Hodgkin and Reed-Sternberg cells produce high levels of the protein TARC, which has a central role in the pathogenesis of classic Hodgkin lymphoma (cHL). Results of a study published recently in Blood indicated increased values of TARC in blood samples of patients with cHL years before their diagnosis.
“The ability to measure the presence of tumor cells by a blood test opens up possibilities for screening and earlier detection of cHL,” said study researcher Arjan Diepstra, MD, PhD, of University Medical Center Groningen in the Netherlands. “Strikingly, no other form of cancer exhibits a biomarker as sensitive and elevated so long before diagnosis as serum TARC (sTARC) in cHL.”
In the study, Dr. Diepstra and colleagues used prediagnostic serum samples from the U.S. Department of Defense Serum Repository of individuals with an initial diagnosis of cHL from between 1990 and 2000. Each cHL case was closely matched with two controls.
During the 10 years prior to diagnosis, TARC levels were higher in individuals diagnosed with HL than in controls (median = 1,305 pg/mL vs. 407 pg/mL; p=2.1 x 10-25). Data showed an estimated 18.6-fold higher TARC level at diagnosis with HL compared with controls. Age and sex appeared to have no confounding effects.
According to Dr. Diepstra, sTARC levels began to increase about six years before individuals received a diagnosis of cHL.
Dr. Diepstra explained that detecting TARC protein in serum is technically simple, and there is interest in developing a point-of-care test to be used in the primary health care setting.
“In our academic hospital we use an ELISA-based assay that works most efficiently if multiple samples are measured at the same time,” Dr. Diepstra said. “At this moment, when considering screening for early diagnosis in the primary health care setting, it will be most logical to centralize samples to a local or regional diagnostics lab.”
The researchers acknowledged that the incidence of cHL is probably too low for population-wide screening; however, screening could potentially benefit individuals at high risk for cHL.
“A common presenting symptom is an enlarged cervical lymph node, which is more often caused by infection than by lymphoma. Personal stories from patients with HL indicate that a watch-and-wait decision may delay referral and subsequent diagnosis by several months,” Dr. Diepstra said. “Another symptom that is relatively rare but quite specific is alcohol-related pain in lymph nodes, which could also be a good trigger for doing an sTARC test.”
There is also a familial component to cHL, with approximately 4% of cases occurring within families.
“Until now, screening strategies for cHL were largely uncharted territory, and it is important to do additional research on potential benefit of using sTARC for screening,” Dr. Diepstra said. “There is an interesting prospect that screening results in a larger proportion of patients identified at early stage, translating to a better prognosis and possibilities for less intensive treatment.
“Although current evidence shows that high sTARC is quite specific for cHL, other rarer types of lymphoma can also secrete TARC,” Dr. Diepstra said.
“In severe atopic dermatitis, sTARC levels can be increased as well, although in general not reaching the levels that we see in cHL. If a high sTARC level is found, further diagnostic workup would be advised, including a physical exam, imaging, and tissue biopsy. A definitive diagnosis of cHL should only be made based on histology and immunohistochemistry,” Dr. Diepstra emphasized.
Any conflicts of interest declared by the authors can be found in the original article.
Diepstra A, Nolte IM, van den Berg A, et al. Elevated serum TARC levels precede classic Hodgkin lymphoma diagnosis by several years [published online ahead of print, 2023 Sep 25]. Blood. doi: 10.1182/blood.2023020959.