Predicting Lymphoma Risk in Sjögren’s with Salivary Gland Biopsy

Johnson SJ, Gudlaugsson E, Skaland I et al, Low Protein A20 Expression in Minor Salivary Glands Is Associated with Lymphoma Development in Primary Sjögren’s Syndrome. Late-Breaking Abstract #3

Studies estimate that people with primary Sjögren's syndrome have up to a 44% greater risk of lymphatic cancers, a third of which are non-Hodgkin’s lymphomas (NHL).

It may be possible to use a salivary gland biopsy in tandem with clinical assessment to identify patients at greater risk at younger ages, in time to give treatments that may prevent those lymphomas, a Swedish researcher told the 2014 meeting of the American College of Rheumatology.

While the actual risk of cancer in Sjögren's is relatively small (only 5% to 10% of patients will develop lymphoma during their lifetime), NHL can be deadly, pointed out Elke Theander MD PhD, an associate professor of medicine at the SkÃ¥ne University Hospital Malmö at Lund University in Sweden, in a Monday session on clinical challenges in Sjögren's syndrome. “In our studies, the risk doubles every 5 years being over 20% after 15 years.”

Malignancies in mucosal associated lymphoid tissue, or MALT lymphomas, are most often seen in Sjogren’s patients, and can be found in almost anywhere from the tear-producing salivary glands to the lungs and kidneys.

Sjögren's patients classified at highest risk have persistent swelling of the salivary (parotid) glands, skin vasculitis, and palpable purpura, coupled with low complement levels, cryoglobulinemia, and hypergammaglobulinemia. Signs of higher disease activity such as fevers, night sweats and weight loss, may also be predictive, she added. Men are at higher risk for lymphomas than women, Thaner said.

Adding tests for biomarkers of NHL risk to a salivary gland biopsy routinely performed as part of the diagnostic process may enable clinicians to find patients in a “pre-lymphoma” stage where drugs like rituximab or abatacept might help prevent cancers from developing.

One target for biopsy testing is germinal centers (CGs),  structures within in lymph nodes where B cells mature, multiply, and differentiate.  The origin of B-cell lymphomas is thought to be in GCs, and recent research suggests GC formation may be a predictor of later lymphoma.

A 2014 study found that patients with germinal center-like structures in minor salivary glands had a 15 times greater risk of developing NHL compared to those without GCs. In addition, absence of GCs had a 99% negative predictive value for NHL.

Increasing GC focal scores also portend a higher risk of lymphoma, Theander said.

An experimental biomarker for lymphoma in Sjögren’s was discussed in a late-breaking abstract session at the ACR meeting.

Svein Joar A. Johnson MD, a researcher at the Stavanger University Hospital in Norway, reported that loss of a tumor suppressor protein called A20 in minor salivary glands could also be involved in the development of lymphomas in patients with pSS. The A20 protein is coded by a gene called TNFAIP3.  

In a nationwide study of biopsy samples from pSS patients in Norway, Johnson and colleagues found that patients with lymphomas had weaker A20 expression. They saw little or no detectable A20 in more than half of pSS-associated MALT tissue samples.