Collagen Core Research Articles

The collagen matrix of the human trabecular meshwork is an extension of the novel pre-Descemet's layer (Dua's layer)

BackgroundThe trabecular meshwork (TM) located at the angle of the anterior chamber of the eye contributes to aqueous drainage. A novel layer in the posterior part of the human cornea...

The nature of collagen in oral submucous fibrosis: A systematic review of the literature

Background: The nature of collagen in the oral potentially malignant disorder of oral submucous fibrosis (OSF) has always been a subject of interest to researchers studying the condition. The type, constitution, and morphology of the collagen has been studied to understand the pathogenesis of the disorder. Aim: The present review attempts to collate literature to assess the changes reported on the nature of collagen in OSF. Materials and Methods: A systematic analysis of literature based on the PRISMA protocol was carried out on studies that analyzed the nature of collagen in OSF. A total of 30 articles were found acceptable for analysis. The reported literature was categorized into histological, immuno-histochemistry (IHC), electron microscopic (EM)/scanning electron microscopic (SEM), biochemical, culture, and genetic studies. Results: Light microscopic studies revealed increased collagen with compaction and condensation as the disease advanced. Polarising microscopy revealed presence of greenish yellow (type I) thick fibers replacing the yellowish orange (type III) thin fibers in the submucosa. Fibrosis originated in the submucosa and subsequently involved the lamina propria as the disease advanced. EM/SEM investigations revealed frayed ends, degeneration of collagen cores. Increased expression of collagen antibodies and total collagen content were observed in IHC and biochemical studies, respectively. Cultured fibroblasts from OSF tend to produce more collagen in comparison to normal fibroblasts indicating a phenotypic change. Increased expression and upregulation of collagen genes were consistent in OSF cases. Conclusion: The collagen deposition in OSF is biochemically normal but quantitatively more. Fibroblast phenotypic change, upregulation of collagen genes, and selective remodeling due to decreased degradation seem to contribute to the increased fibrosis in the disorder.

Utilizing Core–Shell Fibrous Collagen-Alginate Hydrogel Cell Delivery System for Bone Tissue Engineering

Three-dimensional matrices that encapsulate and deliver stem cells with defect-tuned formulations are promising for bone tissue engineering. In this study, we designed a novel stem cell delivery system composed of collagen and alginate as the core and shell, respectively. Mesenchymal stem cells (MSCs) were loaded into the collagen solution and then deposited directly into a fibrous structure while simultaneously sheathing with alginate using a newly designed core-shell nozzle. Alginate encapsulation was achieved by the crosslinking within an adjusted calcium-containing solution that effectively preserved the continuous fibrous structure of the inner cell-collagen part. The constructed hydrogel carriers showed a continuous fiber with a diameter of ~700-1000 μm for the core and 200-500 μm for the shell area, which was largely dependent on the alginate concentration (2%-5%) as well as the injection rate (20-80 mL/h). The water uptake capacity of the core-shell carriers was as high as 98%, which could act as a pore channel to supply nutrients and oxygen to the cells. Degradation of the scaffolds showed a weight loss of ~22% at 7 days and ~43% at 14 days, suggesting a possible role as a degradable tissue-engineered construct. The MSCs encapsulated within the collagen core showed excellent viability, exhibiting significant cellular proliferation up to 21 days with levels comparable to those observed in the pure collagen gel matrix used as a control. A live/dead cell assay also confirmed similar percentages of live cells within the core-shell carrier compared to those in the pure collagen gel, suggesting the carrier was cell compatible and was effective for maintaining a cell population. Cells allowed to differentiate under osteogenic conditions expressed high levels of bone-related genes, including osteocalcin, bone sialoprotein, and osteopontin. Further, when the core-shell fibrous carriers were implanted in a rat calvarium defect, the bone healing was significantly improved when the MSCs were encapsulated, and even more so after an osteogenic induction of MSCs before implantation. Based on these results, the newly designed core-shell collagen-alginate fibrous carrier is considered promising to enable the encapsulation of tissue cells and their delivery into damaged target tissues, including bone with defect-tunability for bone tissue engineering.

