Secondary cold agglutinin disease is early blood cancer sign in man, 53
Lymphoma, CAD vanished following standard treatment for cancer
Clinicians detected B-cell lymphoma, a type of blood cancer, in a 53-year-old man two years after he was diagnosed with cold agglutinin disease (CAD) marked by anemia, or low counts of red blood cells, but no symptoms, a case study indicates.
All signs of lymphoma and CAD disappeared after the man received standard treatment for the blood cancer, suggesting CAD occurred secondary to lymphoma and may have been an early sign of the cancer.
“On the whole, the present study demonstrates that [CAD] may serve as an early indicator of lymphoma,” the researchers wrote.
The case study, “Cold agglutinin syndrome as a precursor for the diagnosis of low‑grade lymphoma: A case report,” was published in Medicine International.
CAD is a rare autoimmune disease where self-reactive antibodies, called cold agglutinins, that bind to red blood cells at cold temperatures are produced. This leads to red blood cell clumping, which marks the cells for destruction (hemolysis) and results in anemia and symptoms like fatigue, weakness, and pale skin. The condition is classified as primary when its cause is unknown or secondary when it arises from underlying illnesses, such as infections and other autoimmune disorders.
Certain cancers can also trigger secondary CAD, most commonly blood cancers affecting B-cells, the immune cells that produce both the healthy antibodies that protect the body from invaders and the self-reactive antibodies that drive autoimmune diseases. CAD associated with solid tumors is rare.
A CAD diagnosis
Here, clinicians at the Dokuz Eylul University Hospital in Turkey write about a man who had no symptoms but sought a second opinion regarding anemia detected during a routine checkup.
Two separate analyses of blood cell counts in the previous week had yielded conflicting results. One indicated normal findings, while the other showed fewer, but larger than normal red blood cells.
The man’s medical records showed a history of diabetes and high blood pressure, for which he was being treated, and an inactive chronic hepatitis B virus infection. He smoked for at least 20 years and consumed alcohol socially. A physical examination revealed no abnormalities.
Blood tests at a clinician’s hospital confirmed the anemia and the larger red blood cells. Blood hemoglobin, the protein that carries oxygen, and markers of hemolysis were within normal range. A blood smear analysis detected red blood cell clumps, indicative of CAD.
A direct Coombs test, which detects antibodies and/or certain immune proteins bound to red blood cells, was positive for bound C3d, an immune protein involved in CAD-related hemolysis. The man also had high levels of cold agglutinins.
Together, the findings confirmed a CAD diagnosis. Subsequent blood cell count and blood smear analyses performed with warmed blood samples showed normal red blood cell counts and no clumping.
Looking for cause of CAD
The man underwent a whole-body CT scan to look for a potential cause of CAD and it revealed a small mass in the right kidney. MRI scans suggested renal cell carcinoma, a type of kidney cancer, and part of his right kidney was surgically removed. A tissue examination confirmed renal cell carcinoma.
A bone marrow biopsy found no signs of blood cancers or evidence of cold agglutinin-associated uncontrolled B-cell growth. These findings and that the man continued to have low red blood cell counts after the kidney tumor was removed suggested no secondary cause of CAD at that point. While persistent clumping of red blood cells was noted during follow-up, there were no notable signs of hemolysis.
Two years after first being seen, the man complained of a growing mass in the groin, but reported no symptoms related to B-cell cancers, such as unexplained weight loss, night sweats, or fever. Blood tests showed marked anemia, red blood cell clumping, and low levels of white blood cells.
Imaging scans were consistent with lymphoma and an analysis of a tissue sample from a lymph node near the groin confirmed the presence of low-grade B-cell lymphoma. A new bone marrow biopsy revealed evidence of cold agglutinin-associated uncontrolled B-cell growth.
The man received several cycles of standard chemotherapy for the lymphoma. The treatment included rituximab, a B-cell depleting treatment also used off-label for severe CAD cases.
The man showed a complete response on imaging scans and tests during follow-up showed no signs of CAD, with normal red blood cell counts and blood smear results. The results suggested the man’s CAD “was attributable to lymphoma” and may have been its “earliest manifestation,” the researchers wrote. “It is imperative to investigate the underlying causes in patients newly diagnosed with CAD.”
CAD “may serve as an early indicator of lymphoma that can manifest years prior, necessitating routine monitoring for these patients,” they wrote.
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