Central Giant Cell Granuloma: A Narrative Review of Radiological Features and Differential Diagnosis

Review Article

Central Giant Cell Granuloma: A Narrative Review of Radiological Features and Differential Diagnosis

  • Luca Viganò 1
  • Joana Berberi 2
  • Francesco Bruno 3
  • Alessandra Caggiula 2
  • Matteo Di Loreto 2
  • Matteo Pettinicchio 2
  • Alex Vendrame 2
  • Cinzia Casu 4

*Corresponding Author: Cinzia Casu, Private Dental Practice, Cagliari, Italy.

Citation: Caggiula A, Di Loreto M, Pettinicchio M, Vendrame A, Casu C. (2020) Central Giant Cell Granuloma: A Narrative Review Of Radiological Features And Differential Diagnosis. General medicine and Clinical Practice. 3(2) DOI: 10.31579/2639-4162/030

Copyright: ©2020 Cinzia Casu. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Received: 14 August 2020 | Accepted: 12 September 2020 | Published: 18 September 2020

Keywords: central giant cell granuloma; maxillary bone lesions; radiographic features of maxillary and jaw lesions

Abstract

The Central Giant Cell Granuloma is an uncommon lesion, accounting less than 7% of all benign jaw lesions. In 1953, Jaffe was the first to describe these lesions as a giant cell reparative granuloma of the jaw bones, and in 1971, thanks to Pindborg and Kramer, it was included in the current nomenclature. The aetiology of CGCG is unknown, there is also a peripheral type that some authors consider the most common in maxillary bones. WHO defines CGCG as an intraosseous lesion consisting of cellular fibrous tissue that contains multiple foci of hemorrhage, aggregations of multinucleated giant cells, and some trabeculae of woven bone. The radiographic appearance of CGCGs is not pathognomonic. CGCGs should be differentiated from other lesions of the jaws such as Brown’s tumour of hyperparathyroidism, fibrous dysplasia, aneurysmal bone cysts, giant cell tumours, fibro-osseous lesions, and other malignancies that arise in the jaw bones. Furthermore, it needs to be differentiated even from some genetic syndromes, such as Cherubism, type 1-neurofibromatosis and Noonan’s syndrome. The aim of this study is to focus on radiographic features of CGCG in order to achieve an appropriate tool for diagnosis.

Introduction

Central giant cell granuloma is a benign intraosseous lesion first described by Jaffe. It was hypothesized that the lesion is not a true neoplasm but merely the result of a local reparative reaction [1]. The WHO defines CGCG as an intraosseous lesion consisting of cellular fibrous tissue that contains multiple foci of hemorrhage, aggregations of multinucleated giant cells, and some trabeculae of woven bone [2]. In 2004 epidemiological findings of CGCG in a general population were published. In this report an incidence of 1.1 per 106 was found for the whole population. They very rarely affect the mandibular condyle [3].

A study published in 2012 highlights that these lesions were more prevalent in women than in men, at a 1.56:1 proportion. The mean age of the patients was 25.8 ± 15.3 years (range 0-85). The lesions were more prevalent in the mandible in comparison with the maxilla, but there was no clear prevalence concerning the different regions of the jaws [4].

The origin of this lesion type remains unknown; the lesion may be reactive, a developmental anomaly or a benign neoplasm [5, 6, 7]. This lesion usually appears as a painless, slow-growing swelling of the jaw. Sensory disturbance and pain are not common. Displacement of tooth sometimes occurs, leading to malocclusion. An appropriate CGCG differential diagnosis is made taking into consideration the following hypothesis: odontogenic keratocyst, odontogenic myxoma, odontogenic fibroma, ossifying fibroma, adenomatoid odontogenic tumor, ameloblastoma and central arteriovenous hemangioma. Also aneurysmal bone cyst, Cherubism, fibrous dysplasia, giant cell tumor and brown tumor from hyperparathyroidism, in addition to being indistinguishable radiographically from CGCG, contain multinucleated giant cells [8, 9]. Moreover, neurofibromatosis type 1 syndrome and Noonan syndrome can show lesions similar to CGCG [10]. Because of the indistinguishable radiological features and histological pattern of all these lesions, it is necessary to consider all of them in the differential diagnosis.

