Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis

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Case presentation We report a case of a 62-year-old male who presented with abdominal pain, dyspepsia, anorexia, and weight loss. On physical examination abdominal masses and hepatomegaly were detected. Radiological imaging showed widespread masses in the abdominal and thoracic regions. Upper gastrointestinal endoscopy identified an umbilicated protruded lesion with central dark pigmentation at the antro-fundic junction. Histopathological examination and immunohistochemical staining were consistent with melanoma. A subsequent rigorous skin examination uncovered a primary malignant skin melanoma. Due to worsening general condition, the patient received palliative hospice care. Conclusion This report highlights the critical need for vigilant skin examination when dealing with widespread metastatic disease. " } { "@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/13-1019/v4", "name": "Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis" } } ] } Home Browse Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis ALL Metrics - Views Downloads Get PDF Get XML Cite How to cite this article Tababi R, Khsiba A, Mahmoudi M et al. Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.12688/f1000research.155815.4 ) 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: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] Previously titled: Case Report: The Elephant in the Room: Skin Melanoma Unveiled by Gastric Metastasis Ramzi Tababi https://orcid.org/0009-0006-1330-6887 1 , Amal Khsiba https://orcid.org/0000-0001-6102-8830 1 , Moufida Mahmoudi 1 , [...] Asma Ben Mohamed 1 , Manel Yakoubi 1 , Ghada Gharbi https://orcid.org/0000-0001-8577-4248 1 , Abir Chaabane 2 , Emna Chelbi 2 , Mouna Medhioub 1 , Mohamed Lamine Hamzaoui https://orcid.org/0000-0001-6350-6779 1 Ramzi Tababi https://orcid.org/0009-0006-1330-6887 1 , Amal Khsiba https://orcid.org/0000-0001-6102-8830 1 , [...] Moufida Mahmoudi 1 , Asma Ben Mohamed 1 , Manel Yakoubi 1 , Ghada Gharbi https://orcid.org/0000-0001-8577-4248 1 , Abir Chaabane 2 , Emna Chelbi 2 , Mouna Medhioub 1 , Mohamed Lamine Hamzaoui https://orcid.org/0000-0001-6350-6779 1 PUBLISHED 03 Jul 2025 Author details Author details 1 Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Nabeul, Tunisia 2 Pathology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Nabeul, Tunisia Ramzi Tababi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Amal Khsiba Roles: Conceptualization, Methodology, Project Administration, Supervision, Validation, Writing – Review & Editing Moufida Mahmoudi Roles: Supervision, Validation, Writing – Review & Editing Asma Ben Mohamed Roles: Supervision, Validation, Writing – Review & Editing Manel Yakoubi Roles: Supervision, Validation, Writing – Review & Editing Ghada Gharbi Roles: Supervision, Validation, Writing – Review & Editing Abir Chaabane Roles: Resources, Validation, Writing – Review & Editing Emna Chelbi Roles: Resources, Validation, Writing – Review & Editing Mouna Medhioub Roles: Project Administration, Supervision, Validation, Writing – Review & Editing Mohamed Lamine Hamzaoui Roles: Project Administration, Supervision, Validation, Writing – Review & Editing OPEN PEER REVIEW DETAILS REVIEWER STATUS This article is included in the Oncology gateway. Abstract Background Gastric metastasis from melanoma is rare and often presents as an unexpected finding, rarely revealing an underlying primary skin melanoma. Case presentation We report a case of a 62-year-old male who presented with abdominal pain, dyspepsia, anorexia, and weight loss. On physical examination abdominal masses and hepatomegaly were detected. Radiological imaging showed widespread masses in the abdominal and thoracic regions. Upper gastrointestinal endoscopy identified an umbilicated protruded lesion with central dark pigmentation at the antro-fundic junction. Histopathological examination and immunohistochemical staining were consistent with melanoma. A subsequent rigorous skin examination uncovered a primary malignant skin melanoma. Due to worsening general condition, the patient received palliative hospice care. Conclusion This report highlights the critical need for vigilant skin examination when dealing with widespread metastatic disease. READ ALL READ LESS Keywords Melanoma, Gastric metastasis, Multi-organ metastases, Digestive endoscopy, Histopathology Corresponding Author(s) Ramzi Tababi ( [email protected] ) Close Corresponding author: Ramzi Tababi Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Tababi R 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: Tababi R, Khsiba A, Mahmoudi M et al. Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.12688/f1000research.155815.4 ) First published: 06 Sep 2024, 13 :1019 ( https://doi.org/10.12688/f1000research.155815.1 ) Latest published: 03 Jul 2025, 13 :1019 ( https://doi.org/10.12688/f1000research.155815.4 ) Revised Amendments from Version 3 In this revised version of the manuscript, we have made few changes in response to the reviewer’s valuable feedback. To avoid any remaining ambiguity and improve clarity, we have modified the title to: “Overlooked Skin Melanoma Unveiled by Gastric Metastasis.” This new title preserves the underlying message of the reviewer’s earlier suggestion while ensuring that the clinical content is conveyed more directly and clearly to the reader. As requested, we have deleted the sentence that described cytological atypia and pleomorphism as typical features of melanoma, acknowledging that these features are indicative of malignancy in general rather than specific to melanoma. Additionally, we have maintained the point about the potential for metastatic melanoma to undergo phenotypic dedifferentiation and lose immunohistochemical marker expression. For accuracy and transparency, we have ensured that references 12 and 13 are appropriately cited to support this statement, as the reviewer recommended. In this revised version of the manuscript, we have made few changes in response to the reviewer’s valuable feedback. To avoid any remaining ambiguity and improve clarity, we have modified the title to: “Overlooked Skin Melanoma Unveiled by Gastric Metastasis.” This new title preserves the underlying message of the reviewer’s earlier suggestion while ensuring that the clinical content is conveyed more directly and clearly to the reader. As requested, we have deleted the sentence that described cytological atypia and pleomorphism as typical features of melanoma, acknowledging that these features are indicative of malignancy in general rather than specific to melanoma. Additionally, we have maintained the point about the potential for metastatic melanoma to undergo phenotypic dedifferentiation and lose immunohistochemical marker expression. For accuracy and transparency, we have ensured that references 12 and 13 are appropriately cited to support this statement, as the reviewer recommended. See the authors' detailed response to the review by Hanen Jaziri See the authors' detailed response to the review by Gerardo Ferrara READ REVIEWER RESPONSES Introduction The incidence of melanoma is on the rise, particularly in developed countries with lighter skin populations, representing 1.7% of global cancer cases. 1 It also constitutes 10% of all skin cancers and remains the primary cause of death among these malignancies. 2 In fact, melanoma embodies a heterogeneous tumour group of distinct precursor cells, biological signature and presentations. 