scholarly journals Monocyte progenitors give rise to multinucleated giant cells

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Anne Kathrin Lösslein ◽  
Florens Lohrmann ◽  
Lisa Scheuermann ◽  
Kourosh Gharun ◽  
Jana Neuber ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Immune Response ◽  
Giant Cell ◽  
Cell Transformation ◽  
Cholesterol Metabolism ◽  
Giant Cells ◽  
Multinucleated Giant Cells ◽  
Toll Like Receptor ◽  
High Cholesterol ◽  
Mycobacterial Infections

AbstractThe immune response to mycobacteria is characterized by granuloma formation, which features multinucleated giant cells as a unique macrophage type. We previously found that multinucleated giant cells result from Toll-like receptor-induced DNA damage and cell autonomous cell cycle modifications. However, the giant cell progenitor identity remained unclear. Here, we show that the giant cell-forming potential is a particular trait of monocyte progenitors. Common monocyte progenitors potently produce cytokines in response to mycobacteria and their immune-active molecules. In addition, common monocyte progenitors accumulate cholesterol and lipids, which are prerequisites for giant cell transformation. Inducible monocyte progenitors are so far undescribed circulating common monocyte progenitor descendants with high giant cell-forming potential. Monocyte progenitors are induced in mycobacterial infections and localize to granulomas. Accordingly, they exhibit important immunological functions in mycobacterial infections. Moreover, their signature trait of high cholesterol metabolism may be piggy-backed by mycobacteria to create a permissive niche.

scholarly journals Cell Cycle Regulatory Protein Expression in Multinucleated Giant Cells of Giant Cell Tumor of Bone: do They Proliferate?

2021 ◽  
Vol 27 ◽  
Author(s):  
Mate E. Maros ◽  
Peter Balla ◽  
Tamas Micsik ◽  
Zoltan Sapi ◽  
Miklos Szendroi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Giant Cell Tumor ◽  
Giant Cell ◽  
Regulatory Protein ◽  
Giant Cells ◽  
Cell Tumor ◽  
G1 Phase ◽  
Cdk Inhibitors ◽  
Multinucleated Giant Cells ◽  
Early Replication

Cells of the monocyte macrophage lineage form multinucleated giant cells (GCs) by fusion, which may express some cell cycle markers. By using a comprehensive marker set, here we looked for potential replication activities in GCs, and investigated whether these have diagnostic or clinical relevance in giant cell tumor of bone (GCTB). GC rich regions of 10 primary and 10 first recurrence GCTB cases were tested using immunohistochemistry in tissue microarrays. The nuclear positivity rate of the general proliferation marker, replication licensing, G1/S-phase, S/G2/M-phase, mitosis promoter, and cyclin dependent kinase (CDK) inhibitor reactions was analyzed in GCs. Concerning Ki67, moderate SP6 reaction was seen in many GC nuclei, while B56 and Mib1 positivity was rare, but the latter could be linked to more aggressive (p = 0.012) phenotype. Regular MCM6 reaction, as opposed to uncommon MCM2, suggested an initial DNA unwinding. Early replication course in GCs was also supported by widely detecting CDK4 and cyclin E, for the first time, and confirming cyclin D1 upregulation. However, post-G1-phase markers CDK2, cyclin A, geminin, topoisomerase-2a, aurora kinase A, and phospho-histone H3 were rare or missing. These were likely silenced by upregulated CDK inhibitors p15INK4b, p16INK4a, p27KIP1, p53 through its effector p21WAF1 and possibly cyclin G1, consistent with the prevention of DNA replication. In conclusion, the upregulation of known and several novel cell cycle progression markers detected here clearly verify early replication activities in GCs, which are controlled by cell cycle arresting CDK inhibitors at G1 phase, and support the functional maturation of GCs in GCTB.

CLINICAL AND MORPHOLOGICAL CORRELATIONS AND HISTOPATHOLOGY OF JOINT DAMAGE IN PATIENTS WITH DIFFUSE-TYPE TENOSYNOVIAL GIANT CELL TUMOR

2019 ◽  
Vol 72 (12) ◽  
Author(s):  
Olena O Dyadyk ◽  
Anastasiia Hryhorovska
Keyword(s):  
Giant Cell Tumor ◽  
Giant Cell ◽  
Cell Size ◽  
Giant Cells ◽  
Cell Tumor ◽  
Multinucleated Giant Cells ◽  
Diffuse Type ◽  
Association Coefficient ◽  
Mean Values ◽  
Tenosynovial Giant Cell Tumor

