Melanoma

LAS VEGAS — Photodynamic therapy continues to be used for many indications, including actinic keratoses, acne, and photorejuvenation, but other potential uses remain.

Perhaps most promising is the technology's role in chemoprevention, based largely on European studies, Dr. Michael Gold said at the annual meeting of the International Society for Dermatologic Surgery.

"Preliminary data are very promising," said Dr. Gold, a dermatologist who practices in Nashville, Tenn. "Anecdotal data in clinical practice are also encouraging, including longer time to development of new actinic keratoses and nonmelanoma skin cancers after treatment."

The two main photodynamic therapy photosensitizers currently being studied include Levulan (Dusa Pharmaceuticals Inc.) and Metvix (PhotoCure ASA).

Levulan is a 20% 5-aminolevulinic acid (ALA) solution. ALA occurs naturally in cells as an intermediate product formed during the endogenous porphyrin synthesis. It is converted to protoporphyrin IX and is activated by an appropriate light source.

In the United States, Levulan is approved for nonhyperkeratotic actinic keratoses of the face and scalp, with an incubation period of 14–18 hours and a treatment delivery time of 16 minutes and 40 seconds. All other uses are off label.

Metvix is a methyl ester of 20% 5-ALA. In the United States, it is approved for the treatment of actinic keratoses while in Europe and Australia it is widely used for the treatment of skin cancer.

"The FDA did not give this approval," Dr. Gold said. "In addition, there have been three reports in the literature of contact allergy to Metvix, so you have to keep that in mind."

Another photosensitizer available in Europe is PhotoSpray (Danish Dermatologic Development), a product that contains a 0.5% liposome encapsulated 5-ALA. "Patients spray themselves with the product every 5–10 minutes for an hour before undergoing an IPL [intense pulsed light] type of treatment, and they've been getting some very nice results," Dr. Gold said.

In the United States, 5-ALA photosensitizers are being used to treat a variety of dermatologic concerns, including photorejuvenation and associated actinic keratoses, acne vulgaris, sebaceous gland hyperplasia, and hidradenitis suppurativa.

In Europe, the primary niche for their use remains in nonmelanoma skin cancer.

Light sources studied with these agents have included blue light, IPL, and pulsed dye lasers. Five split-face clinical trials published in 2005 and 2006 have confirmed the photorejuvenation results. The studies "showed better results with the IPL or pulsed dye lasers compared with the blue light technology," Dr. Gold said.

In the treatment of acne, studies have demonstrated that 5-ALA gets absorbed into the sebaceous glands, causing a partial destruction of the glands.

Two split-face trials of acne patients showed better results when 5-ALA was combined with IPL compared with IPL alone (Dermatol. Surg. 2005;31:910-5; Dermatol. Surg. 2006;32:991-6).

Dr. Gold disclosed that he is a consultant, performed research, and speaks on behalf of many pharmaceutical and medical device companies, including DUSA Pharmaceuticals Inc. and Lumenis.

A patient with severe acne is shown prior to treatment with a blue-light device.

The patient's acne is much improved after undergoing photodynamic therapy. Photos courtesy Dr. Michael Gold

LAS VEGAS — Photodynamic therapy continues to be used for many indications, including actinic keratoses, acne, and photorejuvenation, but other potential uses remain.

Perhaps most promising is the technology's role in chemoprevention, based largely on European studies, Dr. Michael Gold said at the annual meeting of the International Society for Dermatologic Surgery.

"Preliminary data are very promising," said Dr. Gold, a dermatologist who practices in Nashville, Tenn. "Anecdotal data in clinical practice are also encouraging, including longer time to development of new actinic keratoses and nonmelanoma skin cancers after treatment."

The two main photodynamic therapy photosensitizers currently being studied include Levulan (Dusa Pharmaceuticals Inc.) and Metvix (PhotoCure ASA).

Levulan is a 20% 5-aminolevulinic acid (ALA) solution. ALA occurs naturally in cells as an intermediate product formed during the endogenous porphyrin synthesis. It is converted to protoporphyrin IX and is activated by an appropriate light source.

In the United States, Levulan is approved for nonhyperkeratotic actinic keratoses of the face and scalp, with an incubation period of 14–18 hours and a treatment delivery time of 16 minutes and 40 seconds. All other uses are off label.

Metvix is a methyl ester of 20% 5-ALA. In the United States, it is approved for the treatment of actinic keratoses while in Europe and Australia it is widely used for the treatment of skin cancer.

"The FDA did not give this approval," Dr. Gold said. "In addition, there have been three reports in the literature of contact allergy to Metvix, so you have to keep that in mind."

Another photosensitizer available in Europe is PhotoSpray (Danish Dermatologic Development), a product that contains a 0.5% liposome encapsulated 5-ALA. "Patients spray themselves with the product every 5–10 minutes for an hour before undergoing an IPL [intense pulsed light] type of treatment, and they've been getting some very nice results," Dr. Gold said.

In the United States, 5-ALA photosensitizers are being used to treat a variety of dermatologic concerns, including photorejuvenation and associated actinic keratoses, acne vulgaris, sebaceous gland hyperplasia, and hidradenitis suppurativa.

In Europe, the primary niche for their use remains in nonmelanoma skin cancer.

Light sources studied with these agents have included blue light, IPL, and pulsed dye lasers. Five split-face clinical trials published in 2005 and 2006 have confirmed the photorejuvenation results. The studies "showed better results with the IPL or pulsed dye lasers compared with the blue light technology," Dr. Gold said.

In the treatment of acne, studies have demonstrated that 5-ALA gets absorbed into the sebaceous glands, causing a partial destruction of the glands.

Two split-face trials of acne patients showed better results when 5-ALA was combined with IPL compared with IPL alone (Dermatol. Surg. 2005;31:910-5; Dermatol. Surg. 2006;32:991-6).

Dr. Gold disclosed that he is a consultant, performed research, and speaks on behalf of many pharmaceutical and medical device companies, including DUSA Pharmaceuticals Inc. and Lumenis.

A patient with severe acne is shown prior to treatment with a blue-light device.

The patient's acne is much improved after undergoing photodynamic therapy. Photos courtesy Dr. Michael Gold

LAS VEGAS — Photodynamic therapy continues to be used for many indications, including actinic keratoses, acne, and photorejuvenation, but other potential uses remain.

Perhaps most promising is the technology's role in chemoprevention, based largely on European studies, Dr. Michael Gold said at the annual meeting of the International Society for Dermatologic Surgery.

"Preliminary data are very promising," said Dr. Gold, a dermatologist who practices in Nashville, Tenn. "Anecdotal data in clinical practice are also encouraging, including longer time to development of new actinic keratoses and nonmelanoma skin cancers after treatment."

