Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence

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This association is very rare. Case presentation We describe a case of synchronous stromal tumor and adenocarcinoma of the left side colonic localization. Immunohistochemistry identified c-Kit expression. The discovery of colonic adenocarcinoma was on operative specimen after histologic examination. The patient underwent left oncologic colectomy with stoma. Follow-up at one year postoperatively did not detect tumor recurrence. Discussion Clinical implications of the association between these two neoplasms are not clearly described. Treatment depends on the the most aggressive histologic type or obviously highest stage. Knowledge of the genetic data of this association offers opportunity of treatment with the new targeted-therapy molecules. Surgical resection, may remain the curative treatment. Conclusions Synchronous adenocarcinoma and GIST has been more commonly described in the stomach. The pathogeneses of tumorigenesis may not be the same for the two tumors. More studies seem be necessary to clarify a potential role of different genes in the development of adenocarcinomas. And therefore, above all their therapeutic implications. " } { "@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/12-1055/v4", "name": "Case Report: Synchronous primary location of gastrointestinal stromal..." } } ] } Home Browse Case Report: Synchronous primary location of gastrointestinal stromal... ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Sghaier A, El Ghali A, Fradi K et al. Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.12688/f1000research.139536.4 ) 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: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] Asma Sghaier https://orcid.org/0000-0001-7691-2186 1,2 , Amine El Ghali 1,2 , Khalil Fradi 1 , Dorra Chiba 2,3 , Fehmi Hamila 1,2 , Sabri Youssef 1,2 Asma Sghaier https://orcid.org/0000-0001-7691-2186 1,2 , Amine El Ghali 1,2 , [...] Khalil Fradi 1 , Dorra Chiba 2,3 , Fehmi Hamila 1,2 , Sabri Youssef 1,2 PUBLISHED 06 Oct 2025 Author details Author details 1 General surgery, Hospital Farhat Hached, Sousse, Tunisia 2 General surgery, Faculty of Medicine, University of Sousse, Sousse, 4000, Tunisia 3 Cytogenetic and anatomopathology, Hospital Farhat Hached Sousse, Sousse, Tunisia Asma Sghaier Roles: Writing – Review & Editing Amine El Ghali Roles: Writing – Review & Editing Khalil Fradi Roles: Visualization Dorra Chiba Roles: Visualization Fehmi Hamila Roles: Writing – Review & Editing Sabri Youssef Roles: Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. Abstract Background We have little knowledge about the synchronous occurrence of gastrointestinal stromal tumors (GISTs) and other types of histologic tumors. This association is very rare. Case presentation We describe a case of synchronous stromal tumor and adenocarcinoma of the left side colonic localization. Immunohistochemistry identified c-Kit expression. The discovery of colonic adenocarcinoma was on operative specimen after histologic examination. The patient underwent left oncologic colectomy with stoma. Follow-up at one year postoperatively did not detect tumor recurrence. Discussion Clinical implications of the association between these two neoplasms are not clearly described. Treatment depends on the the most aggressive histologic type or obviously highest stage. Knowledge of the genetic data of this association offers opportunity of treatment with the new targeted-therapy molecules. Surgical resection, may remain the curative treatment. Conclusions Synchronous adenocarcinoma and GIST has been more commonly described in the stomach. The pathogeneses of tumorigenesis may not be the same for the two tumors. More studies seem be necessary to clarify a potential role of different genes in the development of adenocarcinomas. And therefore, above all their therapeutic implications. READ ALL READ LESS Keywords Colon- adenocarcinoma-GIST- C-Kit-synchronous Corresponding Author(s) Asma Sghaier ( [email protected] ) Close Corresponding author: Asma Sghaier Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Sghaier A 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: Sghaier A, El Ghali A, Fradi K et al. Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.12688/f1000research.139536.4 ) First published: 30 Aug 2023, 12 :1055 ( https://doi.org/10.12688/f1000research.139536.1 ) Latest published: 06 Oct 2025, 12 :1055 ( https://doi.org/10.12688/f1000research.139536.4 ) Revised Amendments from Version 3 These revisions significantly enhance the manuscript's scientific and translational value by deepening the analysis of the molecular pathology and providing explicit, evidence-based clinical recommendations. The Discussion section is expanded to move beyond the concept of incidental co-occurrence, detailing the potential convergence of oncogenic signaling at the RAS/MAPK pathway as a shared functional dependency that may facilitate co-tumorigenesis, despite the tumors having distinct initial drivers (KIT/PDGFRA in GIST vs. APC/KRAS in CRC). Furthermore, following reviewer input, the manuscript now includes concrete, evidence-based recommendations for the multidisciplinary management of this synchronous disease. This guidance emphasizes that the Very High-Risk GIST component (pT4 with high mitotic rate and capsular rupture) dictates the adjuvant protocol (mandatory Imatinib), and stresses the imperative for exhaustive molecular profiling (KIT/PDGFRA and KRAS/BRAF) of both lesions to maximize therapeutic foresight. These revisions significantly enhance the manuscript's scientific and translational value by deepening the analysis of the molecular pathology and providing explicit, evidence-based clinical recommendations. The Discussion section is expanded to move beyond the concept of incidental co-occurrence, detailing the potential convergence of oncogenic signaling at the RAS/MAPK pathway as a shared functional dependency that may facilitate co-tumorigenesis, despite the tumors having distinct initial drivers (KIT/PDGFRA in GIST vs. APC/KRAS in CRC). Furthermore, following reviewer input, the manuscript now includes concrete, evidence-based recommendations for the multidisciplinary management of this synchronous disease. This guidance emphasizes that the Very High-Risk GIST component (pT4 with high mitotic rate and capsular rupture) dictates the adjuvant protocol (mandatory Imatinib), and stresses the imperative for exhaustive molecular profiling (KIT/PDGFRA and KRAS/BRAF) of both lesions to maximize therapeutic foresight. See the authors' detailed response to the review by Shamus R. Carr See the authors' detailed response to the review by Nafiza Martini READ REVIEWER RESPONSES Introduction Stromal tumors are the most common mesenchymal tumors of the gastrointestinal tract. They derive from the interstitial cells of Cajal. 1 The coexistence of gastrointestinal stromal tumors (GIST) and colorectal adenocarcinomas is unusual. This association has been rather more described in the stomach. Most of them were discovered during surgical intervention for primary gastrointestinal adenocarcinoma. 1 , 2 The synchronous occurrence of primary colonic adenocarcinoma and stromal tumors brings us to think about the possibility of similar origin and carcinogenetic process, and the possibility of similar systemic drugs specially target therapy. Furthermore, the association of specific tumors often leads to the discovery of novel genetic pathways to carcinogenesis that could be important for the development of oncologic therapeutics protocols. Case presentation A 79-year-old White retired school-teacher male was admitted complaining of asthenia and diffuse abdominal pain. The patient had no notable pathological history and had never been operated on. The patient also had no familial pathologic history notably no cancer history. The physical examination revealed a large, solid pelvic mass extending to the epigastrium, which was responsible for abdominal pain and a feeling of tightness ( Figure 1 ). Figure 1. Images showing the abdominal mass in frontal and profile positions. A colonoscopy was performed but was incomplete due to the presence of an impassable stenosis at the sigmoid, which seemed to be extrinsic. An abdominal-pelvic CT scan was performed and described a large abdominal-pelvic mass of 25 cm in length, which was enhanced after injection of contrast product and seemed to have a digestive origin ( Figure 2 ). Figure 2. CT scan showing tumor mass. Laparotomy confirmed the presence of a voluminous mass of the sigmoid adhering and invading the bladder dome extended to the upper rectum. This mass was friable, necrotic in places and centered by a liquefied hematoma ( Figure 3 ). Figure 3. Surgical specimen. There was no evidence of metastatic disease. The patient had undergone extensive resection with lymph node curage according to oncological requirements and the bladder dome was partially resected. In fact, a bladder bezel that was adhering to the tumor was removed. Given the hemorrhagic nature and the precarious nutritional state of the patient. We decided to postpone an anastomosis and perform a Hartmann stoma. Surgical follow-up was favorable, and the patient was discharged on the eighth day of the post-operative period. The surgical resection piece was sent to the department of Pathology, macroscopically, the specimen corresponded to the left colon extended to the rectum measuring 20 cm in length, 3.5 cm at the colonic border and 2.5 cm at the rectal border. The wall was the site of a shredded tumor lesion extending 15 cm in height ( Figure 4 ). Figure 4. Subtype of gastrointestinal stromal tumour (GIST): A(1and2): photomicrographs showing at low magnification (HE*40) a proliferation with a disorganized bundle architecture. B and C: at higher magnification *100 and *400 respectively show spindle cells with eosinophilic cytoplasm and elongated hyperchromatic nuclei that are not very atypical. On opening, the colonic lumen was partially obstructed by a 4 cm high protrusion of the colonic mucosa, under which there was a whitish tumor proliferation with two macroscopic aspects, whitish fasciculated in the submucosa ulcerating the mucosa ( Figure 4 ). This aspect is partially separated by the muscularis propria from the other aspect of the tumor, which shows necrotic and hemorrhagic remodeling, and extends towards the serosa, where there is a capsular rupture. At 1.5 cm from this tumor there was an intraluminal polypoid lesion measuring 1.5 cm long. Regarding histology, the main tumor was a mixed gastrointestinal stromal tumor (GIST), with spindle cells in the submucosa and epithelial cells in the outer layers of the colonic wall, with a high risk of recurrence due to the innumerable mitoses, which exceeded 100 mitoses per 50 fields at high magnification, and the capsular rupture, according to the Miettinen and Joensuu classification ( Figure 5 ) and was classified pT4 according to TNM 2017 in the eighth edition. 