Introduction: Tenosynovial giant cell tumor (TSGCT) (synonym – pigmented villonodular synovitis) – is a rare benign proliferative lesion of the synovial sheath, localized in the joint capsule, bursa or tendon sheath and characterized by locally destructive growth. Depending on the prevalence within the joint elements, the presence of a capsule around the tumor, histophotographic features of cell structure and clinical behavior TSGCT can be divided to localized or diffuse type. The aim of the study was researching of histopathological properties of diffuse-type TSGCT, determine the parameters its morphological indicators and to find out the correlation between these morphological and clinical parameters. Materials and methods: The research material was used biopsy (resect) of pathological lesions from 50 patients who were diagnosed and histologically verified diffuse-type TSGCT. Microscopic examinations of the stained sections and their photo archiving were carried out with use of a Olympus-CX 41 light optical microscope. Group measurable parameters (mean values and Pearson tetrachoric index (association coefficient) were calculated in groups of comparison for morphological and clinical indices of TSGCT. The mean values were compared by Student’s test, P value of ≤0.1 was considered statistically significant. Results:Correlation analysis of indicators that accounted for the pairs of cases «clinic – morphology» revealed the relationships, that had the highest parameters of the association coefficient between such indicators: «presence of villous growths» - «severity of hemosiderosis» (if hypertrophied synovial villi available, with vascular injection and pronounced proliferation of synovial cells, there is also a significant accumulation of hemosiderin pigment); «presence of villous growths» - «type of predominant cellular proliferates» (if cells of TSGCT diffuse type consists of monotonous sheets of stromal cells, with uniform, oval to reniform nuclei, the proliferation of villi in synovial layer is non-distinctive); «presence of nodes» - «kind of stroma» (if nodes predominate, their histological structure is mainly represented by polymorphic clusters of synovitis cells in the form of cells, strands, chains, solid formations, among immature connective tissue with low hyalinosis); «cell size (area, cm²)» - «severity of haemosiderosis» and «cell size (area, cm²)» - «the number of multinucleated giant cells» (there is a pronounced deposition of pigment and accumulation of osteoclast-like multinucleated giant cells type, although usually their number is relatively small compared to the localized type of TSGCT). Conclusions: Morphological parameters, that we have identified, characterize pathological changes in the tissues of TSGCT; careful analysis of the frequency of their occurrence in the different comparison groups made it possible to establish intergroup differences and correlations between individual indicators, which were previously unknown or not obvious. Our study was determine to analyze of incidence rates and correlation relationships, revealed some previously unknown differences and dependencies that are important for understanding the pathogenesis, improvement of diagnosis and prognosis of diffuse-type TSGCT.

scholarly journals Human T-Lymphotropic Virus Type 1 Oncoprotein Tax Promotes S-Phase Entry but Blocks Mitosis

2002 ◽  
Vol 76 (8) ◽  
pp. 4022-4033 ◽  
Author(s):  
Min-Hui Liang ◽  
Thomas Geisbert ◽  
Yao Yao ◽  
Steven H. Hinrichs ◽  
Chou-Zen Giam
Keyword(s):  
Cell Cycle ◽  
Virus Type ◽  
Cell Cycle Progression ◽  
Cell Transformation ◽  
Cell Types ◽  
Giant Cells ◽  
S Phase ◽  
T Lymphotropic Virus ◽  
Transformed Cell Lines

ABSTRACT Human T-lymphotropic virus type 1 (HTLV-1) Tax exerts pleiotropic effects on multiple cellular regulatory processes to bring about NF-κB activation, aberrant cell cycle progression, and cell transformation. Here we report that Tax stimulates cellular G1/S entry but blocks mitosis. Tax expression in naive cells transduced with a retroviral vector, pBabe-Tax, leads to a significant increase in the number of cells in the S phase, with an accompanying rise in the population of cells with a DNA content of 4N or more. In all cell types tested, including BHK-21, mouse NIH 3T3, and human diploid fibroblast WI-38, Tax causes an uncoupling of DNA synthesis from cell division, resulting in the formation of multinucleated giant cells and cells with decondensed, highly convoluted and lobulated nuclei that are reminiscent of the large lymphocytes with cleaved or cerebriform nuclei seen in HTLV-1-positive individuals. This contrasts with the Tax-transformed cell lines, PX1 (fibroblast) and MT4 (lymphocyte), which produce Tax at high levels, but without the accompanying late-stage cell cycle abnormalities. PX1 and MT4 may have been selected to harbor somatic mutations that allow a bypass of the Tax-induced block in mitosis.

scholarly journals A rare coexistence of central giant cell granuloma and parathyroid adenoma: Case report

2021 ◽  
Vol 6 (2) ◽  
pp. 155-158
Author(s):  
Rohini Sebastian ◽  
Meethu Rappai
Keyword(s):  
Case Report ◽  
Connective Tissue ◽  
Parathyroid Adenoma ◽  
Giant Cell ◽  
Stromal Cells ◽  
Giant Cells ◽  
Giant Cell Granuloma ◽  
Multinucleated Giant Cells ◽  
Central Giant Cell Granuloma ◽  
Bony Lesion

Central giant cell granuloma is a reparative bony lesion characterised by abundant multinucleated giant cells within a sea of spindle shaped mesenchymal stromal cells. Giant cells are scattered throughout the fibrovascular connective tissue stroma containing hemorrhage. Its coexistence with parathyroid adenoma is very rare. Brown tumour is a close differential in this scenario. Herein we present the case of a central giant cell granuloma of maxilla and parathyroid adenoma diagnosed almost during the same time in a 58 years old male.

scholarly journals Annular Elastolytic Giant Cell Granuloma - A Rare Case with Systemic Involvement

