Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile

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Owing to the scarcity of the reported cases, the clinical behavior of odontogenic carcinosarcoma remains unexplored. The present work reports a case of odontogenic carcinosarcoma of the mandible with the detailed immuno-histochemical profile. A 28-year-old male presented with a left painless swelling, which recurred after hemimandiblectomy of the lesion. Complete excision of the lesion with a wide safety margin was performed. The histopathological examination revealed cytological malignant features in the follicles as well as in the ectomesenchyme. The immuno-histochemistry demonstrated evidence of epithelial mesenchymal transition. After nine months, the patient demonstrated recurrence in the infra-temporal fossa. Odontogenic carcinosarcoma is a rare highly aggressive malignant odontogenic tumor. Positive expression of smooth muscle actin and vimentin in the epithelial component is a useful aid in the diagnosis of odontogenic carcinosarcoma." } { "@context": "http://schema.org", "@type": "BreadcrumbList", "itemListElement": [ { "@type": "ListItem", "position": "1", "item": { "@id": "https://f1000research.com/", "name": "Home" } }, { "@type": "ListItem", "position": "2", "item": { "@id": "https://f1000research.com/browse/articles", "name": "Browse" } }, { "@type": "ListItem", "position": "3", "item": { "@id": "https://f1000research.com/articles/9-603/v2", "name": "Case Report: Odontogenic carcinosarcoma arising from premature odontoma..." } } ] } Home Browse Case Report: Odontogenic carcinosarcoma arising from premature odontoma... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Salem HMWM, Ahmed Mohamed Mahmoud Badawy S and Amer HW. Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.12688/f1000research.23969.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Case Report Revised Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] Previously titled: Case Report: Odontogenic carcinosarcoma arising from ameloblastic fibrodentinoma with immunohistochemical profile Hend Mohammed Waguih Mahmoud Salem 1,2 , Sarah Ahmed Mohamed Mahmoud Badawy https://orcid.org/0000-0002-6614-6796 2 , Hatem Wael Amer https://orcid.org/0000-0003-3560-5918 2 Hend Mohammed Waguih Mahmoud Salem 1,2 , Sarah Ahmed Mohamed Mahmoud Badawy https://orcid.org/0000-0002-6614-6796 2 , Hatem Wael Amer https://orcid.org/0000-0003-3560-5918 2 PUBLISHED 15 Dec 2020 Author details Author details 1 Basic Dental Services Department, Princess Nourah Bint Abdulrahman University, College of Dentistry, Riyadh, Saudi Arabia 2 Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt Hend Mohammed Waguih Mahmoud Salem Roles: Conceptualization, Funding Acquisition, Resources, Supervision, Writing – Review & Editing Sarah Ahmed Mohamed Mahmoud Badawy Roles: Conceptualization, Formal Analysis, Methodology, Project Administration, Software, Visualization, Writing – Original Draft Preparation Hatem Wael Amer Roles: Data Curation, Investigation, Methodology, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. Abstract Odontogenic carcinosarcoma is an extremely rare mixed malignant odontogenic neoplasm in which both the epithelial and the ectomesenchymal components are cytologically malignant. Owing to the scarcity of the reported cases, the clinical behavior of odontogenic carcinosarcoma remains unexplored. The present work reports a case of odontogenic carcinosarcoma of the mandible with the detailed immuno-histochemical profile. A 28-year-old male presented with a left painless swelling, which recurred after hemimandiblectomy of the lesion. Complete excision of the lesion with a wide safety margin was performed. The histopathological examination revealed cytological malignant features in the follicles as well as in the ectomesenchyme. The immuno-histochemistry demonstrated evidence of epithelial mesenchymal transition. After nine months, the patient demonstrated recurrence in the infra-temporal fossa. Odontogenic carcinosarcoma is a rare highly aggressive malignant odontogenic tumor. Positive expression of smooth muscle actin and vimentin in the epithelial component is a useful aid in the diagnosis of odontogenic carcinosarcoma. READ ALL READ LESS Keywords Odontogenic carcinosarcoma, α-smooth muscle actin, vimentin, epithelial mesenchymal transition, Ki-67. Corresponding Author(s) Sarah Ahmed Mohamed Mahmoud Badawy ( [email protected] ) Close Corresponding author: Sarah Ahmed Mohamed Mahmoud Badawy Competing interests: No competing interests were disclosed. Grant information: This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the fast track Research Funding Program. Copyright: © 2020 Salem HMWM et al . 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 work is properly cited. How to cite: Salem HMWM, Ahmed Mohamed Mahmoud Badawy S and Amer HW. Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.12688/f1000research.23969.2 ) First published: 12 Jun 2020, 9 :603 ( https://doi.org/10.12688/f1000research.23969.1 ) Latest published: 15 Dec 2020, 9 :603 ( https://doi.org/10.12688/f1000research.23969.2 ) Revised Amendments from Version 1 We changed the title because it didn’t follow the nomenclature stated in the new WHO classification. We tried to improve the histopathological description of the lesion. We edited the histopathological Figures 3 & 4 to clarify the features of the lesion. We repeated the ki67 staining and measured the area percent by leica Qwin software Figure 6. We contacted the surgeon to improve the follow-up information of the patient. We tried to improve the discussion as recommended by the reviewer. We wrote the take-home message in the conclusion section. We changed the title because it didn’t follow the nomenclature stated in the new WHO classification. We tried to improve the histopathological description of the lesion. We edited the histopathological Figures 3 & 4 to clarify the features of the lesion. We repeated the ki67 staining and measured the area percent by leica Qwin software Figure 6. We contacted the surgeon to improve the follow-up information of the patient. We tried to improve the discussion as recommended by the reviewer. We wrote the take-home message in the conclusion section. See the authors' detailed response to the review by João Paulo Silva Servato See the authors' detailed response to the review by Oslei Paes de Almeida READ REVIEWER RESPONSES