e142 Letters
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Fig 2. A, Histopathologic appearance of dilation of pores of hair follicles and fibromucinous stroma in the papillary and perifollicular dermis. B, Mucinous material was seen among fibroblasts in the perifollicular dermis. C, Specimen staining with alcian blue at pH 2.5 showed not only diffuse deposition of amorphous materials in the papillary dermis but also deposits in the perifollicular dermis. D, Elastica van Gieson stain showed an absence of collagen and elastic fibers in the mucin-deposited area, and normal collagen and elastic fibers in the unaffected papillary dermis. (A to D, Original magnifications: A, C, and D, 340; B, 3400.)
diversity of mucinous nevus from only mucin deposition to variants. Naoki Oiso, MD, PhD,a Masatomo Kimura, MD, PhD,b and Akira Kawada, MD, PhDa Departments of Dermatologya and Pathology,b Kinki University Faculty of Medicine, OsakaSayama, Osaka, Japan Funding sources: None. Conflicts of interest: None declared. Correspondence to: Naoki Oiso, MD, PhD, Department of Dermatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan E-mail: [email protected] REFERENCES n P, Vazquez-Doval J, Idoate M, Quintanilla E. 1. Redondo Bello Mucinous nevus. J Am Acad Dermatol 1993;28:797-8. 2. Chi CC, Wang SH, Lin PY. Combined epidermal-connective tissue nevus of proteoglycan (a type of mucinous nevus): a case report and literature review. J Cutan Pathol 2009;36:808-11. 3. Chang SE, Kang SK, Kim ES, Lee MW, Choi JH, Sung KJ, et al. A case of congenital mucinous nevus: a connective tissue nevus of the proteoglycan type. Pediatr Dermatol 2003;20: 229-31.
4. Tempark T, Shwayder T. Mucinous eccrine nevus: case report and review of the literature. Clin Exp Dermatol 2013; 38:1-6. 5. Tadini G, Boldrini MP, Brena M, Pezzani L, Marchesi L, Rongioletti F. Nevoid follicular mucinosis: a new type of hair follicle nevus. J Cutan Pathol 2013;40:844-7. http://dx.doi.org/10.1016/j.jaad.2014.04.065
Photo-induced erythema multiforme associated with vandetanib administration To the Editor: Vandetanib is a tyrosine kinase inhibitor used for the treatment of unresectable, locally advanced, or metastatic medullary thyroid cancer. Photo-induced erythema multiforme (PEM) is a rare entity described in relation with several drugs. We report a case of PEM induced by vandetanib. A 66-year-old man presented with a 7 day-history of pruritic skin lesions. In April 2013, the patient was given a diagnosis of a medullary thyroid carcinoma stage IV and treated with subtotal thyroidectomy and oral vandetanib (300 mg/d). The skin lesions appeared on his face 3 weeks after the administration of vandetanib and then spread to other photoexposed areas. Physical examination revealed well-demarcated scaly erythematous papules and plaques, with eczematous appearance on the face,
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Fig 2. Photo-test during vandetanib intake showed a diminished minimal erythema dose (MED) after ultraviolet (UV) A exposure (\1 J/cm2) (second row). MED after UVB exposure ( first row).
Fig 1. Photo-induced erythema multiforme. A and B, Targetoid lesions on both hands. C, Superficial perivascular and interstitial dermatitis with eosinophils, interface dermatitis of vacuolar type with abundant degenerated keratinocytes, and mild spongiosis. (C, Hematoxylin-eosin stain; original magnification: 3200.)
both ears, neck, and back of the hands. Targetoid lesions were also observed on both palms (Fig 1). He denied recent infectious processes, including herpes simplex, or introduction of any other drug. Nonphoto-exposed areas such as the trunk, submental region, and eyelids were spared. There was no mucosal involvement. Two skin biopsy specimens showed superficial perivascular and interstitial dermatitis with eosinophils, interface dermatitis of vacuolar type with abundant degenerated keratinocytes, and mild spongiosis (Fig 1). Antinuclear antibodies were negative. Photo-test showed a diminished minimal erythema dose for ultraviolet A (\1 J/cm2) during vandetanib intake (Fig 2). According to these findings, the diagnosis of PEM was made.