1 , 2 Nodular melanoma is notably a malignant subtype, known for its aggressive behaviour and accounting for 16% to 25.6% of invasive cutaneous melanoma. 2 The most frequent metastatic sites include the skin, lungs, liver, central nervous system and bones. Less frequently, metastases occur in the kidneys, adrenal glands, and gastrointestinal (GI) tract, with gastric involvement being particularly rare. 3 In this report, we present a rare case of gastric metastasis from melanoma that led to the discovery of the initially unnoticed primary skin lesion. We describe the endoscopic and histopathological findings, as well as the nonspecific clinical symptoms that prompted the diagnostic investigation. Case report A 62-year-old Caucasian male patient, with a medical history of hypertension and coronary artery disease, presented with diffuse abdominal pain, along with dyspepsia, anorexia and weight loss for the past 6 months. Physical examination revealed abdominal tenderness and multiple fixed and hard nodules of the thoracic and abdominal walls, as well as in the Douglas pouch on rectal examination, suggestive of carcinomatosis. An enlarged, firm, and tender liver was also noted. No jaundice or palpable lymph nodes were observed. Laboratory findings were within the normal range, notably for complete blood count and liver function tests. Abdominal ultrasound (US) showed a non-dysmorphic liver with a heterogenous lobulated hypoechoic mass, vascularised on Doppler, measuring 83 × 60 mm, associated with omental adipose tissue nodule of 37 mm, sharing the same characteristics. On the CT scan ( Figure 1 ), the hepatic mass was isodense, poorly defined, spanning segments V, VII and VIII, showing weak enhancement with contrast, measuring 100 × 60 mm. There were also multiple scattered tissue masses enhanced with contrast, located in the peritoneum, in the retroperitoneum, and sub-peritoneal, as well as in the left adrenal gland. The pancreas was normal. Plus, multiple solid pulmonary nodules were observed, involving all segments, alongside mediastinal and abdominal lymphadenopathies. Figure 1. Computed tomography scan findings. (A): Subcutaneous soft tissue nodule of the anterior right thoracic wall (arrow). (B): Bilateral pulmonary nodules. (C): Hypodense hepatic mass in the right lobe on the portal phase, measuring 100 × 60 millimetres. (D): Intraperitoneal adenomegalies (circle) and heterogeneous nodules in the right perirenal retroperitoneal region. (E): Heterogeneous peritoneal nodules (arrows) and small subcutaneous soft tissue nodules in the right lateral abdominal wall (circle). At this point, widespread metastases were the leading considered diagnosis based on the clinical context and radiological presentation. Alpha-fetoprotein and prostate specific antigen levels were normal. In the investigation for the primary cancer, and given the recent dyspepsia and epigastric pain, an upper gastrointestinal endoscopy was performed revealing a polypoid lesion at the antro-fundic junction measuring 20 mm in diameter, with a depressed and ulcerated centre, containing dark pigmentation ( Figure 2 ). The histological examination showed a tumour proliferation extensively invading the antro-fundic mucosa, composed of discohesive cells, with deposits of brownish pigments. Immunohistochemistry analysis revealed positive staining for melanocytic markers Melan-A, S100 protein and HMB45 ( Figure 3 ). Other markers were negative, namely pancytokeratin, TTF 1, CD 45, chromogranin, and synaptophysin. These findings were consistent with a gastric localisation a melanoma. Figure 2. Upper gastrointestinal endoscopy findings. Retroflexion shows an elevated lesion at the antrum-fundus junction with a depressed centre, resembling a volcano appearance, with brown pigments. Figure 3. Histopathological findings of the gastric lesion biopsy. (A): Haematoxylin & eosin staining on x200 magnification shows malignant proliferation infiltrating the gastric mucosa. Tumour cells are pleomorphic and disaggregated, exhibiting marked nuclear atypia with hyperchromatic and sometimes monstruous nuclei (black arrows). Some larger cells with clear cytoplasm were present (white arrows). Deposits of brown pigments are also seen (*). Immunohistochemistry demonstrated positive staining with Melan-A (B) and PS 100 (C). With these results in mind, a thorough skin examination was thus undertaken unveiling a cutaneous lesion in the back, manifesting as a circumscribed pink nodule of 8 mm with brown discoloration ( Figure 4 ). Figure 4. Cutaneous lesion in the back. It appears as a circumscribed dark pink nodule measuring 8 millimetres in diameter with areas of brown discoloration. The lesion also has a slightly irregular surface and a surrounding area of erythema. Histological assessment of the skin lesion biopsy confirmed nodular melanoma, with immunohistochemistry showing positive staining for Melan-A, HMB45, and p16 ( Figure 5 ). Figure 5. Histopathological findings of the skin lesion biopsy. (A): Haematoxylin & eosin staining on x100 magnification shows malignant cellular proliferation (*) in the dermis, composed of vaguely naevoid cells and larger cells with abundant eosinophilic cytoplasm, atypical pleomorphic nucleolated nuclei, and no junctional activity. On immunohistochemistry, tumour cells exhibit positive staining for HMB45 (B), Melan-A (C), and p16 (D). Ultimately, the diagnosis of malignant cutaneous melanoma with diffuse multi-organ metastases, particularly involving the stomach, was confirmed. Subsequently, the patient’s general condition deteriorated, precluding the initiation of planned palliative chemotherapy. Supportive care was provided, including pain management, with a documented follow-up of 6 months. Discussion The stomach is an unusual metastatic site, accounting for 2.6% of secondary lesions, particularly from breast, lung, and melanoma. Melanoma frequently metastasizes to the GI tract, with cutaneous melanoma primarily affecting the upper GI tract, while uveal melanoma tends to spread to the liver. 4 , 5 An autopsy study of 216 patients with advanced malignant melanoma found the GI system to be the second most common metastatic site, after lymph nodes (73.6%) and lungs (71.3%). 6 In this series, GI metastases were often part of multiple-organ involvement (95%), with secondary gastric melanoma in 22.7% of cases. Liver metastases were observed in 58.3% of cases. Other GI metastases included the peritoneum (42.6%), pancreas (37.5%), small bowel (35.6%), spleen (30.6%), colon (28.2%), oral cavity, oesophagus (9.3%), and biliary tract (8.8%). A similar autopsy study of 100 patients with cutaneous melanoma found gastric involvement in 26%. 7 Despite these findings, GI metastases seem to be often subclinical, with clinical series showing much lower incidence, such as intestinal metastases in only 1% to 7% of cases. 3 Consistent with these reports, our patient presented with disseminated melanoma affecting multiple organs, including the lungs, liver, stomach, subcutaneous tissue, adrenal gland, peritoneum, and lymph nodes. Also, gastric metastases from melanoma may be present at diagnosis or develop years later, indicating recurrence. 