Spain, Jose Armario-Hita, MD, University Hospital Puerto Real, Puerto Real, Spain INTRODUCTION: The cutaneous echography is based on the basic physical principle of the transmission of high-frequency ultrasonic pulses (⬎10 MHz) from a transducer. This transducer can automatically gives off a sound over the object of study and register it when it comes back (echo). The period of time between the emission of the sound wave and its reflection depends on the physical distance between the surface of the object and the differest layers of the object that reflects the sound. Using different scanning methods certain tissular parameters can be calculated such as in vivo distance, in vivo sections or in vivo volume through methods of non-invasive exploration. These possibilities make of the cutaneous echography a very attractive and useful tool for the investigation as well as for the diagnosis in Dermatology. In present times the most interesting system for the dermatologic clinic is the B-mode scanner with transversal planes of the object of study. CLINICAL APPLICATIONS: The use of the echography to define the cutaneous tumors, from the qualitative and quantitative point of view, is more useful as the study of the true extension and nature of the lesion through the examination and palpation is more difficult. The echographic images can be divided into solid, cystic, vascular and mixed masses. The technical improvements practiced recently in the resolution of the images in the new echographs have allowed a more precise characterization of the tumors and established new indications of the exploration, since the cutaneous lesions vary in their echographic profile. Thus it is possible to make a much reliable diagnosis of epidermic, dermic and hypodermic lesions as well as the possible involvement of the lynphatic nodules. The main use of the cutaneous echography is to provide specific data about the tumors, such as its composition (solid or cystic), tumoral margins, depth and degree of the invasion, involvement of vital structures and the presence of macroscopic metastasis. Today the vascularization of the tumors is being studied to be able to visualize it to value the angiogenesis with non-invasive exploration methods through echo-doppler. The purpose of these works is the differential diagnosis of the pigmented lesions through the measurement of the blood flow. We have used a digital echographic platform with three multifrequent sounds and have had the opportunity of studying diverse cutaneous neoplasias, with which we pretend to establish the echographic morphological characteristics of the non-melanoma cutaneous cancer, specially basal cell and spindle cell carcinomas. CONCLUSIONS: The cutaneous echography is a new diagnostic tool that helps determine the type, size, and degree of invasion and extension, depth and vascularization of a cutaneous neoplasic lesion and thus allows the design of a surgical treatment appropriate to the neoplasm to be treated. Among its main advantages is that it is a non-invasive technique that offers the possibility of observing in real time the internal morphology of a lesion and its degree of vascularization. Key words: Cryosurgery, cutaneous echography, cutaneous tumors, basal cell carcinoma, spindle cell carcinoma. Disclosure not available at press time.
J AM ACAD DERMATOL
P125
P484
SUCCESSFUL TREATMENT OF VULVAR BOWEN’S DISEASE WITH TOPICAL IMIQUIMOD 5% CREAM Bo Kyung Koh, MD, Uijungbu St. Mary’s Hospital, College of Medicine, the Catholic University of Korea, Uijungbu, Korea, Yeon Jeong Kim, Kyung Ho Lee, Jin Woo Kim Bowen’s disease (BD) is a form of intraepithelial (in situ) squamous cell carcinoma. Typical BD presents as a gradually enlarging well demarcated erythematous plaque with an irregular border and scaly surface. But in the vulvar BD, there are more frequent erosion, ulceration and pigmentation. Possible treatments of BD include physical destruction of the lesion, e.g. cryotherapy, curettage, laser therapy or excision. Also, as a non-invasive options, there are photodynamic therapy (PDT) and topical 5-fluorouracil. Especially, in case of vulvar BD we need more non-invasive and tolerable method. So, we think imiquimod is the most suitable method to treat vulvar BD. Patients just apply cream to the lesion by themselves three times a week. Imiquimod’s activity comes through its ability to induce the production of cytokines, which in turn stimulate T cells, thereby enhancing innate and acquired cellular immunity. A 72-year-old female visited our department of dermatology for further evaluation of painful erosive patches on the vulva for 15 years. Based on the history, at first, there were some vesicles on the vulva and the lesion grew erosive with yellowish discharge. Skin biopsy specimen showed, throughout the epidermis, the cells lay in complete disorder, resulting in a “windblown appearance”. Many cells appeared highly atypical, showing large, hyperchromatic nuclei. But, the border between the epidermis and dermis everywhere appeared sharp and the basement membrane remained intact. So, we diagnosed vulvar Bowen’s disease and started the every other day treatment with topical imiquimod 5% cream for 16 weeks. At the bedtime, she applied it on the vulva by herself and the next morning washed it off. After treatment later, the vulvar lesion almost cleared and the skin biopsy showed no atypical cells in the epidermis. Until now there is no recurrence. We believe imiquimod is an effective, tolerated, safe and new tool for the treatment of vulvar BD. We report a case of vulvar BD successfully treated with topical imiquimod 5% cream.