Chuong et al. were the first to differentiate between aggressive and nonaggressive lesions on the basis of signs, symptoms and histological features. Aggressive lesions are characterized by one or more of the following features: pain, paresthesia, root resorption, rapid growth, cortical perforation, and a high recurrence rate after surgical curettage. Aggressive lesions were also larger in size and histologically demonstrated a larger fractional surface area occupied by giant-cells. Currently, clinical signs and symptoms and radiological features are the main criteria to differentiate nonaggressive (indolent) from aggressive lesions. According to the same studies, the number and volume of giant-cells checked with other components of the lesion might give a sort of prediction on its clinical behavior [11, 12]. In CGCG, 2 major histological features are diagnostic. There is a highly cellular, fibroblastic stroma with plump, spindle-shaped cells with a high mitotic rate; also vascular density is high. These spindle- shaped cells probably are the proliferating tumor cells, considering that they survive in culture after passing wells and immunohistochemically stain positive for the proliferation marker PCNA. The multinucleated giant- cells are prominent throughout the fibroblastic stroma but are not necessarily abundant. They are usually irregularly distributed and are often located most numerously around areas of hemorrhage [13, 14, 15, 16, 17, 18].

It is necessary, nowadays, to consider all the different radiological techniques and rely on a histology laboratory in order to achieve correct diagnosis as soon as possible, which is critical on choosing the best therapy option.

Materials and Methods

This narrative review was performed by searching on the PubMed search engine.

MeSH terms and keywords were “central giant cell granuloma” resulting in 3390 articles. Only articles published after 1980 and articles with full text available were included.

Inclusion criteria were:

Case reports

At the end, we obtained 982 potentially useful articles. We excluded not relevant articles after abstracts observation.We analyzed 93 articles (Figure 1) and 21 resulted significant.

Fig 1. Flow-chart of the review's step performed.

Results and Discussions

Although the CGCG does not present a high index of incidence, it requires an appropriate diagnostic framework during the clinical activity, through the use of imaging techniques and appropriate conduct of the objective examination. Most patients present themselves at the clinical examination with an asymptomatic swelling at the facial level or at the level of the oral cavity. It is rarely accompanied by paraesthesia [10].

The imaging results essential to the CGCG diagnosis for its identification, description, pre-surgical evaluation, and post-operatory follow up.OPG is at the moment the referential imaging technique, the CBT with the software emulation dedicated to the study of the dental arches, allows an optimal vision of the bone; it provides meaningful informations in order to differentiate the malign lesion and allows to plan an appropriate surgery [8].

The radiographic features of the CGCG are not specific, for that it is possible to find dissimilar descriptions in literature.

The lesion can present itself as a radiolucent unilocular area or multilocular, to margins well defined or diffused. They described the possibility to resort roots, different degrees of expansion, and the erosion of the cortical bone, which can be appreciative due to the CBT [19, 20].

Radiological characteristics specific to the CGCG

CGCG can present different characteristics. It is a lesion that can vary from small apical osteolysis to a significant destructive lesion that affects the mandible and, with minor frequency, the jaw [10, 21].

It appears as a cyst-like unilocular radiolucent lesion in the majority of the case, or multilocular, with the appearance similar to “soap bubbles” due to the internal presence of septa radiopaque of variable dimensions [10, 22].

The term “multilocular” can, in some instances, be used incorrectly, because of the presence of calcifications  within  the  lithic  lesion  that  can  mimic  a  real  and  proper  multilocular [22]. In the academic literature, it is possible to find lesions cases entirely radiolucent, or radiolucent with variable radiopaque components within the internal radiolucency [23]. The CGCG presents typically well-defined borders to a low index of growth; only in rare cases, they can be diffused [23].

It can cause a dislocation of the dental elements, resorption of the roots and of the inter-radicular bone [9, 23].

The cortical bone usually remains intact but thinned; however, in the academic literature, there are cases of evident cortical resorptions, with the lesion that extends its soft tissues in the surrounding areas [24]. CGCG size can vary from 1 to 7 cm in diameter [22].CBT should be used to determine the greatness, as the orthopantomography (OPG) results inadequate since it tends to underestimate the dimensions [21].

