Macroscopic and histological examination of human bridging veins.

In infantile abusive head injury (AHT), subdural haemorrhage (SDH) is commonly held to result from traumatic damage to bridging veins traversing from the surface of the brain to the dura and dural venous sinuses. However, there are limited published radiological or autopsy demonstrations of ruptured bridging veins and several authors also assert that bridging veins are too large to rupture due to the forces associated with AHT. There have been several studies on the size, locations and numbers of adult bridging veins and there is one small study of infant bridging veins. However, there are no microscopic studies of infant bridging veins and only a select few ultrastructural investigations of adult bridging veins. Hitherto, it has been assumed that bridging veins from infants and younger children will display the same anatomical characteristics as those in adulthood. At 19 neonatal, infant and young child post-mortem examinations, we macroscopically examined and sampled bridging veins for microscopy. We compared the histology of those samples with bridging veins from an older child and two adults. We demonstrate that adult bridging veins are usually surrounded by supportive meningeal tissue that appears to be lacking or minimally present around the bridging veins of younger children. Neonatal, infant and young children's veins had a free 'bridging' section. Neonatal and infant bridging veins had smaller diameter ranges and thinner walls (some only 5-7 µm) than those seen in older children and adults. Bridging vein walls contained both fine strands of elastic fibers and a more pronounced elastic lamina. The presence of an elastic lamina occurred more frequently in the older age groups These anatomical differences between the veins of adults and young children may help to explain apparent increased vulnerability of neonatal/infant bridging veins to the forces associated with a shaking-type traumatic event.

Fibroblasts' secretome from calcified and non-calcified dermis in Pseudoxanthoma elasticum differently contributes to elastin calcification.

Pseudoxanthoma elasticum (PXE) is a rare disease characterized by ectopic calcification, however, despite the widely spread effect of pro/anti-calcifying systemic factors associated with this genetic metabolic condition, it is not known why elastic fibers in the same patient are mainly fragmented or highly mineralized in clinically unaffected (CUS) and affected (CAS) skin, respectively. Cellular morphology and secretome are investigated in vitro in CUS and CAS fibroblasts. Here we show that, compared to CUS, CAS fibroblasts exhibit: a) differently distributed and organized focal adhesions and stress fibers; b) modified cell-matrix interactions (i.e., collagen gel retraction); c) imbalance between matrix metalloproteinases and tissue inhibitor of metalloproteinases; d) differentially expressed pro- and anti-calcifying proteoglycans and elastic-fibers associated glycoproteins. These data emphasize that in the development of pathologic mineral deposition fibroblasts play an active role altering the stability of elastic fibers and of the extracellular matrix milieu creating a local microenvironment guiding the level of matrix remodeling at an extent that may lead to degradation (in CUS) or to degradation and calcification (in CAS) of the elastic component. In conclusion, this study contributes to a better understanding of the mechanisms of the mineral deposition that can be also associated with several inherited or age-related diseases (e.g., diabetes, atherosclerosis, chronic kidney diseases).

Assessment of the association of myofibroblasts and structural components of the extracellular matrix with histopathological parameters of actinic cheilitis and lower lip squamous cell carcinoma.

BACKGROUND: To evaluate the presence of myofibroblasts (MFs) in the development of lip carcinogenesis, through the correlation of clinical, histomorphometric and immunohistochemical parameters, in actinic cheilitis (ACs) and lower lip squamous cell carcinomas (LLSCCs). METHODS: Samples of ACs, LLSCCs, and control group (CG) were prepared by tissue microarray (TMA) for immunohistochemical TGF-ß, α-SMA, and Ki-67 and histochemical hematoxylin and eosin, picrosirius red, and verhoeff van gieson reactions. Clinical and microscopic data were associated using the Mann-Whitney, Kruskal-Wallis/Dunn, and Spearman correlation tests (SPSS, p < 0.05). RESULTS: ACs showed higher number of α-SMA+ MFs when compared to CG (p = 0.034), and these cells were associated with the vertical expansion of solar elastosis (SE) itself (p = 0.027). Areas of SE had lower deposits of collagen (p < 0.001), immunostaining for TGF-ß (p < 0.001), and higher density of elastic fibers (p < 0.05) when compared to areas without SE. A positive correlation was observed between high-risk epithelial dysplasia (ED) and the proximity of SE to the dysplastic epithelium (p = 0.027). LLSCCs showed a higher number of α-SMA+ MFs about CG (p = 0.034), as well as a reduction in the deposition of total collagen (p = 0.009) in relation to ACs and CG. There was also a negative correlation between the amount of α-SMA+ cells and the accumulation of total collagen (p = 0.041). Collagen and elastic density loss was higher in larger tumors (p = 0.045) with nodal invasion (p = 0.047). CONCLUSIONS: Our findings show the possible role of MFs, collagen fibers, and elastosis areas in the lip carcinogenesis process.

