Case report
Linear connective tissue nevus along Blaschko’s lines: literature review and case report Jose C^ andido C. Xavier-J unior1, MD, Pollyanna K. M. Batalha2, MD, Luciana P. F. Abbade2, MD, PhD, and Mariangela E. A. Marques1, MD, PhD
1
Department of Pathology, and Department of Dermatology, Faculty of Medicine, Universidade Estadual Paulista ~o Paulo, Brazil (UNESP) Botucatu, Sa 2
Correspondence C. C. Xavier Ju nior, MD Jose Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP) ~o Ju nior s/n Rubia 18618-970-Botucatu-SP Brazil E-mail: [email protected] Conflicts of interest: None. Funding sources: There are no funding sources.
The connective tissue nevus (CTN) was first reported by Lewandowsky in 1921. It may occur as an isolated finding, without familial history, as an autosomal dominant inheritance that does not compromise other organs, or as
a characteristic component of a number of genetic disorders.1–3 Linear CTN is a rare disease, poorly described and probably underdiagnosed. It differs from the regular CTN by the typical anatomical distribution, by the lack of genetic pattern of inheritance, and/or the absence of
Figure 1 Clustered normal skin-colored papules with linear distribution along Blaschko's lines on the right abdominal region
Figure 2 Acanthosis of epidermis and sclerotic dermis (hematoxylin and eosin 9100)
Introduction
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International Journal of Dermatology 2015, 54, e166–e168
ª 2014 The International Society of Dermatology
Xavier et al.
Linear connective tissue nevus
associated abnormalities in other organs, considering that both dermatoses show similar histopathological patterns.4–6 Case presentation A 13-year-old teenager, male, presented with a 3-year history of asymptomatic lesions on his right hemibody. On physical examination, the patient showed firm, brownish hyperchromic, cobblestone-like plaques distrib-
Case report
uted linearly along Blaschko's lines, interspersed with normal skin-colored and hypochromic plaques, initially on his right lumbar region that progressed to his abdomen, buttock, and right leg (Fig. 1). There was no family history of tuberous sclerosis or consanguinity. A fusiform incisional biopsy was performed on the abdominal lesion to confirm the diagnosis. Histopathology Hematoxylin and eosin staining revealed a normal epidermis containing a discrete papillary hyperplasia (Fig. 2). The Masson's trichrome stain emphasized the collagen deposition of the sclerotic dermis and revealed collagen bundles that formed thick septa in the subcutaneous tissue. The orcein stain showed an increase of elastic fibers throughout the dermis (Fig. 3). Furthermore, discrete perivascular lymphocytic infiltrates were also observed. Discussion
Figure 3 Orcein staining showing an increase of elastic fibers
(9400)
Connective tissue nevus is a hamartomatous lesion of undefined etiology. The most acceptable theory is that it is a disorder involved in the synthesis of collagen, elastic fibers, and/or proteoglycans.5 It is characterized by painless, hypochromic, or pinkish papules or nodules of slow growth, which are mostly found on the trunk and limbs, with lesions normally beginning during childhood.7 Histological features are characterized by an irregular increase
Table 1 Literature review of connective tissue nevus cases with both zosteriform distribution and linear distribution along Blaschko's lines
Author
Sex/age at diagnosis
Location
Histopathological features
Steiner9 (1944) Kozminsky et al.13 (1985) Yeh et al.8 (2003) Chen et al.12 (2006) Amjadi et al.4 (2007)
F/5 F/23 M/at birth F/25 M/25
Lower chest and back Back Abdomen and flank Right scapula Lumbar and upper gluteal
Alterations in collagen and elastic fibers Alterations in elastic fibers Sparse and fragmented elastic fibers Sparse and fragmented elastic fibers Increase in collagen
Brazzelli et al.5 (2007)
F/8
Lumbosacral
Asano et al.1 (2007)
M/4
Rashmi et al.14 (2007) Choi et al.6 (2011)
M/20 F/3 months
Right lower limb, abdomen and forearm Right buttock Chest and abdomen
Thickening of collagen fibers and thinning of elastic fibers. Collagen fibers occurred in fragmented bundles Elastic fibers increased and fragmented
Castellanos-Gonzalez et al.7
F/14
Present case
M/13
Right upper arm and lower back Lumbar region, abdomen and right lower limb
Decrease in elastic fibers Increase in collagen fibers and decrease in elastic fibers Reduction and fragmentation of elastic fibers Increase of both collagen and elastic fibers
Associated systemic diseases None None None None Segmental neurofibromatosis None
None None None None None