Distinctive characteristics to specific locations

The preferred locations of the CGCG are the maxillary bones, with a higher prevalence within the jaw, in particular in the anterior region [10] [21]. Some authors report several jaw cases; the mandible:maxilla ratio is 3:1 [21].

It generally presents itself as an isolated lesion, the rare cases of multiple and simultaneous are often associated to systematic disorders and hereditary syndromes; it is then less likely that such lesions represent cases of bilateral CGCG [21]. In academic research 5 CGCG cases have been documented at the mandibular condyle level, in the specific case, they result to be with prevalence multilocular or surrounded by a well-defined cortical layer [20, 25]. It highlights that through the use of    CT and MRI, it is possible to outline CGCG cases at the neurocranium level. They present themselves in the form of expansive lesions capable of penetrating the soft tissues [24].

The classification of “aggressive” and “not aggressive” CGCG cases

In a few cases, the CGCG can outline some aggressive features in the clinical and radiological analysis. In 1986 Chuong et al. and in 1987 Ficarra et al. suggested a classification between “aggressive” and “non aggressive” CGCGs according to the clinical and radiological characteristics.

The non-aggressive form, the most common, highlights a slow growth associated with more or fewer levels of swelling, painful and paraesthesia. Radiographically, these cases present themselves as unilocular or multilocular radiotransparent distinct areas. It is possible to identify cortical perforations and root resorption, with a lower possibility of recurrence after surgical treatment than the aggressive counterpart. The aggressive form outlines dimensions higher than 5 cm, a rapid growth recurrences after surgical curettage. Also, thinning and/or perforation of the cortical bone, teeth dislocation, and radicular resorption [11, 12].

Kaban et al. modify further the definition; they affirm that in order to classify an aggressive form of CGCG, it is sufficient that it presents dimensions greater than 5 cm and the possibility of recurrences, even when other features are not identified [12]. These cases highlight that aggressive features present themselves more often to pediatric patients [26]. Infantile patients have the cranial bones in the stage of the development and inside the jawbones the process of odontogenesis is still ongoing, with the substitution of deciduous dentition aside the permanent one, these could be etiological factors predisposing to aggressive CGCG cases [27].

It must also be outlined that the radiological diagnosis is challenging to identify in pediatric cases due to the overlapping of the teething elements [27]. The distinction between aggressive and not aggressive CGCG cases is significant because it leads to different therapeutic protocols.  Based on these data, the clinical and radiological CGCG characteristics seem to belong to an aggressive benign tumor, rather than granuloma, with some authors suggesting a nomenclature review [28].

Clinical and radiographic differential diagnosis

The radiographic CGCG appearance is not pathognomonic. It can be confused with different sorts of multilocular, expansive and radiolucent lesions of the maxillary. They are distinguishable between the use of imaging techniques [21, 23, 29].

The CGCG differential diagnosis cases are the following: odontogenic keratocyst, odontogenic myxoma, odontogenic fibroma, ossifying, fibroma, adenomatoid  odontogenic   tumor,  a meloblastoma,and  central arteriovenous hemangioma.Aneurysmal bone cyst, cherubism, fibrous dysplasia, giant cell tumor and brown tumor from hyperparathyroidism, in addition to being indistinguishable radiographically, also contain multinucleated giant cells [8,9].

Moreover, the neurofibromatosis type 1 syndrome and the Noonan syndrome can manifest at the level of maxillary similar lesions of CGCG [10]. The discriminant conditions that allow elaborating a final diagnosis are now discussed.

The aneurismal bone cyst is diagnosed by the identification of sinusoidal blood spaces within the tumor mass.

The giant cell tumor is distinctive from CGCG cases due to typical locations (the tumor is rare within the maxillary area) and histological characteristics: the giant cells of the tumor are distributed in a regular and uniform way, instead, in the granuloma, they are clumped in areas separated by virtually devoid areas. Fibrous dysplasia is characterized by the presence of “Chinese figure-like” trabeculae of woven or immature bone within a proliferating fibroblastic stroma. Besides these lesions, even for odontogenic keratocyst, odontogenic myxoma, odontogenic fibroma, ossifying fibroma, adenomatoid odontogenic tumor, ameloblastoma and central arteriovenous haemangioma, the definitive diagnosis occurs through histological examination [8, 9].

