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Science Advances Nov 2022The fibrocartilage presented on the joint surface was caused by cartilage injury or degeneration. There is still a lack of effective strategies for fibrocartilage. Here,...
The fibrocartilage presented on the joint surface was caused by cartilage injury or degeneration. There is still a lack of effective strategies for fibrocartilage. Here, we hypothesized that the fibrocartilage could be viewed as a raw material for the renewal of hyaline cartilage and proposed a previously unidentified strategy of cartilage regeneration, namely, "fibrocartilage hyalinization." Cytoskeleton remodeling plays a vital role in modifying the cellular phenotype. We identified that microtubule stabilization by docetaxel repressed cartilage fibrosis and increased the hyaline cartilage extracellular matrix. We further designed a fibrocartilage-targeted negatively charged thermosensitive hydrogel for the sustained delivery of docetaxel, which promoted fibrocartilage hyalinization in the cartilage defect model. Moreover, the mechanism of fibrocartilage hyalinization by microtubule stabilization was verified as the inhibition of Sparc (secreted protein acidic and rich in cysteine). Together, our study suggested that articular fibrocartilage-targeted therapy in situ was a promising strategy for hyaline cartilage repair.
PubMed: 36399569
DOI: 10.1126/sciadv.abn8420 -
Modern Pathology : An Official Journal... May 2019Bevacizumab is a humanized monoclonal IgG1 antibody, which neutralizes vascular endothelial growth factor and is used for treating multiple cancer types. As a known and...
Bevacizumab is a humanized monoclonal IgG1 antibody, which neutralizes vascular endothelial growth factor and is used for treating multiple cancer types. As a known and frequent adverse event, this therapy can lead to renal damage including proteinuria and nephrotic syndrome. In a retrospective approach, we analyzed 17 renal biopsies from patients receiving bevacizumab treatment. We observed a distinctive histopathological pseudothrombotic pattern different from the previously reported thrombotic microangiopathy. Since this pattern includes some features similar to acute and chronic thrombotic microangiopathy, focal segmental glomerulosclerosis and cryoglobulinemic membranoproliferative glomerulonephritis, biopsies with these diagnoses were included for comparison. Clinical, laboratory, light microscopic, immunohistochemical (including a proximity ligation assay), proteomic and electron microscopic features were assessed. Nephrotic syndrome was present in 15 of the 17 bevacizumab-treated patients. All 17 displayed a patchy pattern of variably PAS-positive hyaline pseudothrombi occluding markedly dilated glomerular capillaries in their biopsies. Mass spectrometry-based proteome analysis revealed a special protein pattern demonstrating some features of thrombotic microangiopathy and some of cryoglobulinemic glomerulonephritis, including a strong accumulation of IgG in the pseudothrombi. Proximity ligation assay did not show interaction of IgG with C1q, arguing for accumulation without classic pathway complement activation. In contrast to thrombi in thrombotic microangiopathy cases, the hyaline pseudothrombi did not contain clusters of CD61-positive platelets. Electron microscopy of bevacizumab cases did not show fibrin polymers or extensive loss of podocyte foot processes. Even though cases of bevacizumab-associated microangiopathy share some features with thrombotic microangiopathy, its overall histopathological pattern is quite different from acute or chronic thrombotic microangiopathy cases. We conclude that bevacizumab therapy can lead to a unique hyaline occlusive glomerular microangiopathy, likely arising from endothelial leakage followed by subendothelial accumulation of serum proteins. It can be diagnosed by light microscopy and is an important differential diagnosis in cancer patients with nephrotic syndrome.
Topics: Adult; Aged; Angiogenesis Inhibitors; Antineoplastic Agents, Immunological; Bevacizumab; Biomarkers; Female; Glomerulonephritis, Membranoproliferative; Glomerulosclerosis, Focal Segmental; Humans; Hyalin; Kidney Glomerulus; Male; Middle Aged; Nephrotic Syndrome; Retrospective Studies; Thrombotic Microangiopathies
PubMed: 30552416
DOI: 10.1038/s41379-018-0186-4 -
Cancer Jun 2016Salivary gland cancers are an incredibly heterogeneous group of tumors that include 24 histologically distinct tumor types. The use of new genetic methods has paved the... (Review)
Review
Salivary gland cancers are an incredibly heterogeneous group of tumors that include 24 histologically distinct tumor types. The use of new genetic methods has paved the way for promising advancements in our understanding of the molecular biology underlying each type of tumor. The objective of this review was to highlight common oncogenes, tumor suppressor genes, and cytogenetic and epigenetic changes associated with the most common tumor types: mucoepidermoid carcinoma, adenoid cystic carcinoma, salivary duct carcinoma, mammary analogue secretory carcinoma, hyalinizing clear cell carcinoma, carcinoma ex pleomorphic adenoma, and acinic cell carcinoma. Recent insights into the pathogenesis of each cancer subtype have helped better define and classify these tumors. Further research in salivary gland cancers should focus on determining the key genes involved in the tumorigenesis of each distinct malignancy and identifying individualized chemotherapies directed at these targets. Cancer 2016;122:1822-31. © 2016 American Cancer Society.
