Letters to the Editor
Tokyo, Japan) were detected for soy (19.3 UA/mL), Japanese cedar (4.72 UA/mL) and Japanese white birch (1.24 UA/mL). Specific IgE antibodies for Japanese alder, Bet v 1, Gly m 4 and wheat gluten were not detected. A skin prick test (SPT) was positive for soy extract (10 mg/mL) (6 mm 9 5 mm), the cosmetic lotion used by the patient (as is) (10 mm 9 4 mm) and a commercially available soy milk (7 mm 9 5 mm). Results for the positive control (10 mg/mL histamine dihydrochloride; Wako Pure Chemical Industries, Osaka, Japan) and the negative control (saline; Otsuka Pharmaceutical, Tokyo, Japan) were 5 mm 9 5 mm and 0 mm 9 0 mm, respectively. SPT of the same cosmetic lotion yielded negative results in three healthy controls. 2-D western blot analysis using soy extract yielded multiple spots representing IgE binding protein. Based on mass spectrometric analysis, these spots were identified as a partial sequence of glycinin A-2-B-1a subunit (Gly m 6) precursor, a soybean seed storage protein in the glycinin A2 subunit family (Fig. 1). Glycinin A-2-B-1a subunit is one of five subunits of soybean seed storage protein belonging to the glycinin (11S globulin) family.1 Based on the clinical course and results presented above, we considered that the patient with atopic dermatitis, which tends to reduce the barrier function of the skin, was percutaneously sensitized to soy protein through frequent contact with cosmetic lotions containing soy-based ingredients in a humid environment while working as an esthetician and she subsequently developed anaphylactic reaction to soy. Niinimaki et al. reported contact urticaria from protein hydrolysates (PH) in hair conditioners. From one to 22 PH used in hair-care products (collagen, wheat and silk) were tested in their patients. They concluded that PH of hair cosmetics could cause contact urticaria, especially in patients with atopic dermatitis.2 In addition, a study on mice found that exposure of abraded skin to peanuts resulted in the production of peanut-specific IgE antibodies.3 These results indicate that reduced skin barrier function such as atopic dermatitis may be a cause of percutaneous sensitization by various proteins such as food.4 The pathogenesis of food allergy from percutaneous sensitization is yet to
be fully elucidated. Similar case reports are required in the future.
ACKNOWLEDGMENTS: This study is part of the “Study on Quasi Drug Cosmetics Additives Safety” conducted by the Teshima Group under the sponsorship of Pharmaceutical and Medical Device Regulatory Science General Research Project of the Ministry of Health, Labor and Welfare of Japan. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. CONFLICT OF INTEREST:
The
authors
declare
no
conflicts of interest.
Akiko YAGAMI,1 Kayoko SUZUKI,1,2 Masashi NAKAMURA,1,3 Akiyo SANO,1 Yohei IWATA,1 Tsukane KOBAYASHI,1 Mari SUZUKI,4 Kazuhiro HARA,3 Reiko TESHIMA,5 Kayoko MATSUNAGA1 1
Department of Dermatology, Fujita Health University School of Medicine, Toyoake, 2Department of Dermatology, Kariya Toyota General Hospital, Kariya, 3General Research and Development Institute, Hoyu, Nagakute, 4 Mari Skin Clinic, Nagoya, and 5National Institute of Health Sciences, Tokyo, Japan doi: 10.1111/1346-8138.12966
REFERENCES 1 Holzhauser T, Wackermann O, Ballmer-Weber BK et al. Soybean (Glycine max) allergy in Europe: Gly m5 (b-conglycinin) and Gly m6 (glycinin) are potential diagnostic markers for severe allergic reactions to soy. J AIIergy Clin lmmunol 2009; 123: 452–458. €ki A, Niinima €ki M, Ma €kinen-Kiljunen S, Hannuksela M. Contact 2 Niinima urticaria from protein hydrolysates in hair conditioners. Allergy 1998; 53: 1078–1082. 3 Strid J, Hourihans J, Kimber I et al. Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy 2005; 35: 757–766. 4 Yagami A, Suzuki K, Nakamura M et al. Occupational food allergy due to parvalbumin and phaseolin induced by epicutaneous sensitization. Allergol Int 2015. doi: 10.1016/j.alit.2015.03.005.
