Correspondence
Figure 1 Clinical examination in a 29-year-old woman shows (a) perioral erosive lesions, (b) angular cheilitis, (c) erosions with yellowish scales on the right auricle, and (d) an erosive lesion on the right arm
(a)
(b)
(c)
(d)
Scientifico (IRCCS) (Italian Research Hospital Foundation) Ca’ Granda Ospedale Maggiore Policlinico Milan Italy E-mail: [email protected]
References 1 Cusini M, Ramoni S, Alessi E. Syphilis and other treponematoses. In: Giannetti A, Del Forno C, eds. Textbook of Dermatology and Sexually Transmitted Diseases. Padua: Piccin, 2013: 799–854. 2 Workowsky KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Reccom Rep 2010; 59: 1–110. 3 Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol 2005; 23: 555–564. 4 Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol 2014; 53: 1434–1441. 5 Solomon MM, Mayer KH. Evolution of the syphilis epidemic among men who have sex with men. Sex Health 2014; doi: 10.1071/SH14173 [Epub ahead of print].
Spatial co-occurrence of hemangioma and epidermal nevus
Editor, A 4-month-old, healthy girl was referred to our clinic for the evaluation of a lesion on her upper anterior chest wall. ª 2015 The International Society of Dermatology
On physical examination, a plaque measuring 4.1 9 3.2 cm and consisting of two different and adjacent components, namely brownish, papillomatous, warty confluent papules and partially confluent, angiomatous papules, was evident (Fig. 1). Both vascular and keratotic components had appeared in the first week of life and had gradually increased in number and size until the time of presentation. No other cutaneous or adnexal lesion was present, and no extracutaneous manifestations were reported. On the basis of clinical and anamnestic data, a
Figure 1 Clinical examination of a 4-month-old, healthy girl shows a plaque of 4.1 9 3.2 cm on the upper anterior chest wall consisting of two different and adjacent components: brownish, papillomatous, warty, confluent papules, and partially confluent, angiomatous papules. International Journal of Dermatology 2016, 55, e161–e171
e163
e164
Correspondence
double diagnosis of epidermal nevus and skin hemangioma was made. Neither histological assessment nor any treatment was carried out because the girl’s parents refused them. The simultaneous occurrence of a vascular lesion and an epidermal nevus is very rare. In particular, there are only six documented instances of the co-occurrence of a telangiectatic nevus with an epidermal nevus,1–3 for which the denomination phacomatosis vasculokeratotica has been recently proposed.3 By contrast with the previous cases, the vascular lesion in our patient was a hemangioma, which in itself is not a nevus and therefore is not an expression of mosaicism unless it occurs in a segmental form. This eventuality is possible in our case, but the small size of the lesion makes this diagnosis uncertain. The co-occurrence of two different nevi or paired patches of mutant tissue that differ genetically from one another and from the background tissue is defined as didymosis.4,5 This would result from the presence of two different mutant alleles (at the same gene locus or at different loci) and a subsequent post-zygotic recombination that gives rise to two different homozygous daughter cells forming skin lesions that are either allelic (originating from the same type of cell) or non-allelic (originating from different types of cell).4–6 However, the concept of non-allelic didymosis has been questioned recently as molecular research has shown that some skin disorders previously thought to result from such a genetic phenomenon may be caused by a single post-zygotic mutation in a pluripotent progenitor cell that is present in a heterozygous state (pseudodidymosis).5,7 To the best of our knowledge, this is the first report to describe the co-occurrence of an epidermal nevus and skin hemangioma. In our opinion, although we cannot exclude a random co-occurrence of the two lesions, their close spatial arrangement would render a causal relationship rather likely. According to the new concept of pseudodidymosis,5,7 it is possible to speculate that these lesions may have resulted from a single post-zygotic mutation in a pluripotent progenitor cell.
Enzo Errichetti, MD Angelo Piccirillo, MD Department of Dermatology San Carlo Hospital Potenza Italy E-mail: [email protected]
References 1 Ota M, Kawamura T, Ito N. Phakomatosis pigmentovascularis. Jpn J Dermatol 1947; 52: 1–3. International Journal of Dermatology 2016, 55, e161–e171
2 Seifert F, J€ ager T, Ring J, et al. Concurrence of linear epidermal nevus and nevus flammeus in a man with optic pathway glioma: coincidence or phacomatosis? Int J Dermatol 2012; 51: 592–593. 3 Torchia D. Nevus flammeus and keratinocytic epidermal nevus: phacomatosis vasculokeratotica? Int J Dermatol 2014; 53: e221. 4 Singh N, Chandrashekar L, Thappa DM, et al. Nevus depigmentosus and nevus of Ito: pigmentary twin spotting. Int J Dermatol 2014; 53: 1005–1007. 5 Happle R. Two major categories of mosaicism. In: Happle R, ed. Mosaicism in Human Skin. Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin: Springer-Verlag, 2014: 13–37. 6 Aguayo-Leiva I, Alonso J, Echeverrˇa B, et al. Phacomatosis melanovascularis: a new example of nonallelic twin spotting. Eur J Dermatol 2011; 21: 487–489. 7 Happle R. Phacomatosis pigmentokeratotica is a pseudodidymosis. J Invest Dermatol 2013; 133: 1923– 1925.