Pathology Quiz Case 1

A 10-YEAR-OLD GIRL PRESENTED WITH A 4-month history of a large oropharyngeal mass and a left-side upper neck mass that remained stable in size since its discovery. The patient complained of dysphagia without significant weight loss but denied dyspnea, dysphonia, or otalgia. The patient was otherwise healthy, up-to-date on immunizations, and had no prior tobacco exposure. On examination, a well-mucosalized, nonfluctuant, firm mass was palpable on the left side of the base of the tongue, causing leftward deviation of the tongue. There was also a palpable level II neck mass that was contiguous on bimanual palpation intraorally with no other cervical lymphadenopathy. Computed tomography (CT) of the neck revealed a nonenhancing, well-circumscribed, solid 4.3 2.73-cm mass in the region of the sublingual space and tongue base, displacing the sublingual and submandibular glands. The mass appeared contiguous with the tongue musculature and exhibited several dystrophic calcifications. Magnetic resonance imaging (MRI) with gadolinium was obtained to further characterize the lesion shown in Figure 1. Grossly, the mass was well circumscribed, with a thin capsule, and was firm and pale tan in color. Histopathologic findings of the specimen in hematoxylin-eosin stain are shown at both low and high magnifications (original magnification 10 and 20, respectively) in Figure2 and Figure 3, respectively. In the background, prominent thin-walled capillaries were found on CD34 staining. The collagenous cores stained positive for vimentin and negative for desmin, smooth muscle actin, S-100, CD34, anaplastic lymphoma kinase, and epithelial membrane antigen (EMA). Fluorescence in situ hybridization (FISH) using a FUS gene rearrangement probe applied to formalin-fixed, paraffin-embedded tissues is shown in Figure 4. What is your diagnosis?

Pathology Quiz Case 1

A 72-YEAR-OLD WOMAN PRESENTED WITH A mass in the right side of her neck. The mass, which was located in level III, had initially been noticed 4 months earlier and had been slowly enlarging since then. Physical examination revealed that the mass was superficial, freely mobile, and nontender. The patient’s medical history was remarkable for a diagnosis of tuberculosis, which had previously been treated in China. There was no history of neck trauma or surgery. A computed tomographic scan of the neck with contrast demonstrated a heterogeneous vascular mass (1.8 1.7 1.2 cm) just superficial to the sternocleidomastoid muscle in the right side of the neck. The mass appeared to involve or compress the external jugular vein. A fine-needle aspirate yielded grossly bloody fluid that was nondiagnostic. Subsequently, the mass was excised. On low-power magnification, the lesion was found to be completely contained within a vascular lumen, with regions of hemorrhage and thrombosis (Figure 1). The specimen was composed of papillary processes with a single layer of endothelial cells around a collagen core (Figure 2); it also demonstrated significant hemosiderin staining (Figure 3). The endothelial cells were normal in appearance, without mitotic figures or nuclear atypia (Figure 4). What is your diagnosis?

PF4-Positive Thrombi Adhering to the Ventricles of an Excor-VAD in Patients with HIT II

Background: Thromboembolism is a major complication in patients with ventricular assist devices (VAD). Drug- anticoagulation and the use of biocompatible surfaces such as coating with heparin, aim to reduce thromboembolism in these patients. Administration of heparin can lead to heparin induced thrombocytopenia type II (HIT II) mainly through heparin/platelet factor 4 (HPF4) antibodies. We assessed the presence of PF4-antibodies in VAD-thrombi of patients with heparin-coated VADs and HIT II. Methods: Thrombi (n=6) were obtained from the changed Excor-ventricles of patients with HIT II after BiVAD implantation (Excor, Berlin Heart, Germany). Excor-ventricles were changed after clinical examination and suspicion of thrombi in the polyurethane valves. The thrombi were fixed and processed for immunohistochemical analysis. Expression of PF4-antibodies was assessed by means of a polyclonal rabbit antibody (Anti-PF4 antibody; Abcam, Cambridge, USA). Expression was assessed by two independent observers. Results: Biopsies of all thrombi showed an extreme positive immunoreaction for PF4 (Figure 1). No differences between the different thrombi and localisation (left/right Excor-ventricle) were observed. The thrombi were organised, without lamination of fibrin and cellular layers.[Figure 1]Figure 1: Expression of PF-4 positive thrombocytes (brown staining) inside an organized thrombus. Please observe the disposition of the thrombocytes in the external side of the thrombus, surrounding a collagenous core. Conclusions: Platelet surface expression of PF4 in the thrombi reflects HIT antigen presentation. The physical relationship between the PF4- positive thrombi and the heparin-coated surface suggests that onset of HIT II could be influenced by the immobilized coating-heparin.