3 Figure 5. The tumor cells are positive for C-kit (A) and Dog-1 (B: fusiform contingent, C: interface of the two contingents, D: epithelial contingent). They are negative for Desmin (E), AML smooth muscle actin (F) and panCytokeratin (G). The polypoid lesion was an adenocarcinoma NOS type well differentiated developed on degenerated adenoma stadified pT1N0 ( Figure 6 ). Figure 6. A well-differentiated, low-grade NOS-type adenocarcinoma invading the submucosa without going beyond it. The patient medical file was discussed with the multidisciplinary consensus staff indicated treatment with imatinib-based targeted therapies. Follow-up at one year postoperatively did not detect tumor recurrence. Discussion Stromal tumors are the most common mesenchymal tumors of the digestive tract. Yearly incidence rates range between 4.3 to 22 per million in the world, which is due to variability, the improving diagnostic criteria and a lack of GIST registries. 4 Simultaneous presence of colonic adenocarcinoma and stromal tumor is an uncommon occurrence. Because of the high incidence of adenocarcinoma histological type and the frequency of gastrointestinal stromal tumors (GIST), a fortuitous relationship based on the available data cannot be ruled out. The Genetic pathways of tumorigenesis are different for the two histologic types; c-Kit appears to be occasionally expressed in adenocarcinoma, and there is no evidence if the protein is indeed in the carcinogenetic process; this report is not available for stromal tumors. A review concluded that STI571 blocks the growth of colonic carcinoma cell lines. 5 These results justified by preclinical investigations of c-Kit expression in colonic cancers had as objective to evaluate the use of tyrosine kinase inhibitors in the treatment of colorectal carcinomas. We have presented a case of synchronous invasive colonic GIST with adenocarcinoma. Despite the relative common occurrence of GISTs, reports of synchronous adenocarcinoma and GISTs are quite rare. According to Kover et al ., 7 of 43 patients with histologically evidence of GISTs were found with second histological type; three of these GISTs were colorectal adenocarcinomas. 5 A second study realized by Au et al ., found that nearly 41% of the stromal tumors were synchronous association with second malignant tumor, and 38% of these second malignancies were intestinal. 6 Colonic adenocarcinoma and GIST present evidence of familial predisposition, except hereditary cancers. In another case, the patient did not have a family history of gastrointestinal or other malignancies. 7 The genetic polymorphism of these two histologic types has been particularly investigated. Through progression from normal colonic epithelium to adenoma and adenocarcinoma, various genetics cancers can occur. 8 Mechanisms have been clarified in sporadic colorectal cancer: chromosomal instability is responsible for 85% of the whole cases, and microsatellite instability, in the rest 15%. 8 Unusually, none of the most commonly involved genes in colorectal carcinogenesis (APC, DCC, p53, K-ras, DNA mismatch repair genes) have been identified to be associated in the pathway of stromal tumors. Nevertheless, the GISTs seem to be related with the proto-oncogene mutation c-Kit, a tyrosine kinase receptor during embryonic growth and on postnatal. Activation of c-Kit by its ligand, SCF, may generates a cascade of cellular process involving transformation, differentiation, cell proliferation, adhesion, and chemotaxis. 9 While the primary oncogenic drivers are structurally distinct (RTK activation via KIT/PDGFRA mutations in GIST versus CIN/MSI via APC/KRAS mutations in CRC), a crucial convergence point exists in the downstream signaling cascades, specifically the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway. Syndromic cases, such as Neurofibromatosis Type 1 (NF1)-associated dual malignancies, demonstrate that the inactivation of NF1 (a negative regulator of RAS) can simultaneously activate the MAPK pathway in both mesenchymal and epithelial tumor types. In sporadic cases, the simultaneous presence of distinct upstream drivers targeting this ubiquitous proliferative axis suggests a shared functional pathway dependency that may facilitate co-tumorigenesis, moving the discussion beyond purely incidental co-occurrence. Therefore, molecular profiling must exhaustively assess the status of the MAPK pathway components (KIT/PDGFRA in GIST; KRAS/BRAF in CRC) in both lesions to fully elucidate potential shared therapeutic vulnerabilities. When it is possible, surgery is the ideal therapeutic alternative with curative intention for non-metastatic stromal and adenocarcinoma at the same time. The operative strategies are in most situations wide and extensive. 10 The integrated surgical approach should be a one-stage radical resection to ensure simultaneous R0 margins and accurate staging. Since nodal involvement is rare, lymph-node clearance is not recommended. 11 The prognosis of stromal tumors depends on tumor localization, its size, and the mitotic activity. 12 , 13 The stage of synchronous malignancies is crucial because the dominant one is responsible of the outcome and survival. 13 Imatinib provide special focus in the treatment of stromal tumors; particularly, for neoadjuvant process. The benefits of this target therapy are well established to downstage inoperable cases especially by decreasing size. As a result, safe resection margins and therefore an R0 resection are recommended. 14 GIST presents a high rate of recurrence (40% within 2 years). 15 Just such colonic carcinoma, GISTs usually metastasize to the liver. 16 Overall survival after complete resection of stromal tumors ranges from 47% to 66% at 5 years, and seems to be longer in patients with low-grade tumors: 100% at 10 years for tumors with 0–1 mitosis/30 hpf. High-grade lesions:>10 mitosis/10 hpf, have the worst outcome: 0% survival at 10 years. Nevertheless, the absence of a high mitotic index does not guarantee a better outcome. 17 Overall, a 5-year survival for colonic adenocarcinoma correlates with the preoperative staging, and ranges from 3–8% for stage IV to 90% for stage I. 18 For our case the predominant histologic type was the stromal one (GIST), with a high risk of recurrence due to the innumerable mitoses, which exceeded 100 mitoses per 50 fields at high magnification, and the capsular rupture, according to the Miettinen and Joensuu classification and was classified pT4 according to TNM 2017. The adenocarcinoma type was well differentiated developed on degenerated adenoma stadified pT1N0. The patient was treated with imatinib-based targeted therapies. Based on the specific pathological findings in this case (GIST: Very High Risk, pT4, >100 mitoses/50 HPF, capsular rupture; CRC: Stage I, pT1N0), we offer the following evidence-based clinical recommendations for synchronous disease management: 1. Surgical Strategy: A single-stage radical oncologic resection is mandated. The operative strategy must balance the R0 margin requirement for the GIST, which is mandatory, with the definitive staging requirement for the CRC, demanding a complete regional lymphadenectomy (minimum 12 nodes). Adjuvant Therapy Systemic treatment must be dictated by the malignancy carrying the highest prognostic threat. Given the GIST’s classification as very high-risk, adjuvant Imatinib Mesylate therapy is unequivocally indicated. Eticulous immunohistochemical and molecular biology study of all resection specimens are highly recommended whenever the combination of two histological types is found in the primary anatomopathological study. These in-depth and ideally exhaustive studies guarantee the development of new targeted therapies and immunotherapies that would provide these patients with the opportunity of complete remission. Nonetheless, all such cases must be discussed at a multidisciplinary concertation involving all the medical staff. Finally, this case certainly illustrates a rare association of two histological entities. There are few cases described in the literature, which limits the possibility of reaching well-codified conclusions regarding management. However, we believe that this case highlights the necessity for more thorough immunohistochemical and molecular biology studies. The aim is to draw up recommendations with a high level of scientific evidence. Conclusion Synchronous tumors rare cancer of the colonic with the co-existence of two histologically different neoplasms occurring in the same site. This condition is rarely proven in preoperative investigations. Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. Perfect histopathologic examination with multiple biopsies and pathologic examination of resection specimens is required to detect synchronous tumors. Those with advanced or aggressive behavior has pejorative prognostic significance and should receive adjuvant therapy. Pathogeneses of like association are still not yet well identified. More studies are required to understand this incident to provide optimal curative management for patients. However, the biological observation that GIST and CRC pathologies frequently converge on, and share a functional reliance on, the RAS/MAPK signaling cascade provides a compelling molecular mechanism warranting further targeted investigation More studies are required to understand this incident to provide optimal curative management for patients. We believe that sophisticated molecular biology studies are the bridge to innovative, more effective and targeted therapies. Consent Written informed consent was obtained from the patient for publication of this case report and accompanying images. Data availability All data underlying the results are available as part of the article and no additional source data are required. References 1. Wronski M, Ziarkiewicz-Wroblewska B, Gornicka B, et al. : Synchronous occurrence of gastrointestinal tumors and other primary gastrointestinal neoplasms. World J. Gastroenterol. 2006; 12 : 5360–5362. Publisher Full Text 2. Melis M, Choi EA, Anders R, et al. : Synchronous colorectal adenocarcinoma and gastrointestinal tumor (GIST). Int. J. Color. Dis. 2007; 22 : 109–114. 3. Amin MB, Edge S, Green F, et al. : AJCC Cancer Staging Manual (ed 8th Edition). New York: Springer; 2017. Publisher Full Text 4. Waidhauser J, Bornemann A, Trepel M, et al. : Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia. World J. Gastroenterol. 2019; 25 (30): 4261–4277. Publisher Full Text 5. Gonçalves R, Linhares E, Albagli R, et al. : Occurrence of other tumors in patients with GIST. Surg. Oncol. 2010; 19 (4): e140–e143. Publisher Full Text 6. Au WY, Ho KM, Shek TW: Papillary renal cell carcinoma and gastrointestinal stromal tumor: a uniqueassociation. Ann. Oncol. 2004; 15 : 843–844. Publisher Full Text 7. Marcovalerio M, Eugene AC, Robert A, et al. : Synchronous colorectal adenocarcinoma and gastrointestinal stromal tumor (GIST). Int. J. Color. Dis. 2007; 22 : 109–114. Publisher Full Text 8. Hahn M, Koufaki ON, Schackert HK: Molecular biology of colorectal cancer and clinical consequences for colorectal cancer syndromes. Langenbeck’s Arch. Surg. 1998; 383 : 389–396. PubMed Abstract | Publisher Full Text 9. Linnekin D: Early signaling pathways activated by c-Kit in hematopoietic cells. Int. J. Biochem. Cell Biol. 1999; 31 : 1053–1074. PubMed Abstract | Publisher Full Text 10. DeMatteo RP, Lewis JJ, Leung D, et al. : Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann. Surg. 2000; 231 : 51–58. PubMed Abstract | Publisher Full Text | Free Full Text 11. Pidhorecky I, Cheney RT, Kraybill WG, et al. : Gastrointestinal stromal tumors: current diagnosis, biologic behavior, and management. Ann. Surg. Oncol. 2000; 7 : 705–712. PubMed Abstract | Publisher Full Text 12. Schneider-Stock R, Boltze C, Lasota J, et al. : Loss of p16 protein defines high-risk patients with gastrointestinal stromal tumors: a tissue microarray study. Clin. Cancer Res. 2005; 11 : 638–645. PubMed Abstract | Publisher Full Text 13. Miettinen M, El-Rifai W, Sobin LHL, et al. : Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum. Pathol. 2002; 33 : 478–483. Publisher Full Text 14. Vassos N, Agaimy A, Hohenberger W, et al. : Coexistence of gastrointestinal stromal tumors (GIST) and malignant neoplasms of different origin: Prognostic implications. Int. J. Surg. 2014; 12 (5): 371–377. PubMed Abstract | Publisher Full Text 15. DeMatteo RP, Lewis JJ, Leung D, et al. : Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann. Surg. 2000; 231 : 51–58. PubMed Abstract | Publisher Full Text | Free Full Text 16. Mudan SS, Conlon KC, Woodruff JM, et al. : Salvage surgery for patients with recurrent gastrointestinal sarcoma: prognostic factors to guide patient selection. Cancer. 2000; 88 : 66–74. PubMed Abstract | <a target="xrefwindow" id="d25241e969" href="https://doi.org/10.1002/(SICI)1097-0142(20000101)88:1 Publisher Full Text 17. Nowain A, Bhakta H, Pais S, et al. : Gastrointestinal stromal tumors: clinical profile, pathogenesis, treatment strategies and prognosis. J. Gastroenterol. Hepatol. 2005; 20 : 818–824. PubMed Abstract | Publisher Full Text 18. Efron J, Wexner SD: Rectal cancer.Cameron JL, editor. Current surgical therapy. 7th edn.Philadelphia: Elsevier Mosby; 2001; pp. 235–245. Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 30 Aug 2023 ADD YOUR COMMENT Comment Author details Author details 1 General surgery, Hospital Farhat Hached, Sousse, Tunisia 2 General surgery, Faculty of Medicine, University of Sousse, Sousse, 4000, Tunisia 3 Cytogenetic and anatomopathology, Hospital Farhat Hached Sousse, Sousse, Tunisia Asma Sghaier Roles: Writing – Review & Editing Amine El Ghali Roles: Writing – Review & Editing Khalil Fradi Roles: Visualization Dorra Chiba Roles: Visualization Fehmi Hamila Roles: Writing – Review & Editing Sabri Youssef Roles: Writing – Review & Editing Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (4) version 4 Revised Published: 06 Oct 2025, 12:1055 https://doi.org/10.12688/f1000research.139536.4 version 3 Revised Published: 07 Apr 2025, 12:1055 https://doi.org/10.12688/f1000research.139536.3 version 2 Revised Published: 26 Feb 2025, 12:1055 https://doi.org/10.12688/f1000research.139536.2 version 1 Published: 30 Aug 2023, 12:1055 https://doi.org/10.12688/f1000research.139536.1 Copyright © 2025 Sghaier A 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 Sghaier A, El Ghali A, Fradi K et al. Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.12688/f1000research.139536.4 ) 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 4 VERSION 4 PUBLISHED 06 Oct 2025 Revised Views 0 Cite How to cite this report: Martini N. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.188933.r420585 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v4#referee-response-420585 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 20 Oct 2025 Nafiza Martini , University of Illinois Chicago College of Medicine, Chicago, Illinois, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.188933.r420585 Thank you very much for your thoughtful and detailed revisions. I appreciate how comprehensively you addressed each point, particularly the enhanced molecular discussion and the addition of evidence-based management recommendations. The revised version reflects clear improvement in scientific depth and ... Continue reading READ ALL Thank you very much for your thoughtful and detailed revisions. I appreciate how comprehensively you addressed each point, particularly the enhanced molecular discussion and the addition of evidence-based management recommendations. The revised version reflects clear improvement in scientific depth and clinical applicability. Kind regards, Dr. Nafiza Martini Competing Interests: No competing interests were disclosed. Reviewer Expertise: General medicine and molecular biology of cancers 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Martini N. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.188933.r420585 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v4#referee-response-420585 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 3 VERSION 3 PUBLISHED 07 Apr 2025 Revised Views 0 Cite How to cite this report: Martini N. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r401921 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v3#referee-response-401921 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 27 Sep 2025 Nafiza Martini , University of Illinois Chicago College of Medicine, Chicago, Illinois, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.179521.r401921 This is a well-documented and instructive case on synchronous GIST and colonic adenocarcinoma, highlighting the complexity of dual malignancies and the role of multidisciplinary surgical strategies. The histopathological detail and therapeutic implications are clearly presented. This is ... Continue reading READ ALL This is a well-documented and instructive case on synchronous GIST and colonic adenocarcinoma, highlighting the complexity of dual malignancies and the role of multidisciplinary surgical strategies. The histopathological detail and therapeutic implications are clearly presented. This is an instructive and rare case that not only documents a clinical challenge but also raises important questions about shared and divergent oncogenic pathways. Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work. In the Discussion section, authors have mentioned " The aim is to draw up recommendations with a high level of scientific evidence"; actually, it is the author's duty to give the recommendations after finishing the discussion. so, they should read more deeply in literature and empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end! 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? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: General medicine and molecular biology of cancers 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 Martini N. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r401921 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v3#referee-response-401921 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 29 Sep 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 29 Sep 2025 Author Response Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of ... Continue reading Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence." We greatly appreciate your affirmation of the case's instructional value and its clear histopathological detail. We concur completely with your reservations regarding the need to strengthen the translational value, deepen the molecular discussion concerning shared oncogenic pathways, and, most importantly, provide explicit, evidence-based management recommendations. Your comments have been instrumental in significantly enhancing the scientific rigor and clinical utility of our case report. The revised manuscript (Version 3) has been meticulously updated, with all changes highlighted in bold text, to incorporate your expert recommendations. Below is our point-by-point response detailing the revisions made: Reviewer Comment Authors’ Response "Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work." (Referring to shared and divergent oncogenic pathways).We fully agree that a deeper molecular discussion is crucial for the translational value of this rare co-occurrence. We have significantly revised the Discussion section to address the potential molecular link between GIST and colorectal adenocarcinoma (CRC). Specifically, we now elaborate on the convergence of oncogenic signaling at the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway . We argue that while the primary drivers are distinct (KIT/PDGFRA mutations in GIST vs. APC/KRAS mutations in CRC), a shared functional reliance on the hyperactivation of this ubiquitous proliferative cascade may facilitate co-tumorigenesis. This concept moves the analysis beyond a purely incidental co-occurrence. We further strengthen this argument by discussing Neurofibromatosis Type 1 (NF1) as a clear biological paradigm where NF1 inactivation leads to uncontrolled RAS signaling, thereby predisposing patients to both GIST and CRC . "In the Discussion section, authors have mentioned 'The aim is to draw up recommendations with a high level of scientific evidence'; actually, it is the author's duty to give the recommendations after finishing the discussion." We appreciate your guidance on the responsibility of the authors to provide definitive conclusions. We have removed the aspirational sentence and, instead, have added a new, clearly delineated subsection titled (Evidence-Based Clinical Management Recommendations). This section explicitly details the necessary surgical and adjuvant protocols, guided by the most aggressive entity present—the Very High-Risk GIST component—thereby fulfilling our duty to provide clear, evidence-based clinical guidance. "...empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end!" To empower the manuscript and deepen the discussion on molecular mechanisms, we have integrated an emphasis on the imperative of comprehensive molecular profiling for both lesions. This includes sequencing the GIST for KIT/PDGFRA and the CRC for KRAS/BRAF status, a critical step for understanding the full activation status of the MAPK pathway and for future therapeutic considerations. The final Conclusion has also been refined to underscore that the shared functional reliance on the RAS/MAPK signaling cascade provides a compelling molecular mechanism that warrants further targeted investigation. We believe these extensive revisions significantly enhance the scientific depth of the manuscript, particularly concerning the molecular oncology and the practical clinical implications of this rare synchronous malignancy. Thank you once again for your invaluable input. We hope that the revised manuscript now meets the high standards of scientific evidence and clarity expected for publication. Sincerely, Authors Dr Asma SGHAIER On behalf of all authors, Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence." We greatly appreciate your affirmation of the case's instructional value and its clear histopathological detail. We concur completely with your reservations regarding the need to strengthen the translational value, deepen the molecular discussion concerning shared oncogenic pathways, and, most importantly, provide explicit, evidence-based management recommendations. Your comments have been instrumental in significantly enhancing the scientific rigor and clinical utility of our case report. The revised manuscript (Version 3) has been meticulously updated, with all changes highlighted in bold text, to incorporate your expert recommendations. Below is our point-by-point response detailing the revisions made: Reviewer Comment Authors’ Response "Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work." (Referring to shared and divergent oncogenic pathways).We fully agree that a deeper molecular discussion is crucial for the translational value of this rare co-occurrence. We have significantly revised the Discussion section to address the potential molecular link between GIST and colorectal adenocarcinoma (CRC). Specifically, we now elaborate on the convergence of oncogenic signaling at the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway . We argue that while the primary drivers are distinct (KIT/PDGFRA mutations in GIST vs. APC/KRAS mutations in CRC), a shared functional reliance on the hyperactivation of this ubiquitous proliferative cascade may facilitate co-tumorigenesis. This concept moves the analysis beyond a purely incidental co-occurrence. We further strengthen this argument by discussing Neurofibromatosis Type 1 (NF1) as a clear biological paradigm where NF1 inactivation leads to uncontrolled RAS signaling, thereby predisposing patients to both GIST and CRC . "In the Discussion section, authors have mentioned 'The aim is to draw up recommendations with a high level of scientific evidence'; actually, it is the author's duty to give the recommendations after finishing the discussion." We appreciate your guidance on the responsibility of the authors to provide definitive conclusions. We have removed the aspirational sentence and, instead, have added a new, clearly delineated subsection titled (Evidence-Based Clinical Management Recommendations). This section explicitly details the necessary surgical and adjuvant protocols, guided by the most aggressive entity present—the Very High-Risk GIST component—thereby fulfilling our duty to provide clear, evidence-based clinical guidance. "...empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end!" To empower the manuscript and deepen the discussion on molecular mechanisms, we have integrated an emphasis on the imperative of comprehensive molecular profiling for both lesions. This includes sequencing the GIST for KIT/PDGFRA and the CRC for KRAS/BRAF status, a critical step for understanding the full activation status of the MAPK pathway and for future therapeutic considerations. The final Conclusion has also been refined to underscore that the shared functional reliance on the RAS/MAPK signaling cascade provides a compelling molecular mechanism that warrants further targeted investigation. We believe these extensive revisions significantly enhance the scientific depth of the manuscript, particularly concerning the molecular oncology and the practical clinical implications of this rare synchronous malignancy. Thank you once again for your invaluable input. We hope that the revised manuscript now meets the high standards of scientific evidence and clarity expected for publication. Sincerely, Authors Dr Asma SGHAIER On behalf of all authors, Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 29 Sep 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 29 Sep 2025 Author Response Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of ... Continue reading Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence." We greatly appreciate your affirmation of the case's instructional value and its clear histopathological detail. We concur completely with your reservations regarding the need to strengthen the translational value, deepen the molecular discussion concerning shared oncogenic pathways, and, most importantly, provide explicit, evidence-based management recommendations. Your comments have been instrumental in significantly enhancing the scientific rigor and clinical utility of our case report. The revised manuscript (Version 3) has been meticulously updated, with all changes highlighted in bold text, to incorporate your expert recommendations. Below is our point-by-point response detailing the revisions made: Reviewer Comment Authors’ Response "Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work." (Referring to shared and divergent oncogenic pathways).We fully agree that a deeper molecular discussion is crucial for the translational value of this rare co-occurrence. We have significantly revised the Discussion section to address the potential molecular link between GIST and colorectal adenocarcinoma (CRC). Specifically, we now elaborate on the convergence of oncogenic signaling at the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway . We argue that while the primary drivers are distinct (KIT/PDGFRA mutations in GIST vs. APC/KRAS mutations in CRC), a shared functional reliance on the hyperactivation of this ubiquitous proliferative cascade may facilitate co-tumorigenesis. This concept moves the analysis beyond a purely incidental co-occurrence. We further strengthen this argument by discussing Neurofibromatosis Type 1 (NF1) as a clear biological paradigm where NF1 inactivation leads to uncontrolled RAS signaling, thereby predisposing patients to both GIST and CRC . "In the Discussion section, authors have mentioned 'The aim is to draw up recommendations with a high level of scientific evidence'; actually, it is the author's duty to give the recommendations after finishing the discussion." We appreciate your guidance on the responsibility of the authors to provide definitive conclusions. We have removed the aspirational sentence and, instead, have added a new, clearly delineated subsection titled (Evidence-Based Clinical Management Recommendations). This section explicitly details the necessary surgical and adjuvant protocols, guided by the most aggressive entity present—the Very High-Risk GIST component—thereby fulfilling our duty to provide clear, evidence-based clinical guidance. "...empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end!" To empower the manuscript and deepen the discussion on molecular mechanisms, we have integrated an emphasis on the imperative of comprehensive molecular profiling for both lesions. This includes sequencing the GIST for KIT/PDGFRA and the CRC for KRAS/BRAF status, a critical step for understanding the full activation status of the MAPK pathway and for future therapeutic