Two cases of CD8-positive hypopigmented mycosis fungoides without TOX expression
Editor, Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. Clinically, MF presents with scaly patches which, in limited cases, may slowly progress to indurated plaques and ultimately develop into tumors or erythroderma. Hypopigmented MF (HMF) is a rare clinical variant of MF commonly observed in darkskinned people. Patients with HMF are generally young and show a prognosis better than that of typical MF.1 Recently, we documented two Japanese patients with HMF. Immunohistochemical staining for thymocyte selection-associated high-mobility group box factor (TOX) showed almost no positive cells in both cases, which supports the suggestion that tumor cells in most HMF cases are CD8+ cells in the epidermis. The first patient was a 38-year-old man who presented with irregular, oval, pigmented or hypopigmented scaly patches and plaques all over the body that had developed 20 years earlier (Fig. 1a). The second patient was a 20year-old man who had suffered from scaly erythema and hypopigmented macules on his entire body for 4 years (Fig. 1b). As both patients had been diagnosed with atopic dermatitis, they had been treated with topical steroid ointment and antihistamines. Blood examination showed no signs of hematological disorders or viral infection. In Patient 1, histological examination revealed infiltration of medium-sized lymphocytes with folded nuclei in the epidermis with vacuolar changes in the basal layer (Fig. 1c). Histology in Patient 2 showed similar findings together with psoriasiform acanthosis (Fig. 1d). The majority of ª 2015 The International Society of Dermatology
Figure 1 Clinical examination in a 29-year-old woman shows (a) perioral erosive lesions, (b) angular cheilitis, (c) erosions with yellowish scales on the right auricle, and (d) an erosive lesion on the right arm
(a)
(b)
(c)
(d)
Scientifico (IRCCS) (Italian Research Hospital Foundation) Ca’ Granda Ospedale Maggiore Policlinico Milan Italy E-mail: [email protected]
References 1 Cusini M, Ramoni S, Alessi E. Syphilis and other treponematoses. In: Giannetti A, Del Forno C, eds. Textbook of Dermatology and Sexually Transmitted Diseases. Padua: Piccin, 2013: 799–854. 2 Workowsky KA, Berman S; Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2010. MMWR Reccom Rep 2010; 59: 1–110. 3 Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol 2005; 23: 555–564. 4 Balagula Y, Mattei PL, Wisco OJ, et al. The great imitator revisited: the spectrum of atypical cutaneous manifestations of secondary syphilis. Int J Dermatol 2014; 53: 1434–1441. 5 Solomon MM, Mayer KH. Evolution of the syphilis epidemic among men who have sex with men. Sex Health 2014; doi: 10.1071/SH14173 [Epub ahead of print].