Pigmented squamous cell carcinoma of the cheek and its dermoscopic features Dear Editor, Pigmented squamous cell carcinoma (SCC) has been rarely reported and has an incidence that ranges 0.01–7%1,2. Clinically, its differential diagnosis from basal cell carcinoma (BCC) and/or melanoma is usually difficult. Here, we present a case of a pigmented SCC and discuss the significance of large blue-gray ovoid nests and shiny white areas in its dermoscopic features.
A 66-year-old man presented with a black lesion on his left cheek that had been noticed a half year earlier. Physical examination revealed a 9 mm 9 14 mm black plaque with an ulceration in the center region and several small black nodules that were aggregated annularly (Fig. 1a). Dermoscopic examination revealed an ulceration in the center and shiny white areas were observed at the periphery of the ulceration. Large blue-gray ovoid nests and multiple blue-gray globules
Correspondence: Takeshi Namiki, M.D., Ph.D., Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Email: [email protected]
918
© 2015 Japanese Dermatological Association
Letters to the Editor
(a)
(b)
(c)
(d) (e)
(f)
(g)
(h)
Figure 1. (a) A 9 mm 9 14 mm black plaque on the left cheek. (b) Dermoscopic features of the black plaque showing multiple components in an “atoll pattern”. (c) Magnification of dermoscopic features; note the dispersed appearance of the large bluegray ovoid nests and shiny white areas. The black dotted line represents the section used for histopathology. (d) Histopathological findings show melanin deposition around the tumor nests, a thick cornified layer, ulceration and enlargement of vessels between the epidermis and tumor nests (from left to right). The dashed boxes indicate areas shown in panels (e,f) (hematoxylin–eosin [HE], original magnification 910). (e) Most melanin deposition is situated around the tumor nests, however, a small amount of melanin deposition is observed at keratin pearls inside the tumor nests. Dilated vessels are also observed between the epidermis and tumor nests (HE, 9100). (f) Blood vessels, which are situated between the epidermis and the tumor nests, are enlarged in the upper dermis (HE, 9100). (g) Immunohistochemistry for cytokeratin 1 (9100). (h) Immunohistochemistry for Ber-EP4 (9100).
were located circumferentially in the black plaque. Those ovoid nests had a dispersed appearance, which mimicked an atoll (Fig. 1b). Tiny branched vessels were also observed (Fig. 1c). Histopathological examination of the black plaque showed many small tumor nests scattered throughout the dermis and some tumor nests that directly extended from the epidermis. Melanin deposition around the tumor nests, a thick cornified layer, ulceration and enlargement of vessels between the epidermis and tumor nests were also observed (Fig. 1d). Some tumor nests manifested the formation of keratin pearls and melanin deposition. Most melanin deposition was situated around the tumor nests. Clefts surrounding the tumor nests were not recognized (Fig. 1e). Each tumor nest was composed of atypical keratinocytes. Individual tumor cells had pleomorphic nuclei and eosinophilic cytoplasm. Some blood vessels, which were situated between the epidermis and the tumor nests, were enlarged (Fig. 1f). Immunohistochemistry showed positive reactions for AE1/AE3 and cytokeratin (CK)1 in the tumor cells (Fig. 1g), but negative reactions for BerEP4, CK7 and adipophilin (Fig. 1h). The tumor was resected
© 2015 Japanese Dermatological Association
with a 1-cm surgical margin additionally and there has been no relapse 5 months after the surgery. Previous reports have shown that the dermoscopic features of pigmented SCC can be clues for its differential diagnosis.3,4 In our case, the atoll pattern is quite difficult to distinguish from BCC, while the large blue-gray ovoid nests have a dispersed appearance compared with BCC. The shiny white areas may presumably reflect a thick cornified layer as shown in the middle of Figure 1(d), and the dispersed appearance may reflect the distribution of melanin deposition. In pigmented SCC, both dendritic melanocytes in tumor nests and melanophages may participate in this distribution of melanin deposition.2 Although vessels outside the tumor may reflect a senile change, large branched vessels in the tumor may reflect histopathological dilated vessels between the epidermis and tumor nests as shown in Figure 1(e). We speculate that the dispersed appearance and shiny white areas of pigmented SCC can be candidate clues to distinguish it from BCC.5 The accumulation of such cases with pigmented SCC may reveal characteristic dermoscopic features of this rare variant of SCC.