The two main photodynamic therapy photosensitizers currently being studied include Levulan (Dusa Pharmaceuticals Inc.) and Metvix (PhotoCure ASA).

Levulan is a 20% 5-aminolevulinic acid (ALA) solution. ALA occurs naturally in cells as an intermediate product formed during the endogenous porphyrin synthesis. It is converted to protoporphyrin IX and is activated by an appropriate light source.

In the United States, Levulan is approved for nonhyperkeratotic actinic keratoses of the face and scalp, with an incubation period of 14–18 hours and a treatment delivery time of 16 minutes and 40 seconds. All other uses are off label.

Metvix is a methyl ester of 20% 5-ALA. In the United States, it is approved for the treatment of actinic keratoses while in Europe and Australia it is widely used for the treatment of skin cancer.

"The FDA did not give this approval," Dr. Gold said. "In addition, there have been three reports in the literature of contact allergy to Metvix, so you have to keep that in mind."

Another photosensitizer available in Europe is PhotoSpray (Danish Dermatologic Development), a product that contains a 0.5% liposome encapsulated 5-ALA. "Patients spray themselves with the product every 5–10 minutes for an hour before undergoing an IPL [intense pulsed light] type of treatment, and they've been getting some very nice results," Dr. Gold said.

In the United States, 5-ALA photosensitizers are being used to treat a variety of dermatologic concerns, including photorejuvenation and associated actinic keratoses, acne vulgaris, sebaceous gland hyperplasia, and hidradenitis suppurativa.

In Europe, the primary niche for their use remains in nonmelanoma skin cancer.

Light sources studied with these agents have included blue light, IPL, and pulsed dye lasers. Five split-face clinical trials published in 2005 and 2006 have confirmed the photorejuvenation results. The studies "showed better results with the IPL or pulsed dye lasers compared with the blue light technology," Dr. Gold said.

In the treatment of acne, studies have demonstrated that 5-ALA gets absorbed into the sebaceous glands, causing a partial destruction of the glands.

Two split-face trials of acne patients showed better results when 5-ALA was combined with IPL compared with IPL alone (Dermatol. Surg. 2005;31:910-5; Dermatol. Surg. 2006;32:991-6).

Dr. Gold disclosed that he is a consultant, performed research, and speaks on behalf of many pharmaceutical and medical device companies, including DUSA Pharmaceuticals Inc. and Lumenis.

A patient with severe acne is shown prior to treatment with a blue-light device.

The patient's acne is much improved after undergoing photodynamic therapy. Photos courtesy Dr. Michael Gold

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — A rare case of relapsing leukemia cutis appeared only in the skin, in a patient with no evidence of circulating leukemia whose bone marrow appeared to have responded completely to previous treatment.

A 45-year-old patient had undergone chemotherapy in 2007 for myeloid leukemia, Dr. George Elgart and his associates wrote in a poster presented at the annual meeting of the American Society of Dermatopathology. Although he responded initially, he was lost to follow-up before completing therapy. After he returned to care and resumed chemotherapy, remission was confirmed by peripheral blood and bone marrow analyses.

He subsequently developed multiple skin lesions that were nonspecific on clinical exam but that suggested a systemic process. The lesions increased rapidly in number and size. Because of the patient's history, "the diagnosis was not challenging," reported Dr. Elgart, professor of dermatology and cutaneous surgery at the University of Miami.

The lesions first presented as subcutaneous nodules, some in bizarre shapes, such as a plaque shaped like a question mark. Many of the lesions eventually ulcerated or developed an adherent thick crust. A punch biopsy of one of the lesions showed a dramatic infiltrate to all margins of the specimen.

Immunopathology can be helpful but is highly variable in the skin manifestations of hematologic processes and is complicated by the inconsistency of myeloid leukemia immunohistochemistry, Dr. Elgart noted. In this case, review of the primary histology helped to direct the immunohistochemical evaluation.

The punch biopsy specimen was positive on immunostaining for CD56 and CD177 but negative for myeloperoxidase and CD34. The cells had a decidedly geometric configuration and appreciable cytoplasm. They appeared unconstrained by the surrounding dermal anatomy and extended to track among the collagen bundles in a manner parallel to that of metastatic carcinoma. In contrast, a recent review by other investigators reported the most sensitive markers to be lysozyme and CD68.

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

SAN FRANCISCO — It is not uncommon for stasis dermatitis to present as a solitary lesion with no history of venous insufficiency, but it is uncommon for physicians to correctly diagnose it.

Thirty-three (7%) of 483 cases of stasis dermatitis diagnosed from a skin biopsy between 1992 and 2008 at the Cleveland Clinic presented as a solitary lesion. Of these 33 cases, clinical diagnoses mistook 11 cases for squamous cell carcinoma and 8 cases for basal cell carcinoma, Dr. Joshua Weaver and his associates reported in a poster presentation at the annual meeting of the American Society of Dermatopathology.

Physicians also believed that three cases were consistent with granuloma annulare, and another three were deemed consistent with irritated seborrheic keratosis. Other differential diagnoses offered by physicians were scars, pyoderma gangrenosum, actinic keratosis, Kaposi's sarcoma, nevus, or a neoplasm, not otherwise specified.

"We have revealed that there is an early form of stasis dermatitis presenting as a solitary lesion that clinically can look like a neoplasm," said Dr. Weaver of the Cleveland Clinic. "It's important to diagnose stasis dermatitis early so that you can begin treatment as early as possible" to prevent leg ulcers and an increased risk for developing squamous cell carcinoma.

The retrospective study found that the solitary-lesion cases occurred in the usual setting for stasis dermatitis—on the lower extremities of older adults (the cohort's average age was 66 years) and in more females than males.

Detailed clinical descriptions in a subset of 25 cases reported a single erythematous plaque on the lower portion of the leg as the most common presentation, affecting either leg in equal frequency. The lesions averaged 1.6 cm in size.

Out of 21 cases that physicians described, 12 were called plaques, 5 were said to be papules, 3 were described as patches, and 1 was called a nodule. Physicians noted some erythema in 12 cases, scaling in 8, and erosion in 5.

All cases demonstrated the classical morphologic picture of stasis dermatitis—variable acanthosis, mild spongiosis of the epidermis, and underlying proliferation of thick-walled blood vessels in the papillary dermis with deposition of hemosiderin and extravasation of red blood cells. In 27 (82%) of the 33 cases, spongiotic change in the epidermis was mild or absent and no spongiotic vesicles were seen. Parakeratosis was present in 19 (58%) of cases, which correlated approximately half the time with the clinical impression of a scale. Only five cases (15%) had a serum crust, Dr. Weaver reported.

