Persistently Elevated Vitamin B12: A Missed Diagnostic Opportunity?
DOI:
https://doi.org/10.52340/ijch.2026.03.09საკვანძო სიტყვები:
Vitamin B12, Hypercobalaminemia, Gastrointestinal Stromal Tumour, Cancer Biomarker, Diagnostic Challengeანოტაცია
Background
Vitamin B12 testing is primarily performed to identify deficiency; however, persistently elevated serum vitamin B12 levels in patients not receiving supplementation are uncommon and may indicate underlying pathology. Emerging evidence suggests that unexplained hypercobalaminemia is associated with solid and haematological malignancies, although its diagnostic significance remains underrecognized. This study describes a patient with persistently elevated vitamin B12 levels that prompted further investigation and was associated with the diagnosis of a gastrointestinal stromal tumour (GIST).
Methods
We conducted a retrospective analysis of the clinical records of a 69-year-old female presenting with persistently elevated serum vitamin B12 levels (19,717 pg/mL; reference range: 173–700 pg/mL) despite no history of vitamin B12 supplementation. Clinical assessment, laboratory investigations, imaging, endoscopic findings, histopathology, treatment, and follow-up data were reviewed. Relevant literature was examined to place the findings within the context of current evidence.
Results
The patient had a history of type 2 diabetes, autoimmune thyroid disease, and mild iron deficiency anaemia. Gastroenterological evaluation identified a gastrointestinal stromal tumour (GIST), confirmed by positive immunohistochemical staining for CD117, CD34, and CD56. Following tumour resection and partial gastrectomy, vitamin B12 abnormalities persisted alongside hyperhomocysteinemia, despite normal liver and kidney function. The patient subsequently received adjuvant imatinib therapy. Current literature suggests that persistent hypercobalaminemia is associated with an increased risk of several solid malignancies and may reflect tumour-related alterations in vitamin B12 transport proteins or metabolism.
Conclusion
Persistent elevation of serum vitamin B12 in the absence of supplementation should not be dismissed as an incidental laboratory finding. This case highlights the importance of considering occult malignancy in the differential diagnosis of unexplained hypercobalaminemia and supports further investigation into the role of vitamin B12 as a potential biomarker for earlier cancer detection.
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წყაროები
Allen, L. H. (2012). Vitamin B-12. Advances in Nutrition (Bethesda, Md.), 3(1), 54–55. https://doi.org/10.3945/an.111.001370
Andrès, E., Serraj, K., Zhu, J., & Vermorken, A. J. M. (2013). The pathophysiology of elevated vitamin B12 in clinical practice. QJM: Monthly Journal of the Association of Physicians, 106(6), 505–515. https://doi.org/10.1093/qjmed/hct051
Ardeman, S., & Chanarin, I. (1966). Gastric intrinsic factor secretion after partial gastrectomy. Gut, 7(3), 217–219. https://doi.org/10.1136/gut.7.3.217
Arendt, J. F. H., Farkas, D. K., Pedersen, L., Nexo, E., & Sørensen, H. T. (2016). Elevated plasma vitamin B12 levels and cancer prognosis: A population-based cohort study. Cancer Epidemiology, 40, 158–165. https://doi.org/10.1016/j.canep.2015.12.007
Chen, X., Guo, C., Cui, W., Sun, K., Wang, Z., & Chen, X. (2020). CD56 Expression Is Associated with Biological Behavior of Pancreatic Neuroendocrine Neoplasms. Cancer Management and Research, Volume 12, 4625–4631. https://doi.org/10.2147/CMAR.S250071
Cui, L.-H., Quan, Z.-Y., Piao, J.-M., Zhang, T.-T., Jiang, M.-H., Shin, M.-H., & Choi, J.-S. (2016). Plasma Folate and Vitamin B12 Levels in Patients with Hepatocellular Carcinoma. International Journal of Molecular Sciences, 17(7), 1032. https://doi.org/10.3390/ijms17071032