Vandetanib is a tyrosine kinase inhibitor that selectively targets vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and RET (rearranged during transfection) protooncogene.1 It was initially developed for the treatment of nonsmall-cell lung cancer and colorectal cancer, but it has also demonstrated effects in medullary and papillary thyroid cancer mediated by RET inhibition,1 so it was approved for this purpose by the Food and Drug Administration in 2011. Its main adverse events are diarrhea, high blood pressure, elevated liver enzymes, and QTc interval prolongation.1 Reported mucocutaneous complications included photosensitivity, acneiform eruption, dry skin, hand-foot reaction,2 and Stevens-Johnson syndrome.3 Photosensitivity is the most characteristic reaction. It has been observed in up to 37% of patients after median treatment duration of 8 weeks.2 It can manifest as exaggerated sunburn, erythematous or lichenoid eruption, and less frequently as photo-induced subacute cutaneous lupus erythematosus or PEM.2 This last entity is rare and is presented clinically equal to classic erythema multiforme. It can be associated with drugs, herpes simplex virus infection, or polymorphous light eruption.4 Rodrıguez-Pazos et al4 reviewed the drug-induced PEM cases reported at the moment in the literature. In our case, the drug discontinuation was not necessary because the lesions resolved after 2 weeks of extreme photoprotection and topical steroid treatment. Although we cannot guarantee 100% that ultraviolet radiation was involved in the pathogenesis of the cutaneous reaction, it is somehow associated because of the clear decrease of minimal erythema dose for ultraviolet A. In conclusion, we present a case of PEM secondary to vandetanib. It is mandatory to inform patients
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about the need to carry out proper and strict photoprotection to avoid such photosensitivity reactions. Dolores Caro-Gutie rrez, MD, Maria Ux ua Florist an Muruz abal, MD, Enrique G omez de la Fuente, MD, Ana Pampın Franco, MD, and Jose Luis L opez Estebaranz, MD Department of Dermatology, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dolores Caro-Gutie rrez, MD, Hospital Universitario Fundaci on Alcorcon, Calle Budapest 1, 28922, Alcorc on, Madrid, Espa~ na E-mail: [email protected] REFERENCES 1. Campbell MJ, Seib CD, Gosnell J. Vandetanib and the management of advanced medullary thyroid cancer. Curr Opin Oncol 2013;25:39-43. 2. Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, et al. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol 2012;148:1418-20. 3. Yoon J, Oh CW, Kim CY. Stevens-Johnson syndrome induced by vandetanib. Ann Dermatol 2011;23(Suppl):S343-5. 4. Rodrıguez-Pazos L, G omez-Bernal S, Rodrıguez-Granados MT, Toribio J. Photodistributed erythema multiforme. Actas Dermosifiliogr 2013;104:645-53. http://dx.doi.org/10.1016/j.jaad.2014.05.003
Repigmentation of hair associated with melanoma in situ of scalp To the Editor: An 88-year-old woman presented with a slowly darkening patch of previously white hair on her superior scalp (Fig 1). On physical examination, she had an underlying 6.5- 3 3-cm scaly, irregularly pigmented plaque on her superior scalp. A shave biopsy of the plaque showed actinic keratosis as well as melanoma in situ, lentigo maligna type, extending along the dermoepidermal junction and down the hair follicle. Further scouting punch biopsies were performed to identify the extent of disease, including peripheral areas that contained pigmented hair shafts despite clinically normalappearing epidermis. Histopathology of these repeat biopsies showed multiple foci of actinic keratosis and a few areas with atypical melanocytes suspicious for, but not diagnostic of, melanoma in situ. Interestingly, there were 2 areas that showed pigmented hair shafts and hair bulbs with histopathologically normal dendritic melanocytes
Fig 1. Repigmented hair overlying melanoma in situ of scalp. Slowly darkening patch of previously white hair on superior scalp.