All biopsies showed the characteristic lobular proliferation of thick-walled blood vessels in the papillary dermis. Nearly all cases showed evidence of hemorrhage, including extravasated erythrocytes, hemosiderin deposition, and siderophages. All had dermal fibrosis, but in variable proportions, he said.

Additional biopsies performed at the time of the original diagnosis in six cases produced histologic findings similar to the original slides under hematoxylin and eosin stain. Special stains for microorganisms performed in nine cases found no fungal or bacterial organisms. An iron stain was performed in one case and was positive for hemosiderin with macrophages.

Stasis dermatitis is a cutaneous manifestation and marker of increased venous pressure of the lower extremities. It usually presents in middle-aged to elderly people as erythematous with slightly yellow-to-brown pigmented patches over the bilateral lower legs with or without conspicuous varicose veins.

Most cases of stasis dermatitis are caused by insufficient deep venous system valves preventing proper return of blood to the central circulation through the muscular pumping action of the lower legs. Prior thrombophlebitis or congenital fragility can cause venous valvular insufficiency.

All of the single-lesion cases demonstrated the classical morphologic picture of stasis dermatitis. DR. WEAVER

In the late 19th century, Brooke and Spiegler described the familial occurrence of multiple tumors of the skin appendages. Synonyms have included familial cylindromatosis, turban tumor syndrome, and Brooke-Spiegler syndrome (BSS).1 In this report, we describe a patient with pegged teeth and BSS. We discuss the pathogenesis, diagnosis, genetic testing, and treatment options for this interesting syndrome.

Case Report
A 40-year-old white woman presented in 1997 for evaluation of numerous flesh-colored papules on her face. One of the lesions was biopsied in 1999 and diagnosed as a trichoepithelioma (Figure 1). These particular lesions had been present since she was 13 years of age, increasing in size and number with time. Subsequently, in December 2003, she presented with a 0.8-cm pink papule in the left preauricular area; a biopsy was performed and a spiradenoma in association with a trichoepithelioma was diagnosed. In January 2006, she presented with enlarging "bumps" on her scalp. She denied any substantial pain, pruritus, or other symptoms, but was rather concerned about the recent growth of lesions, both in size and number. Her medical history was noncontributory. However, there was a family history of similar lesions on the face and scalp of a great-aunt and uncle. No workup or genetic testing was ever performed.

Physical examination revealed a healthy, well-nourished, middle-aged woman. There were numerous symmetrically distributed flesh-colored to off-white firm papules involving the bilateral nasolabial folds, coalescing in areas to form plaques (Figure 2). There were 3 pink, firm, smooth, well-circumscribed nodules with overlying telangiectases involving the vertex and crown of the scalp, measuring 0.7X0.7 cm, 1.4X1.1 cm, and 1.4X1.4 cm in size. There was mild tenderness to palpation of all 3 lesions. Most interestingly, examination of the oral cavity revealed pegged (conical) teeth (Figure 3). It was not clear if they were primary or secondary teeth. There was no history of incontinentia pigmenti or any other ectodermal dysplasia in the patient or family members. Further evaluation of the hair and nails revealed no additional abnormalities.

The differential diagnoses for the scalp lesions included pilar cysts, basal or squamous cell carcinomas, spiradenomas, cylindromas, trichoblastomas, neurofibromas, and keloids or hypertrophic scars. The patient underwent an excisional biopsy of the smallest lesion in February 2006. Subsequently, excisional biopsies were performed on the other 2 lesions in April and July 2006. The first specimen revealed variably sized discrete aggregations of cuboidal epithelial cells with a rim of thickened eosinophilic basement membrane material surrounding tumor islands. There were 2 types of epithelial cells: cells with small, dark-staining nuclei present at the periphery in a palisading fashion, and light-staining nuclei lying in the center of the aggregations. Sweat duct lumina were appreciated within the tumor islands, and a diagnosis of cylindroma was made. The second biopsy showed a single, large, well-demarcated nodule of cuboidal epithelial cells arranged in interweaving cords present in the dermis. Again, there were 2 types of epithelial cells: smaller cells with dark nuclei lying at the periphery of the cords, and cells with larger pale nuclei in the center of the cords, associated with lumina. A diagnosis of spiradenoma was rendered. Based on the clinical findings and histopathologic diagnoses of trichoepithelioma, cylindroma, and spiradenoma, the patient received a diagnosis of BSS. Treatment for the trichoepitheliomas consisted of several glycolic acid peels, and the patient was pleased with the results. Furthermore, complete excisional biopsies were performed for all tumors on the scalp. The patient considered genetic testing for herself and family members.

