J Cutan Pathol 2014: 41: 646–649 doi: 10.1111/cup.12342 John Wiley & Sons. Printed in Singapore
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Journal of Cutaneous Pathology
Increase of elastic ﬁbers in lichen sclerosus et atrophicus Background: Lichen sclerosus et atrophicus (LSA) is histopathologically characterized by upper dermal hyalinization with vacuolar alteration, whereas no particular microscopic change in the mid to lower dermis has been described. The purpose of this study was to investigate any histopathologic changes involving elastic fibers in the mid to lower dermis in patients with LSA. Methods: We surveyed 22 paraffin-embedded specimens of vulval (18 cases) and extragenital (4 cases) LSA. The sliced skin sections were stained with elastic van Gieson (EVG), and then the degree of elastic fiber change was determined. Results: We found an increase in elastic fibers in the mid to lower dermis in contrast to a decrease or disappearance of elastic fibers in the superficial hyalinized dermis. The level of increase of elastic fibers varies from normal (8/22 cases) to moderate (7/22 cases) to advanced (7/22 cases) levels. Conclusions: An increase in elastic fibers in the mid to lower dermis may reflect a repairing process in response to the degraded upper dermal elastic fibers, which could be related to the pathogenesis of LSA. Keywords: dermatopathology, elastin, pathology dermatopathology Shiba Y, Ono K, Akiyama M, Fujimoto N, Tajima S. Increase of elastic fibers in lichen sclerosus et atrophicus. J Cutan Pathol 2014; 41: 646–649. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
The histopathology of lichen sclerosus et atrophicus (LSA) is characterized by alterations in the epidermis and dermis as well as inflammatory cell infiltration. The epidermis is usually atrophic and often undergoes basal layer vacuolization (‘liquefaction degeneration’). The superficial dermis is edematous and hyalinized. The accumulated extracellular matrix in the hyalinized dermis has not been fully characterized. Accumulation of hyaluronate and tenascin in the hyalinized zone has been reported.1,2 Disappearance of elastic fiber and fibrillin in the superficial dermis has been noted, which is considered to be related to the activation of
Yohei Shiba, Koji Ono, Minoru Akiyama, Norihiro Fujimoto and Shingo Tajima Department of Dermatology, National Defense Medical College, Tokorozawa, Saitama 359-8513, Japan
Yohei Shiba, MD Department of Dermatology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan Tel: +81 4 2995 1665 Fax: +81 4 2996 5209 e-mail: [email protected]
Accepted for publication March 12, 2014
elastase-type proteases.3 – 5 A band-like lymphohistiocytic infiltrate consisting of CD3+, CD8+ and CD57+ lymphocytes situated beneath the homogenized dermis is one of the characteristic features of early involvement, but in old lesions only a very slight inflammatory infiltrate is seen.6 These histopathologic findings suggest that alteration of extracellular matrix plays a central role in the pathology of LSA. In this study, we found an increase in elastic fibers in the mid to lower dermis in some cases of LSA. We discuss the relationship between decreased or increased elastic fibers during the evolution of this disease.
Elastic ﬁbers in LSA
Fig. 1. Various degrees of elastic tissue staining were demonstrated in the lesional skin of vulval lichen sclerosus. Elastic fiber level of normal control skin is shown in (A). The increase in elastic tissue in the mid to lower dermis included three groups; normal (B), moderate (C) and advanced (D) levels. A–D correspond to control case 4 and patients 14, 11, 3 in Table 1, respectively. A) Fine elastic fibers were seen in the upper and lower dermis. B) Upper dermal homogenization with subepidermal separation and disappearance of elasic fibers were seen whereas elastic fibers in the mid to lower dermis mostly appeared normal. C) Mild increase in elastic fibers was found just beneath the hyalinized zone. D) Prominent increase in elastic fibers was seen chiefly in the lower part of hyalinized zone and mid dermis. Scale bars indicate 100 μm.
Materials and methods Patients and skin specimens Skin specimens from 18 cases of patients with vulval LSA and 4 cases of extragenital LSA were collected from the files of our university over the last 20 years (mean age, 62.0 ± 14.2 years; range, 24–87 years). Age-, site- and sex-matched normal skin specimens (n = 5; mean age, 73.4 ± 14.1; range, 64–98) were also obtained from normal-appearing areas of benign skin tumors, such as seborrheic keratoses. The diagnosis of all cases was made on the basis of clinical morphology and histopathologic features with routine hematoxylin/eosin staining of biopsied skin specimens obtained from the lesional skin.7 The patients who participated in this study gave their written informed consent before participation. This study was conducted according
to the Declaration of Helsinki Principles in 1983, and was approved by the Medical Ethical Committee of the National Defense Medical College. Elastic ﬁber staining The paraffin-embedded skin specimens were sliced into 4 μm-thick sections and then stained with EVG. Degree of elastic fiber change in the mid to lower dermis was classified into three groups: normal (with normal-appearing fine elastic fibers in the mid to lower dermis), moderate (with an increase of thick elastic fibers chiefly situated beneath the hyalinized zone) and advanced (with extensive proliferation of thick elastic fibers in the mid to lower dermis, including the lower part of the hyalinized zone).
