- Email: [email protected]
Pigmented mammary Paget disease mimicking melanoma on dermatoscopy
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JUNE 2011
fever and rash occurring before neutrophil engraftment3,4; as such, this case is likewise a case of preengraftment syndrome. UCBT has historically demonstrated delayed hematopoietic recovery; because of the early onset of our patient’s rash, initially a diagnosis of GVHD was not favored. The presence of donor lymphocytes documented by FISH analysis adjacent to the dyskeratotic keratinocytes in the epidermis suggested a causative role for the donor cells in the development of the rash and supported a diagnosis of GVHD. As treatment paradigms continue to change, it is important for dermatologists to maintain a broad differential diagnosis and utilize all the tools at our disposal to attempt to make a diagnosis. FISH analysis may be a useful tool to identify chimerism following sex mismatched transplants, particularly in female recipients with male donors. FISH analysis in general is expensive, but the information it may provide could be potentially life altering when deciding whether to give more immunosuppression to a profoundly immunosuppressed person. Further studies are necessary to determine the clinical utility and reliability of this test. Josephine Nguyen, MD,a Michael T. Tetzlaff, MD,a Paul J. Zhang, MD,b Xaiowei Xu, MD, PhD,b Elizabeth Hexner, MD,c and Misha Rosenbach, MDa
Pigmented mammary Paget disease mimicking melanoma on dermatoscopy To the Editor: Mammary Paget disease (MPD) is an uncommon form of breast cancer that forms around the nipple. MPD skin lesions usually develop insidiously as a scaly, erosive, or oozing erythema of the nipple and the areola, and advanced lesions present as a well-demarcated, round, ovoid or polycyclic eczema-like plaque with a pink or red hue.1 MPD presenting a pigmented skin lesion is called pigmented MPD and is quite rare.1,2 Herein we describe a case of pigmented MPD on the nipple dermatoscopically mimicking malignant melanoma. A 37-year-old Japanese female patient presented with a hyperpigmented, non-painful skin lesion on her right nipple, with gradual growth for 6 years. On physical examination, a 4- 3 4-mm pigmented macule with irregular borders was observed (Fig 1, A). Dermatoscopy revealed irregularly shaped blue-white structures, irregular dots/globules, peppering-like blue-gray dots corresponding to melanophages, and dotted and corkscrew vessels (Fig 1, B). From these dermatoscopic features, the lesion was suspected to be a regressive malignant melanoma, and a skin biopsy was performed. Histologic
Departments of Dermatology,a Pathology,b and Hematology/Oncology,c University of Pennsylvania, Philadelphia Reprint requests: Misha Rosenbach, MD, Department of Dermatology, University of Pennsylvania, 2 Maloney Building, Philadelphia, PA 19104. E-mail: [email protected]
REFERENCES 1. Au WY, Ma SK, Kwong YL, Ng IO, Hawkins BR, Wan TS, et al. Graft-versus-host disease after liver transplantation: documentation by fluorescent in situ hybridization and human leukocyte antigen typing. Clin Transplant 2000;14:174-7. 2. Meves A, el-Azhary RA, Talwalkar JA, Moore SB, Brewer JD, Motsonelidze C, et al. Acute graft-versus-host disease after liver transplantation diagnosed by fluorescent in situ hybridization testing of skin biopsy specimens. J Am Acad Dermatol 2006;55:642-6. 3. Saliba RM, de Lima M, Giralt S, Andersson B, Khouri IF, Hosing C, et al. Hyperacute GVHD: risk factors, outcomes, and clinical implications. Blood 2007;109:2751-8. 4. Sullivan KM, Deeg HJ, Sanders J, Klosterman A, Amos D, Shulman H, et al. Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation. Blood 1986;67:1172-5. doi:10.1016/j.jaad.2010.09.716
Fig 1. Clinical and dermatoscopic appearance of lesion. A, Lesion shows 4- 3 4-mm hyperpigmented plaque on right nipple. B, Dermatoscopy demonstrated irregularly shaped blue-white structures (white triangle), irregular dots/globules (white circle), peppering-like blue-gray dots (black circle), and dotted and corkscrew vessels (white arrowhead ).