Comment
Brooke-Spiegler syndrome is inherited in an autosomal dominant fashion with complete penetrance and variable expression. Both interfamilial and intrafamilial phenotypic variability have been well-documented in BSS; thus, a correlation between genotype and phenotype is lacking.2 Brooke-Spiegler syndrome is uncommon, with a female to male ratio of 2 to 1.1 Characteristically, patients present with the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Often, other adnexal tumors are observed, including but not limited to trichoblastomas, basal cell carcinomas, milia, organoid nevi, and syringomas.3 It was initially believed that cylindromas and spiradenomas showed sweat gland differentiation and trichoepitheliomas showed follicular differentiation.4 This combination represents an unusual inherited tumor diathesis involving neoplasms derived from pluripotential basal cells with adnexal differentiation along both sweat gland and follicular lineages.5-7 Typically, these tumors are located in the head and neck region, appear in puberty to early adulthood, and gradually increase in size and number throughout life.8 Malignant transformation of cylindromas in particular is quite rare, but metastasis in the event of malignancy is not infrequent.9-11 Malignancy is more frequent in patients with BSS rather than solitary cylindroma.10-12 Patients also are at risk for developing benign and malignant tumors of the salivary glands, particularly the parotid, including adenocarcinoma.4,6,8,13 In affected families, mutations have been demonstrated in the cylindromatosis gene, CYLD, located on band 16q12-13.¹⁴ This gene consists of 20 exons and reveals the characteristic attributes of a tumor suppressor gene with loss of heterozygosity.1,15,16 CYLD plays a role in governing cell cycle and apoptosis.9 Mutational changes in the CYLD gene could affect the normal regulation of the stem cell population of the folliculosebaceousapocrine unit. In turn, mutations in the genes that regulate proliferation and differentiation of the putative stem cells, possibly located in the bulge region of the hair follicle,3 could give rise to different combinations of adnexal skin tumors.1,2,17-19 More recently, spiradenomas have been proposed to be apocrine tumors on the basis of adnexal morphogenesis and their close association with follicular and apocrine tumors in BSS.10 The morphogenesis of both apocrine and sebaceous glands is dependent on the hair follicle because the glands develop from epithelial buds arising directly above the isthmus. However, eccrine glands develop from the base of the interfollicular rete ridges of embryonic skin. Cylindromas and spiradenomas are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit, as demonstrated by the occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas. It is hypothesized that cylindromas and spiradenomas may be polar extremes of a spectrum of adnexal neoplasms with apocrine differentiation.13 Since the initial observation of mutations in the CYLD1 gene as cause for BSS,15 a host of different mutations have been reported, including frameshift mutations,1,20 splice site mutations,1 small deletions and insertions,1,15,21 and novel missense mutations.8 Most mutations lead to a premature translational stop, which disrupts the protein function.21 The CYLD gene interacts with several members of the nuclear factor-κΒ signaling pathway, which play important roles in inflammation, immune response, and oncogenesis. Inhibition of the CYLD gene enhances activation of the transcription factor nuclear factor-κΒ and leads to increased resistance to apoptosis and advanced carcinogenesis,21 which also results in compromise of the early steps in the development of epidermal appendages, including hair follicles and sweat glands.22 The exact mechanisms of CYLD-dependent tumorigenesis in the skin remain to be established. Cylindromas located on the head and neck region may eventually cover the entire scalp, resulting in so-called turban tumors.8 Mutational screening for the CYLD gene is beneficial to patients with multiple cylindromas and/or trichoepitheliomas as well as their family members. Physicians caring for patients and family members affected with BSS should contact the medical genetics department of their respective local medical school or academic medical center. Early identification of mutation carriers and appropriate genetic counseling may improve the therapeutic management to avoid complications such as disfigurement (turban tumor) or malignant transformation.21 Excision of all cylindromas and spiradenomas is recommended due to the low risk for malignant potential (cylindrocarcinoma and spiradenocarcinoma).8 If untreated, BSS can cause considerable disfigurement and discomfort, and severely neglected cases may require scalp surgery and reconstruction.23 Additionally, laser treatments, such as CO2 and erbium:YAG lasers, have been used for surgical destruction of several of the adnexal tumors (cylindromas and trichoepitheliomas), though the former ideally should be excised for histology because of the low risk for malignant transformation.5,9 Dermabrasion, chemical peels, electrodesiccation, and cryotherapy also may be considered as alternative treatment modalities.9 Brummelkamp et al24 demonstrated that inhibitory effects caused by CYLD gene mutations potentially can be reversed by application of salicylates or prostaglandin A. This discovery may give hope for novel therapeutic approaches in the future. The presence of pegged (conical) teeth in our patient is unusual, as this finding has not been described in BSS. The question remains, are these truly pegged teeth, and if so, is it merely an incidental (idiopathic) finding or rather part of an altogether new syndrome? As a result, genetic testing is extremely inviting.

Conclusion
Brooke-Spiegler syndrome consists of the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Mutations occur in the CYLD gene on band 16q12-13. Brooke-Spiegler syndrome is theorized as reflecting genetic dysfunction in the regulation of the folliculosebaceousapocrine unit. Early diagnosis is important with confirmatory genetic testing of the patient and family members. Further studies including genetic testing will need to be conducted to determine the relationship between pegged (conical) teeth and BSS.

In the late 19th century, Brooke and Spiegler described the familial occurrence of multiple tumors of the skin appendages. Synonyms have included familial cylindromatosis, turban tumor syndrome, and Brooke-Spiegler syndrome (BSS).1 In this report, we describe a patient with pegged teeth and BSS. We discuss the pathogenesis, diagnosis, genetic testing, and treatment options for this interesting syndrome.

Case Report
A 40-year-old white woman presented in 1997 for evaluation of numerous flesh-colored papules on her face. One of the lesions was biopsied in 1999 and diagnosed as a trichoepithelioma (Figure 1). These particular lesions had been present since she was 13 years of age, increasing in size and number with time. Subsequently, in December 2003, she presented with a 0.8-cm pink papule in the left preauricular area; a biopsy was performed and a spiradenoma in association with a trichoepithelioma was diagnosed. In January 2006, she presented with enlarging "bumps" on her scalp. She denied any substantial pain, pruritus, or other symptoms, but was rather concerned about the recent growth of lesions, both in size and number. Her medical history was noncontributory. However, there was a family history of similar lesions on the face and scalp of a great-aunt and uncle. No workup or genetic testing was ever performed.

Physical examination revealed a healthy, well-nourished, middle-aged woman. There were numerous symmetrically distributed flesh-colored to off-white firm papules involving the bilateral nasolabial folds, coalescing in areas to form plaques (Figure 2). There were 3 pink, firm, smooth, well-circumscribed nodules with overlying telangiectases involving the vertex and crown of the scalp, measuring 0.7X0.7 cm, 1.4X1.1 cm, and 1.4X1.4 cm in size. There was mild tenderness to palpation of all 3 lesions. Most interestingly, examination of the oral cavity revealed pegged (conical) teeth (Figure 3). It was not clear if they were primary or secondary teeth. There was no history of incontinentia pigmenti or any other ectodermal dysplasia in the patient or family members. Further evaluation of the hair and nails revealed no additional abnormalities.

The differential diagnoses for the scalp lesions included pilar cysts, basal or squamous cell carcinomas, spiradenomas, cylindromas, trichoblastomas, neurofibromas, and keloids or hypertrophic scars. The patient underwent an excisional biopsy of the smallest lesion in February 2006. Subsequently, excisional biopsies were performed on the other 2 lesions in April and July 2006. The first specimen revealed variably sized discrete aggregations of cuboidal epithelial cells with a rim of thickened eosinophilic basement membrane material surrounding tumor islands. There were 2 types of epithelial cells: cells with small, dark-staining nuclei present at the periphery in a palisading fashion, and light-staining nuclei lying in the center of the aggregations. Sweat duct lumina were appreciated within the tumor islands, and a diagnosis of cylindroma was made. The second biopsy showed a single, large, well-demarcated nodule of cuboidal epithelial cells arranged in interweaving cords present in the dermis. Again, there were 2 types of epithelial cells: smaller cells with dark nuclei lying at the periphery of the cords, and cells with larger pale nuclei in the center of the cords, associated with lumina. A diagnosis of spiradenoma was rendered. Based on the clinical findings and histopathologic diagnoses of trichoepithelioma, cylindroma, and spiradenoma, the patient received a diagnosis of BSS. Treatment for the trichoepitheliomas consisted of several glycolic acid peels, and the patient was pleased with the results. Furthermore, complete excisional biopsies were performed for all tumors on the scalp. The patient considered genetic testing for herself and family members.