Introduction Malignant odontogenic tumors are rare group of malignant neoplasms that arise from odontogenic remnants 1 . One of these neoplasms is odontogenic carcinosarcoma (OCS), an extremely rare mixed malignant odontogenic neoplasm in which both the epithelial and the ectomesenchymal components are cytologically malignant 2 . In the 1992 World Health Organization (WHO) classification of tumors, OCS was included in the malignant odontogenic tumors after Tanaka and co-workers (1991) first reported an odontogenic tumor with a mixture of malignant epithelial and ectomesenchymal components 3 . In the 2005 WHO classification, the tumor was removed due to an absence of current diagnostic criteria 4 . OCS has been added again in the 2017 edition because of the availability of cases with adequate diagnostic immunohistochemical and molecular criteria 5 , 6 . Owing to the scarcity of reported cases - only eleven reported cases in the English literature - OCS clinical behavior remains unexplored 7 , 8 . In the current work, we report a case of OCS with the detailed clinical, radiographic, histopathological and immunohistochemical description. Case report In December 2016, a 28-year-old Egyptian male patient working as an accountant was referred to the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Cairo University, with a complaint of painless swelling of six months duration in the left side of his face measuring 7 × 6 cm. The patient had a pathological report of an incisional biopsy, performed outside our institute, which was diagnosed as ameloblastoma. There were no palpable lymph nodes. Intra-oral examination revealed an absence of the lower left molars with a fistula opening on the alveolar crest with no oozing pus. A cone beam computed tomography examination revealed an ill-defined multilocular osteolytic lesion with fine radiopacities extending from the lower left second premolar up to the ramus. There was prominent cortical expansion with areas of perforation ( Figure 1 ). A hemi-mandibulectomy was performed based on the incisional biopsy diagnosis and the pathological fracture of the mandible. The ramus was totally destructed and the tumor was invading the masseter muscle ( Figure 2 ). Differential diagnosis was made based on the clinical examination, radiographic appearance and gross examination as: ghost cell odontogenic carcinoma, ameloblastic carcinoma, ameloblastic fibrosarcoma, ameloblastic carcinosarcoma, calcifying epithelial odontogenic tumor, atypical type of ameloblastic fibro-dentinoma 9 and ameloblastoma. Figure 1. Cone beam computed tomography of odontogenic carcinosarcoma, axial view showing the multilocular lesion extending from the left lower second premolar to the condyle involving the whole ramus with buccal perforation. There was scattered radiopacities closely related to the impacted first molar. The second molar was displaced against the angle of the mandible. Figure 2. Gross examination: ( A ) Hemi-mandibulectomy with safety margin including the masseter muscle. ( B ) Cross-section of the resected specimen showing the fleshy neoplasm and the impacted first molar. ( C ) Top view of the resected specimen showing the necrotic fistula on the alveolar ridge. ( D ) The excisional specimen of the recurred lesion. Histopathological examination revealed hypercellular follicles and strands of odontogenic epithelium, that were lined peripherally by multilayers of tall columnar ameloblast like cells. The center of the follicles was filled by stellate reticulum like cells, which were basaloid in appearance in some follicles. In between the follicles, there was a highly cellular primitive ectomesenchyme resembling dental papilla. Some of the nuclei of the ectomesenchymal cells were hyperchromatic. In some fields, dentinoid matrix was detected around the epithelial strands ( Figure 3A ).Based on the histopathological examination and the case report of Giraddi and Garg 2012 9 , and because it was before the publication of the new WHO classification of 2017, a diagnosis was made of ameloblastic fibro-dentinoma (atypical type). Figure 3. Histopathological examination of the resected specimen (hematoxylin and eosin stain, X100). ( A ) Microscopic image showing odontogenic epithelial follicles formed of ameloblast-like cells on the periphery and stellate-reticulum like cells on the center, which were surrounded by primitive ectomesenchyme resembling dental papilla. Dentinoid material was detected in contact with the epithelial follicles (black arrows). ( B ) Microscopic image showing another field which was hypercellular in both components with mild pleomorphism and hyperchromatism. After nine months and after the publication of 2017 WHO classification, the patient returned with another large painless swelling in the left temporal and infra-temporal fossa of three months duration. There were no palpable lymph nodes. An oral and maxillofacial surgeon used local anesthesia and an intra-oral approach to completely excise the recurrent lesion ( Figure 2D ). Augmentin 1gm tablet/12 hours for five days and anti-inflammatory medication were prescribed for the patient after the surgery. Histopathological examination revealed highly cellular neoplasm, which showed cellular atypia and increased nuclear cytoplasmic ratio in both epithelial and ectomesenchymal components. The typical ameloblastic architecture of the epithelial follicles was lost in some areas. The ectomesenchymal component showed large pleomorphic cells ( Figure 4 ). Figure 4. Histopathological examination of the recurred lesion (hematoxylin and eosin stain): ( A & B ) Microscopic image showing hypercellular epithelial follicles with plump hyperchromatic and pleomorphic cells and absence of the stellate reticulum cells in the center, along with hypercellular ectomesenchyme, the basement membrane was vague in some areas (black arrows) (X200). ( C ) Microscopic image showing epithelial follicle with pleomorphism, hyperchromatism, and increased nuclear-cytoplasmic ratio. The basement membrane was lost in some areas (black arrows) (X400). ( D ) Microscopic image showing atypia in ectomesenchymal component with increased mitosis, bizarre shaped nuclei and increased nuclear/ cytoplasmic ratio (X400). The epithelial nests showed strong membranous positivity with AE1/AE3, while vimentin stained the ectomesenchyme diffusely and the epithelial nests patchily. Alpha-smooth muscle actin (α-SMA) showed