F, female; M, male. ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e166–e168
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Case report
Linear connective tissue nevus
of collagen fibers and glycosaminoglycans in the dermis in the absence of fibroblastic proliferation.5,6 Some cases show an increase in both collagen and elastic fibers and are called mixed type.4,9,10 However, diagnostic criteria regarding alterations presented by elastic fibers are yet poorly defined. Zosteriform CTN was first reported by Steiner in 1944 and is distributed in the dermatome area. At present, nine cases of zosteriform CTN have been described in the literature. Apart from these cases, there is only one where the lesion was distributed linearly along Blaschko's lines, not dermatomes, and, therefore, the authors proposed use of the term linear CTN, which also suits our case better1 (Table 1). Dermatomes represent cutaneous regions innerved by fibers of one dorsal root (sensory) of the spinal cord.11 Although their meanings differ, Blaschko's lines and the limits of the dermatome do overlap. In this case, the lesions are clearly distributed along Blaschko's lines. The differential diagnosis of CTN includes tuberous sclerosis and nevus lipomatosus superficialis. In this particular case, other dermatoses that are distributed along Blaschko's lines should also be remembered, such as linear epidermal nevus, linear and whorled nevoid hypermelanosis, linear cutaneous amyloidosis, lichen planus linearis, linear pigmented lentiginous nevus, linear morphea, segmental neurofibromatosis 1 (type 5), lichen striatus, and incontinentia pigmenti, among others.14 Connective tissue lesions might be present as the main symptom of different clinical entities. When clinical suspicions suggest related syndromes, such as Buschke– Ollendorff, there is a tendency to perform radiographic investigations (bone x-rays), mainly in cases of multiple connective tissue nevi. In Buschke–Ollendorff syndrome, the CTN does not show a zosteriform pattern and the skin lesion a collagen type. In these cases, x-ray examination aims at looking for disorders such as osteopoikilosis, which is characterized by grain- to pea-sized spherical condensations or fascicular streaks in the skeletal structure of epiphyses and metaphyses of the long bones, pelvis, and bones of the hands and feet, and are frequently found incidentally.3 In linear CTN along Blaschko's lines, the treatment is a challenge due to the size of the lesions. As the lesions
International Journal of Dermatology 2015, 54, e166–e168
Xavier et al.
remain asymptomatic, with only cosmetic effect,6 the condition needs no specific treatment, and there are no ideal pre-established propedeutics for patient follow-up.8 References 1 Asano Y, Ihn H, Tamaki K. Linear connective tissue nevus. Pediatr Dermatol 2007; 24: 439–441. 2 McCuaig CC, Vera C, Kokta V, et al. Connective tissue nevi in children: institutional experience and review. J Am Acad Dermatol 2012; 25: 1–8. 3 Assmann A, Mandt N, Geilen CC, et al. BuschkeOllendorff syndrome – differential diagnosis of disseminated connective tissue lesions. Eur J Dermatol 2001; 11: 576–579. 4 Amjadi M, Khorrami-Arani N, Mashman G, et al. Zosteriform connective tissue nevus: a case report. Am J Dermatopathol 2007; 29: 303–305. 5 Brazzelli V, Muzio F, Barbagallo T, et al. Zosteriform connective tissue nevus in a pediatric patient. Pediatr Dermatol 2007; 24: 557–575. 6 Choi YJ, Lee SJ, Choi CW, et al. Multiple unilateral zosteriform connective tissue nevi on the trunk. Ann Dermatol 2011; 23: S243–S246. 7 Castellanos-Gonzalez M, Petiti-Martin G, Postigo C, et al. Zosteriform connective tissue nevus: a new case report. Actas Dermosifiliogr 2012; 103: 640–642. 8 Yeh SW, Magalhaes AM, Vasconcellos MRA, et al. Zosteriform connective tissue nevus: a case report. Int J Dermatol 2003; 42: 718–723. 9 Steiner K. Connective tissue nevus. Arch Dermatol Syphilol 1944; 50: 183–190. 10 Uitto J, Santa Cruz DJ, Eisen AZ. Connective tissue of the skin. Clinical, genetic and histopathologic classification of hamartomas of the collagen, elastin and proteoglycan type. J Am Acad Dermatol 1980; 3: 441–461. 11 Bolognia JL, Jorizzo JL, Rapini R. Dermatologia, 2nd edn. Rio de Janeiro, RJ: Elsevier, 2011: 841–855. 12 Chen WC, Tsai TF, Chen YF, et al. An asymptomatic zosterifrom skin-colored plaque on the right upper back in a 25-year-old women. Dermatol Sin 2006; 24: 72–73. 13 Kozminsky ME, Bronson DM, Barsky S. Zosteriform connective tissue nevus. Cutis 1985; 36: 77–78. 14 Rashmi K, Mohan TD, Jayanthi S. A large asymptomatic lesion on buttock since birth. Indian J Dermatol Venereol Leprol 2007; 73: 143–144.