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Letters e115
Fig 2. Histologic examination of lesion. A, Paget tumor cells were present in epidermis. Dermal lymphocytic infiltration and melanophages were seen. B, Appearance of intraductal mammary carcinoma in situ. C and D, Paget cells stained with H-E (C) and PAS (D) contain melanin granules within cytoplasm. E, F, G, H, Immunohistochemical results. Negative staining with S-100 (E) and HMB-45 (F). Strongly positive staining with cytokeratin 7 in Paget cells (G) and intraductal mammary carcinoma cells (H). Original magnifications: 3100 (H); 3200 (A, B, E, F, G); 3600 (C, D).
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examination with hematoxylin-eosin (H-E) staining revealed that atypical cells with large pleomorphic nuclei and abundant cytoplasm had proliferated broadly in the intra-epidermis (Fig 2, A). In the dermis, there was diffuse and perivascular dermal lymphocytic infiltration with numerous melanophages (Fig 2, A). Tumor cells were also observed within lactiferous ducts (Fig 2, B). The tumor cells contained fine melanin granules within the cytoplasm (Fig 2, C ) and were positive for periodic acideSchiff (PAS) staining (Fig 2, D). Immunohistochemical studies demonstrated that the tumor cells were negative for HMB-45 and S-100 protein (Fig 2, E and F ) and positive for cytokeratin 7 (Fig 2, G and H ). From these observations, a confirmed diagnosis of pigmented MPD was made, and the lesion was excised by mastectomy. Pigmented MPD is a rare variant of MPD1; to date only 34 cases have been reported.3 Although the mechanism of hyperpigmentation is not clear, it has been suggested that a melanocytic chemoattractant or basic fibroblast growth factor released from Paget cells might induce proliferation of normal melanocytes in tumor nests.4 Pigmented MPD is problematic because it is often clinically similar to melanoma. Dermatoscopic diagnosis of pigmented MPD is also difficult because it usually shows a nonspecific pattern with irregularly diffuse pigmentation and regression-like structures seen in melanomas.5 Although histopathologic examination is crucially needed for the diagnosis of pigmented MPD, H-E staining alone is not sufficient for correct diagnosis. In our case, PAS staining was useful for differential diagnosis, but it is positive in only 17% to 62% of MPD cases.6 Therefore, in PAS-negative cases, further immunohistochemical staining, such as staining with HMB-45, S-100 protein, and Melan-A or cytokeratin 7, will be needed and is important for correct diagnosis. In summary, not only careful dermatoscopic observation but also histopathologic examination, including immunohistochemical analysis, is needed for correct diagnosis of a pigmented lesion on the nipple. Takeshi Yanagishita, MD, PhD,a Yasuhiko Tamada, MD, PhD,a Masaru Tanaka, MD, PhD,b Chikatoshi Kasugai, MD, PhD,a Emiko Takahashi, MD, PhD,c Yoshinari Matsumoto, MD, PhD,a and Daisuke Watanabe, MD, PhDa Department of Dermatology, Aichi Medical University School of Medicinea; Department of Dermatology, Tokyo Women’s Medical University Medical Center East, Tokyob; Division of Pathology, Aichi Medical University Hospital,c Aichi, Japan
JUNE 2011
Funding sources: None. Conflicts of interest: None declared. Correspondence to: Daisuke Watanabe, MD, PhD, Department of Dermatology, Aichi Medical University School of Medicine, Nagakute, Aichi, 4801195, Japan. E-mail: [email protected] REFERENCES 1. Kanitakis J. Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol 2007;21:581-90. 2. Blum A, Hartmann KW, R€ utten A. Brownish coloration of the left nipple in a 60-year-old woman. Hautarzt 2010;61:64-8. 3. Hilliard NJ, Huang C, Andea A. Pigmented extramammary Paget’s disease of the axilla mimicking melanoma: case report and review of the literature. J Cutan Pathol 2009;36:995-1000. 