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A Discussion on Genetic Testing and Histiocytosis

When diagnosed with a rare disease, there are so many questions that need to be answered. One important aspect of the work of the Histiocytosis Association is to help provide resources and information when you need it. To do this, we often will reach out to other organizations or programs to learn as much as we can, then share that information out in the best way possible.  

For those patients who are diagnosed with hemophagocytic lymphohistiocytosis (HLH), genetic testing is useful in identifying genetic mutations, or changes, in the DNA of cells; knowing whether the cells contain a particular mutation can help guide the best treatment; this can include a treatment that has been developed to target a specific mutation. As HLH can also be familial, family members are able to undergo genetic testing to understand if they also have this mutation.  Besides HLH, other forms of histiocytosis also have genetic mutations. For example, a genetic mutation in the BRAF protein has been detected in over 50% of patients diagnosed with Langerhans cell histiocytosis (LCH) and has been discovered in Erdheim-Chester Disease (ECD), Rosai Dorfman Disease (RDD), Xanthogranuloma, and Histiocytic Sarcoma. You can read more about the BRAF mutation, here.  

Last week, I had the pleasure of sitting down with the team at Machaon Diagnostics, a clinical reference laboratory, specializing in the diagnosis, treatment and monitoring of hemostatic and thrombotic conditions. Machaon’s Medical Director and Hematologist, Dr. Brad Lewis, joined the conversation to help us learn more about genetic testing, including its importance and relevance to HLH patients, how to go about requesting genetic testing, insurance coverage, and why speed to results matter.  

Dr. Lewis joined Machaon during his career as a hematologist, where he formerly worked with malignant hemophilia, sickle cell disease and thrombosis. The Machaon team is passionate about ensuring patients from across the United States have access to laboratory testing, with speed and accuracy of results as the core aim. Dr. Lewis explained, that due to the severity and rarity of HLH, and all histiocytic disorders, patients need to receive proper treatment quickly. Acquiring results can take time and in the instance of rare disease, time is of the utmost importance for patient outcomes as the results can help physicians in identifying whether a targeted therapy will benefit the patient. At Machaon, the genetic testing looks for mutations that affect perforin and related proteins that are involved in the immune response. An individual’s genes are analyzed to look for factors or abnormalities that are known to cause HLH. It is possible that all genetic mutations and receptors are not discovered yet, however if there is a positive detection then a treatment can be determined.  

One interesting point that Dr. Lewis discussed was the prevalence of genetic mutations in pediatric patients, whereas with adult patients it is often less likely that mutations are identified. One key role that genetic testing can play is to help scientists understand commonalities in patients with a diagnosis of HLH, which can in turn help in determining new targets for therapies. 

I inquired more about how Machaon can expedite genetic tests and was interested in learning about the cost and potential for insurance coverage, as well. Dr. Lewis described the process which stems from the goal of putting results in the hands of physicians as quickly as possible. When the test has been received by the lab, the samples are immediately brought in for processing and the interpretation of the samples is streamlined. While doing so in batches is more cost effective, Machaon knows that by interpreting each test as it comes in, they can then turn around results quickly and when the results are in, they contact the physician directly. Furthermore, patients can ask their physician to help them in accessing genetic testing while being treated as an inpatient at their local hospital. Many hospitals have organizations that they typically run their testing through, however turnaround times may not be expedited so patients should advocate for what they know will be best for them. When being treated as an outpatient, so not staying overnight in the hospital, insurance coverage will be needed for most genetic testing. This would also be true for any family members who are hoping to receive testing however have not been diagnosed.  

It was very eye-opening to learn more about the opportunities available to patients and I was incredibly grateful for the time with Dr. Lewis and the Machaon team.  You can discover more about their genetic panel testing here.

Other services are available for those diagnosed with HLH as well as other histiocytic disorders.  The Memorial Sloan Kettering Make-an-IMPACT Initiative is a rare-cancer global outreach initiative that provides free genomic profiling for patients with Langerhans Cell Histiocytosis (LCH), Erdheim-Chester Disease (ECD), Rosai-Dorfman Disease (RDD), Juvenile Xanthogranuloma (JXG), and Histiocytic Sarcoma (HS). Genomic profiling with world class, next-generation sequencing technology developed at Memorial Sloan Kettering Cancer Center aims to identify genetic mutations in these tumors. These tumors often harbor mutations in BRAF or related family of genes and may respond to drugs that target these genetic alterations. Patients who were diagnosed or treated for LCH, RDD, ECD, JXG, or HS within 2 years with current active disease may be eligible to participate. If you would like to learn more, please visit the Make-an-IMPACT site or reach out to the Make-an-IMPACT team: If you are eligible and would like to participate, please complete the volunteer form. 

If you have any questions about genetic testing or genomic profiling, or any other testing that may be beneficial in determining treatment for you or a loved one, please do not hesitate to contact me at