Immunopathogenesis of sarcoidosis and risk of malignancy: a lost truth?

The hypothesis of a relationship between sarcoidosis and malignancy was firstly
formulated in 1972 by Brincker. He documented an association of sarcoid reactions
or sarcoidosis with 19 lymphomas and associated malignancies. Based on various
epidemiological studies, for more than 20 years sarcoidosis has been considered
as a condition at increased risk for cancer, particularly lymphoproliferative
disorders. The existence of a sarcoidosis-lymphoma syndrome was therefore
proposed, highlighting, as a potential mechanism, the uncontrolled lymphocyte
proliferation and mitotic activity. A reduced ability to eliminate an antigen and
chronic inflammation have been suggested as triggering events. Leading to a
reduced tumor immune surveillance, a diminished myeloid dendritic cells (mDC)
function, despite up-regulated co-stimulatory and maturation markers, was also
raised as potential mechanism. However, some subsequent studies have questioned
the presence of a close association between the two entities and have explained
those previously published as the result of selection bias and misclassification.
Recently, a Swedish population-based cohort study documented a significant
overall excess incidence of cancer among sarcoidosis patients, especially those
with multiple hospitalizations or admission in older age, emphasizing again a
potential neoplastic risk. Therefore, currently, whether these patients have an
increased risk of developing malignant lesions is still debated. Larger and
unbiased studies are needed before drawing definite conclusions.