4. Saitoh K, Saga K, Okazaki M, Maeda K. Pigmented primary carcinoma of the breast: a clinical mimic of malignant melanoma. Br J Dermatol 1998;139:287-90. 5. Longo C, Fantini F, Cesinaro AM, Bassoli S, Seidenari S, Pellacani G. Pigmented mammary Paget disease: dermoscopic, in vivo reflectance-mode confocal microscopic, and immunohistochemical study of a case. Arch Dermatol 2007;143:752-4. 6. Ramachandra S, Gillett CE, Millis RR. A comparative immunohistochemical study of mammary and extramammary Paget’s disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. Virchows Arch 1996;429:371-6. doi:10.1016/j.jaad.2010.09.717
Nonbullous pemphigoid treated with doxycycline monotherapy: Report of 4 cases To the Editor: Bullous pemphigoid (BP) is an autoimmune blistering skin disease commonly seen in the elderly population. Nonbullous BP is a relatively newly described entity characterized by pruritic nodules, papules, or eczematous plaques that can precede the onset of blisters by weeks, months, or even years. The diagnosis is confirmed by immunopathologic findings that are identical to those of BP.1 The mainstay of treatment of BP is topical or systemic corticosteroids.2 To reduce therapy-related side effects, several authors have proposed treatment with oral tetracycline (or doxycycline).3 However, these reports described classic BP treated with tetracycline, often in combination with niacinamide and even sometimes with topical corticosteroids. Our objective was to evaluate the efficacy of oral doxycycline monotherapy in patients with nonbullous BP. Four patients newly diagnosed with nonbullous BP participated in this open-label prospective study. The inclusion criteria were as follows: the clinical presence of widespread pruritic excoriated papular lesions, the presence of linear C3 along the basement
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JUNE 2011
fever and rash occurring before neutrophil engraftment3,4; as such, this case is likewise a case of preengraftment syndrome. UCBT has historically demonstrated delayed hematopoietic recovery; because of the early onset of our patient’s rash, initially a diagnosis of GVHD was not favored. The presence of donor lymphocytes documented by FISH analysis adjacent to the dyskeratotic keratinocytes in the epidermis suggested a causative role for the donor cells in the development of the rash and supported a diagnosis of GVHD. As treatment paradigms continue to change, it is important for dermatologists to maintain a broad differential diagnosis and utilize all the tools at our disposal to attempt to make a diagnosis. FISH analysis may be a useful tool to identify chimerism following sex mismatched transplants, particularly in female recipients with male donors. FISH analysis in general is expensive, but the information it may provide could be potentially life altering when deciding whether to give more immunosuppression to a profoundly immunosuppressed person. Further studies are necessary to determine the clinical utility and reliability of this test. Josephine Nguyen, MD,a Michael T. Tetzlaff, MD,a Paul J. Zhang, MD,b Xaiowei Xu, MD, PhD,b Elizabeth Hexner, MD,c and Misha Rosenbach, MDa
Pigmented mammary Paget disease mimicking melanoma on dermatoscopy To the Editor: Mammary Paget disease (MPD) is an uncommon form of breast cancer that forms around the nipple. MPD skin lesions usually develop insidiously as a scaly, erosive, or oozing erythema of the nipple and the areola, and advanced lesions present as a well-demarcated, round, ovoid or polycyclic eczema-like plaque with a pink or red hue.1 MPD presenting a pigmented skin lesion is called pigmented MPD and is quite rare.1,2 Herein we describe a case of pigmented MPD on the nipple dermatoscopically mimicking malignant melanoma. A 37-year-old Japanese female patient presented with a hyperpigmented, non-painful skin lesion on her right nipple, with gradual growth for 6 years. On physical examination, a 4- 3 4-mm pigmented macule with irregular borders was observed (Fig 1, A). Dermatoscopy revealed irregularly shaped blue-white structures, irregular dots/globules, peppering-like blue-gray dots corresponding to melanophages, and dotted and corkscrew vessels (Fig 1, B). From these dermatoscopic features, the lesion was suspected to be a regressive malignant melanoma, and a skin biopsy was performed. Histologic