Comment
Brooke-Spiegler syndrome is inherited in an autosomal dominant fashion with complete penetrance and variable expression. Both interfamilial and intrafamilial phenotypic variability have been well-documented in BSS; thus, a correlation between genotype and phenotype is lacking.2 Brooke-Spiegler syndrome is uncommon, with a female to male ratio of 2 to 1.1 Characteristically, patients present with the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Often, other adnexal tumors are observed, including but not limited to trichoblastomas, basal cell carcinomas, milia, organoid nevi, and syringomas.3 It was initially believed that cylindromas and spiradenomas showed sweat gland differentiation and trichoepitheliomas showed follicular differentiation.4 This combination represents an unusual inherited tumor diathesis involving neoplasms derived from pluripotential basal cells with adnexal differentiation along both sweat gland and follicular lineages.5-7 Typically, these tumors are located in the head and neck region, appear in puberty to early adulthood, and gradually increase in size and number throughout life.8 Malignant transformation of cylindromas in particular is quite rare, but metastasis in the event of malignancy is not infrequent.9-11 Malignancy is more frequent in patients with BSS rather than solitary cylindroma.10-12 Patients also are at risk for developing benign and malignant tumors of the salivary glands, particularly the parotid, including adenocarcinoma.4,6,8,13 In affected families, mutations have been demonstrated in the cylindromatosis gene, CYLD, located on band 16q12-13.¹⁴ This gene consists of 20 exons and reveals the characteristic attributes of a tumor suppressor gene with loss of heterozygosity.1,15,16 CYLD plays a role in governing cell cycle and apoptosis.9 Mutational changes in the CYLD gene could affect the normal regulation of the stem cell population of the folliculosebaceousapocrine unit. In turn, mutations in the genes that regulate proliferation and differentiation of the putative stem cells, possibly located in the bulge region of the hair follicle,3 could give rise to different combinations of adnexal skin tumors.1,2,17-19 More recently, spiradenomas have been proposed to be apocrine tumors on the basis of adnexal morphogenesis and their close association with follicular and apocrine tumors in BSS.10 The morphogenesis of both apocrine and sebaceous glands is dependent on the hair follicle because the glands develop from epithelial buds arising directly above the isthmus. However, eccrine glands develop from the base of the interfollicular rete ridges of embryonic skin. Cylindromas and spiradenomas are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit, as demonstrated by the occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas. It is hypothesized that cylindromas and spiradenomas may be polar extremes of a spectrum of adnexal neoplasms with apocrine differentiation.13 Since the initial observation of mutations in the CYLD1 gene as cause for BSS,15 a host of different mutations have been reported, including frameshift mutations,1,20 splice site mutations,1 small deletions and insertions,1,15,21 and novel missense mutations.8 Most mutations lead to a premature translational stop, which disrupts the protein function.21 The CYLD gene interacts with several members of the nuclear factor-κΒ signaling pathway, which play important roles in inflammation, immune response, and oncogenesis. Inhibition of the CYLD gene enhances activation of the transcription factor nuclear factor-κΒ and leads to increased resistance to apoptosis and advanced carcinogenesis,21 which also results in compromise of the early steps in the development of epidermal appendages, including hair follicles and sweat glands.22 The exact mechanisms of CYLD-dependent tumorigenesis in the skin remain to be established. Cylindromas located on the head and neck region may eventually cover the entire scalp, resulting in so-called turban tumors.8 Mutational screening for the CYLD gene is beneficial to patients with multiple cylindromas and/or trichoepitheliomas as well as their family members. Physicians caring for patients and family members affected with BSS should contact the medical genetics department of their respective local medical school or academic medical center. Early identification of mutation carriers and appropriate genetic counseling may improve the therapeutic management to avoid complications such as disfigurement (turban tumor) or malignant transformation.21 Excision of all cylindromas and spiradenomas is recommended due to the low risk for malignant potential (cylindrocarcinoma and spiradenocarcinoma).8 If untreated, BSS can cause considerable disfigurement and discomfort, and severely neglected cases may require scalp surgery and reconstruction.23 Additionally, laser treatments, such as CO2 and erbium:YAG lasers, have been used for surgical destruction of several of the adnexal tumors (cylindromas and trichoepitheliomas), though the former ideally should be excised for histology because of the low risk for malignant transformation.5,9 Dermabrasion, chemical peels, electrodesiccation, and cryotherapy also may be considered as alternative treatment modalities.9 Brummelkamp et al24 demonstrated that inhibitory effects caused by CYLD gene mutations potentially can be reversed by application of salicylates or prostaglandin A. This discovery may give hope for novel therapeutic approaches in the future. The presence of pegged (conical) teeth in our patient is unusual, as this finding has not been described in BSS. The question remains, are these truly pegged teeth, and if so, is it merely an incidental (idiopathic) finding or rather part of an altogether new syndrome? As a result, genetic testing is extremely inviting.

Conclusion
Brooke-Spiegler syndrome consists of the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Mutations occur in the CYLD gene on band 16q12-13. Brooke-Spiegler syndrome is theorized as reflecting genetic dysfunction in the regulation of the folliculosebaceousapocrine unit. Early diagnosis is important with confirmatory genetic testing of the patient and family members. Further studies including genetic testing will need to be conducted to determine the relationship between pegged (conical) teeth and BSS.

In the late 19th century, Brooke and Spiegler described the familial occurrence of multiple tumors of the skin appendages. Synonyms have included familial cylindromatosis, turban tumor syndrome, and Brooke-Spiegler syndrome (BSS).1 In this report, we describe a patient with pegged teeth and BSS. We discuss the pathogenesis, diagnosis, genetic testing, and treatment options for this interesting syndrome.

Case Report
A 40-year-old white woman presented in 1997 for evaluation of numerous flesh-colored papules on her face. One of the lesions was biopsied in 1999 and diagnosed as a trichoepithelioma (Figure 1). These particular lesions had been present since she was 13 years of age, increasing in size and number with time. Subsequently, in December 2003, she presented with a 0.8-cm pink papule in the left preauricular area; a biopsy was performed and a spiradenoma in association with a trichoepithelioma was diagnosed. In January 2006, she presented with enlarging "bumps" on her scalp. She denied any substantial pain, pruritus, or other symptoms, but was rather concerned about the recent growth of lesions, both in size and number. Her medical history was noncontributory. However, there was a family history of similar lesions on the face and scalp of a great-aunt and uncle. No workup or genetic testing was ever performed.

