NCCN Aids Oncologists in the Diagnosis and Treatment of Rare Histiocytic Neoplasms

In an interview with Targeted Oncology, Ronald S. Go, MD, discussed the new guidelines for the diagnosis and treatment of histiocytic neoplasms, challenges with managing the disease, and toxicity management.

The National Comprehensive Cancer Network (NCCN) recently released Clinical Practice Guidelines in Oncology for histiocytic neoplasms to provide recommendations for the diagnosis and treatment of adults with histiocytic neoplasms. These are a rare group of heterogeneous cancers accounting for less than 1% of cancers of the soft tissue and lymph nodes.1

To compile these guidelines, the NCCN gathered data from small retrospective studies, case series, and case reports, considering the scarcity of prospective data. Some information that supported these recommendations was based upon studies of children and young adults.

The prime focus of the guidelines is Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. Treatments recommended by the NCCN include surgery, radiotherapy, and systemic therapy that is predominantly based on clinical trial research from other hematologic malignancies.

In an interview with Targeted Oncology™, Ronald S. Go, MD, hematologist/oncologist at the Mayo Clinic in Rochester, Michigan, discussed the new guidelines for the diagnosis and treatment of histiocytic neoplasms, challenges with managing the disease, and toxicity management.

TARGETED ONCOLOGY™: Can you provide background on the new NCCN Clinical Practice Guidelines for histiocytic neoplasms?

Go: There are new NCCN guidelines on these specific malignancies, and these were recently published. This guideline has been about 2.5 years in the making. These are the first guidelines that we published on histiocytic neoplasms. The target of this is adults with histiocytic neoplasms. We covered the 3 major histiocytic neoplasms, including, Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease. The presentation focused on how we decided on putting together the guideline, which diseases for cancers to focus on. Then we talked about the evaluation, staging, and some guidance on the treatment.

What are the key challenges with treated histiocytic neoplasms?

These histiocytic neoplasms are very rare cancers. They are not even registered in the SEER registry or cancer registries for the most part. And the estimation is that there are less than about 1,000 cases per year in the United States. Because these are rare diseases, most physicians in the community or even academic oncologists may or may not see 1 in like 5 or 10 years. And therefore, one of the challenges is how to identify these patients. Although these are officially hematologic malignancies, unlike the traditional hematologic malignancies, these cancers typically have normal complete blood count. Also, the organs of involvement are varied. So, it's not localized to like lymph nodes or the bone marrow. And in fact, lymph nodes and bone marrow are not the most common manifestations of these cancers. So, the first challenge is really to identify these disorders, because they are rare, and their presentation can be varied.

The other challenge here is after the diagnosis, how do we stage these patients? What are the appropriate imaging studies? Also, for pathology, what is the appropriate testing to perform to make the diagnosis? After that, what treatment should be used, because there are no randomized trials for these conditions? The evidence in the literature is quite vague and not high-level evidence for the most part. And finally, one thing that we want to overcome is insurance approval for imaging studies, and also treatment, because there's only 1 FDA-approved drug for these conditions. It is a challenge to get these medications, especially the off-label use of some of the chemotherapies, or targeted agents that we use in other cancers that may be applicable in histiocytic neoplasms. With imaging studies over the years, I have personally had and have heard a lot of challenges in getting the insurance to approve, for example, a PET CT scan, and therefore putting together this NCCN guideline helps the clinicians help the patient and also helps the insurance companies on determining what tests to approve and which drug that can be beneficial in these patients.

What do these guidelines state about managing the toxicities associated with these diseases and the FDA-approved drug?

All of these drugs that are used in histiocytic neoplasms are drugs that are used in the other more common cancers. The chemotherapy agents that we use are commonly used in other hematologic cancers. For the targeted agents, they're commonly used in melanoma. And therefore, we did not focus or write a new section on toxicity management, we did refer the readers to the excellent toxicity management sections in the other guidelines, say for example, in melanoma, and in other malignancies. So, the side effects are not unique to these cancers, the side effects are specific for the drugs which are used or have been used for many years in the other cancers.

What else is important for community oncologists to know about the new guidelines or the management of histiocytic neoplasms?

I think one thing that we have learned about these conditions is that the diagnosis can be challenging. For example, it is not uncommon for patients to require multiple biopsies in order to arrive at a histopathologic diagnosis. This is because the tumor cells or the cancer cells are quite scanty in these lesions, whether it's in the bone or the lymph node, or the kidneys, and therefore, multiple biopsies are required.

The other thing that we have learned about these conditions is that in addition to microscopic diagnosis, and immunohistochemistry staining, molecular studies, such as next-generation sequencing for mutations that are common in these diseases, like BRAF, or MAP kinase pathway mutations are very helpful. So, oncologists should perform next-generation sequencing, and if common mutations are found, it helps solidify the diagnosis even though under the microscope or the histopathologic diagnosis case, the pathologic features may not be completely diagnostic. Finally, it helps to have the pathology slides be reviewed. Expert centers can help with this.


Go RS, Jacobsen E, Baocchi R, et al. Histiocytic Neoplasms, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. J Natl Compr Canc Netw. 2021;19(11): 1277-1303. doi: 10.6004/jnccn.2021.0053.