Morphology
Nevus depigmentosus and nevus of Ito: pigmentary twin spotting Nidhi Singh1, MD, Laxmisha Chandrashekar1, MD, Devinder Mohan Thappa1, MD, and Rakhee Kar2, MD
1 Departments of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, and 2 Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
Correspondence Laxmisha Chandrashekar, MD Department of Dermatology Jawaharlal Institute of Postgraduate Medical Education and Research Puducherry 605006, India E-mail: [email protected] Conflicts of interest: None.
Introduction Nevus depigmentosus presents with areas of hypopigmentation along Blaschko’s lines and may be associated with disorders of the central nervous system, musculoskeletal system, eyes, and teeth. Nevus of Ito is a dermal melanocytosis of the acromioclavicular and upper chest area. Although both nevus depigmentosus and nevus of Ito occur commonly, their coexistence in a manner representative of allelic twin spotting has not previously been reported. Case Report A 28-year-old man of normal intellectual ability, born of a non-consanguineous marriage, presented with a birthmark of hypopigmented areas on the left side of the back. There was no history of bullous, verrucous, or hyperpigmented lesions preceding the appearance of the hypopigmentation. The patient had suffered from progressively worsening tremors of the hands over the previous 10 years, as well as from generalized tonic clonic seizures and myoclonus over the previous two years, for which he was receiving sodium valproate. His grandfather, paternal aunt, and father had experienced the onset of seizures and tremors in the third decade of ª 2014 The International Society of Dermatology
life and had died by the end of the fifth decade after developing severe tremors, ataxia, and refractory seizures. His younger brother and sister also had tremors and seizures, the onset of which had occurred in the third decade. Cutaneous examination revealed large hypopigmented macules distributed in a phylloid pattern over the left side of the back and extending to the midline of the back and left side of the abdomen (Fig. 1a,c). The subject also demonstrated ill-defined, bluish-gray macules over the right shoulder which were suggestive of nevus of Ito (Fig. 1a, b). Electroencephalographic recordings and computed tomography of the brain produced normal results. There were no biochemical or hematological abnormalities. The findings of electrocardiography and echocardiography were normal. Ultrasound of the abdomen showed a fatty change in the liver. Histopathological examination of a skin biopsy specimen from a hypopigmented area on the subject’s back revealed an unremarkable epidermis and dermis (Fig. 2a,b). Examination of a biopsy obtained from the bluish-gray area on the patient’s shoulder revealed an unremarkable epidermis and scattered dendritic melanized melanocytes in both the superficial and deep dermis within collagen bundles (Fig. 2c,d), consistent with nevus of Ito. Karyotyping from a blood sample was found to be normal. International Journal of Dermatology 2014, 53, 1005–1007
1005
1006
Morphology
Pigmentary twin spotting
(a)
Singh et al.
(c)
(b)
Figure 1 Clinical examination of a 28-year-old man reveals (a) large, hypopigmented macules over the left side of the back, (b) ill-defined, bluish-gray macules over the right shoulder, and (c) large, hypopigmented macules presenting in a phylloid pattern over the left side of the back up to the midline, and the left side of the abdomen
(a)
(c)
(b) (d)
Figure 2 Histopathology of a biopsy from a hypopigmented area shows (a) an unremarkable epidermis and dermis, and (b) normal melanocytes. Histopathology of a biopsy obtained from an area of bluish-gray macules shows (c) an unremarkable epidermis and scattered dendritic melanocytes in both the superficial and deep dermis within collagen bundles, and (d) scattered dendritic melanocytes in the dermis within collagen bundles. (Hematoxylin and eosin stain; original magnification [a] 9100, [b] 9200, [c] 9100, [d] 9400)
Discussion The terms twin spots and didymoses (didymos means twin in Greek) refer to the co-occurrence of two different International Journal of Dermatology 2014, 53, 1005–1007
nevi or paired patches of structurally or functionally different mutant tissue that differ from the surrounding normal skin and may present adjacently to one another or on contralateral sides.1 Their occurrence may reflect ª 2014 The International Society of Dermatology
Singh et al.