Physical examination revealed a healthy, well-nourished, middle-aged woman. There were numerous symmetrically distributed flesh-colored to off-white firm papules involving the bilateral nasolabial folds, coalescing in areas to form plaques (Figure 2). There were 3 pink, firm, smooth, well-circumscribed nodules with overlying telangiectases involving the vertex and crown of the scalp, measuring 0.7X0.7 cm, 1.4X1.1 cm, and 1.4X1.4 cm in size. There was mild tenderness to palpation of all 3 lesions. Most interestingly, examination of the oral cavity revealed pegged (conical) teeth (Figure 3). It was not clear if they were primary or secondary teeth. There was no history of incontinentia pigmenti or any other ectodermal dysplasia in the patient or family members. Further evaluation of the hair and nails revealed no additional abnormalities.

The differential diagnoses for the scalp lesions included pilar cysts, basal or squamous cell carcinomas, spiradenomas, cylindromas, trichoblastomas, neurofibromas, and keloids or hypertrophic scars. The patient underwent an excisional biopsy of the smallest lesion in February 2006. Subsequently, excisional biopsies were performed on the other 2 lesions in April and July 2006. The first specimen revealed variably sized discrete aggregations of cuboidal epithelial cells with a rim of thickened eosinophilic basement membrane material surrounding tumor islands. There were 2 types of epithelial cells: cells with small, dark-staining nuclei present at the periphery in a palisading fashion, and light-staining nuclei lying in the center of the aggregations. Sweat duct lumina were appreciated within the tumor islands, and a diagnosis of cylindroma was made. The second biopsy showed a single, large, well-demarcated nodule of cuboidal epithelial cells arranged in interweaving cords present in the dermis. Again, there were 2 types of epithelial cells: smaller cells with dark nuclei lying at the periphery of the cords, and cells with larger pale nuclei in the center of the cords, associated with lumina. A diagnosis of spiradenoma was rendered. Based on the clinical findings and histopathologic diagnoses of trichoepithelioma, cylindroma, and spiradenoma, the patient received a diagnosis of BSS. Treatment for the trichoepitheliomas consisted of several glycolic acid peels, and the patient was pleased with the results. Furthermore, complete excisional biopsies were performed for all tumors on the scalp. The patient considered genetic testing for herself and family members.

Comment
Brooke-Spiegler syndrome is inherited in an autosomal dominant fashion with complete penetrance and variable expression. Both interfamilial and intrafamilial phenotypic variability have been well-documented in BSS; thus, a correlation between genotype and phenotype is lacking.2 Brooke-Spiegler syndrome is uncommon, with a female to male ratio of 2 to 1.1 Characteristically, patients present with the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Often, other adnexal tumors are observed, including but not limited to trichoblastomas, basal cell carcinomas, milia, organoid nevi, and syringomas.3 It was initially believed that cylindromas and spiradenomas showed sweat gland differentiation and trichoepitheliomas showed follicular differentiation.4 This combination represents an unusual inherited tumor diathesis involving neoplasms derived from pluripotential basal cells with adnexal differentiation along both sweat gland and follicular lineages.5-7 Typically, these tumors are located in the head and neck region, appear in puberty to early adulthood, and gradually increase in size and number throughout life.8 Malignant transformation of cylindromas in particular is quite rare, but metastasis in the event of malignancy is not infrequent.9-11 Malignancy is more frequent in patients with BSS rather than solitary cylindroma.10-12 Patients also are at risk for developing benign and malignant tumors of the salivary glands, particularly the parotid, including adenocarcinoma.4,6,8,13 In affected families, mutations have been demonstrated in the cylindromatosis gene, CYLD, located on band 16q12-13.¹⁴ This gene consists of 20 exons and reveals the characteristic attributes of a tumor suppressor gene with loss of heterozygosity.1,15,16 CYLD plays a role in governing cell cycle and apoptosis.9 Mutational changes in the CYLD gene could affect the normal regulation of the stem cell population of the folliculosebaceousapocrine unit. In turn, mutations in the genes that regulate proliferation and differentiation of the putative stem cells, possibly located in the bulge region of the hair follicle,3 could give rise to different combinations of adnexal skin tumors.1,2,17-19 More recently, spiradenomas have been proposed to be apocrine tumors on the basis of adnexal morphogenesis and their close association with follicular and apocrine tumors in BSS.10 The morphogenesis of both apocrine and sebaceous glands is dependent on the hair follicle because the glands develop from epithelial buds arising directly above the isthmus. However, eccrine glands develop from the base of the interfollicular rete ridges of embryonic skin. Cylindromas and spiradenomas are not eccrine tumors but neoplasms of the folliculosebaceousapocrine unit, as demonstrated by the occurrence of sebaceous and trichoblastic differentiation in spiradenocylindromas. It is hypothesized that cylindromas and spiradenomas may be polar extremes of a spectrum of adnexal neoplasms with apocrine differentiation.13 Since the initial observation of mutations in the CYLD1 gene as cause for BSS,15 a host of different mutations have been reported, including frameshift mutations,1,20 splice site mutations,1 small deletions and insertions,1,15,21 and novel missense mutations.8 Most mutations lead to a premature translational stop, which disrupts the protein function.21 The CYLD gene interacts with several members of the nuclear factor-κΒ signaling pathway, which play important roles in inflammation, immune response, and oncogenesis. Inhibition of the CYLD gene enhances activation of the transcription factor nuclear factor-κΒ and leads to increased resistance to apoptosis and advanced carcinogenesis,21 which also results in compromise of the early steps in the development of epidermal appendages, including hair follicles and sweat glands.22 The exact mechanisms of CYLD-dependent tumorigenesis in the skin remain to be established. Cylindromas located on the head and neck region may eventually cover the entire scalp, resulting in so-called turban tumors.8 Mutational screening for the CYLD gene is beneficial to patients with multiple cylindromas and/or trichoepitheliomas as well as their family members. Physicians caring for patients and family members affected with BSS should contact the medical genetics department of their respective local medical school or academic medical center. Early identification of mutation carriers and appropriate genetic counseling may improve the therapeutic management to avoid complications such as disfigurement (turban tumor) or malignant transformation.21 Excision of all cylindromas and spiradenomas is recommended due to the low risk for malignant potential (cylindrocarcinoma and spiradenocarcinoma).8 If untreated, BSS can cause considerable disfigurement and discomfort, and severely neglected cases may require scalp surgery and reconstruction.23 Additionally, laser treatments, such as CO2 and erbium:YAG lasers, have been used for surgical destruction of several of the adnexal tumors (cylindromas and trichoepitheliomas), though the former ideally should be excised for histology because of the low risk for malignant transformation.5,9 Dermabrasion, chemical peels, electrodesiccation, and cryotherapy also may be considered as alternative treatment modalities.9 Brummelkamp et al24 demonstrated that inhibitory effects caused by CYLD gene mutations potentially can be reversed by application of salicylates or prostaglandin A. This discovery may give hope for novel therapeutic approaches in the future. The presence of pegged (conical) teeth in our patient is unusual, as this finding has not been described in BSS. The question remains, are these truly pegged teeth, and if so, is it merely an incidental (idiopathic) finding or rather part of an altogether new syndrome? As a result, genetic testing is extremely inviting.