Shiba et al. Results The typical histopathologic appearances of normal control (n = 5) and patient skin (n = 22) with normal, moderate and advanced elastic fiber increase are shown in Fig. 1A–D. In normal control skin, thin elastic fibers ran perpendicularly in the superficial dermis and horizontally in the mid to lower dermis (Fig. 1A). In vulval LSA, we found a normal appearance of elastic fibers in the mid to lower dermis (Fig. 1B) in 5/18 cases, a moderate increase in elastic fibers just beneath the hyalinized superficial dermis (Fig. 1C) in 7/18 cases, and an advanced increase of abnormal aggregates of elastic fibers with a lack of distinct normal elastic fibers in the mid to lower dermis (Fig. 1D) in 6/18 cases (Table 1). The average ages of the patients with normal, moderate and advanced elastic fiber increase were 66.2 ± 11.1, 66.3 ± 13.8 and 61.5 ± 11.9 years, respectively. The average duration of disease in normal, moderate and advanced increase in elastic fibers were 78.6 ± 11.5, 58.8 ± 89.9 and 30.0 ± 18.5 months, respectively. In extragenital LSA, advanced increase in elastic fibers was found 1/4 cases, and three cases remained normal (Table 1). Discussion We found interesting pathologic changes with a prominent dermal increase in elastic fibers in some cases of vulval LSA. The microscopic change consists of increased staining or an increased number of elastic fibers with a smudgy pattern in the reticular dermis. In the literature, there are two papers describing similar changes. One paper entitled Nevus elasticus and lichen sclerosus et atrophicus on the vulva has been previously reported.8 The authors interpreted their case as the co-existence of nevus elasticus and vulval LSA. We do not think that interpretation is probably because nevus elasticus or juvenile elastoma is defined as a type of connective tissue nevus and occurs in childhood on the trunk or thigh as numerous yellowish or skin-colored nodules occurring in groups.9 – 11 Another similar case describes LSA involving a surgical scar and is characterized by the unusual presence of abundant nodules of elastin in the reticular dermis. The authors considered the nodular elastosis as an unusual feature unrelated to LSA but rather related to scar formation.12 To further study this relationship, we surveyed the pathologic files of LSA in our department and collected 18 cases of vulval LSA. EVG staining showed three groups that occurred with
Table 1. Increase in elastic ﬁbers in the mid to lower dermis of lichen sclerosus et atrophicus (LSA) Case no.
Vulval LSA 1 56/F 2 66/F 3 55/F 4 54/F 5 54/F 6 84/F 7 81/F 8 52/F 9 87/F 10 55/F 11 71/F 12 63/F 13 55/F 14 54/F 15 57/F 16 78/F 17 65/F 18 77/F Vulval normal control 1 70/F 2 98/F 3 71/F 4 64/F 5 64/F Extragenital LSA 1 64/F 2 24/M 3 57/F 4 57/F
Duration of disease
Unknown 1 year 1 year 2–3 years 3–4 years 4–5 years Unknown 5 months 6 months 2–3 years 3 years 3 years 20 years Unknown 2–3 months 6 months 5–6 years 20 years
Advanced Advanced Advanced Advanced Advanced Advanced Moderate Moderate Moderate Moderate Moderate Moderate Moderate Normal Normal Normal Normal Normal Normal Normal Normal Normal Normal
Unknown Unknown Unknown Unknown
Advanced Normal Normal Normal
F, female; M, male. *Degree of increase in elastic ﬁbers in the mid to lower dermis was classiﬁed into normal, moderate and advanced levels.
almost equal frequency: almost normal appearance (five cases), moderate increase in elastic fibers (seven cases) and advanced increase in elastic fibers (six cases) in the mid to lower dermis. We think that the increase in elastic fibers in the mid to lower dermis is caused by or is related to the disappearance of elastic fibers in the upper homogenized dermis and represents a repair process associated with this disease, and this finding may be pathogenically important. A nearly complete disappearance of elastic tissue in the upper dermal homogenized zone in LSA has been already described.3,13 The underlying mechanism behind the loss of elastic fibers is unclear but at this time, it is considered to be caused by the degradation of elastic fibers (elastolytic change) by elastase-type proteases secreted from dermal fibroblasts or activated macrophages.3,6 This hypothesis is supported
Elastic ﬁbers in LSA by the presence of prominent elastophagocytosis below the homogenized zone in 7 of 35 extragenital LSA patients.14 Elastophagocytosis has also been observed in dermal elastolytic disorders such as annular elastolytic giant cell granuloma,15 mid-dermal elastolysis16,17 or upper dermal elastolysis.18 Elastic tissue diseases are classified into two categories: diseases with diminished or increased elastic fibers.19 Elastolytic change in the upper dermis and hyperelastic change in mid to lower dermis have been reported in other skin disorders, including pseudoxanthoma elasticum (PXE)-like papillary dermal elastolysis,20 of which a clinical feature is asymptomatic white or skin-colored papules on the neck, axilla and inguinal region. PXE-like papillary dermal elastolysis is characterized by the disappearance of elastic fibers in the superficial dermis and in some cases is accompanied by an accumulation of elastic tissues in the mid to lower dermis. Furthermore, striae distensae and linear focal elastosis also suggest a relationship between elastolysis and elastosis. A stria distensa shows a total absence of elastic fibers or the presence of
thinner elastic fibers, whereas a marked increase in thick elastic fibers is seen in linear focal elastosis.21,22 Because some cases of linear focal elastosis have been found to occur in association with ordinary stria in the same patient, linear focal elastosis is considered to represent a regenerative or repair stage of stria.23,24 These descriptions about the relation between elastolysis and hyperelastic change suggest that an increase in elastic fibers in the lower dermis in LSA may be caused by elastin degradation in the upper dermis. The significance of hyperelastic change in LSA is unclear at present. Because the increase in elastic fibers in the mid to lower dermis seems to be unrelated to the duration of disease, the degree of increase in elastic fibers may be dependent on a tissue reaction to the degraded elastin. In summary, increased staining of elastic fibers in the mid to lower dermis was found in some cases of genital and extragenital LSA. The increase in elastic fibers may reflect a repair process in response to the disappearance of elastic fibers in the upper homogenized dermis and may lend insight into the pathogenesis of LSA.
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