positivity in the endothelial cells as well as in scattered epithelial cells ( Figure 5 ). Ki-67 index was measured by Leica Qwin software and was 7.46% in the epithelial component, while in the ectomesenchymal component it was 2.78% ( Figure 6 ). Based on the histopathological and immunohistochemical findings, the case was diagnosed as OCS. In 2019 and after nearly a year and a half, the patient came to Oral & Maxillofacial Surgery department for the reconstruction surgery and the examination revealed neither a recurrence nor complications. Figure 5. Immunohistochemical staining (X200): ( A ) Microscopic image showing strong membranous expression of AE1/AE3 in the epithelial component with the ectomesenchymal component being completely negative. ( B ) Microscopic image showing strong diffuse cytoplasmic expression of vimentin in ectomesenchymal component along with patchy expression in the epithelial component. ( C ) Microscopic image showing cytoplasmic expression of α-SMA in the endothelial cells and scattered epithelial cells. Figure 6. Immunohistochemical staining and analysis of Ki-67 (X200): ( A ) Microscopic image showing strong positive reaction of both epithelial and ectomesenchymal cells. ( B ) Screenshot showing the measurement of the area percent of Ki-67 expression of epithelial component using Leica Qwin software. ( C ) Screenshot showing the measurement of the area percent of Ki-67 expression of mesenchymal component. Discussion OCS is a rare biphasic malignant odontogenic neoplasm that has the same architecture of ameloblastic fibroma, in which the epithelial and the ectomesenchymal components are cytologically malignant. It can develop de novo from odontogenic remnants or as a transformation from a preexisting odontogenic benign or malignant neoplasm 6 . This transformation may be attributed to multiple surgical procedures or recurrences of the neoplasm 2 . The present case arose from a preexisting immature odontoma which was formerly called ameloblastic fibrodentinoma. Kunkel et al . (2004), DeLair et al . (2007) and Chikosi et al . (2011) reported cases aroused from ameloblastic fibrosarcoma, ameloblastic fibroma and ameloblastoma, respectively 2 , 10 , 11 . Our case was a 28-year-old male with the lesion affecting the posterior mandible. In the English literature, there was a male predilection and only one case that occurred in maxilla 4 . The most common radiographic picture of OCS is ill-defined multilocular radiolucency with cortical perforation 6 . The current case showed multiple radiopacities; may be due to the preexisting immature odontoma. OCS must be distinguished from ameloblastic fibrosarcoma, in which the ectomesenchymal component only shows cellular atypia, and spindle cell variant of ameloblastic carcinoma, which lacks the ectomesenchymal component 2 – 8 . In the present case, there was a patchy positive expression of vimentin in the epithelial component. This could be explained as OCS undergoes epithelial mesenchymal transition, a process in which the polarized immotile epithelial cell changes to gain the mesenchymal phenotype and indicates more aggressive behavior of the neoplasm 7 , 12 , 13 . In accordance with Dos Santos et al . (2018), α-SMA staining in the current case showed scattered staining in the epithelial cells 4 . Its expression in the epithelial cells could be attributed to the epithelial mesenchymal transition process; which increases the potentiality of the tumor cells to invade and metastasize 14 . The proliferative index Ki-67 in our case was around 7.5% in the epithelial component and 3% in the ectomesenchymal component. This is in accordance with the work of Dos Santos et al . (2018) and Soares et al . (2019), who found that Ki-67 index was higher in the epithelial component than the ectomesenchymal component 4 – 7 . Regarding the clinical behavior of OCS, it is a highly aggressive highly recurrent malignant neoplasm 7 . In our case, the patient encountered recurrence of the lesion after 9 months follow up with no evident metastasis. In the English literature, six out of the eleven cases showed recurrence of the lesion and only 4 cases showed metastasis; whether to lungs or lymph nodes 6 . Kunkel et al . (2004) reported the late metastasis of their case; which was evident about 5 years after the first diagnosis 10 . There were five out of the eleven cases encountered death 6 , one of them was actually due to systemic complication after the resection of the lesion 7 . The principle line of treatment, as with other malignant odontogenic neoplasms, is surgical resection with a wide safety margin along with neck dissection. However, adjunctive radiotherapy is still a matter of question, and it may be helpful in cases with soft tissue invasion 6 . Conclusion OCS is an extremely rare odontogenic malignant neoplasm that shows very aggressive clinical behavior with multiple recurrences and possible metastasis. Close long follow-up is recommended; due to the possible late metastasis of the lesion. Immunohistochemical staining with vimentin, α-SMA and Ki-67 is helpful in the diagnosis of OCS. Data availability All data underlying the results are available as part of the article and no additional source data are required. Consent Written informed consent for publication of their clinical details or clinical images was obtained from the patient. Acknowledgments This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the fast track Reaseach Funding Program. Moreover, we are sincerely grateful for our colleges in Oral & Maxillofacial Surgery department, Faculty of Dentistry, Cairo University. Faculty Opinions recommended References 1. El-Naggar AK, Chan JKC, Grandis JR, et al. : WHO Classification of Head and Neck Tumours. 4th edition, Lyon: IARC Press; 2017; 9 : 213. Reference Source 2. DeLair D, Bejarano PA, Peleg M, et al. : Ameloblastic carcinosarcoma of the mandible arising in ameloblastic fibroma: a case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2007; 103 (4): 516–520. PubMed Abstract | Publisher Full Text 3. Tanaka T, Ohkubo T, Fujitsuka H, et al. : Malignant mixed tumor (malignant ameloblastoma and fibrosarcoma) of the maxilla. Arch Pathol Lab Med. 1991; 115 (1): 84–87. PubMed Abstract 4. Dos Santos JN, Servato JPS, Cardoso SV, et al. : Odontogenic carcinosarcoma: morphologic and immunohistochemical description of a case. Oral Surg Oral Med Oral Pathol Oral Radiol. 