ª 2014 The International Society of Dermatology
Linear connective tissue nevus along Blaschko’s lines: literature review and case report Jose C^ andido C. Xavier-J unior1, MD, Pollyanna K. M. Batalha2, MD, Luciana P. F. Abbade2, MD, PhD, and Mariangela E. A. Marques1, MD, PhD
1
Department of Pathology, and Department of Dermatology, Faculty of Medicine, Universidade Estadual Paulista ~o Paulo, Brazil (UNESP) Botucatu, Sa 2
Correspondence C. C. Xavier Ju nior, MD Jose Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual Paulista (UNESP) ~o Ju nior s/n Rubia 18618-970-Botucatu-SP Brazil E-mail: [email protected] Conflicts of interest: None. Funding sources: There are no funding sources.
The connective tissue nevus (CTN) was first reported by Lewandowsky in 1921. It may occur as an isolated finding, without familial history, as an autosomal dominant inheritance that does not compromise other organs, or as
a characteristic component of a number of genetic disorders.1–3 Linear CTN is a rare disease, poorly described and probably underdiagnosed. It differs from the regular CTN by the typical anatomical distribution, by the lack of genetic pattern of inheritance, and/or the absence of
Figure 1 Clustered normal skin-colored papules with linear distribution along Blaschko's lines on the right abdominal region
Figure 2 Acanthosis of epidermis and sclerotic dermis (hematoxylin and eosin 9100)
Introduction
e166
International Journal of Dermatology 2015, 54, e166–e168
ª 2014 The International Society of Dermatology
Xavier et al.
Linear connective tissue nevus
associated abnormalities in other organs, considering that both dermatoses show similar histopathological patterns.4–6 Case presentation A 13-year-old teenager, male, presented with a 3-year history of asymptomatic lesions on his right hemibody. On physical examination, the patient showed firm, brownish hyperchromic, cobblestone-like plaques distrib-
Case report
uted linearly along Blaschko's lines, interspersed with normal skin-colored and hypochromic plaques, initially on his right lumbar region that progressed to his abdomen, buttock, and right leg (Fig. 1). There was no family history of tuberous sclerosis or consanguinity. A fusiform incisional biopsy was performed on the abdominal lesion to confirm the diagnosis. Histopathology Hematoxylin and eosin staining revealed a normal epidermis containing a discrete papillary hyperplasia (Fig. 2). The Masson's trichrome stain emphasized the collagen deposition of the sclerotic dermis and revealed collagen bundles that formed thick septa in the subcutaneous tissue. The orcein stain showed an increase of elastic fibers throughout the dermis (Fig. 3). Furthermore, discrete perivascular lymphocytic infiltrates were also observed. Discussion
Figure 3 Orcein staining showing an increase of elastic fibers
(9400)
Connective tissue nevus is a hamartomatous lesion of undefined etiology. The most acceptable theory is that it is a disorder involved in the synthesis of collagen, elastic fibers, and/or proteoglycans.5 It is characterized by painless, hypochromic, or pinkish papules or nodules of slow growth, which are mostly found on the trunk and limbs, with lesions normally beginning during childhood.7 Histological features are characterized by an irregular increase
Table 1 Literature review of connective tissue nevus cases with both zosteriform distribution and linear distribution along Blaschko's lines
Author
Sex/age at diagnosis
Location
Histopathological features
Steiner9 (1944) Kozminsky et al.13 (1985) Yeh et al.8 (2003) Chen et al.12 (2006) Amjadi et al.4 (2007)
F/5 F/23 M/at birth F/25 M/25
Lower chest and back Back Abdomen and flank Right scapula Lumbar and upper gluteal
Alterations in collagen and elastic fibers Alterations in elastic fibers Sparse and fragmented elastic fibers Sparse and fragmented elastic fibers Increase in collagen
Brazzelli et al.5 (2007)
F/8
Lumbosacral
Asano et al.1 (2007)
M/4
Rashmi et al.14 (2007) Choi et al.6 (2011)
M/20 F/3 months
Right lower limb, abdomen and forearm Right buttock Chest and abdomen
Thickening of collagen fibers and thinning of elastic fibers. Collagen fibers occurred in fragmented bundles Elastic fibers increased and fragmented
Castellanos-Gonzalez et al.7
F/14
Present case
M/13
Right upper arm and lower back Lumbar region, abdomen and right lower limb
Decrease in elastic fibers Increase in collagen fibers and decrease in elastic fibers Reduction and fragmentation of elastic fibers Increase of both collagen and elastic fibers
Associated systemic diseases None None None None Segmental neurofibromatosis None
None None None None None
F, female; M, male. ª 2014 The International Society of Dermatology
