Lymphocytes in Lip Salivary Glands May Predict Lymphoma

The number of lymphocytes — a type of immune blood cell — in the salivary glands of the lip could help identify patients with Sjögren’s syndrome who are at increased risk for developing lymphoma, a new study has found.

The study, “A biomarker for lymphoma development in Sjogren’s syndrome: Salivary gland focus score,” was published in the Journal of Autoimmunity.

Sjögren’s syndrome is an autoimmune disorder that primarily affects the glands producing saliva and tears. These patients also are more likely to develop lymphoma, a blood cancer that arises in lymph nodes.

Given the importance of a prompt diagnosis and early therapeutic intervention, it is key to identify predictors of lymphoma. It is thought that patterns of inflammatory and immune cells in the glands producing saliva may be related to the development of lymphomas.

The amount of lymphocytes in gland tissue, indicating the extent and severity of gland inflammation, often is used to help diagnose Sjögren’s syndrome. Yet, few studies have investigated whether lymphocyte infiltration also can be used to predict lymphoma in people with Sjögren’s.

To address this question, a team of researchers in Greece and Italy investigated the focus score (FS) — a measure of the number of lymphocytes in gland tissue – in 1,997 patients with Sjögren’s syndrome followed from 1984 to 2019.

The score was calculated based on the number of groups of more than 50 lymphocytes in a certain area of tissue taken from the labial minor salivary glands, which are tiny salivary glands located along the lips.

The final group included only the 618 participants with an FS equal to or greater than one and at least a one-year interval between the diagnosis of Sjögren’s syndrome and lymphoma diagnosis (for lymphoma patients) or last follow-up (for non-lymphoma patients).

Participants had been diagnosed at a median age of 53 and had the disease for about six years. In total, there were 560 patients who did not develop lymphoma over their follow-up, and 58 who did.

The researchers sought to identify potential risk factors contributing to the development of lymphoma. Consistent with previous research, they found that cryoglobulinemia (the presence of a large number of cold-sensitive antibodies, called cryoglobulins, in blood) and enlarged salivary glands were independent risk factors for lymphoma. Another independent risk factor was the FS.

Additional analyses found that FS scores correlated negatively with the time between the diagnoses of Sjögren’s syndrome and lymphoma. In other words, the higher the FS at the time of Sjögren’s diagnosis, the shorter the interval to a diagnosis of lymphoma.

Dividing patients in two groups based on their FS scores also confirmed the findings. While patients with an FS smaller than four took about nine years to develop lymphoma, those with FS scores of four or more developed lymphoma after about four years.

In patients with an FS less than four, however, salivary gland enlargement was the only independent risk factor for lymphoma.

Some clinical features also differed between the two groups. For instance, in patients with an FS less than than four, autoimmune thyroiditis (swelling of the thyroid gland) was more common than in patients with higher FS scores. On the contrary, signs related to B-cells (a type of lymphocyte) and lymphoma were less common.

Together, the findings suggested FS could serve as “an excellent biomarker for prediction and early lymphoma diagnosis,” the researchers concluded.

The researchers advise that a second analysis of the number of lymphocytes in the labial minor salivary glands (done at nine years for patients with an FS less than than four and a history of salivary gland enlargement, or at four years for patients with an FS of four or more) could help in timely diagnosis of lymphoma.