2018; 126 (5): e264–e270. PubMed Abstract | Publisher Full Text 5. Soluk-Tekkeşin M, Wright JM: The World Health Organization Classification of Odontogenic Lesions: A Summary of the Changes of the 2017 (4th) Edition. Turk Patoloji Derg. 2018; 34 (1). PubMed Abstract | Publisher Full Text 6. Schuch LF, de Arruda JAA, Silva LVO, et al. : Odontogenic carcinosarcoma: A systematic review. Oral Oncol. 2018; 85 : 52–59. PubMed Abstract | Publisher Full Text 7. Soares CD, Delgado-Azañero W, Morais TMDL, et al. : Odontogenic Carcinosarcoma: Clinicopathologic Features of 2 Cases. Int J Surg Pathol. 2020; 28 (4): 421–426. PubMed Abstract | Publisher Full Text 8. Kim IK, Pae SP, Cho HY, et al. : Odontogenic carcinosarcoma of the mandible: a case report and review. J Korean Assoc Oral Maxillofac Surg. 2015; 41 (3): 139–144. PubMed Abstract | Publisher Full Text | Free Full Text 9. Giraddi GB, Garg V: Aggressive atypical ameloblastic fibrodentinoma: Report of a case. Contemp Clin Dent. 2012; 3 (1): 97–102. PubMed Abstract | Publisher Full Text | Free Full Text 10. Kunkel M, Ghalibafian M, Radner H, et al. : Ameloblastic fibrosarcoma or odontogenic carcinosarcoma: a matter of classification? Oral Oncol. 2004; 40 (4): 444–449. PubMed Abstract | Publisher Full Text 11. Chikosi R, Segall N, Augusto P, et al. : Odontogenic carcinosarcoma: case report and literature review. J Oral Maxillofac Surg. 2011; 69 (5): 1501–1507. PubMed Abstract | Publisher Full Text 12. McLean-Holden AC, Bishop JA, Kessler HP, et al. : Spindle-cell variant of ameloblastic carcinoma: a report of 3 cases and demonstration of epithelial-mesenchymal transition in tumor progression. Oral Surg Oral Med Oral Pathol Oral Radiol. 2019; 128 (3): e113–e121. PubMed Abstract | Publisher Full Text 13. Bello IO, Alanen K, Slootweg PJ, et al. : Alpha-smooth muscle actin within epithelial islands is predictive of ameloblastic carcinoma. Oral Oncol. 2009; 45 (9): 760–5. PubMed Abstract | Publisher Full Text 14. Mahmoud SAM, Amer HW, Mohamed SI: Primary ameloblastic carcinoma: literature review with case series. Pol J Pathol. 2018; 69 (3): 243–253. PubMed Abstract | Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 12 Jun 2020 ADD YOUR COMMENT Comment Author details Author details 1 Basic Dental Services Department, Princess Nourah Bint Abdulrahman University, College of Dentistry, Riyadh, Saudi Arabia 2 Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt Hend Mohammed Waguih Mahmoud Salem Roles: Conceptualization, Funding Acquisition, Resources, Supervision, Writing – Review & Editing Sarah Ahmed Mohamed Mahmoud Badawy Roles: Conceptualization, Formal Analysis, Methodology, Project Administration, Software, Visualization, Writing – Original Draft Preparation Hatem Wael Amer Roles: Data Curation, Investigation, Methodology, Supervision, Validation, Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information This research was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University through the fast track Research Funding Program. Article Versions (2) version 2 Revised Published: 15 Dec 2020, 9:603 https://doi.org/10.12688/f1000research.23969.2 version 1 Published: 12 Jun 2020, 9:603 https://doi.org/10.12688/f1000research.23969.1 Copyright © 2020 Salem HMWM et al . 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 work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Salem HMWM, Ahmed Mohamed Mahmoud Badawy S and Amer HW. Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.12688/f1000research.23969.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 15 Dec 2020 Revised Views 0 Cite How to cite this report: Wright J. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r79791 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-79791 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 23 Feb 2021 John Wright , Department of Diagnostic Sciences, Texas A&M College of Dentistry, Dallas, TX, USA Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.31317.r79791 I have reviewed the case report of an odontogenic carcinosarcoma arising from a premature odontoma and I do not agree with the diagnostic interpretation rendered. While the description provided is more supportive of the diagnosis, the illustrations provided do not ... Continue reading READ ALL I have reviewed the case report of an odontogenic carcinosarcoma arising from a premature odontoma and I do not agree with the diagnostic interpretation rendered. While the description provided is more supportive of the diagnosis, the illustrations provided do not in my opinion confirm the diagnosis. The illustrations are not of the highest quality. In Fig 3, there is nothing to suggest malignancy and I would question the presence of dentinoid. I would have diagnosed this as ameloblastic fibroma. Fig 4 is not obviously malignant to me either, either component. There is some nuclear hyperchromasia in the epithelial component but this does not appear malignant. I admit there is increased cellularity in the ectomesenchymal component along with some limited cytologic atypia, which is concerning but this component is not obviously malignant to me either. The Ki-67 reactivity is more consistent with a benign diagnosis. I don't think the IHC in Fig 5 adds any evidence for a malignant diagnosis. The cytokeratin and vimentin reactivity would be expected with a benign or malignant diagnosis and the SMA illustrated shows only the vessel walls. At best from the illustrations provided, this might be called an atypical ameloblastic fibroma but I am not convinced either component is malignant and must recommend against its indexing. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: I have 40 years of surgical pathology experience with one of the worlds largest biopsy services. I am a past President of the American Board of Oral and Maxillofacial Pathology. I was a member of the WHO working group that published the most current WHO classification of odontogenic cysts and tumors. I am currently a co-editor writing the new AFIP fascicle on head and neck pathology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Wright J. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r79791 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-79791 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Servato JPS. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r76168 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-76168 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 13 Jan 2021 João Paulo Silva Servato , University of Uberaba, Uberaba, Brazil Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.31317.r76168 Most of the required topics were improved in this new version. Although that, some minors points still need some corrections: The title of the manuscript, the diagnosis of the first Histopathological examination and the Figure 3 ... Continue reading READ ALL Most of the required topics were improved in this new version. Although that, some minors points still need some corrections: The title of the manuscript, the diagnosis of the first Histopathological examination and the Figure 3 legend, should be totally reconsidered by the authors to attend the new WHO classification and current nomenclature. Ki-67 image (Figure 06) must be improved to clearly demonstrate the high levels of Ki-67 tagging in both epithelial and mesenchymal components, specially in high pleomorphic areas. The percentual measurement of Ki-67 expression areas, using Leica Qwin software, appears to not validate the picture seen in Figure 06 (A). Analysis/figure should be revised. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral and maxillofacial pathology; Oral medicine; Immunology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Servato JPS. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r76168 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-76168 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 12 Jun 2020 Views 0 Cite How to cite this report: Servato JPS. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r69312 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-69312 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Sep 2020 João Paulo Silva Servato , University of Uberaba, Uberaba, Brazil Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.26443.r69312 1) Is the background of the case’s history and progression described in sufficient detail? Partly - In reason to understand OCS progression and outcomes, more follow up details should be addressed. Moreover, the authors ... Continue reading READ ALL 1) Is the background of the case’s history and progression described in sufficient detail? Partly - In reason to understand OCS progression and outcomes, more follow up details should be addressed. Moreover, the authors should attend to the new WHO classification nomenclature. As stated by Speight PM, and Takata T., 2018: "the ameloblastic fibrodentinoma and ameloblastic fibro-odontoma have been removed as distinct entities" 1 . In this way, the nomenclature should be reviewed. 2) Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No - Please, improve the details in histopathological and immunohistochemical profile. 2.1) High power field images is needed to improve the recognition of the main expected features, as described by El-Mofty, S. K., in the 2017 WHO blue book "The cells in the sarcomatous component are markedly pleomorphic, with enlarged and bizarre nuclei and occasional multinucleation and mitosis. The epithelial component is frankly malignant, with large hyperchromatic nuclei and an increased N:C ratio. The typical ameloblastic features such as peripheral nuclear palisading and inner stellate reticulum may be lost focally." 2 In the same way, Ki-67 images must be improved to clearly demonstrate the high levels of Ki-67 tagging in both epithelial and mesenchymal components. 3) Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly, the discussion section should be expanded to access the relevance of this case in the understand of OCS main epidemiological characteristics, histopathological features, the biological profile and its prognosis/ behavior. Moreover, as describe in CARE guidelines, this section must describe: a) Strengths and limitations in your approach to this case. b) The rationale for your conclusions. c) The primary “take-away” lessons from this case report. 4) Is the case presented with sufficient detail to be useful for other practitioners? No, since it do not attended to most recent WHO classification and to CARE guidelines. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? No References 1. Speight PM, Takata T: New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours. Virchows Arch . 2018; 472 (3): 331-339 PubMed Abstract | Publisher Full Text 2. El-Naggar AK, Chan JKC, Grandis JR, et al. : WHO Classification of Head and Neck Tumours. IARC Press . 2017; 9 : 213 3. Wright JM, Vered M: Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors. Head Neck Pathol . 2017; 11 (1): 68-77 PubMed Abstract | Publisher Full Text 4. Soares CD, Delgado-Azañero W, Morais TML, de Almeida OP, et al.: Odontogenic Carcinosarcoma: Clinicopathologic Features of 2 Cases. Int J Surg Pathol . 2020; 28 (4): 421-426 PubMed Abstract | Publisher Full Text Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral and maxillofacial pathology; Oral medicine; Immunology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Servato JPS. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r69312 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-69312 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 15 Dec 2020 Sarah Ahmed Mohamed Mahmoud Badawy , Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt 15 Dec 2020 Author Response First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: ... Continue reading First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: We did contact the surgeon to collect more details about the follow-up of the patient. We changed the nomenclature of '' ameloblastic fibrodentinoma'' as you recommended, and clarified the reason why we diagnosed it like that. We changed and added histopathological figures as you recommended with more detailed interpretation. We repeated the ki67 staining and analysed it with the image analyser Leica QWin software. We tried to improve the discussion part as you recommended to follow CARE guidelines. We hope that our revisions meet your expectations. Again, thank you for your precious time. First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: We did contact the surgeon to collect more details about the follow-up of the patient. We changed the nomenclature of '' ameloblastic fibrodentinoma'' as you recommended, and clarified the reason why we diagnosed it like that. We changed and added histopathological figures as you recommended with more detailed interpretation. We repeated the ki67 staining and analysed it with the image analyser Leica QWin software. We tried to