Topics: Animals; Humans; Salivary Gland Neoplasms
PubMed: 26928905
DOI: 10.1002/cncr.29890 -
Modern Pathology : An Official Journal... Jan 2016This article reviews the salient features of variants of endometrioid carcinoma (ECa) that can pose a diagnostic challenge and/or are associated with unique... (Review)
Review
This article reviews the salient features of variants of endometrioid carcinoma (ECa) that can pose a diagnostic challenge and/or are associated with unique clinicopathological findings. Variants with distinct architectural and cytologic features include the following: (1) ECa with a villoglandular pattern (tumor with finger-like papillae lined by bland cells with a tendency for vascular/lymphatic invasion and lymph node metastasis once this pattern is seen within the myoinvasive component); (2) papillary ECa of intermediate grade (grade 2) (tumor that can be mistaken for serous carcinoma, as it contains papillae showing slightly irregular contours, moderately atypical cells, and it is associated with vascular/lymphatic invasion/lymph node metastasis, but with common association with mucinous metaplasia, MELF (microcystic, elongated, and fragmented) pattern of invasion, and wild p53 expression); (3) ECa with non-villous papillae (tumor containing pseudopapillae within glands with bland-appearing cytology commonly associated with abortive squamous differentiation and otherwise not different from usual ECa); (4) ECa with microglandular-like pattern (tumor that mimics microglandular hyperplasia of the cervix, often lacking the typical appearance of microglandular hyperplasia and showing Ki-67 index >10%, strong CD10 expression, and negative PAX-2, p63, and CD34); and (5) ECa with sex cord-like formations and hyalinization (tumor with interconnected cords and nests of bland epithelioid and spindled cells that merge with a typical component of low-grade ECa, usually associated with squamous differentiation and hyalinization). This tumor should be distinguished from carcinosarcoma and, in contrast to the latter, it shows nuclear β-catenin expression, ER/PR and patchy p16 positivity, tends to present at a low stage, and has a favorable prognosis and (6) dedifferentiated ECa (tumor showing a low-grade ECa juxtaposed to an undifferentiated carcinoma-the latter characterized by variably sized monotonous, often non-cohesive cells with brisk mitotic activity and usually arranged in sheets). Undifferentiated carcinoma tends to be negative for PAX8 and ER/PR with variable expression of keratins and can be associated with microsatellite instability (may be part of Lynch syndrome). Variants with distinct cytological features include the following: (1) ECa with clear cells (tumors with clearing due to 'clear' (glycogenated) squamous cells, distinct vacuoles, or not otherwise specified. EC with clear cells should be distinguished from clear cell carcinoma by the absence of the variety of architectural patterns, lack of cuboidal/flattened/hobnail cells, and lack of degree of atypia usually detected in clear cell carcinoma. In addition, they are ER/PR positive and Napsin A and p504S negative in contrast to clear cell carcinoma); (2) ECa with spindle cells (tumor with transition from spindle cells to the glandular component of a low-grade ECa. The spindle cells are keratin, ER/PR, and patchy p16 positive and show wild-type p53 expression); (3) ECa with mucinous differentiation (this tumor can be mistaken for a cervical adenocarcinoma, as they have overlapping features. Expression of ER/PR and vimentin in the context of a negative or patchy p16 positivity and the absence of high-risk HPV allows a correct diagnosis).
Topics: Carcinoma, Endometrioid; Endometrial Neoplasms; Female; Humans; Ovarian Neoplasms
PubMed: 26715172
DOI: 10.1038/modpathol.2015.142 -
Journal of Lower Genital Tract Disease Jul 2021The aim of the study was to identify whether erosive lichen sclerosus (LS) is a distinct clinicopathologic subtype.
OBJECTIVE
The aim of the study was to identify whether erosive lichen sclerosus (LS) is a distinct clinicopathologic subtype.
MATERIALS AND METHODS
The pathology database was searched for "erosion," "erosive," "ulcer," and "lichen sclerosus." Inclusion criteria were histopathologic diagnosis of LS and erosion or ulcer overlying a band of hyalinization and/or fibrosis. Exclusions were concurrent neoplasia and insufficient tissue. Histopathologic review documented site, epithelial thickness, adjacent epidermal characteristics, infiltrate, and dermal collagen abnormality. Clinical data included demographics, comorbidities, examination findings, microbiologic results, treatment, and response.