considerations. The final Conclusion has also been refined to underscore that the shared functional reliance on the RAS/MAPK signaling cascade provides a compelling molecular mechanism that warrants further targeted investigation. We believe these extensive revisions significantly enhance the scientific depth of the manuscript, particularly concerning the molecular oncology and the practical clinical implications of this rare synchronous malignancy. Thank you once again for your invaluable input. We hope that the revised manuscript now meets the high standards of scientific evidence and clarity expected for publication. Sincerely, Authors Dr Asma SGHAIER On behalf of all authors, Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence." We greatly appreciate your affirmation of the case's instructional value and its clear histopathological detail. We concur completely with your reservations regarding the need to strengthen the translational value, deepen the molecular discussion concerning shared oncogenic pathways, and, most importantly, provide explicit, evidence-based management recommendations. Your comments have been instrumental in significantly enhancing the scientific rigor and clinical utility of our case report. The revised manuscript (Version 3) has been meticulously updated, with all changes highlighted in bold text, to incorporate your expert recommendations. Below is our point-by-point response detailing the revisions made: Reviewer Comment Authors’ Response "Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work." (Referring to shared and divergent oncogenic pathways).We fully agree that a deeper molecular discussion is crucial for the translational value of this rare co-occurrence. We have significantly revised the Discussion section to address the potential molecular link between GIST and colorectal adenocarcinoma (CRC). Specifically, we now elaborate on the convergence of oncogenic signaling at the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway . We argue that while the primary drivers are distinct (KIT/PDGFRA mutations in GIST vs. APC/KRAS mutations in CRC), a shared functional reliance on the hyperactivation of this ubiquitous proliferative cascade may facilitate co-tumorigenesis. This concept moves the analysis beyond a purely incidental co-occurrence. We further strengthen this argument by discussing Neurofibromatosis Type 1 (NF1) as a clear biological paradigm where NF1 inactivation leads to uncontrolled RAS signaling, thereby predisposing patients to both GIST and CRC . "In the Discussion section, authors have mentioned 'The aim is to draw up recommendations with a high level of scientific evidence'; actually, it is the author's duty to give the recommendations after finishing the discussion." We appreciate your guidance on the responsibility of the authors to provide definitive conclusions. We have removed the aspirational sentence and, instead, have added a new, clearly delineated subsection titled (Evidence-Based Clinical Management Recommendations). This section explicitly details the necessary surgical and adjuvant protocols, guided by the most aggressive entity present—the Very High-Risk GIST component—thereby fulfilling our duty to provide clear, evidence-based clinical guidance. "...empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end!" To empower the manuscript and deepen the discussion on molecular mechanisms, we have integrated an emphasis on the imperative of comprehensive molecular profiling for both lesions. This includes sequencing the GIST for KIT/PDGFRA and the CRC for KRAS/BRAF status, a critical step for understanding the full activation status of the MAPK pathway and for future therapeutic considerations. The final Conclusion has also been refined to underscore that the shared functional reliance on the RAS/MAPK signaling cascade provides a compelling molecular mechanism that warrants further targeted investigation. We believe these extensive revisions significantly enhance the scientific depth of the manuscript, particularly concerning the molecular oncology and the practical clinical implications of this rare synchronous malignancy. Thank you once again for your invaluable input. We hope that the revised manuscript now meets the high standards of scientific evidence and clarity expected for publication. Sincerely, Authors Dr Asma SGHAIER On behalf of all authors, Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r376373 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v3#referee-response-376373 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 22 Apr 2025 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Approved VIEWS 0 https://doi.org/10.5256/f1000research.179521.r376373 I have read and reviewed version 3 of this manuscript. I wish to thank the authors for their careful review of the prior comments and their attention to addressing them with thoughtful edits and clarifications. This case report is now ... Continue reading READ ALL I have read and reviewed version 3 of this manuscript. I wish to thank the authors for their careful review of the prior comments and their attention to addressing them with thoughtful edits and clarifications. This case report is now acceptable for indexed. Competing Interests: No competing interests were disclosed. 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. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r376373 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v3#referee-response-376373 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 2 VERSION 2 PUBLISHED 26 Feb 2025 Revised Views 0 Cite How to cite this report: Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.178351.r368590 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v2#referee-response-368590 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 14 Mar 2025 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.178351.r368590 This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. Supposedly this is a revision, but none of the simple editorial recommendations that were previously made have been addressed from ... Continue reading READ ALL This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. Supposedly this is a revision, but none of the simple editorial recommendations that were previously made have been addressed from the peer review I submitted on October 18, 2023 (Points 1-4 and Points 7-12)5. Therefore, I am resubmitting the points below that need to be addressed before publication. It is also possible that the revision you updated somehow is not what I am able to see. Please either address the points below or provide me with the revision where all the points below are addressed. Two points, one about the PET scan and the other about if the tumor was tested for SDHA deficiency were adequately addressed. Points: In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel laureate Ramón y Cajal. Thank you for the answer about the PET scan. I understand the point about getting this type of study in some countries. I figure SHEA is a typo for “SDHA deficient GIST tumor”. “Colonic” does not need to be capitalized unless it is the first word of a sentence. The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? In the 5 th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. In the 6 th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7 th AJCC edition, but I would double check). Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Competing Interests: No competing interests were disclosed. 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 Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.178351.r368590 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v2#referee-response-368590 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 07 Apr 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 07 Apr 2025 Author Response Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you ... Continue reading Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you have taken and for the time allocated to review our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the Editor’s and reviewer’s comments are as flowing. 1-In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Response: the term mentioned has been removed and substituted with the correct jargon 2- Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. Response: We have adjusted as requested. 3- The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. Response: the appropriate description has been provided in the manuscript in accordance with your well-founded proposal. 4- GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel lureate Ramón y Cajal. Response: We have indeed revised the name. 5- I figure SHEA is a typo for “SDHA deficient GIST tumor”. Response: your comment is well-founded. 6-“Colonic” does not need to be capitalized unless it is the first word of a sentence. Response: Your comment is well-founded, and we have made the necessary corrections. I congratulate you on your careful analysis. 7- The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? Response: we have removed the expression that gives rise to the lapse of understanding and ambiguity. 8- In the 5th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. Response: Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. 10-In the 6th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. Response: We have inserted the recommended term. 11- When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7th AJCC edition, but I would double check). Response: we have checked that the 2017 edition is indeed the 8th edition. However, we are awaiting the results of your research in the event of any discrepancies. 12- Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Response: We have split the paragraph into two concise parts. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you have taken and for the time allocated to review our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the Editor’s and reviewer’s comments are as flowing. 