and no evidence of overlying melanoma in situ or actinic keratosis. Normal hair follicle pigmentation and physiologic graying are under complex genetic, metabolic, enzymatic, and signaling control.1,2 The mechanism responsible for our patient’s follicular repigmentation is unclear, although we believe it is most likely due to her overlying melanoma in situ or chronic sun damage. It is unlikely due to medication use because the patient was not taking any medications previously associated with hair repigmentation. Because the dendritic melanocytes in our patient’s hair bulb appeared normal on histologic examination, the follicular melanocytes were more likely stimulated to produce melanin by external signals rather than by a direct effect of melanoma cells repopulating the hair bulb. These signals could be from the lentigo maligna cells themselves or by changes in the microenvironment. To our knowledge, there is 1 previously reported case of hair repigmentation associated with lentigo maligna, which also showed no invasion of the hair follicles by the melanoma cells.3 In that case, the patient’s hair grew back gray after the melanoma was treated by radiotherapy, suggesting that normal hair physiology was restored once the malignant cells were removed. If these signals arise from the lentigo maligna, it would be interesting to clarify how the neoplastic cells could upregulate melanogenesis in nearby normal follicular melanocytes, and which of the numerous cytokines, enzymes, and metabolites required for normal pigmentation were involved in the process. The repigmentation could also be related to chronic sun exposure and actinic damage, as evidenced by the presence of actinic keratoses. In particular, chronic sun exposure causes upregulation of many molecules associated with melanogenesis, including stem cell
J AM ACAD DERMATOL
OCTOBER 2014
Fig 2. A, Histopathologic appearance of dilation of pores of hair follicles and fibromucinous stroma in the papillary and perifollicular dermis. B, Mucinous material was seen among fibroblasts in the perifollicular dermis. C, Specimen staining with alcian blue at pH 2.5 showed not only diffuse deposition of amorphous materials in the papillary dermis but also deposits in the perifollicular dermis. D, Elastica van Gieson stain showed an absence of collagen and elastic fibers in the mucin-deposited area, and normal collagen and elastic fibers in the unaffected papillary dermis. (A to D, Original magnifications: A, C, and D, 340; B, 3400.)
diversity of mucinous nevus from only mucin deposition to variants. Naoki Oiso, MD, PhD,a Masatomo Kimura, MD, PhD,b and Akira Kawada, MD, PhDa Departments of Dermatologya and Pathology,b Kinki University Faculty of Medicine, OsakaSayama, Osaka, Japan Funding sources: None. Conflicts of interest: None declared. Correspondence to: Naoki Oiso, MD, PhD, Department of Dermatology, Kinki University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan E-mail: [email protected] REFERENCES n P, Vazquez-Doval J, Idoate M, Quintanilla E. 1. Redondo Bello Mucinous nevus. J Am Acad Dermatol 1993;28:797-8. 2. Chi CC, Wang SH, Lin PY. Combined epidermal-connective tissue nevus of proteoglycan (a type of mucinous nevus): a case report and literature review. J Cutan Pathol 2009;36:808-11. 3. Chang SE, Kang SK, Kim ES, Lee MW, Choi JH, Sung KJ, et al. A case of congenital mucinous nevus: a connective tissue nevus of the proteoglycan type. Pediatr Dermatol 2003;20: 229-31.
