Case Report: Bone marrow metastasis revealing gastric signet ring cell carcinoma: a case report

Keywords Gastric signet ring cell carcinoma; bone marrow metastasis; bone marrow biopsy; case report ALL Metrics - Views Downloads How to cite this article Ben Azouz S, Ayari M, Ben Rejeb S et al. Case Report: Bone marrow metastasis revealing gastric signet ring cell carcinoma: a case report [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:477 (https://doi.org/10.12688/f1000research.178901.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente Select a format first ▬ ✚ Case Report [version 1; peer review: awaiting peer review] Sarra Ben Azouz https://orcid.org/0000-0002-9628-265X 1, Myriam Ayari https://orcid.org/0000-0001-7361-8248 1, Sarra Ben Rejeb https://orcid.org/0000-0001-9150-3444 2, [...] Amira Chehaider1, Hiba Bettaieb3, Manel Boudokhane3, Syrine Bellakhal3, Taieb Jomni1Sarra Ben Azouz https://orcid.org/0000-0002-9628-265X 1, Myriam Ayari https://orcid.org/0000-0001-7361-8248 1, [...] Sarra Ben Rejeb https://orcid.org/0000-0001-9150-3444 2, Amira Chehaider1, Hiba Bettaieb3, Manel Boudokhane3, Syrine Bellakhal3, Taieb Jomni1 PUBLISHED 06 Apr 2026 Author details Author details 1 Gastro-enterology Department, Internal Security Forces Hospital, La Marsa, Marsa, Tunisia 2 Pathology Department, Internal Security Forces Hospital, Marsa, Tunisia 3 Internal Medicine Department, Internal Security Forces Hospital, Marsa, Tunisia 2 Pathology Department, Internal Security Forces Hospital, Marsa, Tunisia 3 Internal Medicine Department, Internal Security Forces Hospital, Marsa, Tunisia Sarra Ben Azouz Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation Myriam Ayari Roles: Conceptualization, Visualization, Writing – Original Draft Preparation Roles: Conceptualization, Visualization, Writing – Original Draft Preparation Sarra Ben Rejeb Roles: Conceptualization, Data Curation Roles: Conceptualization, Data Curation Amira Chehaider Roles: Supervision, Writing – Review & Editing Roles: Supervision, Writing – Review & Editing Hiba Bettaieb Roles: Writing – Original Draft Preparation, Writing – Review & Editing Roles: Writing – Original Draft Preparation, Writing – Review & Editing Manel Boudokhane Roles: Supervision, Writing – Review & Editing Roles: Supervision, Writing – Review & Editing Syrine Bellakhal Roles: Supervision, Validation Roles: Supervision, Validation Taieb Jomni Roles: Supervision, Validation Roles: Supervision, Validation OPEN PEER REVIEW REVIEWER STATUS AWAITING PEER REVIEW Bone marrow metastasis from gastric adenocarcinoma is uncommon and may present with cytopenias and diffuse skeletal lesions, mimicking primary hematologic disorders. Herein, we report the case of a 53-year-old man of North African descent who presented with a two-month history of epigastric pain, unintentional weight loss, and functional decline. Laboratory testing revealed thrombocytopenia (80 × 103/mm3) and markedly elevated alkaline phosphatase (1500 IU/L). Contrast-enhanced computed tomography showed diffuse osteolytic lesions without an evident primary tumor. Bone marrow trephine biopsy demonstrated extensive replacement by a malignant epithelial proliferation. Tumor cells stained positive for cytokeratin, consistent with metastatic carcinoma. Upper gastrointestinal endoscopy identified an ill-defined ulceroinfiltrative lesion along the lesser curvature with friable margins and spontaneous bleeding on minimal touch. Biopsies confirmed poorly differentiated signet ring cell adenocarcinoma. The diagnosis of gastric carcinoma with bone marrow metastasis was then retained. The patient was managed with palliative systemic chemotherapy as well as supportive care and remains alive at 10 months of follow-up. This case highlights that diffuse osteolytic disease with unexplained cytopenias and disproportionate alkaline phosphatase elevation should prompt consideration of occult solid malignancy with marrow involvement. Early bone marrow biopsy with immunohistochemistry can rapidly establish epithelial lineage and should prompt evaluation for an occult gastrointestinal primary malignancy. Gastric signet ring cell carcinoma; bone marrow metastasis; bone marrow biopsy; case report Corresponding Author(s) Sarra Ben Azouz ([email protected]) Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2026 Ben Azouz S 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: Ben Azouz S, Ayari M, Ben Rejeb S et al. Case Report: Bone marrow metastasis revealing gastric signet ring cell carcinoma: a case report [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:477 (https://doi.org/10.12688/f1000research.178901.1) First published: 06 Apr 2026, 15:477 (https://doi.org/10.12688/f1000research.178901.1) Latest published: 06 Apr 2026, 15:477 (https://doi.org/10.12688/f1000research.178901.1) Gastric cancer most commonly metastasizes to the peritoneum, liver, and distant lymph nodes, whereas skeletal and bone marrow dissemination are far less frequent.1,2 Diffuse marrow involvement, often described within the spectrum of disseminated carcinomatosis of the bone marrow, may present with