Structural analysis of chordae tendineae in degenerative disease of the mitral valve

BackgroundDegenerative disease of the mitral valve (DDMV) is always accompanied by lengthening and/or rupture of chordae tendineae. However, the mechanisms and the mode of chordal rupture remain controversial, and the pathologic anatomy of the apparently healthy chordae has mostly been overlooked. We analyze the structural aspects of both ruptured and intact chordae tendineae in DDMV. Methods and ResultsStructural and ultrastructural microscopic analyses indicate that both the extracellular matrix and the interstitial cells are severely affected. Degenerative chordae show alterations in the synthesis and deposition of collagen and elastin, disorganization of collagen bundles and rupture of collagen fibres, accumulation of proteoglycans and of cellular and vesicular remnants, and cell transformation into a myofibroblast phenotype. Structural disruption makes the spongiosa and the dense collagenous core separate and break. Degeneration of the chordae is segmental, affecting both chordae that are clearly abnormal, and chordae that appear healthy on visual inspection. ConclusionsChanges in both matrix synthesis and degradation disturb the ordered collagen arrangement and modifiy the structural and physical properties of the chordae. Progressive structural disruption of the diseased chordae is the cause of chordal rupture. Mitral surgery corrects the damage, but the underlying causes of DDMV are not corrected. Thus, progression of the disease and affectation of additional chordae may be at the basis of the late complications and the recurrent mitral regurgitation which occurs several years after surgery. Our results indicate that a more aggressive approach to surgery may be needed.

Pathology Quiz Case 1

A 10-YEAR-OLD GIRL PRESENTED WITH A 4-month history of a large oropharyngeal mass and a left-side upper neck mass that remained stable in size since its discovery. The patient complained of dysphagia without significant weight loss but denied dyspnea, dysphonia, or otalgia. The patient was otherwise healthy, up-to-date on immunizations, and had no prior tobacco exposure. On examination, a well-mucosalized, nonfluctuant, firm mass was palpable on the left side of the base of the tongue, causing leftward deviation of the tongue. There was also a palpable level II neck mass that was contiguous on bimanual palpation intraorally with no other cervical lymphadenopathy. Computed tomography (CT) of the neck revealed a nonenhancing, well-circumscribed, solid 4.3 2.73-cm mass in the region of the sublingual space and tongue base, displacing the sublingual and submandibular glands. The mass appeared contiguous with the tongue musculature and exhibited several dystrophic calcifications. Magnetic resonance imaging (MRI) with gadolinium was obtained to further characterize the lesion shown in Figure 1. Grossly, the mass was well circumscribed, with a thin capsule, and was firm and pale tan in color. Histopathologic findings of the specimen in hematoxylin-eosin stain are shown at both low and high magnifications (original magnification 10 and 20, respectively) in Figure2 and Figure 3, respectively. In the background, prominent thin-walled capillaries were found on CD34 staining. The collagenous cores stained positive for vimentin and negative for desmin, smooth muscle actin, S-100, CD34, anaplastic lymphoma kinase, and epithelial membrane antigen (EMA). Fluorescence in situ hybridization (FISH) using a FUS gene rearrangement probe applied to formalin-fixed, paraffin-embedded tissues is shown in Figure 4. What is your diagnosis?

Controlled Delivery of Gentamicin Antibiotic from Bioactive Electrospun Polylactide‐Based Ultrathin Fibers

AbstractThe purpose of this study was to generate ultrathin fibers based on polylactide (PLA) biopolyester with antimicrobial controlled release capacity to treat bacterial infections. To achieve this objective, gentamicin antibiotic was encapsulated into pure PLA fibers, a blend of PLA–collagen and coaxial fibers containing a skin of PLA and a core of collagen using the electrospinning technique. The morphology of the gentamicin‐loaded fibers and the antibiotic distribution within the fibers were examined by SEM and TEM. The drug delivery profile of the different electrospun fibers was analyzed using a spectrophotometric method. The performance for treating common possible post‐surgical infections was investigated against Staphylococcus epidermis, Pseudomonas aeruginosa and Escherichia coli. The morphology of the electrospun fibers as well as the hydrophilicity of the polymer blends ultimately determined the antibiotic release characteristics. The results indicated that such drug‐loaded fibers can serve as advanced delivery platforms with strong and timing controllable antibacterial properties.