The root resorption index is useful to differentiate between CGCG and ameloblastoma; in the latter is more common compared to the former cases [22].

The brown tumor appears identical to CGCG in terms of histological and radiological conditions; the exclusion basis its foundations on the control of serum calcium values, phosphorous, alkaline phosphatise and kidney functionalities. Even the cherubism is microscopically indistinguishable from the CGCG. However, it usually recognizes, in the aftermath of its bilateral manifestation in juvenile patients, affected by this syndrome [8, 9].

The Granuloma characteristics in the histological examination

The CGCG, at the level of histological/diagnostical matters, is characterized by fibroblastic stroma at high cellular density, often myxoid, with plump, spindle-shaped cells with a high mitotic rate; there is a high vascular density, and there can be trabeculae’s bones [30, 31].

The multinucleated giant cells stand out in the fibroblastic stroma but are nevertheless abundant. They are usually irregularly distributed and are often localized at the level of hemorrhagic areas; morphology and dimensions vary according to each case, with several nuclei that can go from a few to several dozen.

At the periphery of the lesion, dystrophic calcifications and metaplastic ossifications are often presented [28, 29].

Different morphological parameters, including the index of mitotic activity, stromal characteristics, average dimensions of the multinucleated giant cells and percentages of occupied mass, have been tested in the attempt to correlate the histological aspect to the aggressive and non-aggressive CGCG behaviour. However, neither of those have shown a significant association according to the clinical behaviour of the lesion [8].

Conclusion

According to the following review, the CGCG radiological characteristics result to be a fundamental framework for the initial diagnosis but, not being specified, they are insufficient for the final diagnosis. In the clinical framework, it appears that is very important the histological exam to reach the final diagnosis, differentiating, likewise, the differential diagnosis.

Nevertheless, no correlation has been found between the aggressive degree outlined by the imaging response and the histological characteristics of the lesion.

Further studies at large-scales concerning the maxillary granulomatous giant cellular central cells could eventually generate useful data.

Fig 2. orthopantomograph x-ray and a CT of a Central Giant Cell Granuloma in a good health female patient of 45 years old. The hystopatological examination, after biopsy confirmed the diagnostic hypothesis.

Conflict of interest

Authors declared no conflict of interest.

References

Clearly Auctoresonline and particularly Psychology and Mental Health Care Journal is dedicated to improving health care services for individuals and populations. The editorial boards' ability to efficiently recognize and share the global importance of health literacy with a variety of stakeholders. Auctoresonline publishing platform can be used to facilitate of optimal client-based services and should be added to health care professionals' repertoire of evidence-based health care resources.

img

Virginia E. Koenig

Journal of Clinical Cardiology and Cardiovascular Intervention The submission and review process was adequate. However I think that the publication total value should have been enlightened in early fases. Thank you for all.

img

Delcio G Silva Junior

Journal of Women Health Care and Issues By the present mail, I want to say thank to you and tour colleagues for facilitating my published article. Specially thank you for the peer review process, support from the editorial office. I appreciate positively the quality of your journal.

img

Ziemlé Clément Méda

Journal of Clinical Research and Reports I would be very delighted to submit my testimonial regarding the reviewer board and the editorial office. The reviewer board were accurate and helpful regarding any modifications for my manuscript. And the editorial office were very helpful and supportive in contacting and monitoring with any update and offering help. It was my pleasure to contribute with your promising Journal and I am looking forward for more collaboration.

img

Mina Sherif Soliman Georgy

We would like to thank the Journal of Thoracic Disease and Cardiothoracic Surgery because of the services they provided us for our articles. The peer-review process was done in a very excellent time manner, and the opinions of the reviewers helped us to improve our manuscript further. The editorial office had an outstanding correspondence with us and guided us in many ways. During a hard time of the pandemic that is affecting every one of us tremendously, the editorial office helped us make everything easier for publishing scientific work. Hope for a more scientific relationship with your Journal.

img

Layla Shojaie

The peer-review process which consisted high quality queries on the paper. I did answer six reviewers’ questions and comments before the paper was accepted. The support from the editorial office is excellent.

