Gastric lymphoma found to be hidden cause of refractory CAD
Steroid-treated CAD masked early signs of lymphoma, case report finds
A woman with hard-to-treat cold agglutinin disease (CAD) was later found to have high-grade gastric B-cell lymphoma — a type of blood cancer that originates in the stomach — and treating that cancer was key to controlling her CAD symptoms, a case report shows.
The lymphoma, which turned out to be the underlying cause of her CAD, was either missed on early imaging or masked by corticosteroid treatment, a type of anti-inflammatory and immunosuppressive therapy.
Therefore, in cases of treatment-resistant, or refractory, CAD, “it is important to be vigilant to do reassessments and reimaging to exclude underlying secondary causes,” the researchers wrote.
“This case report also highlights that refractory [CAD] can be an initial presentation of gastric B cell lymphoma,” the researchers added.
The case study, “Refractory cold autoimmune hemolytic anemia as initial presentation of gastric B cell lymphoma: a case report,” was published in the Journal of Medical Case Reports.
What CAD is and how secondary causes can drive the disease
CAD is an autoimmune disease caused by self-reactive antibodies, called cold agglutinins, that bind to red blood cells at cold temperatures and trigger their destruction — a process known as hemolysis. This leads to anemia, or low levels of red blood cells or hemoglobin, the protein that carries oxygen.
Antibodies, including the self-reactive ones, are produced by immune cells called B-cells.
There are two main types of CAD. Primary CAD occurs without an identifiable cause, while secondary CAD results from another condition, such as an infection or underlying blood cancer. In secondary CAD, treating the underlying disease is the only effective approach.
When CAD is refractory, “underlying lymphoproliferative disease should be considered and excluded,” the researchers wrote. Lymphoproliferative diseases involve the uncontrolled growth of lymphocytes, a group of immune cells that includes B-cells.
In this patient, the initial imaging may have missed the evolving lymphoma, or treatment with [corticosteroids] may have masked the lymphoma. This also emphasizes the importance of reassessments and reimaging to exclude underlying secondary causes.
Here, the researchers report the case of a 53-year-old woman from Sri Lanka with refractory CAD that was later found to be secondary to a high-grade gastric B-cell lymphoma.
The woman came to the hospital with a five-day history of fever and cough. Over the previous month, she had become increasingly tired, short of breath, and felt palpitations. She also noticed yellowing of the eyes and dark urine, two signs of increased hemolysis.
On examination, she appeared pale and had a moderately enlarged spleen. Her liver and lymph nodes (a type of immune structure) appeared normal. Blood tests showed low levels of hemoglobin, indicating anemia, and high levels of the enzyme lactate dehydrogenase, a marker of hemolysis.
When her blood was examined under a microscope, the sample showed clumps of red blood cells, a hallmark of CAD caused by antibody binding. A direct Coombs test, which checks for antibodies or other immune proteins attached to red blood cells, was positive, confirming a CAD diagnosis.
Tests for possible infections came back negative. CT scans of her chest, abdomen, and pelvis also showed no signs of cancer or enlarged lymph nodes.
Standard CAD treatments failed, prompting deeper search for a hidden cause
The woman began treatment with corticosteroids and the immunosuppressant mycophenolate mofetil. Because she did not respond well, she was prescribed, off-label, the B-cell-depleting therapy rituximab, but her anemia did not improve. She became dependent on blood transfusions.
Because her anemia was resistant to treatment, the doctors searched more deeply for an underlying cause. A repeat CT scan suggested a mass in her stomach, and an endoscopy-guided biopsy — which uses a camera to look inside the stomach — confirmed it was a high-grade B-cell lymphoma, a fast-growing blood cancer. A biopsy involves collecting a small tissue sample for examination under a microscope.
A bone marrow biopsy showed increased production of red blood cells, consistent with what typically happens in CAD as the body tries to compensate for hemolysis. There was no abnormal growth of other blood cells, indicating the lymphoma had not spread into the bone marrow.
The woman then began chemotherapy to treat her lymphoma. After just one cycle, her hemoglobin levels increased, and she no longer needed blood transfusions. With additional cycles, the stomach mass shrank. In total, she received nine cycles of chemotherapy, followed by radiotherapy.
“In this patient, the initial imaging may have missed the evolving lymphoma, or treatment with [corticosteroids] may have masked the lymphoma,” the researchers wrote. “This also emphasizes the importance of reassessments and reimaging to exclude underlying secondary causes” in cases of refractory CAD.
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