Departments of Dermatology,a Pathology,b and Hematology/Oncology,c University of Pennsylvania, Philadelphia Reprint requests: Misha Rosenbach, MD, Department of Dermatology, University of Pennsylvania, 2 Maloney Building, Philadelphia, PA 19104. E-mail: [email protected]
REFERENCES 1. Au WY, Ma SK, Kwong YL, Ng IO, Hawkins BR, Wan TS, et al. Graft-versus-host disease after liver transplantation: documentation by fluorescent in situ hybridization and human leukocyte antigen typing. Clin Transplant 2000;14:174-7. 2. Meves A, el-Azhary RA, Talwalkar JA, Moore SB, Brewer JD, Motsonelidze C, et al. Acute graft-versus-host disease after liver transplantation diagnosed by fluorescent in situ hybridization testing of skin biopsy specimens. J Am Acad Dermatol 2006;55:642-6. 3. Saliba RM, de Lima M, Giralt S, Andersson B, Khouri IF, Hosing C, et al. Hyperacute GVHD: risk factors, outcomes, and clinical implications. Blood 2007;109:2751-8. 4. Sullivan KM, Deeg HJ, Sanders J, Klosterman A, Amos D, Shulman H, et al. Hyperacute graft-v-host disease in patients not given immunosuppression after allogeneic marrow transplantation. Blood 1986;67:1172-5. doi:10.1016/j.jaad.2010.09.716
Fig 1. Clinical and dermatoscopic appearance of lesion. A, Lesion shows 4- 3 4-mm hyperpigmented plaque on right nipple. B, Dermatoscopy demonstrated irregularly shaped blue-white structures (white triangle), irregular dots/globules (white circle), peppering-like blue-gray dots (black circle), and dotted and corkscrew vessels (white arrowhead ).
J AM ACAD DERMATOL VOLUME 64, NUMBER 6
Letters e115
Fig 2. Histologic examination of lesion. A, Paget tumor cells were present in epidermis. Dermal lymphocytic infiltration and melanophages were seen. B, Appearance of intraductal mammary carcinoma in situ. C and D, Paget cells stained with H-E (C) and PAS (D) contain melanin granules within cytoplasm. E, F, G, H, Immunohistochemical results. Negative staining with S-100 (E) and HMB-45 (F). Strongly positive staining with cytokeratin 7 in Paget cells (G) and intraductal mammary carcinoma cells (H). Original magnifications: 3100 (H); 3200 (A, B, E, F, G); 3600 (C, D).
J AM ACAD DERMATOL
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examination with hematoxylin-eosin (H-E) staining revealed that atypical cells with large pleomorphic nuclei and abundant cytoplasm had proliferated broadly in the intra-epidermis (Fig 2, A). In the dermis, there was diffuse and perivascular dermal lymphocytic infiltration with numerous melanophages (Fig 2, A). Tumor cells were also observed within lactiferous ducts (Fig 2, B). The tumor cells contained fine melanin granules within the cytoplasm (Fig 2, C ) and were positive for periodic acideSchiff (PAS) staining (Fig 2, D). Immunohistochemical studies demonstrated that the tumor cells were negative for HMB-45 and S-100 protein (Fig 2, E and F ) and positive for cytokeratin 7 (Fig 2, G and H ). From these observations, a confirmed diagnosis of pigmented MPD was made, and the lesion was excised by mastectomy. Pigmented MPD is a rare variant of MPD1; to date only 34 cases have been reported.3 Although the mechanism of hyperpigmentation is not clear, it has been suggested that a melanocytic chemoattractant or basic fibroblast growth factor released from Paget cells might induce proliferation of normal melanocytes in tumor nests.4 Pigmented MPD is problematic