8 A recent systematic review by Reggiani et al. 9 included 113 patients with gastric melanoma metastases, predominantly from skin primary lesions (62%). Most patients were male (64%) with a median age of 63 years. Only 10% were asymptomatic, while common symptoms included bleeding (34.5%), abdominal pain (34.5%), anorexia and weight loss (23%), and nausea/vomiting (17.7%). Dyspepsia was noted in 5.3%. Gastric metastases were single in 42.5% and mostly located in the gastric body (60.2%). However, variability in lesion descriptions across studies prevented the identification of consistent endoscopic features. Nelson et al. 10 proposed an endoscopic classification for GI melanoma metastases with three types: 1) melanotic nodules on normal folds with ulcerated tips; 2) elevated submucosal lesions with ulcerated centres, sometimes with visible melanin, often described as volcano-like or donut-shaped, 9 as seen in our case; and 3) mass lesions with necrosis and melanosis. Such protruding lesions, especially with brown deposits, should raise suspicion for gastric melanoma. Other descriptions include polypoid masses, small nodules, and black spots. 5 , 8 , 11 GI melanoma metastases can resemble primary gastric cancer or other gastric metastases, 5 , 9 , 11 making histopathological examination and immunohistochemistry essential for diagnosis. These metastases typically show positive staining for melanocytic markers, 12 as seen in both our gastric and skin lesions. However, phenotypic switching during tumour progression can cause loss of typical immunophenotypic features, such as Melan-A, HMB45, S100, and SOX 10. 12 , 13 In such cases, molecular testing for melanoma-related mutations like BRAF, NRAS, and NF1 may be necessary. 13 For our patient, the diagnosis was confirmed by histopathological findings and the typical immunohistochemical profile, without the need for further tests. Metastatic melanoma has a poor prognosis, with distant metastatic burden being a key prognostic factor. Non-pulmonary visceral metastases and elevated serum lactate dehydrogenase are linked to worse survival, with a one-year survival rate of 33%. 14 , 15 In the above-mentioned systematic review of gastric melanoma metastases, the median survival was 3 months, with 16% and 4% survival rates at 1 and 2 years, respectively. 9 Survival was notably lower with multiple gastric lesions compared to a single metastasis. GI resections have been performed in localised metastasis, with evidence of possible prolonged remission, or as an emergency procedure for complicated cases like GI bleeding or perforation. 8 , 16 However, our patient presented extensive metastatic disease and hence was not a proper candidate for surgery. Systemic treatments, particularly immunotherapy, are now the preferred first-line therapy for metastatic melanoma, showing promising survival benefits. 17 Unfortunately, immunotherapy was unavailable at the time, and the patient’s rapid decline precluded chemotherapy. Conclusion GI metastases, particularly in the stomach, are rare, with melanoma being the most common cancer to spread to this site. This case highlights how a gastric metastasis revealed an underlying malignant cutaneous melanoma. A protruding gastric lesion with dark pigmentation during endoscopy should raise suspicion of melanoma, warranting a thorough skin examination for potentially overlooked lesions, which is also crucial in widespread metastatic disease. Histopathological and immunohistochemical analysis remain the gold standards for diagnosis. In cases of widespread metastases, palliative systemic treatment, including chemotherapy or immunotherapy, is preferred, with surgery reserved for selected oligometastatic cases. Despite treatment, the prognosis remains poor. Consent Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient. Data availability No data are associated with this article. Reporting guidelines Zenodo: CARE checklist for ‘Case Report: Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review’. DOI: https://zenodo.org/doi/10.5281/zenodo.13387862 18 Data are available under the terms of the Creative Commons Zero “No rights reserved” data waiver (CC0 1.0 Public domain dedication). Acknowledgements No acknowledgments to declare. References 1. Saginala K, Barsouk A, Aluru JS, et al. : Epidemiology of Melanoma. Med. Sci. 2021; 9 (4): 63. PubMed Abstract | Publisher Full Text | Free Full Text 2. Dessinioti C, Geller AC, Whiteman DC, et al. : Not all melanomas are created equal: a review and call for more research into nodular melanoma. Br. J. Dermatol. 2021; 185 (4): 700–710. PubMed Abstract | Publisher Full Text 3. Damsky WE, Rosenbaum LE, Bosenberg M: Decoding Melanoma Metastasis. Cancers. 2011; 3 (1): 126–163. PubMed Abstract | Publisher Full Text | Free Full Text 4. WHO Classification of Tumours Editorial Board: Digestive System Tumours. 5th ed.International Agency for Research on Cancer; 2019. 5. De Palma GD, Masone S, Rega M, et al. : Metastatic tumors to the stomach: clinical and endoscopic features. World J. Gastroenterol. 2006; 12 (45): 7326–7328. PubMed Abstract | Publisher Full Text | Free Full Text 6. Patel JK, Didolkar MS, Pickren JW, et al. : Metastatic pattern of malignant melanoma. A study of 216 autopsy cases. Am. J. Surg. 1978; 135 (6): 807–810. Publisher Full Text 7. Gupta TKD: Metastatic Melanoma of the Gastrointestinal Tract. Arch. Surg. 1964; 88 (6): 969. Publisher Full Text 8. La Selva D, Kozarek RA, Dorer RK, et al. : Primary and metastatic melanoma of the GI tract: clinical presentation, endoscopic findings, and patient outcomes. Surg. Endosc. 2020; 34 (10): 4456–4462. PubMed Abstract | Publisher Full Text 9. Reggiani HC, Pongeluppi ACA, Ferreira VFMM, et al. : Endoscopic diagnosis of gastric metastases from malignant melanoma: systematic review. Clin. Endosc. 2022; 55 (4): 507–515. PubMed Abstract | Publisher Full Text | Free Full Text 10. Nelson RS, Lanza F: Malignant melanoma metastatic to the upper gastrointestinal tract: Endoscopic and radiologic correlations, form and evolution of lesions, and value of directed biopsy in diagnosis. Gastrointest. Endosc. 1978; 24 (4): 156–158. PubMed Abstract | Publisher Full Text 11. Maksimaityte V, Reivytyte R, Milaknyte G, et al. : Metastatic multifocal melanoma of multiple organ systems: A case report. World J. Clin. Cases. 2022; 10 (28): 10136–10145. PubMed Abstract | Publisher Full Text | Free Full Text 12. Saliba E, Bhawan J: Aberrant Expression of Immunohistochemical Markers in Malignant Melanoma: A Review. Dermatopathology. 2021; 8 (3): 359–370. PubMed Abstract | Publisher Full Text | Free Full Text 13. Agaimy A, Stoehr R, Hornung A, et al. : Dedifferentiated and Undifferentiated Melanomas: Report of 35 New Cases With Literature Review and Proposal of Diagnostic Criteria. Am. J. Surg. Pathol. 2021; 45 (2): 240–254. Publisher Full Text 14. Balch CM, Gershenwald JE, Soong SJ, et al. : Final Version of 2009 AJCC Melanoma Staging and Classification. J. Clin. Oncol. 2009; 27 (36): 6199–6206. PubMed Abstract | Publisher Full Text | Free Full Text 15. Gershenwald JE, Scolyer RA, Hess KR, et al. : Melanoma staging: Evidence-based changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J. Clin. 2017; 67 (6): 472–492. PubMed Abstract | Publisher Full Text | Free Full Text 16. Patel K, Ward ST, Packer T, et al. : Malignant melanoma of the gastro-intestinal tract: a case series. Int. J. Surg. Lond. Engl. 2014; 12 (5): 523–527. PubMed Abstract | Publisher Full Text 17. Seth R, Agarwala SS, Messersmith H, et al. : Systemic Therapy for Melanoma: ASCO Guideline Update. J. Clin. Oncol. 2023; 41 (30): 4794–4820. PubMed Abstract | Publisher Full Text 18. Tababi R: CARE checklist for “Case Report: Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review.”