improve the discussion part as you recommended to follow CARE guidelines. We hope that our revisions meet your expectations. Again, thank you for your precious time. Competing Interests: No competing interests Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 15 Dec 2020 Sarah Ahmed Mohamed Mahmoud Badawy , Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt 15 Dec 2020 Author Response First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: ... Continue reading First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: We did contact the surgeon to collect more details about the follow-up of the patient. We changed the nomenclature of '' ameloblastic fibrodentinoma'' as you recommended, and clarified the reason why we diagnosed it like that. We changed and added histopathological figures as you recommended with more detailed interpretation. We repeated the ki67 staining and analysed it with the image analyser Leica QWin software. We tried to improve the discussion part as you recommended to follow CARE guidelines. We hope that our revisions meet your expectations. Again, thank you for your precious time. First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: We did contact the surgeon to collect more details about the follow-up of the patient. We changed the nomenclature of '' ameloblastic fibrodentinoma'' as you recommended, and clarified the reason why we diagnosed it like that. We changed and added histopathological figures as you recommended with more detailed interpretation. We repeated the ki67 staining and analysed it with the image analyser Leica QWin software. We tried to improve the discussion part as you recommended to follow CARE guidelines. We hope that our revisions meet your expectations. Again, thank you for your precious time. Competing Interests: No competing interests Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: de Almeida OP. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r65932 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-65932 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 18 Aug 2020 Oslei Paes de Almeida , Diagnosis Department, Oral Pathology Section, Dentistry Faculty of Piracicaba, State University of Campinas, São Paulo, Brazil Not Approved VIEWS 0 https://doi.org/10.5256/f1000research.26443.r65932 I read this article and below are my comments for the journal: Based on documentations included in the article some points should be reconsidered by the authors. Diagnosis of ameloblastic fibrodentinoma does ... Continue reading READ ALL I read this article and below are my comments for the journal: Based on documentations included in the article some points should be reconsidered by the authors. Diagnosis of ameloblastic fibrodentinoma does not seem to be correct, dentinoid material is not evident. Possibly from the beginning the lesion is an ameloblastic fibrosarcoma, therefore the microscopical aspects should be carefully reviewed including a Ki-67 staining. Diagnosis of carcinosarcoma should be reconsidered and most immune reactions repeated and reanalysed, including Ki-67. Interpretation of some reactions does not seem to be appropriate. Is the background of the case’s history and progression described in sufficient detail? No Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests: No competing interests were disclosed. Reviewer Expertise: Oral Pathology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT de Almeida OP. Reviewer Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r65932 ) The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-65932 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 17 Sep 2020 Sarah Ahmed Mohamed Mahmoud Badawy , Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt 17 Sep 2020 Author Response First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy ... Continue reading First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy was based on the presence of dentinoid material which is evident in figure 3.A. Moreover, both the ectomesenchymal and the epithelial compartments in the first biopsy showed little cellular activity without cellular atypia in all fields, there was no way to consider it as a malignancy back then without histopathological evidence; even if the clinical behavior was doubted. The immunohistochemical reaction of Ki67 was interpreted with 3 pathologists last, I wished you can mention clearly what the details do you need us to clarify in the sections of case history, physical examination, investigations, and discussion? Thank you for your time. First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy was based on the presence of dentinoid material which is evident in figure 3.A. Moreover, both the ectomesenchymal and the epithelial compartments in the first biopsy showed little cellular activity without cellular atypia in all fields, there was no way to consider it as a malignancy back then without histopathological evidence; even if the clinical behavior was doubted. The immunohistochemical reaction of Ki67 was interpreted with 3 pathologists last, I wished you can mention clearly what the details do you need us to clarify in the sections of case history, physical examination, investigations, and discussion? Thank you for your time. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 17 Sep 2020 Sarah Ahmed Mohamed Mahmoud Badawy , Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt 17 Sep 2020 Author Response First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy ... Continue reading First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy was based on the presence of dentinoid material which is evident in figure 3.A. Moreover, both the ectomesenchymal and the epithelial compartments in the first biopsy showed little cellular activity without cellular atypia in all fields, there was no way to consider it as a malignancy back then without histopathological evidence; even if the clinical behavior was doubted. The immunohistochemical reaction of Ki67 was interpreted with 3 pathologists last, I wished you can mention clearly what the details do you need us to clarify in the sections of case history, physical examination, investigations, and discussion? Thank you for your time. First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy was based on the presence of dentinoid material which is evident in figure 3.A. Moreover, both the ectomesenchymal and the epithelial compartments in the first biopsy showed little cellular activity without cellular atypia in all fields, there was no way to consider it as a malignancy back then without histopathological evidence; even if the clinical behavior was doubted. The immunohistochemical reaction of Ki67 was interpreted with 3 pathologists last, I wished you can mention clearly what the details do you need us to clarify in the sections of case history, physical examination, investigations, and discussion? Thank you for your time. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 12 Jun 2020 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 15 Dec 20 read read Version 1 12 Jun 20 read read Oslei Paes de Almeida , State University of Campinas, São Paulo, Brazil João Paulo Silva Servato , University of Uberaba, Uberaba, Brazil John Wright , Texas A&M College of Dentistry, Dallas, USA Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Wright J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 23 Feb 2021 | for Version 2 John Wright , Department of Diagnostic Sciences, Texas A&M College of Dentistry, Dallas, TX, USA 0 Views copyright © 2021 Wright J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I have reviewed the case report of an odontogenic carcinosarcoma arising from a premature odontoma and I do not agree with the diagnostic interpretation rendered. While the description provided is more supportive of the diagnosis, the illustrations provided do not in my opinion confirm the diagnosis. The illustrations are not of the highest quality. In Fig 3, there is nothing to suggest malignancy and I would question the presence of dentinoid. I would have diagnosed this as ameloblastic fibroma. Fig 4 is not obviously malignant to me either, either component. There is some nuclear hyperchromasia in the epithelial component but this does not appear malignant. I admit there is increased cellularity in the ectomesenchymal component along with some limited cytologic atypia, which is concerning but this component is not obviously malignant to me either. The Ki-67 reactivity is more consistent with a benign diagnosis. I don't think the IHC in Fig 5 adds any evidence for a malignant diagnosis. The cytokeratin and vimentin reactivity would be expected with a benign or malignant diagnosis and the SMA illustrated shows only the vessel walls. At best from the illustrations provided, this might be called an atypical ameloblastic fibroma but I am not convinced either component is malignant and must recommend against its indexing. Is the background of the case’s history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests No competing interests were disclosed. Reviewer Expertise I have 40 years of surgical pathology experience with one of the worlds largest biopsy services. I am a past President of the American Board of Oral and Maxillofacial Pathology. I was a member of the WHO working group that published the most current WHO classification of odontogenic cysts and tumors. I am currently a co-editor writing the new AFIP fascicle on head and neck pathology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (0) Wright J. Peer Review Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r79791) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-79791 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2021 Servato J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 13 Jan 2021 | for Version 2 João Paulo Silva Servato , University of Uberaba, Uberaba, Brazil 0 Views copyright © 2021 Servato J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Most of the required topics were improved in this new version. Although that, some minors points still need some corrections: The title of the manuscript, the diagnosis of the first Histopathological examination and the Figure 3 legend, should be totally reconsidered by the authors to attend the new WHO classification and current nomenclature. Ki-67 image (Figure 06) must be improved to clearly demonstrate the high levels of Ki-67 tagging in both epithelial and mesenchymal components, specially in high pleomorphic areas. The percentual measurement of Ki-67 expression areas, using Leica Qwin software, appears to not validate the picture seen in Figure 06 (A). Analysis/figure should be revised. Competing Interests No competing interests were disclosed. Reviewer Expertise Oral and maxillofacial pathology; Oral medicine; Immunology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (0) Servato JPS. Peer Review Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.31317.r76168) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-603/v2#referee-response-76168 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2020 Servato J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Sep 2020 | for Version 1 João Paulo Silva Servato , University of Uberaba, Uberaba, Brazil 0 Views copyright © 2020 Servato J. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions 1) Is the background of the case’s history and progression described in sufficient detail? Partly - In reason to understand OCS progression and outcomes, more follow up details should be addressed. Moreover, the authors should attend to the new WHO classification nomenclature. As stated by Speight PM, and Takata T., 2018: "the ameloblastic fibrodentinoma and ameloblastic fibro-odontoma have been removed as distinct entities" 1 . In this way, the nomenclature should be reviewed. 2) Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No - Please, improve the details in histopathological and immunohistochemical profile. 2.1) High power field images is needed to improve the recognition of the main expected features, as described by El-Mofty, S. K., in the 2017 WHO blue book "The cells in the sarcomatous component are markedly pleomorphic, with enlarged and bizarre nuclei and occasional multinucleation and mitosis. The epithelial component is frankly malignant, with large hyperchromatic nuclei and an increased N:C ratio. The typical ameloblastic features such as peripheral nuclear palisading and inner stellate reticulum may be lost focally." 2 In the same way, Ki-67 images must be improved to clearly demonstrate the high levels of Ki-67 tagging in both epithelial and mesenchymal components. 3) Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly, the discussion section should be expanded to access the relevance of this case in the understand of OCS main epidemiological characteristics, histopathological features, the biological profile and its prognosis/ behavior. Moreover, as describe in CARE guidelines, this section must describe: a) Strengths and limitations in your approach to this case. b) The rationale for your conclusions. c) The primary “take-away” lessons from this case report. 