Morphological study of incompetent saphenous veins: apoptosis and ultrastructural changes of smooth muscle cells.

BACKGROUND: Varicose veins affect approximately 25% of people in industrialized countries. METHODS: The study aimed at detecting apoptotic cells and histopathological changes in varicose vein walls. Patients (N.=41) with varicose veins and 30 control group patients were divided into two groups according to their age (younger and older than 50 years). Apoptosis was determined by the TUNEL assay, elastin and collagen IV expression by immunohistochemistry and ultrastructural changes by transmission electron microscopy. RESULTS: The results show that the number of apoptotic cells in the layers of varicose veins increased, in particular in a group of patients aged over 50 years. In the varicose veins as compared to control veins the elastic fibers were found to be thinner, more fragmented and disorderly arranged. Elastin and collagen IV expression was found to decline in the intima and the media of varicose veins in both age groups. Electron microscopy demonstrated hypertrophy and degeneration of smooth muscle cells. Furthermore, cells with ultrastructural feature of apoptosis were noted. In the disorganized and expanded extracellular matrix membrane-bound vesicles, ghost bodies with different size and electron density were observed. Ghost bodies seem to bud off from smooth muscle cells and are likely to be involved in extracellular matrix remodeling as they are seen in close contact with collagen fibers. CONCLUSIONS: The study demonstrates increase of apoptotic cells in the wall of varicose veins along with vein wall structural abnormalities including alterations of smooth muscle cells and decline of elastin and collagen IV expression.

Enhanced Optic Nerve Expansion and Altered Ultrastructure of Elastic Fibers Induced by Lysyl Oxidase Inhibition in a Mouse Model of Marfan Syndrome.

Two major constituents of exfoliation material, fibrillin-1 and lysyl oxidase-like 1 (encoded by FBN1 and LOXL1), are implicated in exfoliation glaucoma, yet their individual contributions to ocular phenotype are minor. To test the hypothesis that a combination of FBN1 mutation and LOXL1 deficiency exacerbates ocular phenotypes, the pan-lysyl oxidase inhibitor ß-aminopropionitrile (BAPN) was used to treat adult wild-type (WT) mice and mice heterozygous for a missense mutation in Fbn1 (Fbn1C1041G/+) for 8 weeks and their eyes were examined. Although intraocular pressure did not change and exfoliation material was not detected in the eyes, BAPN treatment worsened optic nerve and axon expansion in Fbn1C1041G/+ mice, an early sign of axonal damage in rodent models of glaucoma. Disruption of elastic fibers was detected only in Fbn1C1041G/+ mice, which increased with BAPN treatment, as shown by histologic and immunohistochemical staining of the optic nerve pia mater. Transmission electron microscopy showed that Fbn1C1041G/+ mice had fewer microfibrils, smaller elastin cores, and a lower density of elastic fibers compared with WT mice in control groups. BAPN treatment led to elastin core expansion in both WT and Fbn1C1041G/+ mice, but an increase in the density of elastic fiber was confined to Fbn1C1041G/+ mice. LOX inhibition had a stronger effect on optic nerve and elastic fiber parameters in the context of Fbn1 mutation, indicating the Marfan mouse model with LOX inhibition warrants further investigation for exfoliation glaucoma pathogenesis.

Alterations in epidermal stem cells within the pilosebaceous unit in atrophic acne scars.