img

Sing-yung Wu

Journal of Neuroscience and Neurological Surgery. I had the experience of publishing a research article recently. The whole process was simple from submission to publication. The reviewers made specific and valuable recommendations and corrections that improved the quality of my publication. I strongly recommend this Journal.

img

Orlando Villarreal

Dr. Katarzyna Byczkowska My testimonial covering: "The peer review process is quick and effective. The support from the editorial office is very professional and friendly. Quality of the Clinical Cardiology and Cardiovascular Interventions is scientific and publishes ground-breaking research on cardiology that is useful for other professionals in the field.

img

Katarzyna Byczkowska

Thank you most sincerely, with regard to the support you have given in relation to the reviewing process and the processing of my article entitled "Large Cell Neuroendocrine Carcinoma of The Prostate Gland: A Review and Update" for publication in your esteemed Journal, Journal of Cancer Research and Cellular Therapeutics". The editorial team has been very supportive.

img

Anthony Kodzo-Grey Venyo

Testimony of Journal of Clinical Otorhinolaryngology: work with your Reviews has been a educational and constructive experience. The editorial office were very helpful and supportive. It was a pleasure to contribute to your Journal.

img

Pedro Marques Gomes

Dr. Bernard Terkimbi Utoo, I am happy to publish my scientific work in Journal of Women Health Care and Issues (JWHCI). The manuscript submission was seamless and peer review process was top notch. I was amazed that 4 reviewers worked on the manuscript which made it a highly technical, standard and excellent quality paper. I appreciate the format and consideration for the APC as well as the speed of publication. It is my pleasure to continue with this scientific relationship with the esteem JWHCI.

img

Bernard Terkimbi Utoo

This is an acknowledgment for peer reviewers, editorial board of Journal of Clinical Research and Reports. They show a lot of consideration for us as publishers for our research article “Evaluation of the different factors associated with side effects of COVID-19 vaccination on medical students, Mutah university, Al-Karak, Jordan”, in a very professional and easy way. This journal is one of outstanding medical journal.

img

Prof Sherif W Mansour

Dear Hao Jiang, to Journal of Nutrition and Food Processing We greatly appreciate the efficient, professional and rapid processing of our paper by your team. If there is anything else we should do, please do not hesitate to let us know. On behalf of my co-authors, we would like to express our great appreciation to editor and reviewers.

img

Hao Jiang

As an author who has recently published in the journal "Brain and Neurological Disorders". I am delighted to provide a testimonial on the peer review process, editorial office support, and the overall quality of the journal. The peer review process at Brain and Neurological Disorders is rigorous and meticulous, ensuring that only high-quality, evidence-based research is published. The reviewers are experts in their fields, and their comments and suggestions were constructive and helped improve the quality of my manuscript. The review process was timely and efficient, with clear communication from the editorial office at each stage. The support from the editorial office was exceptional throughout the entire process. The editorial staff was responsive, professional, and always willing to help. They provided valuable guidance on formatting, structure, and ethical considerations, making the submission process seamless. Moreover, they kept me informed about the status of my manuscript and provided timely updates, which made the process less stressful. The journal Brain and Neurological Disorders is of the highest quality, with a strong focus on publishing cutting-edge research in the field of neurology. The articles published in this journal are well-researched, rigorously peer-reviewed, and written by experts in the field. The journal maintains high standards, ensuring that readers are provided with the most up-to-date and reliable information on brain and neurological disorders. In conclusion, I had a wonderful experience publishing in Brain and Neurological Disorders. The peer review process was thorough, the editorial office provided exceptional support, and the journal's quality is second to none. I would highly recommend this journal to any researcher working in the field of neurology and brain disorders.

img

Dr Shiming Tang

Dear Agrippa Hilda, Journal of Neuroscience and Neurological Surgery, Editorial Coordinator, I trust this message finds you well. I want to extend my appreciation for considering my article for publication in your esteemed journal. I am pleased to provide a testimonial regarding the peer review process and the support received from your editorial office. The peer review process for my paper was carried out in a highly professional and thorough manner. The feedback and comments provided by the authors were constructive and very useful in improving the quality of the manuscript. This rigorous assessment process undoubtedly contributes to the high standards maintained by your journal.