4) Is the case presented with sufficient detail to be useful for other practitioners? No, since it do not attended to most recent WHO classification and to CARE guidelines. Is the background of the case’s history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the case presented with sufficient detail to be useful for other practitioners? No References 1. Speight PM, Takata T: New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours. Virchows Arch . 2018; 472 (3): 331-339 PubMed Abstract | Publisher Full Text 2. El-Naggar AK, Chan JKC, Grandis JR, et al. : WHO Classification of Head and Neck Tumours. IARC Press . 2017; 9 : 213 3. Wright JM, Vered M: Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors. Head Neck Pathol . 2017; 11 (1): 68-77 PubMed Abstract | Publisher Full Text 4. Soares CD, Delgado-Azañero W, Morais TML, de Almeida OP, et al.: Odontogenic Carcinosarcoma: Clinicopathologic Features of 2 Cases. Int J Surg Pathol . 2020; 28 (4): 421-426 PubMed Abstract | Publisher Full Text Competing Interests No competing interests were disclosed. Reviewer Expertise Oral and maxillofacial pathology; Oral medicine; Immunology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 15 Dec 2020 Sarah Ahmed Mohamed Mahmoud Badawy, Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt First, we can't thank you enough for your sincere and detailed review. We made a second version of the article with the revisions you recommended in your review; as follow: We did contact the surgeon to collect more details about the follow-up of the patient. We changed the nomenclature of '' ameloblastic fibrodentinoma'' as you recommended, and clarified the reason why we diagnosed it like that. We changed and added histopathological figures as you recommended with more detailed interpretation. We repeated the ki67 staining and analysed it with the image analyser Leica QWin software. We tried to improve the discussion part as you recommended to follow CARE guidelines. We hope that our revisions meet your expectations. Again, thank you for your precious time. View more View less Competing Interests No competing interests reply Respond Report a concern Servato JPS. Peer Review Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r69312) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-69312 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2020 de Almeida O. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 18 Aug 2020 | for Version 1 Oslei Paes de Almeida , Diagnosis Department, Oral Pathology Section, Dentistry Faculty of Piracicaba, State University of Campinas, São Paulo, Brazil 0 Views copyright © 2020 de Almeida O. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Not Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions I read this article and below are my comments for the journal: Based on documentations included in the article some points should be reconsidered by the authors. Diagnosis of ameloblastic fibrodentinoma does not seem to be correct, dentinoid material is not evident. Possibly from the beginning the lesion is an ameloblastic fibrosarcoma, therefore the microscopical aspects should be carefully reviewed including a Ki-67 staining. Diagnosis of carcinosarcoma should be reconsidered and most immune reactions repeated and reanalysed, including Ki-67. Interpretation of some reactions does not seem to be appropriate. Is the background of the case’s history and progression described in sufficient detail? No Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? No Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? No Is the case presented with sufficient detail to be useful for other practitioners? No Competing Interests No competing interests were disclosed. Reviewer Expertise Oral Pathology. I confirm that I have read this submission and believe that I have an appropriate level of expertise to state that I do not consider it to be of an acceptable scientific standard, for reasons outlined above. reply Respond to this report Responses (1) Author Response 17 Sep 2020 Sarah Ahmed Mohamed Mahmoud Badawy, Oral & Maxillo-facial Pathology Department, Faculty of Dentistry, Cairo University, 11553, Egypt First of all, thank you for your review. I hope that in my response, I will be able to clarify some points: The diagnosis of the first biopsy was based on the presence of dentinoid material which is evident in figure 3.A. Moreover, both the ectomesenchymal and the epithelial compartments in the first biopsy showed little cellular activity without cellular atypia in all fields, there was no way to consider it as a malignancy back then without histopathological evidence; even if the clinical behavior was doubted. The immunohistochemical reaction of Ki67 was interpreted with 3 pathologists last, I wished you can mention clearly what the details do you need us to clarify in the sections of case history, physical examination, investigations, and discussion? Thank you for your time. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern de Almeida OP. Peer Review Report For: Case Report: Odontogenic carcinosarcoma arising from premature odontoma with immunohistochemical profile [version 2; peer review: 1 approved with reservations, 2 not approved] . F1000Research 2020, 9 :603 ( https://doi.org/10.5256/f1000research.26443.r65932) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/9-603/v1#referee-response-65932 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved - fundamental flaws in the paper seriously undermine the findings and conclusions Adjust parameters to alter display View on desktop for interactive features Includes Interactive Elements View on desktop for interactive features Competing Interests Policy Provide sufficient details of any financial or non-financial competing interests to enable users to assess whether your comments might lead a reasonable person to question your impartiality. 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Register $(document).ready(function () { signIn.createSignInAsRow($("#sign-in-form-gfb-popup")); $(".target-field").each(function () { var uris = $(this).val().split("/"); if (uris.pop() === "login") { $(this).val(uris.toString().replace(",","/")); } }); });