.August 28, 2024. Publisher Full Text Comments on this article Comments (0) Version 4 VERSION 4 PUBLISHED 06 Sep 2024 ADD YOUR COMMENT Comment Author details Author details 1 Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Nabeul, Tunisia 2 Pathology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Nabeul, Tunisia Ramzi Tababi Roles: Conceptualization, Data Curation, Investigation, Methodology, Resources, Writing – Original Draft Preparation, Writing – Review & Editing Amal Khsiba Roles: Conceptualization, Methodology, Project Administration, Supervision, Validation, Writing – Review & Editing Moufida Mahmoudi Roles: Supervision, Validation, Writing – Review & Editing Asma Ben Mohamed Roles: Supervision, Validation, Writing – Review & Editing Manel Yakoubi Roles: Supervision, Validation, Writing – Review & Editing Ghada Gharbi Roles: Supervision, Validation, Writing – Review & Editing Abir Chaabane Roles: Resources, Validation, Writing – Review & Editing Emna Chelbi Roles: Resources, Validation, Writing – Review & Editing Mouna Medhioub Roles: Project Administration, Supervision, Validation, Writing – Review & Editing Mohamed Lamine Hamzaoui Roles: Project Administration, Supervision, Validation, 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: 03 Jul 2025, 13:1019 https://doi.org/10.12688/f1000research.155815.4 version 3 Revised Published: 07 Jan 2025, 13:1019 https://doi.org/10.12688/f1000research.155815.3 version 2 Revised Published: 16 Dec 2024, 13:1019 https://doi.org/10.12688/f1000research.155815.2 version 1 Published: 06 Sep 2024, 13:1019 https://doi.org/10.12688/f1000research.155815.1 Copyright © 2025 Tababi R 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 Tababi R, Khsiba A, Mahmoudi M et al. Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.12688/f1000research.155815.4 ) 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 03 Jul 2025 Revised Views 0 Cite How to cite this report: Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.184176.r396415 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v4#referee-response-396415 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 Jul 2025 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy Approved VIEWS 0 https://doi.org/10.5256/f1000research.184176.r396415 I have no further comments. ... Continue reading READ ALL I have no further comments. The manuscript is now acceptable. 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 Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.184176.r396415 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v4#referee-response-396415 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 11 Sep 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 11 Sep 2025 Author Response We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked ... Continue reading We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked Skin Melanoma Unveiled by Gastric Metastasis” to improve clarity and lift any confusion noted in previous versions, while preserving the intended message. As requested, we have removed the sentence referring to cytological atypia and pleomorphism as typical features of melanoma. The statement regarding phenotypic dedifferentiation of metastatic melanoma has been retained, with references 12 and 13 appropriately cited to support the information, as suggested. We hope these revisions meet the reviewer’s expectations and further enhance the clarity and value of the manuscript. We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked Skin Melanoma Unveiled by Gastric Metastasis” to improve clarity and lift any confusion noted in previous versions, while preserving the intended message. As requested, we have removed the sentence referring to cytological atypia and pleomorphism as typical features of melanoma. The statement regarding phenotypic dedifferentiation of metastatic melanoma has been retained, with references 12 and 13 appropriately cited to support the information, as suggested. We hope these revisions meet the reviewer’s expectations and further enhance the clarity and value of the manuscript. Competing Interests: No competing interests to disclose. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 11 Sep 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 11 Sep 2025 Author Response We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked ... Continue reading We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked Skin Melanoma Unveiled by Gastric Metastasis” to improve clarity and lift any confusion noted in previous versions, while preserving the intended message. As requested, we have removed the sentence referring to cytological atypia and pleomorphism as typical features of melanoma. The statement regarding phenotypic dedifferentiation of metastatic melanoma has been retained, with references 12 and 13 appropriately cited to support the information, as suggested. We hope these revisions meet the reviewer’s expectations and further enhance the clarity and value of the manuscript. We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked Skin Melanoma Unveiled by Gastric Metastasis” to improve clarity and lift any confusion noted in previous versions, while preserving the intended message. As requested, we have removed the sentence referring to cytological atypia and pleomorphism as typical features of melanoma. The statement regarding phenotypic dedifferentiation of metastatic melanoma has been retained, with references 12 and 13 appropriately cited to support the information, as suggested. We hope these revisions meet the reviewer’s expectations and further enhance the clarity and value of the manuscript. Competing Interests: No competing interests to disclose. Close Report a concern COMMENT ON THIS REPORT Version 3 VERSION 3 PUBLISHED 07 Jan 2025 Revised Views 0 Cite How to cite this report: Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.176558.r357035 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v3#referee-response-357035 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 08 Jan 2025 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.176558.r357035 I have two queries: 1. The authors should rewrite the following sentence : ". These metastases typically show melanocytic features, including cytological atypia, pleomorphism, and positive staining for melanocytic markers, 12 as seen in both our gastric and ... Continue reading READ ALL I have two queries: 1. The authors should rewrite the following sentence : ". These metastases typically show melanocytic features, including cytological atypia, pleomorphism, and positive staining for melanocytic markers, 12 as seen in both our gastric and skin lesions. However, phenotypic switching during tumour progression can cause loss of typical immunophenotypic features, such as Melan-A, HMB45, S100, and SOX 10. 12 , 13 In such cases, molecular testing for melanoma-related mutations like BRAF, NRAS, and NF1 may be necessary. 13 " Cytologic atypia and pleomorphism are clues to malignancy and not clues to melanoma. Having said this, I agree that metastatic melanoma may 'dedifferentiate' (the Authors might add a reference) and lose some or even ALL the pan-melanocytic immunohistochemical markers, thereby requiring molecular investigation. 2. The Authors should explain the meaning of the sentence 'who can see the elephant in the room?': something which is self-evident (in this case, the cutaneous primary) and is nevertheless at risk of being missed. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Anatomic Pathology, Dermatopathology 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 Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.176558.r357035 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v3#referee-response-357035 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 11 Sep 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 11 Sep 2025 Author Response Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, ... Continue reading Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, we changed it to "Who can see the elephant in the room?" to reflect the idea of an obvious but potentially overlooked primary lesion. However, we understand that the current version may still be unclear. As we have revised the title multiple times based on your feedback, we would be very grateful if you could kindly suggest the exact title you believe would be most appropriate for the manuscript. In the meantime, we are working on addressing the other comments you raised. Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, we changed it to "Who can see the elephant in the room?" to reflect the idea of an obvious but potentially overlooked primary lesion. However, we understand that the current version may still be unclear. As we have revised the title multiple times based on your feedback, we would be very grateful if you could kindly suggest the exact title you believe would be most appropriate for the manuscript. In the meantime, we are working on addressing the other comments you raised. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 11 Sep 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 11 Sep 2025 Author Response Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, ... Continue reading Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, we changed it to "Who can see the elephant in the room?" to reflect the idea of an obvious but potentially overlooked primary lesion. However, we understand that the current version may still be unclear. As we have revised the title multiple times based on your feedback, we would be very grateful if you could kindly suggest the exact title you believe would be most appropriate for the manuscript. In the meantime, we are working on addressing the other comments you raised. Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, we changed it to "Who can see the elephant in the room?" to reflect the idea of an obvious but potentially overlooked primary lesion. However, we understand that the current version may still be unclear. As we have revised the title multiple times based on your feedback, we would be very grateful if you could kindly suggest the exact title you believe would be most appropriate for the manuscript. In the meantime, we are working on addressing the other comments you raised. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Version 2 VERSION 2 PUBLISHED 16 Dec 2024 Revised Views 0 Cite How to cite this report: Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.175503.r349179 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v2#referee-response-349179 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 30 Dec 2024 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.175503.r349179 I have minor suggestions. 1. The Authors should explain the title. Who can see the elephant in the room? this means that something self-evident is at risk of being missed. 2. This case highlights the need for a ... Continue reading READ ALL I have minor suggestions. 1. The Authors should explain the title. Who can see the elephant in the room? this means that something self-evident is at risk of being missed. 2. This case highlights the need for a rigorous skin examination when dealing with widespread metastatic disease 3. "Disintegrated cells" is funny. Discohesive is better 4. Is Figure 3B a MART1 stain. Looks like an S100 5. I think that liver mets must be not included among the mets to the GI apparatus 6. Discussion, para 2 after ref 8: please delete 7. Discussion, Para 8: please delete. Competing Interests: No competing interests were disclosed. Reviewer Expertise: Anatomic Pathology, Dermatopathology 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 Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.175503.r349179 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v2#referee-response-349179 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 Jan 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 07 Jan 2025 Author Response We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the ... Continue reading We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the metaphor clearer and more understandable. 2) We emphasised the importance of a rigorous skin examination in widespread metastatic disease in both the abstract and conclusion. 3) We have changed "disintegrated cells" to "discohesive cells". 4) We have double-checked and can confirm that Figure 3B shows a MART1 stain. 5) Although the liver is generally considered part of the digestive system and is often grouped with GI organs in the literature (including the reference we cited), we have, as suggested, placed it in a separate sentence to avoid any confusion. 6+7) We have deleted these paragraphs (no.2 and 8) as recommended. We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the metaphor clearer and more understandable. 2) We emphasised the importance of a rigorous skin examination in widespread metastatic disease in both the abstract and conclusion. 3) We have changed "disintegrated cells" to "discohesive cells". 4) We have double-checked and can confirm that Figure 3B shows a MART1 stain. 5) Although the liver is generally considered part of the digestive system and is often grouped with GI organs in the literature (including the reference we cited), we have, as suggested, placed it in a separate sentence to avoid any confusion. 6+7) We have deleted these paragraphs (no.2 and 8) as recommended. Competing Interests: No competing interests to declare. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 07 Jan 2025 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 07 Jan 2025 Author Response We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the ... Continue reading We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the metaphor clearer and more understandable. 2) We emphasised the importance of a rigorous skin examination in widespread metastatic disease in both the abstract and conclusion. 3) We have changed "disintegrated cells" to "discohesive cells". 4) We have double-checked and can confirm that Figure 3B shows a MART1 stain. 5) Although the liver is generally considered part of the digestive system and is often grouped with GI organs in the literature (including the reference we cited), we have, as suggested, placed it in a separate sentence to avoid any confusion. 6+7) We have deleted these paragraphs (no.2 and 8) as recommended. We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the metaphor clearer and more understandable. 2) We emphasised the importance of a rigorous skin examination in widespread metastatic disease in both the abstract and conclusion. 3) We have changed "disintegrated cells" to "discohesive cells". 4) We have double-checked and can confirm that Figure 3B shows a MART1 stain. 5) Although the liver is generally considered part of the digestive system and is often grouped with GI organs in the literature (including the reference we cited), we have, as suggested, placed it in a separate sentence to avoid any confusion. 6+7) We have deleted these paragraphs (no.2 and 8) as recommended. Competing Interests: No competing interests to declare. Close Report a concern COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 06 Sep 2024 Views 0 Cite How to cite this report: Jaziri H. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r322061 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v1#referee-response-322061 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 06 Nov 2024 Hanen Jaziri , University of Sousse, Sousse, Tunisia Approved VIEWS 0 https://doi.org/10.5256/f1000research.171029.r322061 This an original case report because gastric metastasis of melanoma is very rare and uncommon and in this case the metastases revelled the skin melanoma Vigilant skin examination is very important because the prognosis of ... Continue reading READ ALL This an original case report because gastric metastasis of melanoma is very rare and uncommon and in this case the metastases revelled the skin melanoma Vigilant skin examination is very important because the prognosis of this tumour is worse This case is illustrated by computed tomography scan endoscopic and histological fundings No modification is needed 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: gasroenterology 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 Jaziri H. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r322061 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v1#referee-response-322061 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 02 Dec 2024 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 02 Dec 2024 Author Response Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. ... Continue reading Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. We are also glad that the use of imaging and histological findings was well-illustrated. Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. We are also glad that the use of imaging and histological findings was well-illustrated. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 02 Dec 2024 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 02 Dec 2024 Author Response Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. ... Continue reading Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. We are also glad that the use of imaging and histological findings was well-illustrated. Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. We are also glad that the use of imaging and histological findings was well-illustrated. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r325913 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v1#referee-response-325913 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 05 Nov 2024 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.171029.r325913 Overall the manuscript seems to be worth of indexing, because physical examination of the skin may be neglected when a patient discloses severe systemic symptoms. I have the following suggestions: 1. I suggest the Authors to rethink of the ... Continue reading READ ALL Overall the manuscript seems to be worth of indexing, because physical examination of the skin may be neglected when a patient discloses severe systemic symptoms. I have the following suggestions: 1. I suggest the Authors to rethink of the title by looking for some appealing features of the case (e.g.: can you see the elephant in the room?) 2. The manuscript must be shortened; no need to define melanoma; no need to itemize the cytomorphological feature of the cells on gastric biopsy 3. Besides being too long, the discussion is untidy. I suggest grouping clinical studies on one side, and autopsy studies on the other one 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: Anatomic Pathology, Dermatopathology 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 Ferrara G. Reviewer Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r325913 ) The direct URL for this report is: https://f1000research.com/articles/13-1019/v1#referee-response-325913 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 16 Dec 2024 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 16 Dec 2024 Author Response We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we ... Continue reading We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we have revised the title to make it more engaging and reflective of the core aspect of the case. We believe the new title highlights the critical role of the gastric metastasis in revealing the previously undetected cutaneous melanoma, aligning with the key feature of the case. Manuscript Shortening : As recommended, we have shortened the manuscript by removing the definition of melanoma and the detailed itemization of the cytomorphological features in the gastric biopsy section. Several sentences have also been reformulated in order to reduce the word count. These changes have streamlined the manuscript, keeping the focus on the essential points of the case. Discussion Structure : We have reorganized the discussion section as per your suggestion. We have followed a structured approach in presenting this section, starting with the frequency of GI and gastric metastasis (referencing two autopsy studies in the first paragraph to highlight the prevalence of GI involvement). Subsequent sections discuss (in order) clinical presentation, endoscopic findings, histopathological findings, prognosis, treatment, and finally, the strengths and limitations of the case. Autopsy studies were only included in the first paragraph to support the epidemiology of GI metastasis, while the remainder of the references are clinical studies. To improve conciseness and readability, we have streamlined the discussion by removing redundant sentences without compromising key points. We believe these revisions have enhanced the clarity and focus of the manuscript. Thank you once again for your valuable suggestions, which have significantly improved our work. We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we have revised the title to make it more engaging and reflective of the core aspect of the case. We believe the new title highlights the critical role of the gastric metastasis in revealing the previously undetected cutaneous melanoma, aligning with the key feature of the case. Manuscript Shortening : As recommended, we have shortened the manuscript by removing the definition of melanoma and the detailed itemization of the cytomorphological features in the gastric biopsy section. Several sentences have also been reformulated in order to reduce the word count. These changes have streamlined the manuscript, keeping the focus on the essential points of the case. Discussion Structure : We have reorganized the discussion section as per your suggestion. We have followed a structured approach in presenting this section, starting with the frequency of GI and gastric metastasis (referencing two autopsy studies in the first paragraph to highlight the prevalence of GI involvement). Subsequent sections discuss (in order) clinical presentation, endoscopic findings, histopathological findings, prognosis, treatment, and finally, the strengths and limitations of the case. Autopsy studies were only included in the first paragraph to support the epidemiology of GI metastasis, while the remainder of the references are clinical studies. To improve conciseness and readability, we have streamlined the discussion by removing redundant sentences without compromising key points. We believe these revisions have enhanced the clarity and focus of the manuscript. Thank you once again for your valuable suggestions, which have significantly improved our work. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 16 Dec 2024 Ramzi Tababi , Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia 16 Dec 2024 Author Response We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we ... Continue reading We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we have revised the title to make it more engaging and reflective of the core aspect of the case. We believe the new title highlights the critical role of the gastric metastasis in revealing the previously undetected cutaneous melanoma, aligning with the key feature of the case. Manuscript Shortening : As recommended, we have shortened the manuscript by removing the definition of melanoma and the detailed itemization of the cytomorphological features in the gastric biopsy section. Several sentences have also been reformulated in order to reduce the word count. These changes have streamlined the manuscript, keeping the focus on the essential points of the case. Discussion Structure : We have reorganized the discussion section as per your suggestion. We have followed a structured approach in presenting this section, starting with the frequency of GI and gastric metastasis (referencing two autopsy studies in the first paragraph to highlight the prevalence of GI involvement). Subsequent sections discuss (in order) clinical presentation, endoscopic findings, histopathological findings, prognosis, treatment, and finally, the strengths and limitations of the case. Autopsy studies were only included in the first paragraph to support the epidemiology of GI metastasis, while the remainder of the references are clinical studies. To improve conciseness and readability, we have streamlined the discussion by removing redundant sentences without compromising key points. We believe these revisions have enhanced the clarity and focus of the manuscript. Thank you once again for your valuable suggestions, which have significantly improved our work. We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we have revised the title to make it more engaging and reflective of the core aspect of the case. We believe the new title highlights the critical role of the gastric metastasis in revealing the previously undetected cutaneous melanoma, aligning with the key feature of the case. Manuscript Shortening : As recommended, we have shortened the manuscript by removing the definition of melanoma and the detailed itemization of the cytomorphological features in the gastric biopsy section. Several sentences have also been reformulated in order to reduce the word count. These changes have streamlined the manuscript, keeping the focus on the essential points of the case. Discussion Structure : We have reorganized the discussion section as per your suggestion. We have followed a structured approach in presenting this section, starting with the frequency of GI and gastric metastasis (referencing two autopsy studies in the first paragraph to highlight the prevalence of GI involvement). Subsequent sections discuss (in order) clinical presentation, endoscopic findings, histopathological findings, prognosis, treatment, and finally, the strengths and limitations of the case. Autopsy studies were only included in the first paragraph to support the epidemiology of GI metastasis, while the remainder of the references are clinical studies. To improve conciseness and readability, we have streamlined the discussion by removing redundant sentences without compromising key points. We believe these revisions have enhanced the clarity and focus of the manuscript. Thank you once again for your valuable suggestions, which have significantly improved our work. 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 06 Sep 2024 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) 03 Jul 25 read Version 3 (revision) 07 Jan 25 read Version 2 (revision) 16 Dec 24 read Version 1 06 Sep 24 read read Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy Hanen Jaziri , University of Sousse, Sousse, Tunisia 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 Ferrara G. 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 Jul 2025 | for Version 4 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy 0 Views copyright © 2025 Ferrara G. 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 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 no further comments. The manuscript is now acceptable. 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 (1) Author Response 11 Sep 2025 Ramzi Tababi, Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia We thank the reviewer for the constructive feedback, which has been very helpful in improving our manuscript. In this revised version: We have changed the title to “Overlooked Skin Melanoma Unveiled by Gastric Metastasis” to improve clarity and lift any confusion noted in previous versions, while preserving the intended message. As requested, we have removed the sentence referring to cytological atypia and pleomorphism as typical features of melanoma. The statement regarding phenotypic dedifferentiation of metastatic melanoma has been retained, with references 12 and 13 appropriately cited to support the information, as suggested. We hope these revisions meet the reviewer’s expectations and further enhance the clarity and value of the manuscript. View more View less Competing Interests No competing interests to disclose. reply Respond Report a concern Ferrara G. Peer Review Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.184176.r396415) 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/13-1019/v4#referee-response-396415 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Ferrara G. 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. 08 Jan 2025 | for Version 3 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy 0 Views copyright © 2025 Ferrara G. 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 I have two queries: 1. The authors should rewrite the following sentence : ". These metastases typically show melanocytic features, including cytological atypia, pleomorphism, and positive staining for melanocytic markers, 12 as seen in both our gastric and skin lesions. However, phenotypic switching during tumour progression can cause loss of typical immunophenotypic features, such as Melan-A, HMB45, S100, and SOX 10. 12 , 13 In such cases, molecular testing for melanoma-related mutations like BRAF, NRAS, and NF1 may be necessary. 13 " Cytologic atypia and pleomorphism are clues to malignancy and not clues to melanoma. Having said this, I agree that metastatic melanoma may 'dedifferentiate' (the Authors might add a reference) and lose some or even ALL the pan-melanocytic immunohistochemical markers, thereby requiring molecular investigation. 2. The Authors should explain the meaning of the sentence 'who can see the elephant in the room?': something which is self-evident (in this case, the cutaneous primary) and is nevertheless at risk of being missed. Competing Interests No competing interests were disclosed. Reviewer Expertise Anatomic Pathology, Dermatopathology 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 11 Sep 2025 Ramzi Tababi, Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia Professor, Thank you for your continued guidance. Regarding the title, we initially proposed "Gastric Metastasis revealing a Disseminated Skin Melanoma: A Case Report and Literature Review." Following your previous suggestion, we changed it to "Who can see the elephant in the room?" to reflect the idea of an obvious but potentially overlooked primary lesion. However, we understand that the current version may still be unclear. As we have revised the title multiple times based on your feedback, we would be very grateful if you could kindly suggest the exact title you believe would be most appropriate for the manuscript. In the meantime, we are working on addressing the other comments you raised. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Ferrara G. Peer Review Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.176558.r357035) 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/13-1019/v3#referee-response-357035 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Ferrara G. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 30 Dec 2024 | for Version 2 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy 0 Views copyright © 2025 Ferrara G. 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 I have minor suggestions. 1. The Authors should explain the title. Who can see the elephant in the room? this means that something self-evident is at risk of being missed. 2. This case highlights the need for a rigorous skin examination when dealing with widespread metastatic disease 3. "Disintegrated cells" is funny. Discohesive is better 4. Is Figure 3B a MART1 stain. Looks like an S100 5. I think that liver mets must be not included among the mets to the GI apparatus 6. Discussion, para 2 after ref 8: please delete 7. Discussion, Para 8: please delete. Competing Interests No competing interests were disclosed. Reviewer Expertise Anatomic Pathology, Dermatopathology 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 Jan 2025 Ramzi Tababi, Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia We appreciate the valuable suggestions and have addressed the comments as follows: 1) The title has been revised to "Can You See the Elephant in the Room?" to make the metaphor clearer and more understandable. 2) We emphasised the importance of a rigorous skin examination in widespread metastatic disease in both the abstract and conclusion. 3) We have changed "disintegrated cells" to "discohesive cells". 4) We have double-checked and can confirm that Figure 3B shows a MART1 stain. 5) Although the liver is generally considered part of the digestive system and is often grouped with GI organs in the literature (including the reference we cited), we have, as suggested, placed it in a separate sentence to avoid any confusion. 6+7) We have deleted these paragraphs (no.2 and 8) as recommended. View more View less Competing Interests No competing interests to declare. reply Respond Report a concern Ferrara G. Peer Review Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.175503.r349179) 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/13-1019/v2#referee-response-349179 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Jaziri H. 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. 06 Nov 2024 | for Version 1 Hanen Jaziri , University of Sousse, Sousse, Tunisia 0 Views copyright © 2024 Jaziri H. 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 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 an original case report because gastric metastasis of melanoma is very rare and uncommon and in this case the metastases revelled the skin melanoma Vigilant skin examination is very important because the prognosis of this tumour is worse This case is illustrated by computed tomography scan endoscopic and histological fundings No modification is needed 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 gasroenterology 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 (1) Author Response 02 Dec 2024 Ramzi Tababi, Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia Thank you for your positive feedback. We appreciate your recognition of the rarity and significance of the case, as well as the importance of vigilant skin examination in such patients. We are also glad that the use of imaging and histological findings was well-illustrated. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Jaziri H. Peer Review Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r322061) 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/13-1019/v1#referee-response-322061 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Ferrara G. 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. 05 Nov 2024 | for Version 1 Gerardo Ferrara , G. Pascale Foundation National Cancer Institute IRCCS,, Naples, Italy 0 Views copyright © 2024 Ferrara G. 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 Overall the manuscript seems to be worth of indexing, because physical examination of the skin may be neglected when a patient discloses severe systemic symptoms. I have the following suggestions: 1. I suggest the Authors to rethink of the title by looking for some appealing features of the case (e.g.: can you see the elephant in the room?) 2. The manuscript must be shortened; no need to define melanoma; no need to itemize the cytomorphological feature of the cells on gastric biopsy 3. Besides being too long, the discussion is untidy. I suggest grouping clinical studies on one side, and autopsy studies on the other one 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 Anatomic Pathology, Dermatopathology 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 16 Dec 2024 Ramzi Tababi, Gastroenterology Department, Mohamed Taher Maamouri University Hospital Nabeul, Mrezga, Tunisia We greatly appreciate your constructive feedback on our manuscript. We have carefully considered your suggestions and made the following revisions: Title Revision : In response to your suggestion, we have revised the title to make it more engaging and reflective of the core aspect of the case. We believe the new title highlights the critical role of the gastric metastasis in revealing the previously undetected cutaneous melanoma, aligning with the key feature of the case. Manuscript Shortening : As recommended, we have shortened the manuscript by removing the definition of melanoma and the detailed itemization of the cytomorphological features in the gastric biopsy section. Several sentences have also been reformulated in order to reduce the word count. These changes have streamlined the manuscript, keeping the focus on the essential points of the case. Discussion Structure : We have reorganized the discussion section as per your suggestion. We have followed a structured approach in presenting this section, starting with the frequency of GI and gastric metastasis (referencing two autopsy studies in the first paragraph to highlight the prevalence of GI involvement). Subsequent sections discuss (in order) clinical presentation, endoscopic findings, histopathological findings, prognosis, treatment, and finally, the strengths and limitations of the case. Autopsy studies were only included in the first paragraph to support the epidemiology of GI metastasis, while the remainder of the references are clinical studies. To improve conciseness and readability, we have streamlined the discussion by removing redundant sentences without compromising key points. We believe these revisions have enhanced the clarity and focus of the manuscript. Thank you once again for your valuable suggestions, which have significantly improved our work. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Ferrara G. Peer Review Report For: Case Report: Overlooked Skin Melanoma Unveiled by Gastric Metastasis [version 4; peer review: 2 approved] . F1000Research 2025, 13 :1019 ( https://doi.org/10.5256/f1000research.171029.r325913) 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/13-1019/v1#referee-response-325913 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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