A CASE OF CUTANEOUS METASTASIS FROM HEPATIC LEIOMYOSARCOMA Jeong-Soo Kim, MD, Hanyang University Guri Hospital, Seoul, Korea, Hee-Joon Yu, MD, PhD, Hanyang University Guri Hospital, Seoul, Korea, Kwang-Yeoll Yeo, MD, Hanyang University Guri Hospital, Seoul, Korea Cutaneous leiomyosarcoma is a rare malignant neoplasm. It constitutes about 2-3% of all superficial soft tissue malignancies. On the biologic behavior, these neoplasms can be divided into three types: cutaneous (intradermal), subcutaneous and secondary (metastatic) leiomyosarcomas. Clinically, secondary type of leiomyosarcoma usually presents as multiple nodules of varying sizes. In the literature review, metastasis to the skin from leiomyosarcoma of extracutaneous organs has been reported in 12 cases. Of these, metastasis from the liver was identified in only one case. A 48-year-old man was referred to the dermatology department from the gastroenterology department for three subcutaneous nodules on the forehead and scalp. Cutaneous examination revealed three, well-defined, hard, movable, subcutaneous nodules. Six months ago, he visited a local clinic and computed tomography showed a hepatic mass in segment I. On admission, 7 days ago, computed tomography showed variable sized multiple hepatic masses in the both lobe, suggesting liver to liver metastasis. A fine needle aspiration biopsy specimen of hepatic mass showed irregular arranged spindle cells possessed elongated nuclei with blunt ends and many mitoses. Biopsy specimens from skin nodules showed spindle cells of same histologic features. The patient was diagnosed as cutaneous metastasis from hepatic leiomyosarcoma. Disclosure not available at press time.
Disclosure not available at press time.
P485
P483 DETECTION AND CLEARANCE OF SUBCLINICAL ACTINIC KERATOSIS (AK) WITH IMIQUIMOD (5%) TREATMENT Eggert Stockfleth, MD, University of Berlin, Berlin, Germany, Jens Bichel, MD, University of Berlin, Berlin, Germany, Claas Ulrich, MD, University of Berlin, Berlin, Germany, Wolfram Sterry, MD, University of Berlin, Berlin, Germany Background: Actinic keratosis is a crucial element in the multistage process of carcinogenesis leading to invasive squamous cell carcinoma (SCC). AK usually develops on sun-damaged skin and frequently involves an extensive area, identified as an ultravioletinduced “field of cancerization.” This area is characterized by the coexistence of early “subclinical” AK lesions and cumulates in multifocal SCC. Most ablative procedures do not target all lesions in a dysplastic area but focus on clearly visible lesions. Yet, untreated subclinical lesions might explain the high recurrence rate of AK after treatment. Thus, simultaneous treatment of clinical and subclinical AK lesions may mitigate disease recurrence. Recent case studies have demonstrated that imiquimod cream (5%) is a safe and effective treatment for AK. We examined the potential efficacy of topical imiquimod (5%) in treating clinical and subclinical AK lesions. Methods: A randomized, double-blind study was conducted in patients with biopsyproven AK (3-10 lesions/patient). Patients applied imiquimod cream (5%) or vehicle 3 times/week for up to 12 weeks. A rest period of up to 3 weeks, followed by resumption at a decreased application frequency (1-2 times/week), was permitted to manage adverse events. The number, size, and appearance of AK lesions were evaluated during each clinic visit. Complete or partial clearance was verified by histologic analysis. Results: Thirty-six patients (treatment group ⫽ 25, vehicle-control group ⫽ 11) completed the 12-week study. After 2-3 weeks of imiquimod (5%) treatment, AK lesion counts were elevated over baseline as subclinical lesions became clinically visible. The treatment area was characterized by mild erythema, and subclinical lesions appeared red and inflamed. On histologic examination, these lesions displayed signs of early AK. With the detection of subclinical lesions, the total number of AK lesions during treatment increased by ⬃300%. At the end of the 12-week study, complete clearance of clinical and subclinical AK lesions was observed in 21 of 25 (84%) patients, and an additional 2 of 25 (8%) patients exhibited partial clearance. The control group had no reductions in the number or size of AK lesions. Conclusions: Imiquimod cream (5%) was effective in clearing baseline AK lesions and early subclinical AK lesions. These findings suggest imiquimod therapy may lead to a lower recurrence rate relative to therapies that only treat visible lesions. Dr Stockfleth is a 3M consultant and Dr. Bichel is a employee of 3M Medica. Approximately 10% is supported by 3M Pharmaceuticals for poster production.