an early post-zygotic mutation or a form of loss of heterozygosity.2 The concept of twin spotting was introduced initially to explain the occurrence of twin vascular nevi, since then several examples of allelic and non-allelic twin spots have been reported. Two or more nevi that originate from the same type of cell are referred to as allelic twin spots. Their occurrence probably reflects different recessive mutations on the same gene locus on either pair of homologous chromosomes post-mitotic crossover. Nevi that originate from different types of cell are referred to as non-allelic twin spots.1,2 In the present patient, the nevus depigmentosus and nevus of Ito were present on contralateral sides in a semi-checkerboard pattern; we believe these can be characterized as allelic twin spots because both arise from disturbances in melanocytes. Instances of nevus depigmentosus with segmental lentiginoses occurring on the same side3 as well as on contralateral sides4 have been reported in the literature. In addition, the occurrence of nevus depigmentosus with Becker’s nevus has been reported as representative of
ª 2014 The International Society of Dermatology
Pigmentary twin spotting
Morphology
allelic twin spotting.5 This clinical presentation of twin nevi, nevus depigmentosus and nevus of Ito, is another example of allelic twin spotting, and its association with seizures is indeed interesting. References 1 Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999; 41: 143–161. 2 Happle R. Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol 1993; 129: 1460–1470. 3 Baba M, Akcali C, Seckin D, et al. Segmental lentiginosis with ipsilateral nevus depigmentosus: another example of twin spotting? Eur J Dermatol 2002; 12: 319–321. 4 Alkemade H, Juhlin L. Unilateral lentiginosis with nevus depigmentosus on the other side. J Am Acad Dermatol 2000; 43: 361–363. 5 Afsar FS, Aktas S, Oratc R. Beckers nevus and segmental nevus depigmentosus: an example of twin spotting? Australas J Dermatol 2007; 48: 224–226.
International Journal of Dermatology 2014, 53, 1005–1007
1007
Nevus depigmentosus and nevus of Ito: pigmentary twin spotting Nidhi Singh1, MD, Laxmisha Chandrashekar1, MD, Devinder Mohan Thappa1, MD, and Rakhee Kar2, MD
1 Departments of Dermatology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India, and 2 Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
Correspondence Laxmisha Chandrashekar, MD Department of Dermatology Jawaharlal Institute of Postgraduate Medical Education and Research Puducherry 605006, India E-mail: [email protected] Conflicts of interest: None.
Introduction Nevus depigmentosus presents with areas of hypopigmentation along Blaschko’s lines and may be associated with disorders of the central nervous system, musculoskeletal system, eyes, and teeth. Nevus of Ito is a dermal melanocytosis of the acromioclavicular and upper chest area. Although both nevus depigmentosus and nevus of Ito occur commonly, their coexistence in a manner representative of allelic twin spotting has not previously been reported. Case Report A 28-year-old man of normal intellectual ability, born of a non-consanguineous marriage, presented with a birthmark of hypopigmented areas on the left side of the back. There was no history of bullous, verrucous, or hyperpigmented lesions preceding the appearance of the hypopigmentation. The patient had suffered from progressively worsening tremors of the hands over the previous 10 years, as well as from generalized tonic clonic seizures and myoclonus over the previous two years, for which he was receiving sodium valproate. His grandfather, paternal aunt, and father had experienced the onset of seizures and tremors in the third decade of ª 2014 The International Society of Dermatology
life and had died by the end of the fifth decade after developing severe tremors, ataxia, and refractory seizures. His younger brother and sister also had tremors and seizures, the onset of which had occurred in the third decade. Cutaneous examination revealed large hypopigmented macules distributed in a phylloid pattern over the left side of the back and extending to the midline of the back and left side of the abdomen (Fig. 1a,c). The subject also demonstrated ill-defined, bluish-gray macules over the right shoulder which were suggestive of nevus of Ito (Fig. 1a, b). Electroencephalographic recordings and computed tomography of the brain produced normal results. There were no biochemical or hematological abnormalities. The findings of electrocardiography and echocardiography were normal. Ultrasound of the abdomen showed a fatty change in the liver. Histopathological examination of a skin biopsy specimen from a hypopigmented area on the subject’s back revealed an unremarkable epidermis and dermis (Fig. 2a,b). Examination of a biopsy obtained from the bluish-gray area on the patient’s shoulder revealed an unremarkable epidermis and scattered dendritic melanized melanocytes in both the superficial and deep dermis within collagen bundles (Fig. 2c,d), consistent with nevus of Ito. Karyotyping from a blood sample was found to be normal. International Journal of Dermatology 2014, 53, 1005–1007
1005
1006
Morphology
Pigmentary twin spotting
(a)
Singh et al.