img

Raed Mualem

International Journal of Clinical Case Reports and Reviews. I strongly recommend to consider submitting your work to this high-quality journal. The support and availability of the Editorial staff is outstanding and the review process was both efficient and rigorous.

img

Andreas Filippaios

Thank you very much for publishing my Research Article titled “Comparing Treatment Outcome Of Allergic Rhinitis Patients After Using Fluticasone Nasal Spray And Nasal Douching" in the Journal of Clinical Otorhinolaryngology. As Medical Professionals we are immensely benefited from study of various informative Articles and Papers published in this high quality Journal. I look forward to enriching my knowledge by regular study of the Journal and contribute my future work in the field of ENT through the Journal for use by the medical fraternity. The support from the Editorial office was excellent and very prompt. I also welcome the comments received from the readers of my Research Article.

img

Dr Suramya Dhamija

Dear Erica Kelsey, Editorial Coordinator of Cancer Research and Cellular Therapeutics Our team is very satisfied with the processing of our paper by your journal. That was fast, efficient, rigorous, but without unnecessary complications. We appreciated the very short time between the submission of the paper and its publication on line on your site.

img

Bruno Chauffert

I am very glad to say that the peer review process is very successful and fast and support from the Editorial Office. Therefore, I would like to continue our scientific relationship for a long time. And I especially thank you for your kindly attention towards my article. Have a good day!

img

Baheci Selen

"We recently published an article entitled “Influence of beta-Cyclodextrins upon the Degradation of Carbofuran Derivatives under Alkaline Conditions" in the Journal of “Pesticides and Biofertilizers” to show that the cyclodextrins protect the carbamates increasing their half-life time in the presence of basic conditions This will be very helpful to understand carbofuran behaviour in the analytical, agro-environmental and food areas. We greatly appreciated the interaction with the editor and the editorial team; we were particularly well accompanied during the course of the revision process, since all various steps towards publication were short and without delay".

img

Jesus Simal-Gandara

I would like to express my gratitude towards you process of article review and submission. I found this to be very fair and expedient. Your follow up has been excellent. I have many publications in national and international journal and your process has been one of the best so far. Keep up the great work.

img

Douglas Miyazaki

We are grateful for this opportunity to provide a glowing recommendation to the Journal of Psychiatry and Psychotherapy. We found that the editorial team were very supportive, helpful, kept us abreast of timelines and over all very professional in nature. The peer review process was rigorous, efficient and constructive that really enhanced our article submission. The experience with this journal remains one of our best ever and we look forward to providing future submissions in the near future.

img

Dr Griffith

I am very pleased to serve as EBM of the journal, I hope many years of my experience in stem cells can help the journal from one way or another. As we know, stem cells hold great potential for regenerative medicine, which are mostly used to promote the repair response of diseased, dysfunctional or injured tissue using stem cells or their derivatives. I think Stem Cell Research and Therapeutics International is a great platform to publish and share the understanding towards the biology and translational or clinical application of stem cells.

img

Dr Tong Ming Liu

I would like to give my testimony in the support I have got by the peer review process and to support the editorial office where they were of asset to support young author like me to be encouraged to publish their work in your respected journal and globalize and share knowledge across the globe. I really give my great gratitude to your journal and the peer review including the editorial office.

img

Husain Taha Radhi

I am delighted to publish our manuscript entitled "A Perspective on Cocaine Induced Stroke - Its Mechanisms and Management" in the Journal of Neuroscience and Neurological Surgery. The peer review process, support from the editorial office, and quality of the journal are excellent. The manuscripts published are of high quality and of excellent scientific value. I recommend this journal very much to colleagues.

img

S Munshi

Dr.Tania Muñoz, My experience as researcher and author of a review article in The Journal Clinical Cardiology and Interventions has been very enriching and stimulating. The editorial team is excellent, performs its work with absolute responsibility and delivery. They are proactive, dynamic and receptive to all proposals. Supporting at all times the vast universe of authors who choose them as an option for publication. The team of review specialists, members of the editorial board, are brilliant professionals, with remarkable performance in medical research and scientific methodology. Together they form a frontline team that consolidates the JCCI as a magnificent option for the publication and review of high-level medical articles and broad collective interest. I am honored to be able to share my review article and open to receive all your comments.