Fanidi, A., Carreras-Torres, R., Larose, T. L., Yuan, J.-M., Stevens, V. L., Weinstein, S. J., Albanes, D., Prentice, R., Pettinger, M., Cai, Q., Blot, W. J., Arslan, A. A., Zeleniuch-Jacquotte, A., McCullough, M. L., Le Marchand, L., Wilkens, L. R., Haiman, C. A., Zhang, X., Stampfer, M. J., … LC3 consortium and the TRICL consortium. (2019). Is high vitamin B12 status a cause of lung cancer? International Journal of Cancer, 145(6), 1499–1503. https://doi.org/10.1002/ijc.32033
Infante, M., Leoni, M., Caprio, M., & Fabbri, A. (2021). Long-term metformin therapy and vitamin B12 deficiency: An association to bear in mind. World Journal of Diabetes, 12(7), 916–931. https://doi.org/10.4239/wjd.v12.i7.916
Jammal, M., Deneuville, T., Mario, N., Tiev, K., Tolédano, C., Josselin-Mahr, L., Pateron, D., Guidet, B., Retbi, A., Taright, N., Cabane, J., & Kettaneh, A. (2013). [High plasmatic concentration of vitamin B12: An indicator of hepatic diseases or tumours]. La Revue De Medecine Interne, 34(6), 337–341. https://doi.org/10.1016/j.revmed.2012.10.006
Lacombe, V., Chabrun, F., Lacout, C., Ghali, A., Capitain, O., Patsouris, A., Lavigne, C., & Urbanski, G. (2021). Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Scientific Reports, 11(1), 13361. https://doi.org/10.1038/s41598-021-92945-y
Lin, C.-Y., Kuo, C.-S., Lu, C.-L., Wu, M.-Y., & Huang, R.-F. S. (2010). Elevated serum vitamin B(12) levels in association with tumour markers as the prognostic factors predictive for poor survival in patients with hepatocellular carcinoma. Nutrition and Cancer, 62(2), 190–197. https://doi.org/10.1080/01635580903305334
Luu, H. N., Wang, R., Jin, A., Koh, W.-P., & Yuan, J.-M. (2021). The association between dietary vitamin B12 and lung cancer risk: Findings from a prospective cohort study. European Journal of Cancer Prevention: The Official Journal of the European Cancer Prevention Organisation (ECP), 30(3), 275–281. https://doi.org/10.1097/CEJ.0000000000000660
Obeid, R. (2022). High Plasma Vitamin B12 and Cancer in Human Studies: A Scoping Review to Judge Causality and Alternative Explanations. Nutrients, 14(21), 4476. https://doi.org/10.3390/nu14214476
Price, A. J., Travis, R. C., Appleby, P. N., Albanes, D., Barricarte Gurrea, A., Bjørge, T., Bueno-de-Mesquita, H. B., Chen, C., Donovan, J., Gislefoss, R., Goodman, G., Gunter, M., Hamdy, F. C., Johansson, M., King, I. B., Kühn, T., Männistö, S., Martin, R. M., Meyer, K., … Endogenous Hormones, Nutritional Biomarkers, and Prostate Cancer Collaborative Group. (2016). Circulating Folate and Vitamin B12 and Risk of Prostate Cancer: A Collaborative Analysis of Individual Participant Data from Six Cohorts Including 6875 Cases and 8104 Controls. European Urology, 70(6), 941–951. https://doi.org/10.1016/j.eururo.2016.03.029
Sarlomo-Rikala, M., Kovatich, A. J., Barusevicius, A., & Miettinen, M. (1998). CD117: A sensitive marker for gastrointestinal stromal tumours that is more specific than CD34. Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc, 11(8), 728–734.
Serraj, K., Mecili, M., Housni, I., & Andrès, E. (2011). [Hypervitaminemia B12 (high level of cobalamin): Physiopathology, role and interest in clinical practice]. Presse Medicale (Paris, France: 1983), 40(12 Pt 1), 1120–1127. https://doi.org/10.1016/j.lpm.2011.08.010
Simonsen, K., Rode, A., Nicoll, A., Villadsen, G., Espelund, U., Lim, L., Angus, P., Arachchi, N., Vilstrup, H., Nexo, E., & Grønbæk, H. (2014). Vitamin B₁₂ and its binding proteins in hepatocellular carcinoma and chronic liver diseases. Scandinavian Journal of Gastroenterology, 49(9), 1096–1102. https://doi.org/10.3109/00365521.2014.921325