Conclusion
Brooke-Spiegler syndrome consists of the classic triad of cylindromas, trichoepitheliomas, and spiradenomas. Mutations occur in the CYLD gene on band 16q12-13. Brooke-Spiegler syndrome is theorized as reflecting genetic dysfunction in the regulation of the folliculosebaceousapocrine unit. Early diagnosis is important with confirmatory genetic testing of the patient and family members. Further studies including genetic testing will need to be conducted to determine the relationship between pegged (conical) teeth and BSS.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

PARIS — Treatment of atypical nevi with high-dose interferon alfa-2b may induce at least partial involution, based on the results of a small study.

Six of eight atypical nevi demonstrated a decrease in their greatest diameter, perimeter, or surface area, suggesting partial involution following treatment with high-dose interferon alfa-2b, reported Dr. Mona Amini-Adle of the department of dermatology at Hôpital de l'Hôtel Dieu, Lyon, France.

Partial clinical involution of atypical nevi was associated with an upregulation of CD4/CD8 ratio in the intra-nevi compartment, Dr. Amini-Adle said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, 10 patients with stage IIB-III melanoma, and at least four atypical nevi from each patient, were enrolled. The four nevi were identified as A-D at enrollment and photographed.

Two nevi were selected at random for removal prior to treatment; the remaining two were removed after 3 months of treatment. All nevi were evaluated clinically, pathologically, and with a double immunohistochemistry procedure (CD4-CD8; CD1a-CD83).

Patients were treated according to their melanoma status. Patients at high risk for melanoma were treated with a regimen of 20 million U/m

Dr. Amini-Adle reported on eight patients with a mean age of 36 years, half of whom were women. Sixteen clinical photos (eight pre- and eight posttreatment) from five patients were informative. Biopsy samples from eight patients were informative for 27 lesions—14 pre- and 13 posttreatment nevi. "We did not observe any histologic regression," said Dr. Amini-Adle.

Clinical atypia and histologic dysplasia were correlated in half of the lesions. The clinical changes were not accompanied by histologic signs of involution. Immunohistochemistry analysis showed alterations in lymphocyte infiltrates in nevi that were focal, with histologic signs of dysplasia and a significant upregulation of the CD4/CD8 ratio in the intra-nevi compartment (P = .0076).

No changes in lymphocyte response were observed after treatment, nor were any changes seen in the degree of atypia of these lesions. With regard to lymphocytic infiltrates, there was a trend of upregulation of CD4 cells and downregulation of CD8 cells, Dr. Amini-Adle said.

This resulted in upregulation of the CD4/CD8 ratio. These changes, however, were observed only in dysplastic nevi, not normal melanocytic nevi.

Dissociated responses of lymphocytes in both normal and atypical nevi suggest differential immunologic response to these entities. The dendritic cell infiltrate was not found to be influenced either in atypical nevi or normal nevi following treatment.

Atypical nevi have been shown to be nonobligate precursors of, and risk markers for, melanoma. Interferon alfa-2b is the only agent that has been shown to have a consistent and durable impact on relapse-free survival in melanoma patients, but it has not been studied for atypical nevi.

Interferon is known to enhance the immunogenicity of tumors. It is also known to suppress immune tolerance and to increase the degree of lymphocytic infiltrate in lesions that progress under treatment. Interestingly, in spontaneous regressive melanoma, the CD4/CD8 ratio is upregulated.

The meaning of upregulation in dysplastic nevi is unclear.

Dr. Amini-Adle noted that CD4 cells appear to play an important role in this regression.

Dr. Donald L. Morton has been given the Association of Community Cancer Centers' 2008 Clinical Research Award. He was honored for his extensive leadership and research, including work with intratumoral bacille Calmette-Guérin for melanoma that led to successful immunotherapy.

Dr. Morton is chief of the melanoma program at the John Wayne Cancer Institute in Santa Monica, Calif.

DR. DONALD L. MORTON

Dr. Donald L. Morton has been given the Association of Community Cancer Centers' 2008 Clinical Research Award. He was honored for his extensive leadership and research, including work with intratumoral bacille Calmette-Guérin for melanoma that led to successful immunotherapy.

Dr. Morton is chief of the melanoma program at the John Wayne Cancer Institute in Santa Monica, Calif.

DR. DONALD L. MORTON

Dr. Donald L. Morton has been given the Association of Community Cancer Centers' 2008 Clinical Research Award. He was honored for his extensive leadership and research, including work with intratumoral bacille Calmette-Guérin for melanoma that led to successful immunotherapy.

Dr. Morton is chief of the melanoma program at the John Wayne Cancer Institute in Santa Monica, Calif.

DR. DONALD L. MORTON

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Surgical excision is more effective than photodynamic therapy for the treatment of nodular basal cell carcinoma, based on the results of a study of more than 100 patients.

The cumulative incidence of failure was 2% for surgical excision, compared with 30% for photodynamic therapy at a 3-year interim analysis.

In all, 171 primary basal cell carcinomas in 149 patients were treated—88 in the surgical excision group and 83 in the phototherapy group. At 3-month follow-up, there were five basal cell carcinoma treatment failures in the phototherapy group (6%) and two (2.3%) in the surgical excision group.

"There's actually a higher risk of incomplete treatment after treatment with photodynamic therapy for primary basal cell carcinomas," Dr. Klara Mosterd of the department of dermatology at the University Hospital Maastricht (the Netherlands), said at the annual congress of the European Academy of Dermatology and Venereology.

For the study, primary basal cell carcinomas with a maximum size of 2 cm were randomly assigned to either photodynamic therapy or surgical excision. Exclusion criteria included tumors with mixed histology, recurrent basal cell carcinoma, three or more tumors per patient, and short life expectancy, among others.

Tumors treated with photodynamic therapy first underwent surgical debulking 2 weeks prior to treatment. Illumination was performed 4 hours after application of 5-aminolevulinic acid (ALA) cream. Tumors that were illuminated were illuminated again an hour later (from 585 nm to 720 nm, 75 J/cm

Surgical excision was performed under local anesthesia, using a 3-mm margin. Histologic examination then was performed. Any residual tumor found on follow-up was excised again, Dr. Mosterd said at the meeting.