MARCH 2004
MORPHOLOGIC CHARACTERISTICS OF SKIN CANCER AS STUDIED THROUGH ECHOGRAPHY Jose M. Fernandez-Vozmediano, MD, University Hospital Puerto Real, Puerto Real, Spain, Jose Armario-Hita, MD, University Hospital Puerto Real, Puerto Real, Spain INTRODUCTION: The cutaneous echography is based on the basic physical principle of the transmission of high-frequency ultrasonic pulses (⬎10 MHz) from a transducer. This transducer can automatically gives off a sound over the object of study and register it when it comes back (echo). The period of time between the emission of the sound wave and its reflection depends on the physical distance between the surface of the object and the differest layers of the object that reflects the sound. Using different scanning methods certain tissular parameters can be calculated such as in vivo distance, in vivo sections or in vivo volume through methods of non-invasive exploration. These possibilities make of the cutaneous echography a very attractive and useful tool for the investigation as well as for the diagnosis in Dermatology. In present times the most interesting system for the dermatologic clinic is the B-mode scanner with transversal planes of the object of study. CLINICAL APPLICATIONS: The use of the echography to define the cutaneous tumors, from the qualitative and quantitative point of view, is more useful as the study of the true extension and nature of the lesion through the examination and palpation is more difficult. The echographic images can be divided into solid, cystic, vascular and mixed masses. The technical improvements practiced recently in the resolution of the images in the new echographs have allowed a more precise characterization of the tumors and established new indications of the exploration, since the cutaneous lesions vary in their echographic profile. Thus it is possible to make a much reliable diagnosis of epidermic, dermic and hypodermic lesions as well as the possible involvement of the lynphatic nodules. The main use of the cutaneous echography is to provide specific data about the tumors, such as its composition (solid or cystic), tumoral margins, depth and degree of the invasion, involvement of vital structures and the presence of macroscopic metastasis. Today the vascularization of the tumors is being studied to be able to visualize it to value the angiogenesis with non-invasive exploration methods through echo-doppler. The purpose of these works is the differential diagnosis of the pigmented lesions through the measurement of the blood flow. We have used a digital echographic platform with three multifrequent sounds and have had the opportunity of studying diverse cutaneous neoplasias, with which we pretend to establish the echographic morphological characteristics of the non-melanoma cutaneous cancer, specially basal cell and spindle cell carcinomas. CONCLUSIONS: The cutaneous echography is a new diagnostic tool that helps determine the type, size, and degree of invasion and extension, depth and vascularization of a cutaneous neoplasic lesion and thus allows the design of a surgical treatment appropriate to the neoplasm to be treated. Among its main advantages is that it is a non-invasive technique that offers the possibility of observing in real time the internal morphology of a lesion and its degree of vascularization. Key words: Cryosurgery, cutaneous echography, cutaneous tumors, basal cell carcinoma, spindle cell carcinoma. Disclosure not available at press time.
J AM ACAD DERMATOL
P125