Spatial co-occurrence of hemangioma and epidermal nevus
Editor, A 4-month-old, healthy girl was referred to our clinic for the evaluation of a lesion on her upper anterior chest wall. ª 2015 The International Society of Dermatology
On physical examination, a plaque measuring 4.1 9 3.2 cm and consisting of two different and adjacent components, namely brownish, papillomatous, warty confluent papules and partially confluent, angiomatous papules, was evident (Fig. 1). Both vascular and keratotic components had appeared in the first week of life and had gradually increased in number and size until the time of presentation. No other cutaneous or adnexal lesion was present, and no extracutaneous manifestations were reported. On the basis of clinical and anamnestic data, a
Figure 1 Clinical examination of a 4-month-old, healthy girl shows a plaque of 4.1 9 3.2 cm on the upper anterior chest wall consisting of two different and adjacent components: brownish, papillomatous, warty, confluent papules, and partially confluent, angiomatous papules. International Journal of Dermatology 2016, 55, e161–e171
e163
e164
Correspondence
double diagnosis of epidermal nevus and skin hemangioma was made. Neither histological assessment nor any treatment was carried out because the girl’s parents refused them. The simultaneous occurrence of a vascular lesion and an epidermal nevus is very rare. In particular, there are only six documented instances of the co-occurrence of a telangiectatic nevus with an epidermal nevus,1–3 for which the denomination phacomatosis vasculokeratotica has been recently proposed.3 By contrast with the previous cases, the vascular lesion in our patient was a hemangioma, which in itself is not a nevus and therefore is not an expression of mosaicism unless it occurs in a segmental form. This eventuality is possible in our case, but the small size of the lesion makes this diagnosis uncertain. The co-occurrence of two different nevi or paired patches of mutant tissue that differ genetically from one another and from the background tissue is defined as didymosis.4,5 This would result from the presence of two different mutant alleles (at the same gene locus or at different loci) and a subsequent post-zygotic recombination that gives rise to two different homozygous daughter cells forming skin lesions that are either allelic (originating from the same type of cell) or non-allelic (originating from different types of cell).4–6 However, the concept of non-allelic didymosis has been questioned recently as molecular research has shown that some skin disorders previously thought to result from such a genetic phenomenon may be caused by a single post-zygotic mutation in a pluripotent progenitor cell that is present in a heterozygous state (pseudodidymosis).5,7 To the best of our knowledge, this is the first report to describe the co-occurrence of an epidermal nevus and skin hemangioma. In our opinion, although we cannot exclude a random co-occurrence of the two lesions, their close spatial arrangement would render a causal relationship rather likely. According to the new concept of pseudodidymosis,5,7 it is possible to speculate that these lesions may have resulted from a single post-zygotic mutation in a pluripotent progenitor cell.
Enzo Errichetti, MD Angelo Piccirillo, MD Department of Dermatology San Carlo Hospital Potenza Italy E-mail: [email protected]
References 1 Ota M, Kawamura T, Ito N. Phakomatosis pigmentovascularis. Jpn J Dermatol 1947; 52: 1–3. International Journal of Dermatology 2016, 55, e161–e171
2 Seifert F, J€ ager T, Ring J, et al. Concurrence of linear epidermal nevus and nevus flammeus in a man with optic pathway glioma: coincidence or phacomatosis? Int J Dermatol 2012; 51: 592–593. 3 Torchia D. Nevus flammeus and keratinocytic epidermal nevus: phacomatosis vasculokeratotica? Int J Dermatol 2014; 53: e221. 4 Singh N, Chandrashekar L, Thappa DM, et al. Nevus depigmentosus and nevus of Ito: pigmentary twin spotting. Int J Dermatol 2014; 53: 1005–1007. 5 Happle R. Two major categories of mosaicism. In: Happle R, ed. Mosaicism in Human Skin. Understanding Nevi, Nevoid Skin Disorders, and Cutaneous Neoplasia. Berlin: Springer-Verlag, 2014: 13–37. 6 Aguayo-Leiva I, Alonso J, Echeverrˇa B, et al. Phacomatosis melanovascularis: a new example of nonallelic twin spotting. Eur J Dermatol 2011; 21: 487–489. 7 Happle R. Phacomatosis pigmentokeratotica is a pseudodidymosis. J Invest Dermatol 2013; 133: 1923– 1925.
Two cases of CD8-positive hypopigmented mycosis fungoides without TOX expression
Editor, Mycosis fungoides (MF) is the most common type of cutaneous T cell lymphoma. Clinically, MF presents with scaly patches which, in limited cases, may slowly progress to indurated plaques and ultimately develop into tumors or erythroderma. Hypopigmented MF (HMF) is a rare clinical variant of MF commonly observed in darkskinned people. Patients with HMF are generally young and show a prognosis better than that of typical MF.1 Recently, we documented two Japanese patients with HMF. Immunohistochemical staining for thymocyte selection-associated high-mobility group box factor (TOX) showed almost no positive cells in both cases, which supports the suggestion that tumor cells in most HMF cases are CD8+ cells in the epidermis. The first patient was a 38-year-old man who presented with irregular, oval, pigmented or hypopigmented scaly patches and plaques all over the body that had developed 20 years earlier (Fig. 1a). The second patient was a 20year-old man who had suffered from scaly erythema and hypopigmented macules on his entire body for 4 years (Fig. 1b). As both patients had been diagnosed with atopic dermatitis, they had been treated with topical steroid ointment and antihistamines. Blood examination showed no signs of hematological disorders or viral infection. In Patient 1, histological examination revealed infiltration of medium-sized lymphocytes with folded nuclei in the epidermis with vacuolar changes in the basal layer (Fig. 1c). Histology in Patient 2 showed similar findings together with psoriasiform acanthosis (Fig. 1d). The majority of ª 2015 The International Society of Dermatology