RESULTS
Ten examples of erosive LS and 15 of ulcerated LS occurred in 24 women with a mean age of 67 years. Ulcerated LS was associated with diabetes and nontreatment at time of biopsy. Clinicians identified red patches in all but 1 case of erosive LS. Ulcerated LS was documented as fissure, ulcer, or white plaque, with 8 (53%) described as lichenified LS with epidermal breaches. Erosive LS favored hairless skin with normal adjacent stratum corneum sloping gently into erosion, whereas most ulcers in LS had an abrupt slope from hair-bearing skin. All cases were treated with topical steroids; 2 patients with erosive LS and 10 with ulcerated LS also had oral antifungals, topical estrogen, antibiotics, and/or lesional excision. Treatment yielded complete resolution in 50%.
CONCLUSIONS
Erosive LS is an unusual clinicopathologic subtype characterized by red patches on hairless skin seen microscopically as eroded epithelium overlying a band of hyalinized or fibrotic collagen. In contrast, ulcerated LS is usually a traumatic secondary effect in an uncontrolled dermatosis.
Topics: Aged; Female; Humans; Lichen Sclerosus et Atrophicus; Middle Aged; Vulvar Lichen Sclerosus
PubMed: 33859124
DOI: 10.1097/LGT.0000000000000607 -
Frontiers in Medicine 2022To identify the pathological classification of benign ureteral strictures according to the histological features and explore the relationship between various...
OBJECTIVE
To identify the pathological classification of benign ureteral strictures according to the histological features and explore the relationship between various pathological types and inflammatory cells, fibroblasts, and collagen.
PATIENTS AND METHODS
Thirty one specimens from patients diagnosed with ureteral strictures between 2013 and 2021 were included and classified according to the histopathological characteristics. The number of fibroblasts and inflammatory cells was counted, and the proportion of type I and type III collagen in ureteral stricture tissues was detected by picrosirius red staining.
RESULTS
We identified three types of benign ureteral strictures in 31 specimens: inflammatory cell infiltration ( = 10, 32%), fibroplasia ( = 14, 45%), and hyalinization ( = 7, 23%), with significant differences in obstruction history and hydronephrosis grades among the three types. The number of inflammatory cells (lymphocytes, neutrophils and eosinophils) was significantly lower in hyalinization ureteral strictures than in the other two types ( < 0.05). The number of foreign-body giant cells associated with foreign-body reactions increased significantly in suture-induced ureteral strictures ( < 0.05). Fibroplasia type had the largest number of fibroblasts, whereas the other two types had smaller numbers. The results of type I and III collagen analysis showed that type I and III collagen were the most abundant in hyalinization among all ureteral stricture types ( < 0.05). Compared to ureteral strictures, the content of type I and III collagen in atresia increased significantly ( < 0.05).
CONCLUSION
Common pathological types of benign ureteral strictures include inflammatory cell infiltration, fibroplasia, and hyalinization. Changes in type I and III collagen, inflammatory cells, and fibroblasts in different pathological types may be related to the progression of ureteral strictures.
PubMed: 35872768
DOI: 10.3389/fmed.2022.916145 -
Pneumologie (Stuttgart, Germany) Jan 2015Benign lesions as pulmonary hyalinizing granuloma may mimic a malign disease. A 63-year old patient complained dyspnea and a weight loss of 30 kg. CT-thorax scans...
Benign lesions as pulmonary hyalinizing granuloma may mimic a malign disease. A 63-year old patient complained dyspnea and a weight loss of 30 kg. CT-thorax scans showed a destructive and infiltrative pulmonary process with pleural thickening. Histologic examination of transbronchial and transthoracic biopsies as well as of biopsies taken by minithoracotomy was not conclusive. Due to further progression the patient underwent a left-sided pleuropneumonectomy despite a VO2 peak of 9 ml/kg/min. Histology revealed DIP-like infiltrations, a histiocytic reaction and hyaline granulomas. Among less than 100 published cases of pulmonary hyaline granuloma a comparable rapid progression with a total functional loss of the affected lung is not reported. Mostly hyalinizing granuloma presents with infiltrations, which may mimic lung cancer, or nodular lesions, partly with cavitations or calcifications. The etiology is unknown, a persistent immunologic response to an antigenic stimulus is discussed. Associations with infections, lymphomas, amyloidosis or IgG4-related disease are reported. Some cases have features of multifocal fibrosis. In the case reported none of these associations could be found. The prognosis of pulmonary hyaline granuloma is regarded as benign. There is no effective treatment yet. Once the diagnosis has been established a conservative approach as well as a resection of nodules and a therapeutic attempt with steroids are an option. Extensive resections as pleuropneumonectomy are an exception.