(c)
(b)
Figure 1 Clinical examination of a 28-year-old man reveals (a) large, hypopigmented macules over the left side of the back, (b) ill-defined, bluish-gray macules over the right shoulder, and (c) large, hypopigmented macules presenting in a phylloid pattern over the left side of the back up to the midline, and the left side of the abdomen
(a)
(c)
(b) (d)
Figure 2 Histopathology of a biopsy from a hypopigmented area shows (a) an unremarkable epidermis and dermis, and (b) normal melanocytes. Histopathology of a biopsy obtained from an area of bluish-gray macules shows (c) an unremarkable epidermis and scattered dendritic melanocytes in both the superficial and deep dermis within collagen bundles, and (d) scattered dendritic melanocytes in the dermis within collagen bundles. (Hematoxylin and eosin stain; original magnification [a] 9100, [b] 9200, [c] 9100, [d] 9400)
Discussion The terms twin spots and didymoses (didymos means twin in Greek) refer to the co-occurrence of two different International Journal of Dermatology 2014, 53, 1005–1007
nevi or paired patches of structurally or functionally different mutant tissue that differ from the surrounding normal skin and may present adjacently to one another or on contralateral sides.1 Their occurrence may reflect ª 2014 The International Society of Dermatology
Singh et al.
an early post-zygotic mutation or a form of loss of heterozygosity.2 The concept of twin spotting was introduced initially to explain the occurrence of twin vascular nevi, since then several examples of allelic and non-allelic twin spots have been reported. Two or more nevi that originate from the same type of cell are referred to as allelic twin spots. Their occurrence probably reflects different recessive mutations on the same gene locus on either pair of homologous chromosomes post-mitotic crossover. Nevi that originate from different types of cell are referred to as non-allelic twin spots.1,2 In the present patient, the nevus depigmentosus and nevus of Ito were present on contralateral sides in a semi-checkerboard pattern; we believe these can be characterized as allelic twin spots because both arise from disturbances in melanocytes. Instances of nevus depigmentosus with segmental lentiginoses occurring on the same side3 as well as on contralateral sides4 have been reported in the literature. In addition, the occurrence of nevus depigmentosus with Becker’s nevus has been reported as representative of
ª 2014 The International Society of Dermatology
Pigmentary twin spotting
Morphology
allelic twin spotting.5 This clinical presentation of twin nevi, nevus depigmentosus and nevus of Ito, is another example of allelic twin spotting, and its association with seizures is indeed interesting. References 1 Happle R. Loss of heterozygosity in human skin. J Am Acad Dermatol 1999; 41: 143–161. 2 Happle R. Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol 1993; 129: 1460–1470. 3 Baba M, Akcali C, Seckin D, et al. Segmental lentiginosis with ipsilateral nevus depigmentosus: another example of twin spotting? Eur J Dermatol 2002; 12: 319–321. 4 Alkemade H, Juhlin L. Unilateral lentiginosis with nevus depigmentosus on the other side. J Am Acad Dermatol 2000; 43: 361–363. 5 Afsar FS, Aktas S, Oratc R. Beckers nevus and segmental nevus depigmentosus: an example of twin spotting? Australas J Dermatol 2007; 48: 224–226.
International Journal of Dermatology 2014, 53, 1005–1007
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