919
Letters to the Editor
CONFLICT OF INTEREST:
The authors declare no conflicts
REFERENCES
of interest. 1
1
1
Yumi ARIMA, Takeshi NAMIKI, Kohei KATO, Makiko UENO,1 Madoka IIKAWA,1 Shown TOKORO,1 Kaoru TAKAYAMA,1 Keiko MIURA,2 Hiroo YOKOZEKI1 Departments of 1Dermatology, and 2Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan doi: 10.1111/1346-8138.12933
1 Morgan MB, Lima-Maribona J, Miller RA, Kilpatrick T, Tannenbaum M. Pigmented squamous cell carcinoma of the skin: morphologic and immunohistochemical study of five cases. J Cutan Pathol 2000; 27: 381–386. 2 Satter EK. Pigmented squamous cell carcinoma. Am J Dermatopathol 2007; 29: 486–489. 3 Fraga-Braghiroli N, Stephens A, Oliviero M, Rabinovitz H, Scope A. Small brown circles: an important diagnostic clue for pigmented squamous cell carcinoma. J Am Acad Dermatol 2013; 69: e161–e163. 4 Zalaudek I, Citarella L, Soyer HP, Hofmann-Wellenhof R, Argenziano G. Dermoscopy features of pigmented squamous cell carcinoma: a case report. Dermatol Surg 2004; 30: 539–540. 5 Chung E, Marchetti MA, Pulitzer MP, Marghoob AA. Streaks in pigmented squamous cell carcinoma in situ. J Am Acad Dermatol 2015; 72: S64–S65.
Successful treatment of Bowen’s disease with ingenol mebutate 0.05% gel Dear Editor, Bowen’s disease (BD) is a squamous cell carcinoma in situ with approximately 3–5% risk of progression to invasive carcinoma.1 Although surgical excision is the definitive treatment, non-surgical treatment modalities including photodynamic therapy, 5-fluorouracil and 5% imiquimod cream could be effective
alternatives for BD, especially in patients who are poor candidates for surgery.2 We herein report a case of BD successfully treated with ingenol mebutate 0.05% gel. A 79-year-old woman presented with a 2-year history of an asymptomatic gradually enlarged tumor on her right calf. On physical examination, a well-defined hyperkeratotic erythema-
(a)
(b)
Figure 1. (a) Clinical pictures of use of ingenol mebutate 0.05% gel for the treatment of Bowen’s disease. Local skin reactions including erythema, vesicles, erosion and ulceration at the application site were observed. Ten weeks after the treatment (day 70), all the lesions were clinically resolved. (b) Histopathology of the lesion before and after treatment. Before treatment, histopathological features of the primary lesion showed hyperkeratosis and epidermal replacement by atypical squamous cells with intermingled dyskeratotic cells and mitotic figures, confirming Bowen’s disease. At day 70, no evidence of residual tumor was observed (hematoxylin–eosin, original magnification 9200).