BACKGROUND: Atrophic acne scarring is a common sequela of inflammatory acne, causing significant problems for affected patients. Although prolonged inflammation and subsequent aberrant tissue regeneration are considered the underlying pathogenesis, the role of epidermal stem cells, which are crucial to the regeneration of pilosebaceous units, remains unknown. OBJECTIVES: To examine the changes occurring in epidermal stem cells in atrophic acne scars. METHODS: Changes in collagen, elastic fibre and human leukocyte antigen (HLA)-DR expression were analysed in normal skin and inflammatory acne lesions at days 1, 3 and 7 after development. The expression of epidermal stem cell markers and proliferation markers was compared between normal skin and mature atrophic acne scar tissue. RESULTS: In acne lesions, inflammation had invaded into pilosebaceous units over time. Their normal structure had been destructed and replaced with a reduced amount of collagen and elastic fibre. Expression of stem cell markers including CD34, p63, leucine-rich repeat-containing G protein-coupled receptor (LGR)6 and LGR5, which are expressed in the interfollicular epidermis, isthmus and bulge of hair follicles, significantly decreased in atrophic acne scar tissue compared to normal skin. Epidermal proliferation was significantly reduced in scar tissue. CONCLUSIONS: These findings suggest that as inflammatory acne lesions progress, inflammation gradually infiltrates the pilosebaceous unit and affects the resident stem cells. This disruption impedes the normal regeneration of the interfollicular epidermis and adnexal structures, resulting in atrophic acne scars.

The prognostic values of plasma desmosines, crosslinking molecules of elastic fibers, in the disease progression of Moyamoya disease.

Moyamoya disease (MMD) is a cerebrovascular disease which is characterized by the chronic progression of steno-occlusive changes at the terminal portion of internal carotid arteries and the development of "moyamoya vessels." Dysregulation of the extracellular matrix is regarded as a key pathophysiology underlying unique vascular remodeling. Here, we measured the concentration of elastin crosslinkers desmosine and isodesmosine in the plasma of MMD patients. We aimed to reveal its diagnostic values of desmosines in the progression of steno-occlusive lesions. The concentrations of plasma desmosines were determined by liquid chromatography-tandem mass spectrometry. The temporal profiles of steno-occlusive lesions on magnetic resonance angiography were retrospectively evaluated, and the correlation between the progression of steno-occlusive changes in intracranial arteries and plasma desmosines concentrations was further analyzed. Plasma desmosines were significantly higher in MMD patients with disease progression compared to MMD patients without disease progression. Also, the incidence of disease progression was higher in MMD patients with plasma desmosines levels over limit of quantitation (LOQ) than those with plasma desmosines levels below LOQ. In conclusion, plasma desmosines could be potential biomarkers to predict the progression of steno-occlusive changes in MMD patients.

Stereological comparison of smooth muscle, collagen, and elastic fibers of the clitoris and glans penis in young adults.

OBJECTIVE: To compare the collagen, elastic fibers, and smooth muscle content of the clitoris and the glans penis in young adults. MATERIALS AND METHODS: The clitoris and the glans penis of six women and six men (mean age 25±3) who died as a result of accidents were excised. The samples were placed under a formaldehyde solution and histologically processed. Masson's trichrome and Weigert's resorcin-fuchsin stain was used to highlight the elastic fibers, smooth muscle, and collagen. Stereological analysis was conducted in 5 random fields of 5 slides for each sample. For statistical analysis, the unpaired t-test was used to compare values between groups, and a value of P<0.05 was considered as significant for all analyses. RESULTS: Stereology revealed a mean smooth muscle content of 35.84±6.46% and 31.64±4.74% for the clitoris and glans penis, respectively, while it also revealed collagen content of 26.11±7.41% and 28.44±3.55% and elastic fibers content of 24.12±4.34% and 30.97±6.13% for the clitoris and glans penis, respectively. The statistical analysis showed no significant differences between them. CONCLUSION: Regardless of anatomical differences, the volumetric density of collagen, elastic fibers, and smooth muscle were similar for the clitoris and glans penis in young adults, a feature possibly explained by their embryology.

Evaluation of microneedling depth of penetration in management of atrophic acne scars: a split-face comparative study.

