Patients with germinal center-like structures face greater risk of developing non-Hodgkin's lymphoma

Biopsying the glands that produce saliva to test for germinal center-like formation when someone is diagnosed with primary Sjögren's Syndrome can predict later development of non-Hodgkin's lymphoma, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Atlanta.

Sjögren's syndrome is an inflammatory disease that can affect many different parts of the body, but most often affects the tear and saliva glands. Patients with this condition may notice irritation, a gritty feeling, or painful burning in the eyes. Dry mouth or difficulty eating dry foods, and swelling of the glands around the face and neck are also common. Some patients experience dryness of other mucous membranes (such as the nasal passages, throat, and vagina) and skin. Between 400,000 and 3.1 million adults have Sjögren's syndrome. Primary Sjögren's syndrome occurs in people with no other rheumatic diseases. Secondary Sjögren's occurs in people who do have another rheumatologic disease, most often lupus and rheumatoid arthritis.

Germinal centers are sites within lymph nodes or lymph nodules where B cells maturate, proliferate, differentiate, and adapt as a component of the immune response. The centers develop dynamically after both B and T lymphocytes are activated after exposure to an antigen.

"Despite the fact that a connection between GC formation and lymphoma has been proposed and hypothesized, nobody has been able to prove this in an epidemiological setting in real patients," explains Elke Theander, MD, PhD; head of the Department of Rheumatology at the Skane University Hospital, Malmö, Sweden and lead investigator in the study.

Until now, that is. Dr. Theander's team recently followed patients from salivary gland biopsy until diagnosis of lymphoma, death, or end of follow up, which was anywhere from one month to 26 years. They reviewed 174 salivary gland biopsies from patients with primary Sjögren's syndrome for the presence of germinal center-like structures. The samples were examined using light-microscopy, and the pathologists who examined them did not know a patient's status with regard to lymphoma - nor did they have access to patient data such as their treatment or risk factors for Sjögren's.

Germinal center-like structures, defined for this study as a densely packed dark zone and a light zone in biopsies with classical focal infiltration within otherwise normal salivary glands, were detected in 43 biopsies. Seven of the patients studied developed non-Hodgkin's lymphoma, six of whom had germinal center-like structures in their salivary gland biopsies at the time they were diagnosed with Sjögren's syndrome. The median time between salivary gland biopsy and non-Hodgkin's lymphoma diagnosis was eight years.

Overall, patients with germinal center-like structures had a 15 times greater risk of developing non-Hodgkin's lymphoma compared to those without. Furthermore, absence of these structures had a 99 percent negative predictive value — suggesting that those patients would not go on to develop lymphoma.

"If germinal center-like structures are present in the diagnostic salivary gland biopsy, the patient should be followed and screened for possible lymphoma development, while patients without are less likely to develop the malignancy complication," Dr. Theander says. "Being germinal-center positive might, under certain circumstances, support use of biological treatment, such as anti-B cell directed therapy. Still unclear is when to start such treatment."

Source:

American College of Rheumatology

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