A New Mechanism for Pillar Formation during Tumor-Induced Intussusceptive Angiogenesis: Inverse Sprouting

One of the hallmarks of intussusceptive angiogenesis is the development of intraluminal connective tissue pillars. The exact mechanism of pillar formation has not yet been elucidated. By using electron and confocal microscopy, we observed intraluminal nascent pillars that contain a collagen bundle covered by endothelial cells (ECs) in the vasculature of experimental tumors. We proposed a new mechanism for the development of these pillars. First, intraluminal endothelial bridges are formed. Second, localized dissolution of the basement membrane occurs and a bridging EC attaches to a collagen bundle in the underlying connective tissue. A pulling force is then exerted by the actin cytoskeleton of the ECs via specific attachment points, which contain vinculin, to the collagen bundle, resulting in suction and subsequent transport of the collagen bundle into and through the vessel lumen. Third, the pillar matures through the immigration of connective tissue cells and the deposition of new collagenous connective tissue. The proposed simple mechanism generates a connection between the processes of endothelial bridging and intussusceptive angiogenesis and identifies the source of the force behind pillar formation. Moreover, it ensures the rapid formation of pillars from pre-existing building blocks and the maintenance of EC polarity. To describe it, we coined the term inverse sprouting.

Mussel collagen molecules with silk-like domains as load-bearing elements in distal byssal threads

Mechanically stressed biological materials like tendon, spider silk or mussel byssal threads are typically composite materials comprising multi-domain proteins, in which molecular building blocks contribute to overall material function. Mussel byssal threads are the anchorage of sessile mytilid mussels, which withstand recurring external loads from waves and tides. A single thread is elastic and ductile proximally, while the distal portion exhibits an extraordinary stiffness and toughness with a transient gradient of both mechanical features along the thread. The main components of byssal threads include a set of various collagen-like structural proteins (preCols) consisting of a collagenous core sequence flanked by globular domains. Here, structural analysis using polarized Fourier-transform infrared spectroscopy (FTIR) on stretched distal portions of mussel byssal threads determines the impact of external linear load on various molecular moieties. It is concluded that the preCol collagenous core domain is the main load-bearing element in distal byssal threads, while polyalanine beta-sheets in the flanking domains, similar to those found in spider silk proteins, provide high stiffness at low strains. Load dissipation is mediated by domain stretching of amorphous glycine-rich helical moieties followed by complete unfolding of the preCol flanking domains.

Cutaneous neuroblastoma‐like schwannoma: a report of two cases, one with a plexiform pattern, and a review of the literature

Cutaneous schwannomas in their classical form are readily identified histologically. A number of variants, including ancient, cellular, epithelioid, plexiform, microcystic and neuroblastoma-like, may cause diagnostic difficulty and rarely be confused with malignancy. Neuroblastoma-like schwannoma was first described by Goldblum et al. in 1994, and very few cases have since been reported. It is a benign sporadic neoplasm with no reported association with neurofibromatosis, and is characterized histologically by small round lesional cells surrounding collagenous cores forming rosette-like structures. The differential diagnosis includes other lesions with the formation of rosettes including neuroblastoma, low-grade fibromyxoid sarcoma and dendritic cell neurofibroma, as well as primitive neuroectodermal tumors and rare malignant transformation in a schwannoma. We describe two further cases of this rare entity and review the literature on the subject. Our first case additionally has a plexiform multinodular pattern, a feature described in only one previous report.

Immunosuppression-Related Fibroproliferative Polyps: A Substantial Subset of Acquired Pediatric Mucocutaneous Polyps

A distinct group of fibroproliferative polyps of the tongue arising in immunosuppressed children and often associated with chromosomal breakpoints at chromosomes 9p34 or 22q11 was recently described. Based on this finding, we reviewed fibroepithelial polyps arising in nonlingual sites in the pediatric population to investigate a possible relationship with immunosuppression. We identified 8 fibroepithelial polyps arising in 6 immunosuppressed patients (4 males and 2 females, median age 17 years) in a wide range of mucocutaneous sites. Histologic features were identical to the common fibroepithelial polyp, or skin tag, with a variably collagenous fibrovascular core covered by unremarkable squamous epithelium. No viral cytopathic changes were identified in any case. Although cytogenetic studies were not performed on any of the biopsy material, 1 patient had a constitutional deletion of chromosome 22q11. We suggest that there may be a relationship between these polyps and the previously described tongue lesions and that immunosuppression may be an important factor in their pathogenesis.

Abstract 3578: Local Atherosclerotic Plaques Hide Information That Is Predictive For The Occurrence Of Adverse Cardiovascular Events And Will Help To Identify The Vulnerable Patient: A Prospective Cohort Study In 667 Patients.