After the first follow-up visit at 3 months, all patients were seen every 6 months up to 2 years and then once yearly up to 5 years.

Although surgical excision is the treatment of choice in patients with nodular basal cell carcinoma, photodynamic therapy has been shown to be an effective treatment for superficial basal cell carcinoma. This prompted the researchers to explore the effectiveness of photodynamic therapy on nodular basal cell carcinoma.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.

PARIS — Not only are patients with cutaneous T-cell lymphoma more likely to be colonized with Staphylococcus aureus, compared with healthy individuals, but S. aureus colonization appears to be directly related to the body surface area involvement, according to a study of 100 adults.

Researchers at Northwestern University, Chicago, compared colonization rates for 50 CTCL patients, 25 patients with psoriasis, and 25 healthy controls enrolled from a single dermatology clinic. S. aureus colonization was found in 44% of CTCL patients, 48% of psoriasis patients, and 28% of healthy controls.

Colonization with S. aureus was significantly associated with increased body surface area involvement of CTCL, Dr. Victoria Nguyen reported at the annual congress of the European Academy of Dermatology and Venereology.

Healthy controls were seen for routine skin examination. Patients with CTCL and psoriasis had to have active lesions in order to be included in the study.

The control participants were matched with case patients by age, sex, and anatomical skin site.

Potential participants were excluded if they had active infections, had taken antibiotics in the previous 3 months, or had undergone decolonization in the last 6 months. Patients who had HIV infection, were on chemotherapy, or were otherwise immunocompromised were also excluded.

Culture swabs were obtained from nares and lesional skin or normal skin in the healthy control group. Body surface examination was performed on CTCL patients.

Of the patients found to have S. aureus colonization, the majority was community associated (68%, 83%, and 71% for the CTCL, psoriasis, and control groups, respectively). The rate of methicillin-resistant S. aureus colonization was 2% in the CTCL group, 12% in the psoriasis group, and 8% in the healthy control group.

"Our study is likely an underestimation of S. aureus colonization, given that our excluded population [of CTCL patients] did have a greater rate of S. aureus colonization, up to 80%," noted Dr. Nguyen.

Infection is a common complication of CTCL, with S. aureus being the most common pathogen behind these infections, said Dr. Nguyen, who is a dermatology resident at Northwestern.

The reason for this predisposition to infection among CTCL patients may be threefold. First, these patients have an impaired skin barrier. They also have a decreased repertoire of normal circulating T cells. Lastly, these patients may also be immunosuppressed.

"CTCL is a Th-2-mediated pathway. So, similar to atopic dermatitis, there's perhaps a decrease in antimicrobial peptides in these patients, predisposing them to Staphylococcus aureus colonization," she said.

"The reason for the similarity in the colonization rates among the CTCL and psoriasis groups may be because these patients have an impaired skin barrier; both groups may have more frequent visits to the clinic; and hospitalizations and procedures may be higher in these groups," she added.

Prior studies have shown in vitro stimulation of CTCL cell lines with staphylococcal toxins, positive S. aureus cultures in half of Sézary syndrome patients, and the improvement of Sézary syndrome with antibiotic use.

"It may be that perhaps treating the colonization and infection in CTCL patients may improve severity," said Dr. Nguyen.

At Northwestern, she and her colleagues have treated S. aureus colonization in CTCL patients with resulting improvements in severity.

"We do recommend for our patients, who look like they've got crusting or excoriation, that they get sodium hypochlorite baths—a quarter cup of 6% sodium hypochlorite in a bath tub—daily or weekly to decrease colonization," she concluded.

PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.

PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.

PALM BEACH, FLA. — Patients with multiple recurrent skin cancers may do better with targeted medical therapy if surgical excision is inadequate, according to a dermatologist who treated a particularly difficult case.

The patient was a 52-year-old man, a Florida native who had had a great deal of sun exposure early in life. He developed renal failure and had a kidney transplant at age 26, and subsequently required a second transplant after the failure of the first transplanted kidney. For more than 25 years he has required ongoing immunosuppression.

"In the 11 years I have been taking care of this patient, he has had terrible problems with squamous cell carcinomas, actinic keratoses, and numerous other lesions, and I have taken off more than 2,000 skin cancers at this point," Dr. Leonard Slazinski said at the annual meeting of the Florida Society of Dermatologic Surgeons.

Every time the patient came in he had new lesions as well as multiple areas that were previously treated but had not healed. Even the skin under his nails has been involved, and some of the nails have had to be removed when squamous cell carcinomas developed under them.

"I was tired of seeing his ongoing oncogenesis," so he referred the patient to the department of dermatology at the Mayo Clinic, where a triple-therapy regimen was recommended, explained Dr. Slazinski, who is in private practice in Sarasota, Fla.

The patient began treatment with an oral retinoid, a continuous cyclooxygenasecox-2 inhibitor, and repeated topical 5-fluorouracil. However, the patient was unable to tolerate the triple-therapy regimen, he noted.

"So in consultation with my local oncologist I decided to try using the newer chemotherapeutic agents that target the epidermal growth factor receptor," Dr. Slazinski said.

The first agent he tried was cetuximab (Erbitux), which is a chimeric monoclonal antibody given by intravenous infusion that is used in metastatic colon cancer and head and neck carcinoma. The drug binds extracellularly to all cells that express epidermal growth factor, leading to a decrease in growth and proliferation.

After six doses of cetuximab, little improvement was seen, so the patient was switched to gefitinib (Iressa), which is an orally administered selective inhibitor of epidermal growth factor receptor tyrosine kinase. This drug blocks the Ras pathway, which is the antiapoptosis tumor pathway, and has been used for non-small cell lung cancer.

"The patient was on this treatment for 3 months and had a wonderful clinical response," Dr. Slazinski said. "For the first time I actually saw a decrease in the rate of cancer development, with a 60% decrease in tumors."

The tumors that did develop were smaller and less aggressive. "This drug really seemed to make a difference," he said.

Gefitinib has faced problems in the U.S. market, however. It did not do well in a trial of lung cancer and, therefore, has been severely restricted by the manufacturer, and requests for compassionate use in this patient were denied.

The next drug tried was erlotinib (Tarceva), which also targets the epidermal growth factor receptor tyrosine kinase and has shown promise in lung cancer. The patient responded well once again, with marked decreases in the numbers of squamous cell carcinomas and actinic keratoses, especially on the hands and arms, which were the most severely affected areas.

"He has been my most difficult case, but I would say for patients who are essentially failing surgical therapy, these new medical advances may offer a chance to get the disease under control. I don't think we can ever talk about curing them or stopping the progression entirely, but this has been a real advance," he said.