4. Tempark T, Shwayder T. Mucinous eccrine nevus: case report and review of the literature. Clin Exp Dermatol 2013; 38:1-6. 5. Tadini G, Boldrini MP, Brena M, Pezzani L, Marchesi L, Rongioletti F. Nevoid follicular mucinosis: a new type of hair follicle nevus. J Cutan Pathol 2013;40:844-7. http://dx.doi.org/10.1016/j.jaad.2014.04.065
Photo-induced erythema multiforme associated with vandetanib administration To the Editor: Vandetanib is a tyrosine kinase inhibitor used for the treatment of unresectable, locally advanced, or metastatic medullary thyroid cancer. Photo-induced erythema multiforme (PEM) is a rare entity described in relation with several drugs. We report a case of PEM induced by vandetanib. A 66-year-old man presented with a 7 day-history of pruritic skin lesions. In April 2013, the patient was given a diagnosis of a medullary thyroid carcinoma stage IV and treated with subtotal thyroidectomy and oral vandetanib (300 mg/d). The skin lesions appeared on his face 3 weeks after the administration of vandetanib and then spread to other photoexposed areas. Physical examination revealed well-demarcated scaly erythematous papules and plaques, with eczematous appearance on the face,
J AM ACAD DERMATOL VOLUME 71, NUMBER 4
Letters e143
Fig 2. Photo-test during vandetanib intake showed a diminished minimal erythema dose (MED) after ultraviolet (UV) A exposure (\1 J/cm2) (second row). MED after UVB exposure ( first row).
Fig 1. Photo-induced erythema multiforme. A and B, Targetoid lesions on both hands. C, Superficial perivascular and interstitial dermatitis with eosinophils, interface dermatitis of vacuolar type with abundant degenerated keratinocytes, and mild spongiosis. (C, Hematoxylin-eosin stain; original magnification: 3200.)
both ears, neck, and back of the hands. Targetoid lesions were also observed on both palms (Fig 1). He denied recent infectious processes, including herpes simplex, or introduction of any other drug. Nonphoto-exposed areas such as the trunk, submental region, and eyelids were spared. There was no mucosal involvement. Two skin biopsy specimens showed superficial perivascular and interstitial dermatitis with eosinophils, interface dermatitis of vacuolar type with abundant degenerated keratinocytes, and mild spongiosis (Fig 1). Antinuclear antibodies were negative. Photo-test showed a diminished minimal erythema dose for ultraviolet A (\1 J/cm2) during vandetanib intake (Fig 2). According to these findings, the diagnosis of PEM was made.
Vandetanib is a tyrosine kinase inhibitor that selectively targets vascular endothelial growth factor receptor-2, epidermal growth factor receptor, and RET (rearranged during transfection) protooncogene.1 It was initially developed for the treatment of nonsmall-cell lung cancer and colorectal cancer, but it has also demonstrated effects in medullary and papillary thyroid cancer mediated by RET inhibition,1 so it was approved for this purpose by the Food and Drug Administration in 2011. Its main adverse events are diarrhea, high blood pressure, elevated liver enzymes, and QTc interval prolongation.1 Reported mucocutaneous complications included photosensitivity, acneiform eruption, dry skin, hand-foot reaction,2 and Stevens-Johnson syndrome.3 Photosensitivity is the most characteristic reaction. It has been observed in up to 37% of patients after median treatment duration of 8 weeks.2 It can manifest as exaggerated sunburn, erythematous or lichenoid eruption, and less frequently as photo-induced subacute cutaneous lupus erythematosus or PEM.2 This last entity is rare and is presented clinically equal to classic erythema multiforme. It can be associated with drugs, herpes simplex virus infection, or polymorphous light eruption.4 Rodrıguez-Pazos et al4 reviewed the drug-induced PEM cases reported at the moment in the literature. In our case, the drug discontinuation was not necessary because the lesions resolved after 2 weeks of extreme photoprotection and topical steroid treatment. Although we cannot guarantee 100% that ultraviolet radiation was involved in the pathogenesis of the cutaneous reaction, it is somehow associated because of the clear decrease of minimal erythema dose for ultraviolet A. In conclusion, we present a case of PEM secondary to vandetanib. It is mandatory to inform patients