because it is often clinically similar to melanoma. Dermatoscopic diagnosis of pigmented MPD is also difficult because it usually shows a nonspecific pattern with irregularly diffuse pigmentation and regression-like structures seen in melanomas.5 Although histopathologic examination is crucially needed for the diagnosis of pigmented MPD, H-E staining alone is not sufficient for correct diagnosis. In our case, PAS staining was useful for differential diagnosis, but it is positive in only 17% to 62% of MPD cases.6 Therefore, in PAS-negative cases, further immunohistochemical staining, such as staining with HMB-45, S-100 protein, and Melan-A or cytokeratin 7, will be needed and is important for correct diagnosis. In summary, not only careful dermatoscopic observation but also histopathologic examination, including immunohistochemical analysis, is needed for correct diagnosis of a pigmented lesion on the nipple. Takeshi Yanagishita, MD, PhD,a Yasuhiko Tamada, MD, PhD,a Masaru Tanaka, MD, PhD,b Chikatoshi Kasugai, MD, PhD,a Emiko Takahashi, MD, PhD,c Yoshinari Matsumoto, MD, PhD,a and Daisuke Watanabe, MD, PhDa Department of Dermatology, Aichi Medical University School of Medicinea; Department of Dermatology, Tokyo Women’s Medical University Medical Center East, Tokyob; Division of Pathology, Aichi Medical University Hospital,c Aichi, Japan
JUNE 2011
Funding sources: None. Conflicts of interest: None declared. Correspondence to: Daisuke Watanabe, MD, PhD, Department of Dermatology, Aichi Medical University School of Medicine, Nagakute, Aichi, 4801195, Japan. E-mail: [email protected] REFERENCES 1. Kanitakis J. Mammary and extramammary Paget’s disease. J Eur Acad Dermatol Venereol 2007;21:581-90. 2. Blum A, Hartmann KW, R€ utten A. Brownish coloration of the left nipple in a 60-year-old woman. Hautarzt 2010;61:64-8. 3. Hilliard NJ, Huang C, Andea A. Pigmented extramammary Paget’s disease of the axilla mimicking melanoma: case report and review of the literature. J Cutan Pathol 2009;36:995-1000. 4. Saitoh K, Saga K, Okazaki M, Maeda K. Pigmented primary carcinoma of the breast: a clinical mimic of malignant melanoma. Br J Dermatol 1998;139:287-90. 5. Longo C, Fantini F, Cesinaro AM, Bassoli S, Seidenari S, Pellacani G. Pigmented mammary Paget disease: dermoscopic, in vivo reflectance-mode confocal microscopic, and immunohistochemical study of a case. Arch Dermatol 2007;143:752-4. 6. Ramachandra S, Gillett CE, Millis RR. A comparative immunohistochemical study of mammary and extramammary Paget’s disease and superficial spreading melanoma, with particular emphasis on melanocytic markers. Virchows Arch 1996;429:371-6. doi:10.1016/j.jaad.2010.09.717
Nonbullous pemphigoid treated with doxycycline monotherapy: Report of 4 cases To the Editor: Bullous pemphigoid (BP) is an autoimmune blistering skin disease commonly seen in the elderly population. Nonbullous BP is a relatively newly described entity characterized by pruritic nodules, papules, or eczematous plaques that can precede the onset of blisters by weeks, months, or even years. The diagnosis is confirmed by immunopathologic findings that are identical to those of BP.1 The mainstay of treatment of BP is topical or systemic corticosteroids.2 To reduce therapy-related side effects, several authors have proposed treatment with oral tetracycline (or doxycycline).3 However, these reports described classic BP treated with tetracycline, often in combination with niacinamide and even sometimes with topical corticosteroids. Our objective was to evaluate the efficacy of oral doxycycline monotherapy in patients with nonbullous BP. Four patients newly diagnosed with nonbullous BP participated in this open-label prospective study. The inclusion criteria were as follows: the clinical presence of widespread pruritic excoriated papular lesions, the presence of linear C3 along the basement