1-In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Response: the term mentioned has been removed and substituted with the correct jargon 2- Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. Response: We have adjusted as requested. 3- The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. Response: the appropriate description has been provided in the manuscript in accordance with your well-founded proposal. 4- GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel lureate Ramón y Cajal. Response: We have indeed revised the name. 5- I figure SHEA is a typo for “SDHA deficient GIST tumor”. Response: your comment is well-founded. 6-“Colonic” does not need to be capitalized unless it is the first word of a sentence. Response: Your comment is well-founded, and we have made the necessary corrections. I congratulate you on your careful analysis. 7- The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? Response: we have removed the expression that gives rise to the lapse of understanding and ambiguity. 8- In the 5th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. Response: Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. 10-In the 6th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. Response: We have inserted the recommended term. 11- When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7th AJCC edition, but I would double check). Response: we have checked that the 2017 edition is indeed the 8th edition. However, we are awaiting the results of your research in the event of any discrepancies. 12- Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Response: We have split the paragraph into two concise parts. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. Competing Interests: no interest competing Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 07 Apr 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 07 Apr 2025 Author Response Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you ... Continue reading Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you have taken and for the time allocated to review our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the Editor’s and reviewer’s comments are as flowing. 1-In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Response: the term mentioned has been removed and substituted with the correct jargon 2- Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. Response: We have adjusted as requested. 3- The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. Response: the appropriate description has been provided in the manuscript in accordance with your well-founded proposal. 4- GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel lureate Ramón y Cajal. Response: We have indeed revised the name. 5- I figure SHEA is a typo for “SDHA deficient GIST tumor”. Response: your comment is well-founded. 6-“Colonic” does not need to be capitalized unless it is the first word of a sentence. Response: Your comment is well-founded, and we have made the necessary corrections. I congratulate you on your careful analysis. 7- The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? Response: we have removed the expression that gives rise to the lapse of understanding and ambiguity. 8- In the 5th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. Response: Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. 10-In the 6th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. Response: We have inserted the recommended term. 11- When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7th AJCC edition, but I would double check). Response: we have checked that the 2017 edition is indeed the 8th edition. However, we are awaiting the results of your research in the event of any discrepancies. 12- Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Response: We have split the paragraph into two concise parts. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you have taken and for the time allocated to review our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the Editor’s and reviewer’s comments are as flowing. 1-In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Response: the term mentioned has been removed and substituted with the correct jargon 2- Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. Response: We have adjusted as requested. 3- The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. Response: the appropriate description has been provided in the manuscript in accordance with your well-founded proposal. 4- GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel lureate Ramón y Cajal. Response: We have indeed revised the name. 5- I figure SHEA is a typo for “SDHA deficient GIST tumor”. Response: your comment is well-founded. 6-“Colonic” does not need to be capitalized unless it is the first word of a sentence. Response: Your comment is well-founded, and we have made the necessary corrections. I congratulate you on your careful analysis. 7- The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? Response: we have removed the expression that gives rise to the lapse of understanding and ambiguity. 8- In the 5th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. Response: Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. 10-In the 6th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. Response: We have inserted the recommended term. 11- When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7th AJCC edition, but I would double check). Response: we have checked that the 2017 edition is indeed the 8th edition. However, we are awaiting the results of your research in the event of any discrepancies. 12- Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Response: We have split the paragraph into two concise parts. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. Competing Interests: no interest competing Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 30 Aug 2023 Views 0 Cite How to cite this report: Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.152818.r215037 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v1#referee-response-215037 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 20 Oct 2023 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.152818.r215037 This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. There are areas where some editing would enhance the clarity of the text. The authors should consider offering some thought ... Continue reading READ ALL This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. There are areas where some editing would enhance the clarity of the text. The authors should consider offering some thought or recommendations on how they might further delve into the question of common carcinogenic pathways. Points: In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel laureate Ramón y Cajal. Was a PET scan done prior to surgery to evaluate for distant metastatic disease? If the case was deemed emergent, and therefore a PET would not have been able to be performed, please note that about the operation. Was the GIST tumor checked to see if it was SDHA deficient? “Colonic” does not need to be capitalized unless it is the first word of a sentence. The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? In the 5 th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. In the 6 th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7 th AJCC edition, but I would double check). Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? 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? Partly 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? Partly Competing Interests: No competing interests were disclosed. 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 Carr SR. Reviewer Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.152818.r215037 ) The direct URL for this report is: https://f1000research.com/articles/12-1055/v1#referee-response-215037 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 Feb 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 17 Feb 2025 Author Response Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for ... Continue reading Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Modifications were made . The PET scan was not performed preoperatively. This is an expensive test, the reliability of which is not always available in our country. A thoracic-abdominal-pelvic CT scan was used to assess the extent of the disease, which did not reveal any secondary locations. The immunohistochemical study of a possible SHEA deficiency could not be performed because of the lack of suitable reactive chemicals in our hospital. We have verified the AJCC 2017 version and found that it is the eighth edition. The precisions required by the reviewer was conducted in concertation with all the authors. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. We hope, nevertheless, to receive positive feedback and acceptance of our work by allowing it to be published in this prestigious journal. Sincerely The corresponding author Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Modifications were made . The PET scan was not performed preoperatively. This is an expensive test, the reliability of which is not always available in our country. A thoracic-abdominal-pelvic CT scan was used to assess the extent of the disease, which did not reveal any secondary locations. The immunohistochemical study of a possible SHEA deficiency could not be performed because of the lack of suitable reactive chemicals in our hospital. We have verified the AJCC 2017 version and found that it is the eighth edition. The precisions required by the reviewer was conducted in concertation with all the authors. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. We hope, nevertheless, to receive positive feedback and acceptance of our work by allowing it to be published in this prestigious journal. Sincerely The corresponding author Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 17 Feb 2025 Asma SGHAIER , General surgery, Hospital Farhat Hached, Sousse, Tunisia 17 Feb 2025 Author Response Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for ... Continue reading Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Modifications were made . The PET scan was not performed preoperatively. This is an expensive test, the reliability of which is not always available in our country. A thoracic-abdominal-pelvic CT scan was used to assess the extent of the disease, which did not reveal any secondary locations. The immunohistochemical study of a possible SHEA deficiency could not be performed because of the lack of suitable reactive chemicals in our hospital. We have verified the AJCC 2017 version and found that it is the eighth edition. The precisions required by the reviewer was conducted in concertation with all the authors. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. We hope, nevertheless, to receive positive feedback and acceptance of our work by allowing it to be published in this prestigious journal. Sincerely The corresponding author Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Modifications were made . The PET scan was not performed preoperatively. This is an expensive test, the reliability of which is not always available in our country. A thoracic-abdominal-pelvic CT scan was used to assess the extent of the disease, which did not reveal any secondary locations. The immunohistochemical study of a possible SHEA deficiency could not be performed because of the lack of suitable reactive chemicals in our hospital. We have verified the AJCC 2017 version and found that it is the eighth edition. The precisions required by the reviewer was conducted in concertation with all the authors. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. We hope, nevertheless, to receive positive feedback and acceptance of our work by allowing it to be published in this prestigious journal. Sincerely The corresponding author Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 30 Aug 2023 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 Version 4 (revision) 06 Oct 25 read Version 3 (revision) 07 Apr 25 read read Version 2 (revision) 26 Feb 25 read Version 1 30 Aug 23 read Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, USA Nafiza Martini , University of Illinois Chicago College of Medicine, Chicago, 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 © 2025 Martini N. 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. 20 Oct 2025 | for Version 4 Nafiza Martini , University of Illinois Chicago College of Medicine, Chicago, Illinois, USA 0 Views copyright © 2025 Martini N. 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 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 Thank you very much for your thoughtful and detailed revisions. I appreciate how comprehensively you addressed each point, particularly the enhanced molecular discussion and the addition of evidence-based management recommendations. The revised version reflects clear improvement in scientific depth and clinical applicability. Kind regards, Dr. Nafiza Martini Competing Interests No competing interests were disclosed. Reviewer Expertise General medicine and molecular biology of cancers 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. reply Respond to this report Responses (0) Martini N. Peer Review Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.188933.r420585) 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/12-1055/v4#referee-response-420585 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Martini N. 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. 27 Sep 2025 | for Version 3 Nafiza Martini , University of Illinois Chicago College of Medicine, Chicago, Illinois, USA 0 Views copyright © 2025 Martini N. 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) 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 This is a well-documented and instructive case on synchronous GIST and colonic adenocarcinoma, highlighting the complexity of dual malignancies and the role of multidisciplinary surgical strategies. The histopathological detail and therapeutic implications are clearly presented. This is an instructive and rare case that not only documents a clinical challenge but also raises important questions about shared and divergent oncogenic pathways. Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work. In the Discussion section, authors have mentioned " The aim is to draw up recommendations with a high level of scientific evidence"; actually, it is the author's duty to give the recommendations after finishing the discussion. so, they should read more deeply in literature and empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end! 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? Yes Is the case presented with sufficient detail to be useful for other practitioners? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise General medicine and molecular biology of cancers 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 (1) Author Response 29 Sep 2025 Asma SGHAIER, General surgery, Hospital Farhat Hached, Sousse, Tunisia Dear Dr. Martini, We are writing to thank you sincerely for your careful and insightful review of our manuscript, "Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence." We greatly appreciate your affirmation of the case's instructional value and its clear histopathological detail. We concur completely with your reservations regarding the need to strengthen the translational value, deepen the molecular discussion concerning shared oncogenic pathways, and, most importantly, provide explicit, evidence-based management recommendations. Your comments have been instrumental in significantly enhancing the scientific rigor and clinical utility of our case report. The revised manuscript (Version 3) has been meticulously updated, with all changes highlighted in bold text, to incorporate your expert recommendations. Below is our point-by-point response detailing the revisions made: Reviewer Comment Authors’ Response "Highlighting these molecular aspects, along with similar reports in the literature, would strengthen the translational value of the work." (Referring to shared and divergent oncogenic pathways).We fully agree that a deeper molecular discussion is crucial for the translational value of this rare co-occurrence. We have significantly revised the Discussion section to address the potential molecular link between GIST and colorectal adenocarcinoma (CRC). Specifically, we now elaborate on the convergence of oncogenic signaling at the RAS/MAPK (Mitogen-Activated Protein Kinase) pathway . We argue that while the primary drivers are distinct (KIT/PDGFRA mutations in GIST vs. APC/KRAS mutations in CRC), a shared functional reliance on the hyperactivation of this ubiquitous proliferative cascade may facilitate co-tumorigenesis. This concept moves the analysis beyond a purely incidental co-occurrence. We further strengthen this argument by discussing Neurofibromatosis Type 1 (NF1) as a clear biological paradigm where NF1 inactivation leads to uncontrolled RAS signaling, thereby predisposing patients to both GIST and CRC . "In the Discussion section, authors have mentioned 'The aim is to draw up recommendations with a high level of scientific evidence'; actually, it is the author's duty to give the recommendations after finishing the discussion." We appreciate your guidance on the responsibility of the authors to provide definitive conclusions. We have removed the aspirational sentence and, instead, have added a new, clearly delineated subsection titled (Evidence-Based Clinical Management Recommendations). This section explicitly details the necessary surgical and adjuvant protocols, guided by the most aggressive entity present—the Very High-Risk GIST component—thereby fulfilling our duty to provide clear, evidence-based clinical guidance. "...empower the paper in a way that fills the gaps and goes deep inside the molecular mechanism with respect of focusing on the type of this paper as a clinical case report in the end!" To empower the manuscript and deepen the discussion on molecular mechanisms, we have integrated an emphasis on the imperative of comprehensive molecular profiling for both lesions. This includes sequencing the GIST for KIT/PDGFRA and the CRC for KRAS/BRAF status, a critical step for understanding the full activation status of the MAPK pathway and for future therapeutic considerations. The final Conclusion has also been refined to underscore that the shared functional reliance on the RAS/MAPK signaling cascade provides a compelling molecular mechanism that warrants further targeted investigation. We believe these extensive revisions significantly enhance the scientific depth of the manuscript, particularly concerning the molecular oncology and the practical clinical implications of this rare synchronous malignancy. Thank you once again for your invaluable input. We hope that the revised manuscript now meets the high standards of scientific evidence and clarity expected for publication. Sincerely, Authors Dr Asma SGHAIER On behalf of all authors, View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Martini N. Peer Review Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r401921) 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/12-1055/v3#referee-response-401921 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Carr S. 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. 22 Apr 2025 | for Version 3 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA 0 Views copyright © 2025 Carr S. 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 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 read and reviewed version 3 of this manuscript. I wish to thank the authors for their careful review of the prior comments and their attention to addressing them with thoughtful edits and clarifications. This case report is now acceptable for indexed. Competing Interests No competing interests were disclosed. 