Correspondence: Jung Min Bae, M.D., Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon 442-723, Korea. Email: [email protected]
920
© 2015 Japanese Dermatological Association
Tokyo, Japan) were detected for soy (19.3 UA/mL), Japanese cedar (4.72 UA/mL) and Japanese white birch (1.24 UA/mL). Specific IgE antibodies for Japanese alder, Bet v 1, Gly m 4 and wheat gluten were not detected. A skin prick test (SPT) was positive for soy extract (10 mg/mL) (6 mm 9 5 mm), the cosmetic lotion used by the patient (as is) (10 mm 9 4 mm) and a commercially available soy milk (7 mm 9 5 mm). Results for the positive control (10 mg/mL histamine dihydrochloride; Wako Pure Chemical Industries, Osaka, Japan) and the negative control (saline; Otsuka Pharmaceutical, Tokyo, Japan) were 5 mm 9 5 mm and 0 mm 9 0 mm, respectively. SPT of the same cosmetic lotion yielded negative results in three healthy controls. 2-D western blot analysis using soy extract yielded multiple spots representing IgE binding protein. Based on mass spectrometric analysis, these spots were identified as a partial sequence of glycinin A-2-B-1a subunit (Gly m 6) precursor, a soybean seed storage protein in the glycinin A2 subunit family (Fig. 1). Glycinin A-2-B-1a subunit is one of five subunits of soybean seed storage protein belonging to the glycinin (11S globulin) family.1 Based on the clinical course and results presented above, we considered that the patient with atopic dermatitis, which tends to reduce the barrier function of the skin, was percutaneously sensitized to soy protein through frequent contact with cosmetic lotions containing soy-based ingredients in a humid environment while working as an esthetician and she subsequently developed anaphylactic reaction to soy. Niinimaki et al. reported contact urticaria from protein hydrolysates (PH) in hair conditioners. From one to 22 PH used in hair-care products (collagen, wheat and silk) were tested in their patients. They concluded that PH of hair cosmetics could cause contact urticaria, especially in patients with atopic dermatitis.2 In addition, a study on mice found that exposure of abraded skin to peanuts resulted in the production of peanut-specific IgE antibodies.3 These results indicate that reduced skin barrier function such as atopic dermatitis may be a cause of percutaneous sensitization by various proteins such as food.4 The pathogenesis of food allergy from percutaneous sensitization is yet to
be fully elucidated. Similar case reports are required in the future.
ACKNOWLEDGMENTS: This study is part of the “Study on Quasi Drug Cosmetics Additives Safety” conducted by the Teshima Group under the sponsorship of Pharmaceutical and Medical Device Regulatory Science General Research Project of the Ministry of Health, Labor and Welfare of Japan. This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. CONFLICT OF INTEREST:
The
authors
declare
no
conflicts of interest.
Akiko YAGAMI,1 Kayoko SUZUKI,1,2 Masashi NAKAMURA,1,3 Akiyo SANO,1 Yohei IWATA,1 Tsukane KOBAYASHI,1 Mari SUZUKI,4 Kazuhiro HARA,3 Reiko TESHIMA,5 Kayoko MATSUNAGA1 1
Department of Dermatology, Fujita Health University School of Medicine, Toyoake, 2Department of Dermatology, Kariya Toyota General Hospital, Kariya, 3General Research and Development Institute, Hoyu, Nagakute, 4 Mari Skin Clinic, Nagoya, and 5National Institute of Health Sciences, Tokyo, Japan doi: 10.1111/1346-8138.12966
REFERENCES 1 Holzhauser T, Wackermann O, Ballmer-Weber BK et al. Soybean (Glycine max) allergy in Europe: Gly m5 (b-conglycinin) and Gly m6 (glycinin) are potential diagnostic markers for severe allergic reactions to soy. J AIIergy Clin lmmunol 2009; 123: 452–458. €ki A, Niinima €ki M, Ma €kinen-Kiljunen S, Hannuksela M. Contact 2 Niinima urticaria from protein hydrolysates in hair conditioners. Allergy 1998; 53: 1078–1082. 3 Strid J, Hourihans J, Kimber I et al. Epicutaneous exposure to peanut protein prevents oral tolerance and enhances allergic sensitization. Clin Exp Allergy 2005; 35: 757–766. 4 Yagami A, Suzuki K, Nakamura M et al. Occupational food allergy due to parvalbumin and phaseolin induced by epicutaneous sensitization. Allergol Int 2015. doi: 10.1016/j.alit.2015.03.005.