Introduction Atherosclerosis is a systemic disease and the risk for ischemic events in any vascular bed increases when one arterial bed has been affected. It could be speculated that atherosclerotic lesions within the vascular bed share common denominators that destabilize multiple atherosclerotic lesions and increase risk for a subsequent cardiovascular event. We hypothesized that atherosclerotic plaques hide a cellular and molecular fingerprint that is shared by many plaques within the same individual, and that some of these characteristics would be predictive for the occurrence of clinical events due to progression of atherosclerotic disease. Methods Atherosclerotic specimens were collected after carotid endarterectomy and patients underwent clinical follow-up for the duration of 3 years. This first report summarizes the results of a study which investigated the predictive value of histological examination atherosclerotic plaques (macrophage and smooth muscle cell infiltration, collagen, calcifications, thrombus and lipid core) for the occurrence of future adverse cardiovascular events. Results A total of 164 (24.7%) of 667 patients reached the composite primary endpoint of myocardial infarction [n=11], PCI [n=14], CABG [n=6] cardiovascular death [n=12], stroke [n=24], cerebral bleeding [n=14], aneurysm surgery [n=8], peripheral artery surgery [n=64], non cardiovascular death [n=11]. The extent of macrophage or smooth muscle cell infiltration, collagen, calcification and lipid core size within the plaque did not predict systemic adverse cardiovascular events during follow up [p>0.20]. However, the presence of thrombus in the dissected plaque was strongly positively associated with reaching the primary endpoint [Cox Regression: Hazard ratio = 1.6; 95% Confidence interval = 1.1 – 2.5]. Conclusion This atherosclerotic biobank with a longitudinal study design allows identifying local plaque markers related with progression of atherosclerotic disease in the entire vascular system. For the first time we show proof of concept that local plaques hide information that may help to identify the vulnerable patient who is likely to suffer a cardiovascular event.

Abstract 2994: Atherosclerotic Plaque Histology Predicts Restenosis after Carotid Endarterectomy: a Prospective Cohort Study in 500 Patients.

Introduction: Many studies have addressed clinical and angiographic risk factors for restenosis development after vascular interventions, but the composition of the atherosclerotic plaque at the intervention site has not been studied as a determinant of luminal re-narrowing after intervention. The aim of this study was to investigate the association between atherosclerotic plaque histology at baseline and restenosis development after carotid endarterectomy. Methods: Patients undergoing carotid endarterectomy were included in a longitudinal vascular biobank study. After surgical excision, the plaques were subjected to histological examination. The patients were prospectively followed-up with duplex ultrasound to assess restenosis (cut-off points: >50% and >70% renarrowing) one year after the intervention. The risk of restenosis was related to predefined plaque histological characteristics (macrophage and smooth muscle cell infiltration, collagen, calcifications, intra-plaque bleeding, luminal thrombus and lipid core size) adjusted for clinical characteristics (multivariable logistic regression analysis). Measurements of vessel diameter and intima-media thickness were performed using B-mode ultrasound in a subgroup of patients to discriminate between the roles of geometric vascular remodeling and neointima formation during follow-up. Results: In 500 consecutive patients (April 2002 – April 2007), plaque macrophage infiltration and a large lipid core were strongly associated with decreased risk of >50% restenosis (adjusted odds ratio = 0.43 [0.26 – 0.70]; 0.38 [0.19 – 0.70]) and >70% restenosis during follow-up (adjusted odds ratio = 0.36 [0.18 – 0.74]; 0.42 [0.17–1.03]), independent of clinical characteristics. The other histological characteristics were not related with restenosis. Duplex measurements (n=50) showed that vessels holding macrophage rich plaques revealed increased expansive geometric vascular remodeling during 1 year follow-up (+1.19 mm [0.03 – 2.36]). Conclusions: The absence of plaque macrophages and lipid core are powerful independent predictors of restenosis development after carotid endarterectomy. Plaque composition is linked with restenosis via geometric vascular remodeling.