img

Tania Munoz

“The peer review process of JPMHC is quick and effective. Authors are benefited by good and professional reviewers with huge experience in the field of psychology and mental health. The support from the editorial office is very professional. People to contact to are friendly and happy to help and assist any query authors might have. Quality of the Journal is scientific and publishes ground-breaking research on mental health that is useful for other professionals in the field”.

img

George Varvatsoulias

Dear editorial department: On behalf of our team, I hereby certify the reliability and superiority of the International Journal of Clinical Case Reports and Reviews in the peer review process, editorial support, and journal quality. Firstly, the peer review process of the International Journal of Clinical Case Reports and Reviews is rigorous, fair, transparent, fast, and of high quality. The editorial department invites experts from relevant fields as anonymous reviewers to review all submitted manuscripts. These experts have rich academic backgrounds and experience, and can accurately evaluate the academic quality, originality, and suitability of manuscripts. The editorial department is committed to ensuring the rigor of the peer review process, while also making every effort to ensure a fast review cycle to meet the needs of authors and the academic community. Secondly, the editorial team of the International Journal of Clinical Case Reports and Reviews is composed of a group of senior scholars and professionals with rich experience and professional knowledge in related fields. The editorial department is committed to assisting authors in improving their manuscripts, ensuring their academic accuracy, clarity, and completeness. Editors actively collaborate with authors, providing useful suggestions and feedback to promote the improvement and development of the manuscript. We believe that the support of the editorial department is one of the key factors in ensuring the quality of the journal. Finally, the International Journal of Clinical Case Reports and Reviews is renowned for its high- quality articles and strict academic standards. The editorial department is committed to publishing innovative and academically valuable research results to promote the development and progress of related fields. The International Journal of Clinical Case Reports and Reviews is reasonably priced and ensures excellent service and quality ratio, allowing authors to obtain high-level academic publishing opportunities in an affordable manner. I hereby solemnly declare that the International Journal of Clinical Case Reports and Reviews has a high level of credibility and superiority in terms of peer review process, editorial support, reasonable fees, and journal quality. Sincerely, Rui Tao.

img

Rui Tao

Clinical Cardiology and Cardiovascular Interventions I testity the covering of the peer review process, support from the editorial office, and quality of the journal.

img

Khurram Arshad

Clinical Cardiology and Cardiovascular Interventions, we deeply appreciate the interest shown in our work and its publication. It has been a true pleasure to collaborate with you. The peer review process, as well as the support provided by the editorial office, have been exceptional, and the quality of the journal is very high, which was a determining factor in our decision to publish with you.

img

Gomez Barriga Maria Dolores

The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews journal clinically in the future time.

img

Lin Shaw Chin

Clinical Cardiology and Cardiovascular Interventions, I would like to express my sincerest gratitude for the trust placed in our team for the publication in your journal. It has been a true pleasure to collaborate with you on this project. I am pleased to inform you that both the peer review process and the attention from the editorial coordination have been excellent. Your team has worked with dedication and professionalism to ensure that your publication meets the highest standards of quality. We are confident that this collaboration will result in mutual success, and we are eager to see the fruits of this shared effort.

img

Maria Dolores Gomez Barriga

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, I hope this message finds you well. I want to express my utmost gratitude for your excellent work and for the dedication and speed in the publication process of my article titled "Navigating Innovation: Qualitative Insights on Using Technology for Health Education in Acute Coronary Syndrome Patients." I am very satisfied with the peer review process, the support from the editorial office, and the quality of the journal. I hope we can maintain our scientific relationship in the long term.

img

Dr Maria Dolores Gomez Barriga

Dear Monica Gissare, - Editorial Coordinator of Nutrition and Food Processing. ¨My testimony with you is truly professional, with a positive response regarding the follow-up of the article and its review, you took into account my qualities and the importance of the topic¨.

img

Dr Maria Regina Penchyna Nieto

Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.

img

Dr Marcelo Flavio Gomes Jardim Filho

Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”

img

Zsuzsanna Bene

Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner

img

Dr Susan Weiner

My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.

img

Lin-Show Chin

My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.

img

Sonila Qirko

My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.

img

Luiz Sellmann