BACKGROUND: Microneedling is a technique of repeated puncturing or drilling of the skin to induce repair and collagen induction. There are many reported important factors determining the efficacy of microneedling treatment. The extent of injury needed to produce the desired effect in each condition is one of these important factors. OBJECTIVES: We designed the present split-face comparative study to evaluate the use and effectiveness of two different depths of penetration of Dermapen needles in the management of atrophic postacne scars. PATIENTS AND METHODS: The present study involved 14 subjects with atrophic postacne scars. In each patient, both sides of the face were treated with six sessions of microneedling, using Dermapen at 2-week intervals. A split-face study design was performed. The right (Rt) side of the face was treated with Dermapen using 2.5 mm needle length, while the left (Lt) side was treated using 1.5 mm needle length. RESULTS: There was a significantly better percentage of improvement of acne scars on the Rt side of the face compared to the Lt side (P = 0.02) after six sessions. Both sides of the face showed improvement of collagen bundles and elastic fibers characteristics after six sessions. CONCLUSIONS: The use of 2.5 mm depth proved to be more effective both clinically and histologically in the management of atrophic postacne scars.

Qualitative Assessment of Collagen and Elastic Fibers in Oral Submucous Fibrosis (OSMF), OSMF with Dysplasia and Oral Squamous Cell Carcinoma Arising from OSMF: A Histochemical Study.

BACKGROUND: Oral submucous fibrosis (OSMF) is a habit related potentially malignant disorder seen mainly in South Asian people. The malignancy arising from OSMF has been regarded as low grade with better outcome. The present study was orchestrated to histochemically analyze collagen and elastic fibres in OSMF without dysplasia, OSMF with dysplasia and OSMF turning malignant. MATERIALS AND METHODS: 100 cases (80 cases and 20 healthy controls) were included after obtaining clearance from ethical committee. All cases were subjected to Van Gieson staining for collagen and a novel simple method for elastic fibres (Orcein staining). Data were analyzed using SPSS software. RESULTS: Controls showed haphazard arrangement of collagen and elastic fibres. The collagen bundles were parallelly arranged in OSMF without dysplasia and OSMF with dysplasia; the collagen was however haphazard in cases of OSMF turning malignant. As with collagen, elastic fibres were also haphazardly arranged in the control group; in contrast, the elastic fibres were predominantly arranged in a criss-cross pattern in the other study groups. The difference in orientation and density among the groups was statistically significant. CONCLUSION: With advancement of stage there is increased collagenization of OSMF, as the condition acquires dysplastic changes and turns malignant, microenvironment alters resulting in increased activity of collagenases. However, the arrangement of more resistant elastic fibres depicts the better outcome, once OSMF shows malignant transformation, limiting locoregional and distant spread.

Insights into elastic fiber fragmentation: Mechanisms and treatment of aortic aneurysm in Marfan syndrome.

Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutations in fibrillin 1 (FBN1) gene. These mutations result in defects in the skeletal, ocular, and cardiovascular systems. Aortic aneurysm is the leading cause of premature mortality in untreated MFS patients. Elastic fiber fragmentation in the aortic vessel wall is a hallmark of MFS-associated aortic aneurysms. FBN1 mutations result in FBN1 fragments that also contribute to elastic fiber fragmentation. Although recent research has advanced our understanding of MFS, the contribution of elastic fiber fragmentation to the pathogenesis of aneurysm formation remains poorly understood. This review provides a comprehensive overview of the molecular mechanisms of elastic fiber fragmentation and its role in the pathogenesis of aortic aneurysm progression. Increased comprehension of elastic fragmentation has significant clinical implications for developing targeted interventions to block aneurysm progression, which would benefit not only individuals with Marfan syndrome but also other patients with aneurysms. Moreover, this review highlights an overlooked connection between inhibiting aneurysm and the restoration of elastic fibers in the vessel wall with various aneurysm inhibitors, including drugs and chemicals. Investigating the underlying molecular mechanisms could uncover innovative therapeutic strategies to inhibit elastin fragmentation and prevent the progression of aneurysms.

Differentiating morphea from lichen Sclerosus by using multiphoton microscopy combined with U-Net model for elastic fiber segmentation.