J AM ACAD DERMATOL
e144 Letters
OCTOBER 2014
about the need to carry out proper and strict photoprotection to avoid such photosensitivity reactions. Dolores Caro-Gutie rrez, MD, Maria Ux ua Florist an Muruz abal, MD, Enrique G omez de la Fuente, MD, Ana Pampın Franco, MD, and Jose Luis L opez Estebaranz, MD Department of Dermatology, Hospital Universitario Fundaci on Alcorc on, Madrid, Spain Funding sources: None. Conflicts of interest: None declared. Correspondence to: Dolores Caro-Gutie rrez, MD, Hospital Universitario Fundaci on Alcorcon, Calle Budapest 1, 28922, Alcorc on, Madrid, Espa~ na E-mail: [email protected] REFERENCES 1. Campbell MJ, Seib CD, Gosnell J. Vandetanib and the management of advanced medullary thyroid cancer. Curr Opin Oncol 2013;25:39-43. 2. Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, et al. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol 2012;148:1418-20. 3. Yoon J, Oh CW, Kim CY. Stevens-Johnson syndrome induced by vandetanib. Ann Dermatol 2011;23(Suppl):S343-5. 4. Rodrıguez-Pazos L, G omez-Bernal S, Rodrıguez-Granados MT, Toribio J. Photodistributed erythema multiforme. Actas Dermosifiliogr 2013;104:645-53. http://dx.doi.org/10.1016/j.jaad.2014.05.003
Repigmentation of hair associated with melanoma in situ of scalp To the Editor: An 88-year-old woman presented with a slowly darkening patch of previously white hair on her superior scalp (Fig 1). On physical examination, she had an underlying 6.5- 3 3-cm scaly, irregularly pigmented plaque on her superior scalp. A shave biopsy of the plaque showed actinic keratosis as well as melanoma in situ, lentigo maligna type, extending along the dermoepidermal junction and down the hair follicle. Further scouting punch biopsies were performed to identify the extent of disease, including peripheral areas that contained pigmented hair shafts despite clinically normalappearing epidermis. Histopathology of these repeat biopsies showed multiple foci of actinic keratosis and a few areas with atypical melanocytes suspicious for, but not diagnostic of, melanoma in situ. Interestingly, there were 2 areas that showed pigmented hair shafts and hair bulbs with histopathologically normal dendritic melanocytes
Fig 1. Repigmented hair overlying melanoma in situ of scalp. Slowly darkening patch of previously white hair on superior scalp.
and no evidence of overlying melanoma in situ or actinic keratosis. Normal hair follicle pigmentation and physiologic graying are under complex genetic, metabolic, enzymatic, and signaling control.1,2 The mechanism responsible for our patient’s follicular repigmentation is unclear, although we believe it is most likely due to her overlying melanoma in situ or chronic sun damage. It is unlikely due to medication use because the patient was not taking any medications previously associated with hair repigmentation. Because the dendritic melanocytes in our patient’s hair bulb appeared normal on histologic examination, the follicular melanocytes were more likely stimulated to produce melanin by external signals rather than by a direct effect of melanoma cells repopulating the hair bulb. These signals could be from the lentigo maligna cells themselves or by changes in the microenvironment. To our knowledge, there is 1 previously reported case of hair repigmentation associated with lentigo maligna, which also showed no invasion of the hair follicles by the melanoma cells.3 In that case, the patient’s hair grew back gray after the melanoma was treated by radiotherapy, suggesting that normal hair physiology was restored once the malignant cells were removed. If these signals arise from the lentigo maligna, it would be interesting to clarify how the neoplastic cells could upregulate melanogenesis in nearby normal follicular melanocytes, and which of the numerous cytokines, enzymes, and metabolites required for normal pigmentation were involved in the process. The repigmentation could also be related to chronic sun exposure and actinic damage, as evidenced by the presence of actinic keratoses. In particular, chronic sun exposure causes upregulation of many molecules associated with melanogenesis, including stem cell