2016 ◽  
Vol 15 (3) ◽  
pp. 488-491
Author(s):  
Suchibrata Das ◽  
Joyeeta Chowdhury ◽  
Sangita Patra ◽  
Arun Achar
Keyword(s):  
Giant Cell ◽  
Cell Lymphoma ◽  
Medical Science ◽  
Giant Cells ◽  
Elastic Fibers ◽  
Cutaneous T Cell Lymphoma ◽  
Giant Cell Granuloma ◽  
Multinucleated Giant Cells ◽  
Systemic Involvement ◽  
Exposed Skin

Annular elastolytic giant cell granuloma (AEGCG) is a rare granulomatous dermatosis characterized by loss of elastic fibers and elastophagocytosis by multinucleated giant cells. It is characterized by annular plaques that are similar to those observed in granuloma annulare but that specifically appear in sun-exposed skin and occurs more commonly in females than males. There have been reported cases of AEGCG associated with diabetes mellitus, systemic sarcoidosis, cutaneous amyloidosis, molluscum contagiosum, squamous cell carcinoma of the lung and cutaneous T-cell lymphoma. We report a case of AEGCG in both sun-exposed as well as covered areas of a middle aged lady with hepatic nodules and Barret’s esophagus.Bangladesh Journal of Medical Science Vol.15(3) 2016 p.488-491

Feline giant-cell pleomorphic sarcoma: cytologic, histologic and immunohistochemical characterization

2020 ◽  
pp. 1098612X2097266
Author(s):  
Bianca S de Cecco ◽  
Fernando F Argenta ◽  
Ronaldo M Bianchi ◽  
Cíntia De Lorenzo ◽  
Júlia G Wronski ◽  
...  
Keyword(s):  
Giant Cell ◽  
Calcium Binding ◽  
Giant Cells ◽  
Multinucleated Giant Cells ◽  
Pleomorphic Sarcoma ◽  
Spindle Cells ◽  
S 100 ◽  
Veterinary Pathology ◽  
Hematoxylin And Eosin ◽  
Giant Cell Type

Objectives This study aimed to characterize the cytologic, pathologic and immunohistochemical (IHC) aspects of feline giant-cell sarcoma. Methods Biopsy and necropsy reports from the Department of Veterinary Pathology were retrieved, and 13 cases of pleomorphic sarcoma (PS) were selected according to the established epidemiologic, pathologic and IHC criteria. All samples were fixed in 10% formalin, routinely processed for histology, and stained with hematoxylin and eosin. Samples also underwent IHC testing for vimentin, ionized calcium-binding adaptor molecule 1 (Iba-1), desmin, actin and S-100. Results The mean age of the affected cats was 9.5 years, and females were over-represented. Most neoplasms were observed in the flank, lateral thorax, limbs and interscapular region, and were >2 cm in diameter. Cytology analysis revealed highly cellular preparations with three distinct populations (spindle cells, small round cells and multinucleated giant cells) in a dense eosinophilic stroma. Histologically, PS was composed of a combination of these three populations. IHC labeling for vimentin and Iba-1 was strongly positive for spindle cells and multinucleated giant cells, respectively. Desmin/actin showed variable labeling among the samples. S-100 was negative in all samples. Conclusions and relevance PS is a neoplasm of mesenchymal origin, also known as malignant fibrous histiocytoma. The predominant subtype in this study that affected the cats was the giant-cell type, characterized by the presence of multinucleated giant cells among spindle-shaped cells. These findings are similar to those described in human patients; thus, a comparison between the neoplasms seen in these species might be useful, and the knowledge of biologic behavior and overall treatment approach for humans could be extrapolated to cats.

Towards better understanding of giant cell granulomas of the oral cavity

2021 ◽  
pp. jclinpath-2020-206858
Author(s):  
Atif Ahmed ◽  
Aparna Naidu
Keyword(s):  
Oral Cavity ◽  
Giant Cell ◽  
Giant Cell Tumour ◽  
Bone Cyst ◽  
Giant Cells ◽  
Multinucleated Giant Cells ◽  
Biological Behaviour ◽  
Precise Diagnosis ◽  
Insight Into ◽  
Recent Insight

Giant cell granulomas are enigmatic lesions of the oral cavity characterised by a peculiar combined proliferation of mononuclear and multinucleated giant cells in a mesenchymal stromal background. Central and peripheral giant cell granulomas may have similar pathogenesis and histology but differ in their location and biological behaviour. It is important to differentiate them from other giant cell lesions that can occur in the oral cavity, such as giant cell tumour of the bone, aneurysmal bone cyst, brown tumour of hyperparathyroidism, and giant cell lesions of Ramon syndrome, Noonan syndrome, neurofibromatosis and Jaffe-Campanacci syndrome. A recent insight into their molecular genetics and pathogenesis, with identification of KRAS, FGFR1 and TRPV4 mutations, allows for better diagnostic differentiation and opens the door to the use of pathway inhibitors in the treatment of recurrent or dysmorphic lesions. In this review, we provide an updated summary of the clinical and pathological features of oral cavity giant cell granulomas that help with their precise diagnosis and management.

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