Pigmented squamous cell carcinoma of the cheek and its dermoscopic features Dear Editor, Pigmented squamous cell carcinoma (SCC) has been rarely reported and has an incidence that ranges 0.01–7%1,2. Clinically, its differential diagnosis from basal cell carcinoma (BCC) and/or melanoma is usually difficult. Here, we present a case of a pigmented SCC and discuss the significance of large blue-gray ovoid nests and shiny white areas in its dermoscopic features.
A 66-year-old man presented with a black lesion on his left cheek that had been noticed a half year earlier. Physical examination revealed a 9 mm 9 14 mm black plaque with an ulceration in the center region and several small black nodules that were aggregated annularly (Fig. 1a). Dermoscopic examination revealed an ulceration in the center and shiny white areas were observed at the periphery of the ulceration. Large blue-gray ovoid nests and multiple blue-gray globules
Correspondence: Takeshi Namiki, M.D., Ph.D., Department of Dermatology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8510, Japan. Email: [email protected]
918
© 2015 Japanese Dermatological Association
Letters to the Editor
(a)
(b)
(c)
(d) (e)
(f)
(g)
(h)
Figure 1. (a) A 9 mm 9 14 mm black plaque on the left cheek. (b) Dermoscopic features of the black plaque showing multiple components in an “atoll pattern”. (c) Magnification of dermoscopic features; note the dispersed appearance of the large bluegray ovoid nests and shiny white areas. The black dotted line represents the section used for histopathology. (d) Histopathological findings show melanin deposition around the tumor nests, a thick cornified layer, ulceration and enlargement of vessels between the epidermis and tumor nests (from left to right). The dashed boxes indicate areas shown in panels (e,f) (hematoxylin–eosin [HE], original magnification 910). (e) Most melanin deposition is situated around the tumor nests, however, a small amount of melanin deposition is observed at keratin pearls inside the tumor nests. Dilated vessels are also observed between the epidermis and tumor nests (HE, 9100). (f) Blood vessels, which are situated between the epidermis and the tumor nests, are enlarged in the upper dermis (HE, 9100). (g) Immunohistochemistry for cytokeratin 1 (9100). (h) Immunohistochemistry for Ber-EP4 (9100).
were located circumferentially in the black plaque. Those ovoid nests had a dispersed appearance, which mimicked an atoll (Fig. 1b). Tiny branched vessels were also observed (Fig. 1c). Histopathological examination of the black plaque showed many small tumor nests scattered throughout the dermis and some tumor nests that directly extended from the epidermis. Melanin deposition around the tumor nests, a thick cornified layer, ulceration and enlargement of vessels between the epidermis and tumor nests were also observed (Fig. 1d). Some tumor nests manifested the formation of keratin pearls and melanin deposition. Most melanin deposition was situated around the tumor nests. Clefts surrounding the tumor nests were not recognized (Fig. 1e). Each tumor nest was composed of atypical keratinocytes. Individual tumor cells had pleomorphic nuclei and eosinophilic cytoplasm. Some blood vessels, which were situated between the epidermis and the tumor nests, were enlarged (Fig. 1f). Immunohistochemistry showed positive reactions for AE1/AE3 and cytokeratin (CK)1 in the tumor cells (Fig. 1g), but negative reactions for BerEP4, CK7 and adipophilin (Fig. 1h). The tumor was resected
© 2015 Japanese Dermatological Association
with a 1-cm surgical margin additionally and there has been no relapse 5 months after the surgery. Previous reports have shown that the dermoscopic features of pigmented SCC can be clues for its differential diagnosis.3,4 In our case, the atoll pattern is quite difficult to distinguish from BCC, while the large blue-gray ovoid nests have a dispersed appearance compared with BCC. The shiny white areas may presumably reflect a thick cornified layer as shown in the middle of Figure 1(d), and the dispersed appearance may reflect the distribution of melanin deposition. In pigmented SCC, both dendritic melanocytes in tumor nests and melanophages may participate in this distribution of melanin deposition.2 Although vessels outside the tumor may reflect a senile change, large branched vessels in the tumor may reflect histopathological dilated vessels between the epidermis and tumor nests as shown in Figure 1(e). We speculate that the dispersed appearance and shiny white areas of pigmented SCC can be candidate clues to distinguish it from BCC.5 The accumulation of such cases with pigmented SCC may reveal characteristic dermoscopic features of this rare variant of SCC.