This paper describes a methodology to differentiate morphea from lichen sclerosus based on examination with multiphoton microscopy (MPM) composed of two-photon excited fluorescence (TPEF) and second harmonic generation (SHG). Subcellular-resolution images were acquired by MPM from unstained lesion tissues then process spectral analysis to quantify the TPEF and SHG signals. Moreover, U-Net was employed to segment elastic fiber in TPEF images to combine with collagen fiber in SHG images for precise fiber quantification. Predictions of segmentation showed excellent performance on several evaluation indicators. The mIoU, mPA, and F1 score reach 0.8516, 0.9281, and 0.941. The quantitative analysis demonstrated the increase of collagen fibers in morphea compared to that in lichen sclerosus cases. Meanwhile, the great diminution of elastic fiber in the dermis of lichen sclerosus was depicted based on MPM imaging. Thus, MPM was comparable to the histopathological examination and our experimental results accurately distinguish between morphea and lichen sclerosus.

Pseudoxanthoma-elasticum-like changes on the soft palate.

Pseudoxanthoma elasticum (PXE) is an autosomal recessive genetic disorder characterized by aberrant fragmentation and calcification of elastic fibers, leading to characteristic cutaneous, ophthalmic, and cardiovascular manifestations. PXE demonstrates significant phenotypic variability; involvement of the oral mucosa may be the only clue to the diagnosis. Reports on mucous membrane involvement in PXE are scarce. Here, we present a case of PXE-like changes in the oral cavity. A 70-year-old male patient presented with a painless leukoplakic lesion on the soft palate. Biopsy revealed numerous degenerated fibers in the lamina propria. Verhoeff-van Gieson and von Kossa staining confirmed their identity as calcified elastic fibers. A histopathological diagnosis of PXE-like changes was made; the patient was referred to ophthalmology where angioid streaks were visualized fundoscopically. PXE-like changes in the absence of the characteristic genetic mutation have also been reported with or without systemic manifestations. Furthermore, PXE-like changes have been reported in up to 10% of oral biopsy specimens undertaken without clinical suspicion for PXE. Therefore, the significance of such changes in isolation is unclear. Clinicians and pathologists should be aware of the potential oral manifestations of PXE to facilitate prompt diagnosis and subspecialist referral.

Linear focal elastosis.

Linear focal elastosis (LFE) is an uncommon, benign, acquired elastotic condition with uncertain pathogenesis. It is characterized clinically by asymptomatic, multiple, yellowish, elevated, irregularly indurated, striae-like lines or bands distributed horizontally across the lower and middle part of the posterior trunk. The histopathological hallmark of LFE is a focal increase of elastic fibres in the dermis. The differential diagnosis is varied, and striae distensae is the closest mimic of LFE. Response of LFE to treatment is often poor. The focus of this article is to provide insights into this condition for dermatologists.

Papillary dermal elastolysis histopathology mimicking folliculotropic mycosis fungoides.

Papillary dermal elastolysis is a rare acquired disease of the elastic tissue that mainly affects elderly women with a clinical presentation of small firm papules in the neck, the supraclavicular areas and the upper back. Histopathologically, it is characteristic to find a complete or almost complete absence of elastic fibers in the papillary dermis with stains such as orcein or Verhoeff-Van Gieson. We present the case of an adult female patient presenting a clinical picture of years of evolution of elastic skin-colored papules on her neck, occasionally pruritic. Two biopsies were performed. In one of them an inflammatory infiltrate affecting the hair follicles was observed, and she was diagnosed with mycosis fungoides. The other biopsy showed a total absence of elastic fibers in the papillary dermis and was diagnosed as elastolysis of the papillary dermis. In early stages of papillary dermal elastolysis, a perivascular and periadnexal lymphocytic inflammatory infiltrate has been described, as is the case described above. It is important for dermatopathologist to know this atypical but possible presentation, as it may require a differential diagnosis with other entities such as follicular mycosis fungoides.

Perieccrine Coil Elastosis: An Unusual and Previously Unrecognized Aging-Related Phenomenon.

