This type of cancer should be considered in the differential diagnosis of patients with HLH, especially those of Asian descent and experiencing a series of neurological disease manifestations, the researchers said.
HLH is a disease characterized by excessive inflammation and organ damage due to an overactivation of the immune system. It can be inherited (primary HLH) or caused by non-genetic factors, including infections, autoimmune diseases, or cancer (secondary HLH).
Malignancies are thought to cause up to one-fourth of all cases of secondary HLH, with most being blood cancers that affect the normal function of infection-fighting immune cells, such as T-cells and natural killer (NK) cells.
Intravascular large B-cell lymphoma, or IVLBCL, is a rare type of blood cancer that can be difficult to diagnose because its symptoms — fever, pain, skin conditions, and neurological problems — are usually subtle and nonspecific.
In the study, researchers at the California Northstate University College of Medicine and Mayo Clinic described the case of a 68-year-old Korean woman who, despite the initial diagnosis of HLH, was later found to have IVLBCL associated with HLH.
The patient was admitted to hospital in April 2018 after experiencing episodes of recurring fever, weight loss, and generalized weakness for the past four weeks. She had no medical problems until she developed a viral infection that past winter. Since then, her appetite had decreased, and she lost around 20 pounds (10 kg) over a period of two months, and became increasingly confused and forgetful.
Following examination, she was diagnosed with HLH based on her recurring fever, low blood cell counts in all blood cell types and platelets, high levels of ferritin (a protein responsible for storing iron in the body), and the presence of hemophagocytosis in bone marrow and liver biopsies. Hemophagocytosis refers to the ingestion of blood cells, platelets, and their precursors by immune cells known as phagocytes, and is considered a hallmark of HLH.
Although the patient showed no signs of infection, autoimmune conditions, or malignancies at the time, physicians suspected that she might have an underlying cancer, given her advanced age. For that reason, she began treatment with chemotherapy and a regimen of anti-inflammatory medications (HLH-2004 treatment protocol).
After five days of chemotherapy, she experienced two seizures. Brain magnetic resonance imaging (MRI) scans and cerebrospinal fluid (the liquid that circulates in the brain and spinal cord) analyses were performed, which revealed the presence of brain lesions, and hemophagocytosis in the central nervous system (the brain and spinal cord). As a result, the patient was treated with hydrocortisone, an anti-inflammatory medication, in combination with methotrexate, an anti-cancer agent.
After 30 days of treatment, the patient was discharged and sent home. However, she was readmitted the following week due to impairments in speech and thinking. Brain MRI scans revealed the presence of lesions caused by strokes. She was then placed on anticoagulants to thin her blood and prevent further strokes.
By July 2018, after three months of therapy, her fever subsided, and her blood cell counts and ferritin levels normalized. However, in October 2018, she was hospitalized with fever, poor appetite, and confusion. She had low blood cell counts and elevated ferritin levels, suggesting that HLH had relapsed.
A second biopsy of her liver and bone marrow revealed large atypical immune B-cells, and she was diagnosed with IVLBCL.
The patient underwent lymphoma-directed therapy, and within seven days, her fever resolved, and her mental status and blood cell counts all normalized. She slowly improved her speech, and by June 2019, showed no evidence of systemic or neurological disease.
“Primary HLH is extremely rare in adults, and a secondary cause should be carefully investigated. Our case serves as a reminder that IVLBCL is truly a ‘chameleon with multiple faces,’ ” the researchers wrote.
“A high index of suspicion is needed for prompt diagnosis and initiation of lymphoma-directed therapy,” which may lead to improved patient outcomes in those with IVLBCL associated with HLH, the team said.