cytopenias, disproportionate elevation of alkaline phosphatase, and diffuse lytic or mixed skeletal lesions on imaging.1,3 Because this clinical and radiologic profile can mimic hematologic malignancies particularly multiple myeloma, timely histologic confirmation is critical to avoid diagnostic delay and to expedite appropriate oncologic management.4 What makes the present case unique is that the malignancy was first suggested by osteo-medullary metastases, while cross-sectional imaging did not reveal an obvious primary tumor, and the gastric origin was ultimately established only after marrow immunohistochemistry prompted targeted upper endoscopy. A 53-year-old man with no significant past medical history was admitted for evaluation of chronic epigastric pain for the past two months associated with unintentional weight loss and functional decline. He reported progressive anorexia and fatigue, without vomiting, overt gastrointestinal bleeding, or fever. Physical examination was unremarkable except for epigastric tenderness, with no palpable abdominal mass, peripheral lymphadenopathy, or clinically evident hepatosplenomegaly. The patient’s clinical course is summarized in Table 1. Thoraco-abdominopelvic computed tomography (CT) demonstrated diffuse osteolytic lesions involving the vertebral bodies and pelvis, without radiologic spinal cord compression and without an obvious primary tumor ( Figure 1). Given new-onset thrombocytopenia in association with diffuse bone disease, bone marrow infiltration was suspected. A bone marrow trephine biopsy showed a markedly hypercellular marrow with reduced adipocytes, extensively replaced by a malignant epithelial proliferation composed of isolated, non-cohesive cells and single-file infiltration within a fibrous stroma. Immunohistochemistry demonstrated cytokeratin positivity, supporting metastatic carcinoma ( Figure 2). Upper gastrointestinal endoscopy was performed to identify a possible primary. It revealed an ill-defined ulceroinfiltrative lesion at the incisura angularis along the lesser curvature, with friable margins and spontaneous bleeding on minimal touch. Biopsies from the ulcer margins showed a poorly differentiated gastric adenocarcinoma with signet-ring cells, consistent with a gastric primary ( Figure 3). The diagnosis of gastric carcinoma with bone marrow metastasis was then retained. Immunohistochemistry demonstrated retained expression of mismatch repair (MMR) proteins consistent with proficient MMR (microsatellite stable), and Human epidermal growth factor receptor 2 (HER2) immunostaining was negative. The case was discussed in a multidisciplinary tumor board. Palliative systemic chemotherapy based on fluoropyrimidine and platinum as well as supportive management were initiated. At 10 months of follow-up, the patient remains alive while continuing palliative treatment. Strengths of this report include early use of bone marrow trephine biopsy with immunohistochemistry, which promptly established an epithelial origin and prompted the search for an occult primary, leading to a definitive diagnosis. In addition, the multidisciplinary approach and documented 10-month survival under palliative chemotherapy provide clinically relevant, practice-oriented insights. Limitations include the single-patient design and the absence of standardized longitudinal imaging and biomarker follow-up. Bone marrow metastasis from solid tumors is uncommon and under-recognized, as it may masquerade as a primary hematologic disorder and can be the initial clue to an occult malignancy.4 In gastric cancer, marrow dissemination is most often associated with poorly differentiated or signet ring cell histology and may occur with extensive skeletal involvement. Retrospective series have shown poor outcomes, particularly when marrow carcinomatosis is associated with coagulopathy or rapid clinical deterioration.3,5 In our patient, the combination of thrombocytopenia and disproportionate alkaline phosphatase elevation in the setting of diffuse osteolytic lesions raised suspicion for marrow infiltration. The differential diagnosis includes multiple myeloma, lymphoma, leukemia, and metastatic solid tumors.6–8 While advanced imaging methods including radiomics approaches are being explored to differentiate myeloma from metastases, histology remains the key determinant in routine practice.8,9 Accordingly, early bone marrow trephine biopsy is a high-yield step when cytopenias coexist with diffuse bone lesions and can rapidly establish epithelial lineage through immunohistochemistry.10,11 Disseminated carcinomatosis of the bone marrow is thought to reflect a distinctive metastatic behavior characterized by rapid diffuse marrow infiltration with limited nodularity. Tumor–bone microenvironment interactions, including osteoclast activation, may contribute to aggressive marrow tropism and osteolysis in susceptible gastric cancer phenotypes. Clinically, red flags include disproportionate alkaline phosphatase and/or lactate dehydrogenase elevation, cytopenia, particularly thrombocytopenia, and diffuse bone pain or constitutional