ABSTRACT: Elastic fibers are present as a thin line around the normal secretory coil of eccrine and apocrine glands, although they are virtually imperceptible with hematoxylin-eosin staining. Skin aging is a consequence of intrinsic and extrinsic factors, and glycation and ultraviolet irradiation are involved in this process favoring elastosis. We report an unusual and prominent perieccrine elastosis on the left temple in the vicinity of a basal cell carcinoma in a 78-year old man with type 2 diabetes, dyslipidemia, and hypertension. Very thick multilamellar and tortuous elastic fibers surrounded the eccrine coils. This increased amount of elastic fibers was confirmed by orcein staining as well as amyloid-P and lysozyme immunostaining. Perieccrine coil elastosis is a very unusual phenomenon that to the best of our knowledge has not been reported. Similar to dermal actinic elastosis, the presence of perieccrine coil elastosis in a skin cancer microenvironment might hypothetically promote tumor growth because of the release of elastin-derived peptides.

Specific Overexpression of YAP in Vascular Smooth Muscle Attenuated Abdominal Aortic Aneurysm Formation by Activating Elastic Fiber Assembly via LTBP4.

Abdominal aortic aneurysm (AAA) is a fatal vascular disease. Vascular smooth muscle cells (VSMCs) play a crucial role in the pathogenesis of AAA. Increasing evidence has shown that Yes-associated protein (YAP) is involved in diverse vascular diseases. However, the role of YAP in AAA remains unclear. The current study aimed to determine the role of YAP in AAA formation and the underlying mechanism. We found that YAP expression in VSMCs was markedly decreased in human and experimental AAA samples. Furthermore, VSMC-specific YAP overexpression prevented several pathogenic factor-induced AAA. Mechanistically, YAP overexpression in VSMCs promoted latent transforming growth factor-ß binding protein 4 (LTBP4) expression, an important factor in elastic fiber assembly. Finally, silencing of LTBP4 in VSMCs abolished the protective role of YAP in AAA formation in vivo. Our results suggest that YAP promotes LTBP4-mediated elastic fibril assembly in VSMCs, which mitigates elastin degradation and AAA formation.

[Idiopathic pleuroparenehymal fibroelastosis: five case reports and review of literature].

Objective: To raise the awareness of idiopathic pleuroparenehymal fibroelastosis (iPPFE) through investigating the clinical, radiographic and pathological features. Methods: Five cases of iPPFE proved by pathology. The clinical data were studied respectively, and the relevant literature was reviewed. Results: All the cases of iPPFE were manifested by cough and dyspnea. The patients including 3 males and 2 females, aged from 30 to 70 years Chest CT scan showed pleural thickening, subpleural consolidation in both upper lungs complicated with tractive bronchiectasis.Computed tomography-guided percutaneous lung biopsy or surgical lung were performed and the same pathological showed pleura and subpleural dense elastic and collagen fibers. The elastic fibers stain was also positive,which was consistent with PPFE. One patient received low-dose corticosteroid, two received pirfenidone therapy, the others received no treatment. Three patients were stable during the follow-up. Conclusions: iPPFE has characteristic pathological features. However, the number of clinically reported cases is low due to missed diagnosis or misdiagnosed. Improving the understanding of features of iPPFE is helpful for the dianosis, therapy, and prognosis of this disease.

A Retrospective Study of 105 Patients with Elastolytic Giant Cell Granuloma and a Proposal for a New Clinical Classification.

Elastolytic giant cell granuloma, an idiopathic granulomatous dermatosis, is characterized by annular plaques on sun-exposed areas, and has been termed actinic granuloma or annular elastolytic giant cell granuloma. Many atypical clinical manifestations and lesions involving sun-protected areas have been reported. The aims of this retrospective study of 105 patients were to summarize the clinical and histological features of patients with this condition; to provide evidence for the viewpoint that elastolytic giant cell granuloma is a better term to include all clinical morphological types presenting with elastolysis, elastophagocytosis, and an infiltrate of multinucleated giant cells histologically; and to establish a new clinical classification. The varying clinical manifestations were further categorized into annular, papular, giant, mixed and generalized forms. The pathological manifestations were classified into giant cell, necrobiotic, histiocytic, sarcoidal and mixed patterns. Diabetes mellitus or impaired glucose tolerance were the most commonly identified comorbidities. Oral low-dose corticosteroid may be an effective treatment.