From the Guidelines
Hyperferritinemia is most commonly associated with hematologic malignancies, particularly myelodysplastic syndromes (MDS), as evidenced by elevated serum ferritin levels in over 90% of MDS patients at the time of diagnosis 1.
Malignancies Causing Hyperferritinemia
The following malignancies are known to cause hyperferritinemia:
- Hematologic malignancies:
- Myelodysplastic syndromes (MDS)
- Leukemias, such as acute myeloid leukemia
- Lymphomas, including both Hodgkin and non-Hodgkin
- Multiple myeloma
- Solid tumors:
- Hepatocellular carcinoma
- Breast cancer
- Lung cancer
- Colorectal cancer
- Renal cell carcinoma
Mechanisms of Hyperferritinemia
These malignancies lead to elevated ferritin levels through various mechanisms, including:
- Increased production of ferritin as an acute phase reactant in response to inflammation
- Direct production by tumor cells
- Release from damaged cells during tumor lysis
- Altered iron metabolism, as seen in patients with MDS who develop secondary iron overload due to regular red blood cell transfusions 1
Clinical Implications
When evaluating a patient with unexplained hyperferritinemia, clinicians should consider these malignancies in their differential diagnosis, particularly if accompanied by other concerning symptoms such as unexplained weight loss, night sweats, lymphadenopathy, or organomegaly. Management involves treating the underlying malignancy rather than focusing solely on reducing ferritin levels. In patients with MDS, chelation therapy may be considered to preserve quality of life and organ function, and possibly improve survival 1.
From the Research
Malignancies Causing Hyperferritinemia
- Hematologic malignancies, such as acute leukemias, are associated with elevated ferritin levels 2
- Malignant lymphomas, including Hodgkin disease and histiocytic lymphoma, can also cause hyperferritinemia 2
- Hematological malignancy is a common cause of hyperferritinemia, with 16% of cases attributed to this condition 3
- Specific hematological malignancies, such as T/NK cell lymphoma and acute myeloblastic leukemia, are positively associated with maximum ferritin levels 4
- Solid malignancies can also contribute to hyperferritinemia, although to a lesser extent than hematological malignancies 3, 5
Other Conditions Associated with Hyperferritinemia
- Infections, such as sepsis and septic shock, are common causes of hyperferritinemia 6, 4
- Liver disease, including acute hepatitis and hepatic veno-occlusive disease, can also lead to elevated ferritin levels 5, 6, 4
- Hemophagocytic lymphohistiocytosis (HLH) is a well-known cause of extreme hyperferritinemia 3, 6, 4
- Iron overload syndromes and chronic transfusion can also contribute to hyperferritinemia 3, 6