International Journal of Dermatology 2015, 54, e166–e168
e167
e168
Case report
Linear connective tissue nevus
of collagen fibers and glycosaminoglycans in the dermis in the absence of fibroblastic proliferation.5,6 Some cases show an increase in both collagen and elastic fibers and are called mixed type.4,9,10 However, diagnostic criteria regarding alterations presented by elastic fibers are yet poorly defined. Zosteriform CTN was first reported by Steiner in 1944 and is distributed in the dermatome area. At present, nine cases of zosteriform CTN have been described in the literature. Apart from these cases, there is only one where the lesion was distributed linearly along Blaschko's lines, not dermatomes, and, therefore, the authors proposed use of the term linear CTN, which also suits our case better1 (Table 1). Dermatomes represent cutaneous regions innerved by fibers of one dorsal root (sensory) of the spinal cord.11 Although their meanings differ, Blaschko's lines and the limits of the dermatome do overlap. In this case, the lesions are clearly distributed along Blaschko's lines. The differential diagnosis of CTN includes tuberous sclerosis and nevus lipomatosus superficialis. In this particular case, other dermatoses that are distributed along Blaschko's lines should also be remembered, such as linear epidermal nevus, linear and whorled nevoid hypermelanosis, linear cutaneous amyloidosis, lichen planus linearis, linear pigmented lentiginous nevus, linear morphea, segmental neurofibromatosis 1 (type 5), lichen striatus, and incontinentia pigmenti, among others.14 Connective tissue lesions might be present as the main symptom of different clinical entities. When clinical suspicions suggest related syndromes, such as Buschke– Ollendorff, there is a tendency to perform radiographic investigations (bone x-rays), mainly in cases of multiple connective tissue nevi. In Buschke–Ollendorff syndrome, the CTN does not show a zosteriform pattern and the skin lesion a collagen type. In these cases, x-ray examination aims at looking for disorders such as osteopoikilosis, which is characterized by grain- to pea-sized spherical condensations or fascicular streaks in the skeletal structure of epiphyses and metaphyses of the long bones, pelvis, and bones of the hands and feet, and are frequently found incidentally.3 In linear CTN along Blaschko's lines, the treatment is a challenge due to the size of the lesions. As the lesions
International Journal of Dermatology 2015, 54, e166–e168
Xavier et al.
remain asymptomatic, with only cosmetic effect,6 the condition needs no specific treatment, and there are no ideal pre-established propedeutics for patient follow-up.8 References 1 Asano Y, Ihn H, Tamaki K. Linear connective tissue nevus. Pediatr Dermatol 2007; 24: 439–441. 2 McCuaig CC, Vera C, Kokta V, et al. Connective tissue nevi in children: institutional experience and review. J Am Acad Dermatol 2012; 25: 1–8. 3 Assmann A, Mandt N, Geilen CC, et al. BuschkeOllendorff syndrome – differential diagnosis of disseminated connective tissue lesions. Eur J Dermatol 2001; 11: 576–579. 4 Amjadi M, Khorrami-Arani N, Mashman G, et al. Zosteriform connective tissue nevus: a case report. Am J Dermatopathol 2007; 29: 303–305. 5 Brazzelli V, Muzio F, Barbagallo T, et al. Zosteriform connective tissue nevus in a pediatric patient. Pediatr Dermatol 2007; 24: 557–575. 6 Choi YJ, Lee SJ, Choi CW, et al. Multiple unilateral zosteriform connective tissue nevi on the trunk. Ann Dermatol 2011; 23: S243–S246. 7 Castellanos-Gonzalez M, Petiti-Martin G, Postigo C, et al. Zosteriform connective tissue nevus: a new case report. Actas Dermosifiliogr 2012; 103: 640–642. 8 Yeh SW, Magalhaes AM, Vasconcellos MRA, et al. Zosteriform connective tissue nevus: a case report. Int J Dermatol 2003; 42: 718–723. 9 Steiner K. Connective tissue nevus. Arch Dermatol Syphilol 1944; 50: 183–190. 10 Uitto J, Santa Cruz DJ, Eisen AZ. Connective tissue of the skin. Clinical, genetic and histopathologic classification of hamartomas of the collagen, elastin and proteoglycan type. J Am Acad Dermatol 1980; 3: 441–461. 11 Bolognia JL, Jorizzo JL, Rapini R. Dermatologia, 2nd edn. Rio de Janeiro, RJ: Elsevier, 2011: 841–855. 12 Chen WC, Tsai TF, Chen YF, et al. An asymptomatic zosterifrom skin-colored plaque on the right upper back in a 25-year-old women. Dermatol Sin 2006; 24: 72–73. 13 Kozminsky ME, Bronson DM, Barsky S. Zosteriform connective tissue nevus. Cutis 1985; 36: 77–78. 14 Rashmi K, Mohan TD, Jayanthi S. A large asymptomatic lesion on buttock since birth. Indian J Dermatol Venereol Leprol 2007; 73: 143–144.
ª 2014 The International Society of Dermatology