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. reply Respond to this report Responses (0) Carr SR. Peer Review Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.179521.r376373) 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/12-1055/v3#referee-response-376373 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Carr S. 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. 14 Mar 2025 | for Version 2 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA 0 Views copyright © 2025 Carr S. 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) 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 This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. Supposedly this is a revision, but none of the simple editorial recommendations that were previously made have been addressed from the peer review I submitted on October 18, 2023 (Points 1-4 and Points 7-12)5. Therefore, I am resubmitting the points below that need to be addressed before publication. It is also possible that the revision you updated somehow is not what I am able to see. Please either address the points below or provide me with the revision where all the points below are addressed. Two points, one about the PET scan and the other about if the tumor was tested for SDHA deficiency were adequately addressed. Points: In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel laureate Ramón y Cajal. Thank you for the answer about the PET scan. I understand the point about getting this type of study in some countries. I figure SHEA is a typo for “SDHA deficient GIST tumor”. “Colonic” does not need to be capitalized unless it is the first word of a sentence. The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? In the 5 th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. In the 6 th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7 th AJCC edition, but I would double check). Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Competing Interests No competing interests were disclosed. 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 (1) Author Response 07 Apr 2025 Asma SGHAIER, General surgery, Hospital Farhat Hached, Sousse, Tunisia Dear Shamus R. Carr Thank you for your letter and for the ’ comments concerning our manuscript. I would like to express my gratitude once again for the great care you have taken and for the time allocated to review our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Revised portion are marked in red in the paper. The main corrections in the paper and the responds to the Editor’s and reviewer’s comments are as flowing. 1-In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Response: the term mentioned has been removed and substituted with the correct jargon 2- Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. Response: We have adjusted as requested. 3- The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. Response: the appropriate description has been provided in the manuscript in accordance with your well-founded proposal. 4- GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel lureate Ramón y Cajal. Response: We have indeed revised the name. 5- I figure SHEA is a typo for “SDHA deficient GIST tumor”. Response: your comment is well-founded. 6-“Colonic” does not need to be capitalized unless it is the first word of a sentence. Response: Your comment is well-founded, and we have made the necessary corrections. I congratulate you on your careful analysis. 7- The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? Response: we have removed the expression that gives rise to the lapse of understanding and ambiguity. 8- In the 5th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. Response: Lymph node dissection is essential and must be performed according to the relevant guidelines for oncology. 10-In the 6th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. Response: We have inserted the recommended term. 11- When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7th AJCC edition, but I would double check). Response: we have checked that the 2017 edition is indeed the 8th edition. However, we are awaiting the results of your research in the event of any discrepancies. 12- Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? Response: We have split the paragraph into two concise parts. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. View more View less Competing Interests no interest competing reply Respond Report a concern Carr SR. Peer Review Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.178351.r368590) 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/12-1055/v2#referee-response-368590 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2023 Carr S. 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. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. 20 Oct 2023 | for Version 1 Shamus R. Carr , National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA 0 Views copyright © 2023 Carr S. 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. The author(s) is/are employees of the US Government and therefore domestic copyright protection in USA does not apply to this work. The work may be protected under the copyright laws of other jurisdictions when used in those jurisdictions. format_quote Cite this report speaker_notes Responses (1) 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 This case report highlights a unique finding of a patient with synchronous GIST tumor of the colon and colonic adenocarcinoma. There are areas where some editing would enhance the clarity of the text. The authors should consider offering some thought or recommendations on how they might further delve into the question of common carcinogenic pathways. Points: In the Abstract, the work “carcinologic” is used. The root of this work “carcinology” means “study of crustaceans”. This word is therefore incorrect and either should be deleted or changed. Please add a “period” at the end of the last sentence in the Conclusions of the Abstract. The term “dominance of one histologic type” is unclear as it is known that GIST arise from the stroma and adenocarcinoma of the colon arise from the mucosal lining. This also has implications on distant spread. Could the authors rewrite this sentence? I think they mean “the more aggressive or higher stage”, but I may be wrong. GIST tumors are thought to arise from the interstitial cells of Cajal (not Kajal). Named after the Spanish neuropathologist and Nobel laureate Ramón y Cajal. Was a PET scan done prior to surgery to evaluate for distant metastatic disease? If the case was deemed emergent, and therefore a PET would not have been able to be performed, please note that about the operation. Was the GIST tumor checked to see if it was SDHA deficient? “Colonic” does not need to be capitalized unless it is the first word of a sentence. The last sentence of the third paragraph of in the Conclusions section is unclear. Can this be rewritten for clarity? In the 5 th paragraph of the Conclusions section, the authors imply that lymphadenectomy is not required for colon cancer. This is clearly not what the authors intend. Please review and rewrite to clarify. In the 6 th paragraph of the Conclusions section, the second sentence needs a small edit. It should read “Just like…” and not as written, “Just such…”. When mentioning the TNM staging system update from 2017 for GIST tumors, it is probably better to state the edition of the AJCC staging (which I believe was the 7 th AJCC edition, but I would double check). Would the authors consider rewriting the last 7 paragraph of the Conclusions section into one or two paragraphs? 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? Partly 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? Partly Competing Interests No competing interests were disclosed. 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 (1) Author Response 17 Feb 2025 Asma SGHAIER, General surgery, Hospital Farhat Hached, Sousse, Tunisia Detailed Response to Reviewer Submission date: 16/02/2025 Dear Professor Shamus R. Carr, Thank you for your letter and for the reviewers’ comments concerning our manuscript. Thank you very much for your consideration, and we really appreciate the comments and have learned a lot. Appropriate changes were made according to the suggestions of reviewers and editor. Those comments are all valuable and very helpful for revising and improving our paper, as well as the important guiding significance to our researches. We have studied comments carefully and have made correction which we hope meet with approval. Modifications were made . The PET scan was not performed preoperatively. This is an expensive test, the reliability of which is not always available in our country. A thoracic-abdominal-pelvic CT scan was used to assess the extent of the disease, which did not reveal any secondary locations. The immunohistochemical study of a possible SHEA deficiency could not be performed because of the lack of suitable reactive chemicals in our hospital. We have verified the AJCC 2017 version and found that it is the eighth edition. The precisions required by the reviewer was conducted in concertation with all the authors. We express once again our sincere appreciation and deep gratitude to all the reviewers and to the editorial board for providing us with the opportunity to revise our manuscript and to improve the quality of our submission. We hope, nevertheless, to receive positive feedback and acceptance of our work by allowing it to be published in this prestigious journal. Sincerely The corresponding author View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Carr SR. Peer Review Report For: Case Report: Synchronous primary location of gastrointestinal stromal tumors (GIST) and adenocarcinoma of the colon: an unusual occurrence [version 4; peer review: 2 approved] . F1000Research 2025, 12 :1055 ( https://doi.org/10.5256/f1000research.152818.r215037) 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/12-1055/v1#referee-response-215037 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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