Doctors issue caution over missed cancer diagnoses tied to immune disorder

October 1, 2018, Cincinnati Children's Hospital Medical Center
Credit: CC0 Public Domain

Physicians who specialize in a devastating and aggressive immune disorder called hemophagocytic lymphohistiocytosis (HLH) report in a new study that extra care should be taken to ensure an HLH diagnosis doesn't obscure possible underlying cancers.

Because HLH is dangerously aggressive in its progression and attack on vital organs—often causing death—doctors frequently pursue immediate treatment for the immune disorder after a . But researchers at the Cincinnati Children's HLH Center of Excellence caution in the journal Pediatric Blood & Cancer that expediting HLH treatment may miss underlying malignancies that could end up being fatal to the patient.

"Our study found several cases where HLH diagnoses that fulfilled current criteria obscured the diagnosis of underlying malignancies. This delayed curative therapy for the cancers," said Ashish Kumar, MD, Ph.D., of the Cincinnati Children's Cancer and Blood Diseases Institute. "These issues can be remedied by using alternative and improved diagnostic techniques to also look for underlying malignancy prior to administering HLH therapy."

Although earlier diagnostic technologies for cancer have required waiting for genetic testing, study authors recommend speeding up diagnosis with some newer technologies now available. One newer option highlighted by the study is flow cytometry based immunological assays—a cell-analysis technique that can provide useful diagnostic results in a couple days.

Abnormal Immune Response

HLH causes abnormally strong immune responses that attack vital organs and other healthy tissues. There are two types: primary HLH triggered by hereditary genetic defects in immune cells and secondary HLH fueled by infections, autoimmune disorders, or malignancies. About half of secondary HLH cases in adults are associated with malignancy.

Although previous studies estimate that 10 percent of children with secondary HLH have an associated malignancy, Kumar and his research colleagues suggest it may be higher. Their study involved close evaluation of nine patients diagnosed with HLH between the ages of 8 days to 30 years. Seven of the patients had been referred to Cincinnati Children's after their HLH diagnosis.

The diagnoses were based on the patients meeting current diagnostic criteria for the disease. Further investigations by physicians at Cincinnati Children's revealed that all but one of the nine patients had an underlying lymphoma, or cancer of the lymphatic system, and one patient had AML (acute myeloid leukemia).

By the time the malignancies were discovered, only two of the nine patients were able to receive full doses of chemotherapy because of infections and/or organ dysfunction, the researchers write. Seven of the patients died from multi-organ failure with active malignancies still present. Two patients who were able to receive full-doses of chemotherapy survive with no evidence of disease, according to the researchers.

Understanding Limitations

HLH is a difficult to diagnose early and can hide behind a maze of contradictory symptoms. This often results in misdiagnosis. The only curative therapy for primary HLH is bone marrow transplant, a high-risk procedure that isn't suitable for all . Standardized diagnostic criteria for HLH were adopted in 2004 by the Histiocyte Society to help enhance detection of the disease.

Standard recommended treatment is the same for primary and secondary HLH, according to Kumar. Given the disease's aggressiveness nature and impact, guidelines recommend that treatment for HLH begin before determining if the disease is primary or secondary. The current study suggests this approach could lead to a missed diagnosis.

"The cases in this study highlight the importance of understanding there are limitations to current HLH diagnosis criteria, especially in detecting HLH that is associated with ," said Kumar.

The HLH Center of Excellence works to refine and improve diagnosis and treatment for the complex disease. The center is now considered a leading referral center for the immune disorder.

Kumar said one of his goals is to spread awareness with other physicians about the new study's findings, as well as new diagnostic and treatment methods. In the meantime, the research team continues to analyze HLH cases and obtain more data about its biology and progression.

Explore further: Doctors treat deadly cancerous disorders with gene-guided, targeted therapy

More information: Arun Gurunathan et al, Limitations of HLH-2004 criteria in distinguishing malignancy-associated hemophagocytic lymphohistiocytosis, Pediatric Blood & Cancer (2018). DOI: 10.1002/pbc.27400

Related Stories

Doctors treat deadly cancerous disorders with gene-guided, targeted therapy

February 16, 2017
Genomic testing of biopsies from patients with deadly, treatment-resistant cancerous blood syndromes called histiocytoses allowed doctors to identify genes fueling the ailments and use targeted molecular drugs to successfully ...

Evaluating the accuracy of the Curacao Criteria in diagnosing HHT in children

April 12, 2018
Though hereditary hemorrhagic telangiectasia (HHT) is – as the name suggests – a hereditary disorder, most people are not diagnosed with the disease until they are adults because the telltale symptoms often do not develop ...

Biologics do not increase the risk of second malignancy in rheumatoid arthritis patients

November 5, 2017
Treatment with biologics does not increase the risk of a second malignancy in rheumatoid arthritis patients who have a history of cancer, according to new research findings presented this week at the 2017 ACR/ARHP Annual ...

Second cancers deadlier in young patients

April 20, 2017
Second cancers in children and adolescents and young adults (AYA) are far deadlier than they are in older adults and may partially account for the relatively poor outcomes of cancer patients ages 15-39 overall, a new study ...

Patients with rheumatoid arthritis have an increased risk of certain types of malignancy

June 13, 2018
The results of a study presented at the Annual European Congress of Rheumatology (EULAR 2018) examined rates of malignancy in patients with rheumatoid arthritis (RA), excluding non-melanoma skin cancer (NMSC), and found no ...

Secondary thyroid cancer more deadly than primary malignancy in young individuals

February 24, 2014
A new analysis has found that adolescents and young adults who develop thyroid cancer as a secondary cancer have a significantly greater risk of dying than those with primary thyroid cancer. Published early online in Cancer, ...

Recommended for you

Some brain tumors may respond to immunotherapy, new study suggests

December 10, 2018
Immunotherapy has proved effective in treating a number of cancers, but brain tumors have remained stubbornly resistant. Now, a new study suggests that a slow-growing brain tumor arising in patients affected by neurofibromatosis ...

Study finds higher risk of breast cancer for women after giving birth

December 10, 2018
Younger women who have recently had a child may have a higher risk of breast cancer than their peers of the same age who do not have children, according to a large-scale analysis co-led by a University of North Carolina Lineberger ...

A code for reprogramming immune sentinels

December 10, 2018
For the first time, a research team at Lund University in Sweden has successfully reprogrammed mouse and human skin cells into immune cells called dendritic cells. The process is quick and effective, representing a pioneering ...

Researchers develop personalized medicine tool for inherited colorectal cancer syndrome

December 10, 2018
An international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U) has developed, calibrated, and validated a novel tool for identifying the genetic changes in Lynch syndrome genes ...

Study shows key enzyme linked to therapy resistance in deadly lung cancer

December 10, 2018
Researchers at The University of Texas MD Anderson Cancer Center have identified a link between an enzyme tied to cancer formation and therapy resistance in patients with epidermal growth factor receptor (EGFR)-mutant non-small ...

Potential seen for tailoring treatment for acute myeloid leukemia

December 8, 2018
Advances in rapid screening of leukemia cells for drug susceptibility and resistance are bringing scientists closer to patient-tailored treatment for acute myeloid leukemia (AML).

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.