CA: A Cancer Journal for Clinicians, Vol 27, 88-99, Copyright
© 1977 by American Cancer Society
Differential Diagnosis of Anemia and Cancer
Carol Leite M.D.1 and
Barth Hoogstraten M.D.2
1 Associate in Medicine, Clinical Oncology, Kansas University Medical Center, Kansas City, Kansas.
2 American Cancer Society Professor of Clinical Oncology, Kansas University Medical Center, Kansas City.
Many patients have multiple causes of anemia. These mixed states render the classical guidelines of peripheral smear, indices, reticulocyte counts and levels of serum iron inadequate for diagnosis. Since the patient with cancer is often under chemotherapy and/or radiation therapy, it is important to ascertain whether the anemia is secondary to bone marrow suppression by treatment, bone marrow suppression by tumor or peripheral destruction or loss. Crucial studies are CBC, platelet count and peripheral smear. (Figure.)
Pancytopenia may be caused by drugs, irradiation, marrow infiltration (leukoerythroblastosis), hypersplenism or severe folate or B12 dificiency. If the patient is at the expected time of a chemotherapeutic or radiation nadir, and the peripheral smear is not unusual, then nothing further is indicated and a "wait and watch" policy may be undertaken. If the patient is not at the usual time for chemotherapy or radiation-induced bone marrow depression, bone marrow aspiration and biopsy should be performed. If the marrow is hyperplastic, the anemia may be caused by peripheral destruction (hypersplenism) or dyserythropoiesis. (B12 or folate deficiency should have megaloblastoid features.) If the marrow is hypoplastic and/or dyserythropoietic, the patient is probably experiencing bone marrow depression from chemotherapy, although preleukemia can also evolve from this type of a picture.
The peripheral smear can be of help, but should not be regarded as diagnostic. In leukoerythroblastic anemia secondary to marrow infiltration, metamyelocytes, myelocytes, nucleated red cells and tear drop red blood cells may be seen. In B12 and folate deficiencies, there may be oval macrocytes and hypersegmented polys. An elevation in the reticulocyte count should always point to hemolysis or blood loss, and red cell fragments in the peripheral smear should alert one to hemolysis. If microangiopathic hemolytic anemia is demonstrated, coagulation studies should also be performed.
Iron deficiency anemia is most commonly seen with gastrointestinal, genitourinary and head and neck tumors, while pure red cell aplasia is usually associated with thymoma. Leukoerythroblastic anemia may be found with any tumor metastatic to the bone marrow, but most often the breast, prostate and lung. Warm antibody hemolytic anemia is generally associated with chronic lymphocytic leukemia, Hodgkin's and non-Hodgkin's lymphomas and multiple myeloma. Cold agglutinin hemolytic anemia is seen with histiocytic lymphoma (formerly, reticulum cell sarcoma) and Waldenström's macroglobulinemia. Folate deficiencies producing megaloblastic anemia may occur in multiple myeloma and leukemia. Gastric, cancer is more common in patients with pernicious anemia. Microangiopathic hemolytic anemia most often occurs in patients with adenocarcinomas, particularly of the breast, pancreas and mucin-producing tumors of the gastrointestinal tract.