symptoms.3,12 Marrow metastasis may also occur years after gastrectomy or during chemotherapy, underscoring the need for vigilance when unexplained cytopenias or biochemical abnormalities arise.13–15 Management is multidisciplinary and primarily palliative, integrating systemic therapy, transfusion support, and symptom control. Current guideline-based strategies favor fluoropyrimidine–platinum doublets with treatment individualization based on HER2 status, Programmed Death-Ligand 1 (PD-L1), Microsatellite Instability (MSI) status, performance status, and comorbidities, and reinforce that systemic therapy should be initiated promptly when clinically appropriate.16,17 Although prospective evidence is limited, retrospective analyses and case-based experience suggest that palliative chemotherapy can improve cytopenias and performance status in selected patients and may prolong survival compared with best supportive care alone. Reports describe survival beyond several months in patients treated with modern fluoropyrimidine–platinum based regimens when adequate supportive care is available.18–20 Consistent with these data, our patient remains alive at 10 months after diagnosis, supporting the concept that palliative chemotherapy may translate into meaningful survival in carefully selected patients with gastric cancer and marrow involvement. Diffuse osteolytic disease with unexplained cytopenias and disproportionate alkaline phosphatase elevation should prompt consideration of occult solid malignancy with bone marrow involvement. Early bone marrow biopsy with immunohistochemistry can rapidly confirm metastatic carcinoma and prompt evaluation for a gastrointestinal primary, shortening time to appropriate multidisciplinary management. Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The completed CARE checklist for “Bone marrow metastasis revealing gastric signet ring cell carcinoma: a case report” is available in an external repository. Repository: Zenodo; Title: CARE checklist: Bone marrow metastasis revealing gastric signet ring cell carcinoma; DOI: https://doi.org/10.5281/zenodo.1888457821; License: CC0 1.0. Declaration of generative AI in scientific writing: Generative AI (chat GPT) was used for the correction of spelling mistakes of the final version of the manuscript. Not applicable. - Kwon JY, Yun J, Kim HJ, et al.:Clinical Outcome of Gastric Cancer Patients with Bone Marrow Metastases.Cancer Res Treat.2011 Dec 27; 43(4): 244–249. PubMed Abstract | Publisher Full Text | Free Full Text - Kim YJ, Kim SH, Kim JW, et al.:Gastric cancer with initial bone metastasis: A distinct group of diseases with poor prognosis.Eur J Cancer.2014 Nov; 50(16): 2810–2821. 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Publisher Full Text Author details Author details 1 Gastro-enterology Department, Internal Security Forces Hospital, La Marsa, Marsa, Tunisia 2 Pathology Department, Internal Security Forces Hospital, Marsa, Tunisia 3 Internal Medicine Department, Internal Security Forces Hospital, Marsa, Tunisia 2 Pathology Department, Internal Security Forces Hospital, Marsa, Tunisia 3 Internal Medicine Department, Internal Security Forces Hospital, Marsa, Tunisia Sarra Ben Azouz Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation Roles: Conceptualization, Data Curation, Investigation, Writing – Original Draft Preparation Myriam Ayari Roles: Conceptualization, Visualization, Writing – Original Draft Preparation Roles: Conceptualization, Visualization, Writing – Original Draft Preparation Sarra Ben Rejeb Roles: Conceptualization, Data Curation Roles: Conceptualization, Data Curation Amira Chehaider Roles: Supervision, Writing – Review & Editing Roles: Supervision, Writing – Review & Editing Hiba Bettaieb Roles: Writing – Original Draft Preparation, Writing – Review & Editing Roles: Writing – Original Draft Preparation, Writing – Review & Editing Manel Boudokhane Roles: Supervision, Writing – Review & Editing Roles: Supervision, Writing – Review & Editing Syrine Bellakhal Roles: Supervision, Validation Roles: Supervision, Validation Taieb Jomni Roles: Supervision, Validation Roles: Supervision, Validation Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Copyright © 2026 Ben Azouz S 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. metrics | Views | Downloads | | |---|---|---| | F1000Research | - | - | | PubMed Central Data from PMC are received and updated monthly. | - | - | Citations CITE how to cite this article Ben Azouz S, Ayari M, Ben Rejeb S et al. Case Report: Bone marrow metastasis revealing gastric signet ring cell carcinoma: a case report [version 1; peer review: awaiting peer review]. F1000Research 2026, 15:477 (https://doi.org/10.12688/f1000research.178901.1) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. track receive updates on this article Track an article to receive email alerts on any updates to this article. Current Reviewer Status: AWAITING PEER REVIEW AWAITING PEER REVIEW ? Key to Reviewer Statuses VIEW HIDE ApprovedThe 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. 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