919
Letters to the Editor
CONFLICT OF INTEREST:
The authors declare no conflicts
REFERENCES
of interest. 1
1
1
Yumi ARIMA, Takeshi NAMIKI, Kohei KATO, Makiko UENO,1 Madoka IIKAWA,1 Shown TOKORO,1 Kaoru TAKAYAMA,1 Keiko MIURA,2 Hiroo YOKOZEKI1 Departments of 1Dermatology, and 2Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan doi: 10.1111/1346-8138.12933
1 Morgan MB, Lima-Maribona J, Miller RA, Kilpatrick T, Tannenbaum M. Pigmented squamous cell carcinoma of the skin: morphologic and immunohistochemical study of five cases. J Cutan Pathol 2000; 27: 381–386. 2 Satter EK. Pigmented squamous cell carcinoma. Am J Dermatopathol 2007; 29: 486–489. 3 Fraga-Braghiroli N, Stephens A, Oliviero M, Rabinovitz H, Scope A. Small brown circles: an important diagnostic clue for pigmented squamous cell carcinoma. J Am Acad Dermatol 2013; 69: e161–e163. 4 Zalaudek I, Citarella L, Soyer HP, Hofmann-Wellenhof R, Argenziano G. Dermoscopy features of pigmented squamous cell carcinoma: a case report. Dermatol Surg 2004; 30: 539–540. 5 Chung E, Marchetti MA, Pulitzer MP, Marghoob AA. Streaks in pigmented squamous cell carcinoma in situ. J Am Acad Dermatol 2015; 72: S64–S65.
Successful treatment of Bowen’s disease with ingenol mebutate 0.05% gel Dear Editor, Bowen’s disease (BD) is a squamous cell carcinoma in situ with approximately 3–5% risk of progression to invasive carcinoma.1 Although surgical excision is the definitive treatment, non-surgical treatment modalities including photodynamic therapy, 5-fluorouracil and 5% imiquimod cream could be effective
alternatives for BD, especially in patients who are poor candidates for surgery.2 We herein report a case of BD successfully treated with ingenol mebutate 0.05% gel. A 79-year-old woman presented with a 2-year history of an asymptomatic gradually enlarged tumor on her right calf. On physical examination, a well-defined hyperkeratotic erythema-
(a)
(b)
Figure 1. (a) Clinical pictures of use of ingenol mebutate 0.05% gel for the treatment of Bowen’s disease. Local skin reactions including erythema, vesicles, erosion and ulceration at the application site were observed. Ten weeks after the treatment (day 70), all the lesions were clinically resolved. (b) Histopathology of the lesion before and after treatment. Before treatment, histopathological features of the primary lesion showed hyperkeratosis and epidermal replacement by atypical squamous cells with intermingled dyskeratotic cells and mitotic figures, confirming Bowen’s disease. At day 70, no evidence of residual tumor was observed (hematoxylin–eosin, original magnification 9200).
Correspondence: Jung Min Bae, M.D., Department of Dermatology, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93 Jungbu-daero, Paldal-gu, Suwon 442-723, Korea. Email: [email protected]
920
© 2015 Japanese Dermatological Association