Matrix metalloproteinase induction in fibrosis and fibrotic nodule formation due to silica inhalation

Matrix metalloproteinases (MMPs) are the principle enzymes that initiate degradation of collagen. We examined the role of MMPs during alveolar wall fibrosis and fibrotic nodule formation from silica exposure. Rats were exposed to filtered air or 15 mg/m(3) silica by inhalation for 5 days/wk, 6 h/day. Lungs were preserved by intratracheal instillation of fixative at 20, 40, 60, 79, and 116 days of exposure. Additional groups were fixed after 20, 40, and 60 days of exposure followed by 36 days of recovery. The number of nodules, defined by a collagenous core and a bounding cell layer detached from the alveolar wall, was determined by morphometry. Lungs showed increased alveolar wall collagen and fibrotic nodules at 79 and 116 days of exposure with increased collagenase and gelatinase activity. The number of nodules per lung in exposed groups increased from 619 +/- 447 at 40 days to 13,221 +/- 1,096 at 116 days (means +/- SE, n = 5). No nodules were seen in control lungs. Silica-exposed rats with a 36-day recovery in filtered air showed enhanced MMP activity over exposure to silica for the same duration with no recovery. MMP-2 and MMP-9 were significantly elevated in alveolar macrophages after 40-day exposure. Stromelysin expression was demonstrated in alveolar macrophages and cells within fibrotic nodules. TIMP-1 expression was not significantly altered. In summary, MMP activity was upregulated at 40 days of silica exposure and progressively increased during ensuing fibrotic responses. Early expression of stromelysin was found in fibrosing alveolar walls and fibrotic nodules.

Giant bent-core mesogens in the thread forming process of marine mussels.

In marine mussels (Mytilus), byssal threads are made in minutes from prefabricated smectic polymer liquid crystals by a process resembling reaction injection molding. The mesogens in these arrays are known to be natural block copolymers with rodlike collagen cores. Using atomic force microscopy, it was shown that these collagenous mesogens are bent-core or banana-shaped in a manner that is consistent with and predictable from their amino acid sequence. The overall bend angle in preCOL-NG in Mytilus galloprovincialis is about 130 degrees. The mesogens have a center-to-center separation of approximately 22 nm and a length of 200 nm. It is evident that the smectic structure of the prefabricated mesophases remains largely intact over 1-3 microm distances in the molded fibers and is presumably locked in place during molding by cross-linking. Like the smectic liquid crystals of many synthetic banana mesogens, the collagenous mesogens of the byssal threads exhibit SmC(2) symmetry with a characteristic tilt of 24.6 degrees. At about 100% extension, this tilt is considerably reduced and the globular end domains are no longer visible presumably because they have been unraveled.

Characterization of statically loaded tissue-engineered mitral valve chordae tendineae.

Chordae tendineae are essential to the proper function of the mitral valve. Native chordae contain a dense collagenous core and an outer elastin sheath. We have been using the principle of directed collagen gel shrinkage to fabricate tissue-engineered mitral valve chordae. Because the microstructure of biologic tissues determines their mechanical behavior, the morphology of collagen and elastin in tissue-engineered chordae should mimic that of native chordae. The objective of this study, therefore, was to examine the morphology of our tissue-engineered constructs in comparison to native chordae. A collagen-cell suspension was cast into silicon rubber wells with microporous anchors at the ends and cultured in an incubator. The anchors allowed shrinkage to occur only transverse to the long axis of the wells, thus creating highly aligned collagen fibril constructs. The collagen constructs were cultured for 8 weeks and characterized mechanically, histologically, and biochemically at different culture time points. Histologic sections showed that in all mature constructs collagen fibers were oriented parallel to the long axis of the constructs. At the edge of the tissue collagen fibers were in general straight, whereas in the middle of the tissue they were wavy. Transmission electron microscopy showed a progressive increase in the density and longitudinal orientation of collagen fibrils with culture time. Light and scanning electron microscopy showed the presence of an elastin sheath around the collagen core. Immunostaining demonstrated that smooth muscle cells differentiate during tissue development and TUNEL assay showed that cells in the interior of the constructs undergo apoptosis. This study has demonstrated that collagen-cell constructs, with material properties and microstructure similar to native mitral valve chordae, can be developed using static culture.

Hyalinizing Spindle Cell Tumor with Giant Rosettes: A Case Report

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) is characterized by both giant rosette-like structures with collagen cores sparsely distributed throughout the tumor and fibromyxoid stroma. It is a rare low-grade sarcoma with indolent behavior, and wide excision with long-term follow-up is the best treatment. Although originally considered a distinct entity, it is now regarded as a variant of low-grade fibromyxoid sarcoma. We present a case of HSCTGR arising in the deep soft tissue of the left knee in a 50-year-old woman and provide a brief review of the literature for comparison.

Hyalinizing Spindle Cell Tumor with Giant Rosettes and Low-grade Fibromyxoid Sarcoma: An Immunohistochemical and Ultrastructural Comparative Investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.