Topics: Diagnosis, Differential; Granuloma, Respiratory Tract; Humans; Male; Middle Aged; Pneumonectomy; Pulmonary Fibrosis; Radiography; Treatment Outcome
PubMed: 25599140
DOI: 10.1055/s-0034-1391218 -
Acta Stomatologica Croatica Mar 2020Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive genetic disorder characterized by accumulation of hyalinized fibrous tissue with cutaneous, mucosal,... (Review)
Review
Hyaline fibromatosis syndrome (HFS) is a rare autosomal recessive genetic disorder characterized by accumulation of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular, and systemic involvement. The condition is caused by a mutation of ANTXR2 gene that results in a faulty synthesis of a transmembrane protein which leads up to excessive deposition of hyaline material in extracellular space. The first signs may be present at birth or appear during infancy, and joint stiffness is the first, most common, symptom. Other manifestations include joint contractures, hyperpigmented macules over bony prominences of the joints, and gingival hypertrophy. The symptom that raises suspicion of HFS is present later, along with subcutaneous growths. The progression of the disease includes enteropathy with extensive protein loss, chronic diarrhea and frequent infections. We present a case of a five-year-old girl with severe gingival hypertrophy that caused difficulties in eating and speaking. To the best of our knowledge, this is also the first patient in Croatia with a confirmed ANTXR2 gene mutation described in the literature.
PubMed: 32523159
DOI: 10.15644/asc54/1/8 -
International Journal of Clinical and... 2014Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most frequently occur at the cerebellopontine angle. This morphologic study examines...
Schwannomas or neurilemmoma are benign peripheral nerve sheath tumors, which most frequently occur at the cerebellopontine angle. This morphologic study examines vascular alterations in these tumors, comparing them to other benign spindle cell neoplasms of the nervous system, while correlating these findings with evidence of vascular permeability. Thirty-four nervous system spindle cell neoplasms, sixteen schwannomas, nine fibroblastic/transitional meningiomas and nine peripheral neurofibromas were stained with H&E, Prussian-blue stain, and immunoreacted for factor VIII-related antigen and interstitial albumin. Schwannomas had focal clusters of vascular proliferation including groups of small thin-walled vessels, as well as larger vessels with extensive hyalinization. Neurofibromas and meningiomas almost uniformly had modest numbers of well-defined, thin walled individual vessels. Free hemosiderin and hemosiderin-laden macrophages were frequently identified in schwannomas. Prussian-blue stain for iron revealed focal or fairly widespread positivity in almost all schwannomas, only one meningioma and none of the neurofibromas. Immunoreaction for albumin demonstrated leakage of vascular proteins into the interstitium confirming tumor vessel permeability in schwannomas. Neither neurofibromas nor meningiomas displayed any detectable interstitial albumin. The above findings confirm a degree of reactive proliferation of vessels in schwannoma along with functional deficits in their vascular integrity with permeability to protein and blood. The presence of hyalinized vessels, hemosiderin, both free and within macrophages, and more readily evident Prussian blue staining, may provide an additional diagnostic clue in discriminating between histologically similar spindle cell lesions. The study however raises the possibility that these changes likely precede or facilitate the degenerative 'ancient change' seen in some schwannoma.
Topics: Biomarkers, Tumor; Humans; Nerve Sheath Neoplasms; Neurilemmoma
PubMed: 25120781
DOI: No ID Found -
Journal of Oral Biology and... 2021Hyalinization is a process of conversion of stromal connective tissue into a homogeneous, acellular translucent material. Nevertheless, hyalinization could provide... (Review)
Review
BACKGROUND
Hyalinization is a process of conversion of stromal connective tissue into a homogeneous, acellular translucent material. Nevertheless, hyalinization could provide insights into the biologic behaviour and prognosis of pathological lesions. Few studies with limited sample size have intended to assess the correlation of hyalinization and biologic behaviour in oral lesions.
AIM
The current review aims to comprehensively appraise the mechanism of hyalinization in pathological oral hyalinizing lesions (OHL) and its clinical implications with emphasis on differential stains employed.
METHODS
An electronic search was performed in the PubMed database (from year 2000-2020) using the keywords "special stains in oral hyalinizing lesions", "significance of hyalinization in oral lesions" and "hyalinization and biologic behaviour". Original research articles analyzing the effect of hyalinization on biologic characteristics of the lesion were evaluated in this review. Narrative review articles that provided insights into the mechanism of hyalinization and maturity of collagen fibers were also considered for analysis.
CONCLUSION
The presence of hyalinization does seem to have a significant effect on the biologic behaviour of pathological lesions. There is substantial scope to further investigate the process of hyalinization on larger samples and its correlation with the aggressive behaviour of OHLs. Special stains and advanced investigations such as immunohistochemistry for stromal markers would define the nature of hyalinized material and validate the correlation.
CLINICAL SIGNIFICANCE
The prediction of the biologic behaviour of a lesion established through assessment of hyalinization would prevent unwanted over or under treatment leading to a better prognosis.
PubMed: 34094841
DOI: 10.1016/j.jobcr.2021.05.002