Photo Credit: Jose Luis Calvo Martin & Jose Enrique Garcia-Maurino Muzquiz

Langerhans cell histiocytosis is more common in children than adults, resulting in sparse data and uncertainty in diagnosing and treating adult-onset disease.

Adult-onset Langerhans cell histiocytosis (LCH) that first presents in bone is rare, has a variable clinical course, and can easily be misdiagnosed, authors of a small retrospective case series report.

“Patients in our series ranged from having a single bone lesion to multiple bone sites or even other system involvement,” says senior study author Armita Bahrami, MD. “This variation highlights the importance of a comprehensive staging workup, other diagnostic evaluations, and close monitoring after diagnosis to fully determine the extent of the disease and to ensure that every patient receives the appropriate level of care.”

“Even in cases where the disease appears to be localized at presentation, there is a risk of multifocal involvement or multisystem disease,” Dr. Bahrami and colleagues wrote in an article in Annals of Diagnostic Pathology. “Adults with LCH exhibit a high frequency of additional hematologic and solid malignancies.”

Adult-Onset LCH Natural History Is Largely Unknown

Physicians and researchers mainly consider LCH, a myeloid neoplastic disorder derived from LCH precursor cells, a pediatric condition with an estimated incidence of 2.6 to 8.9 cases per million in patients aged less than 15 years. LCH has been well studied in children, the authors note; however, in adults, it occurs in an estimated 1 to 2 cases per million, and data about its natural history are noticeably sparse.

LCH most often occurs in bone, but other common sites include bone marrow, skin, lung, spleen, liver, and gastrointestinal tract. In LCH, modified dendritic cells with the Langerhans cell phenotype grow in one or more tissues or organs, typically with an eosinophil-rich inflammatory background. BRAF^V600E and other mutations may be present.

LCH is diagnosed by tissue examination and confirmed by histopathologic examination that shows proliferation of characteristic neoplastic Langerhans cells with pale eosinophilic cytoplasm and coffee bean-shaped or cleaved nuclei, along with inflammatory cells including eosinophils, giant cells, lymphocytes, macrophages, and neutrophils. The diagnosis is confirmed by immunohistochemical evidence of neoplastic cells expressing CD1a, Langerin, and S100 proteins.

The most common clinical presentation in this case series was localized pain lasting from 2 weeks to 2 years.

Dr. Bahrami talked with Physician’s Weekly about her research to better understand the clinical course of adult-onset LCH diagnosed by bone biopsies.

PW: Why was it important to do this study?

Dr. Bahrami: Given the rarity of the disease in adults, the diagnosis of LCH may not be expected or even considered, so patients may not receive the care they need.

None of the patients in our series had LCH considered as a possibility before tissue diagnosis was obtained. However, one patient with hearing loss was found to have a lesion in the mastoid bone, and another with a presumed tooth infection for over a year was found to have LCH of bone instead. Although none of the patients presented with multifocal lesions or with constitutional symptoms, staging workup found multifocal osseous LCH or multisystem involvement in half of them.

PW: How could your findings affect patient care? 

Dr. Bahrami: Given the diverse manifestations of LCH and their impact on outcomes, these results remind us that a comprehensive assessment is crucial. A staging workup to determine the disease’s extent is important, and we need to tailor our therapeutic strategies accordingly.

PW: Did the results surprise you?

Dr. Bahrami: We were intrigued by the extent to which LCH in patients initially presenting with a single bone lesion varied more than we had anticipated. Also, the high prevalence of smoking history among these patients—63%—was noteworthy, considering the well-documented association between smoking and pulmonary LCH.

PW: What questions remain unanswered?

Dr. Bahrami: A critical area for future research involves assessing whether the genetic characteristics of LCH, including specific mutations, are associated with the disease’s extent.

PW: Is there anything else you would like to mention?

Dr. Bahrami: For pathologists working on the diagnosis of osseous LCH and for physicians managing the condition, early collaboration with a hematology-oncology team specializing in histiocytic neoplasms is essential. Their specialized expertise becomes critical when LCH presents with multisystem involvement, a scenario in which the hematology-oncology team ideally takes a leading role in formulating the treatment strategy to ensure that each patient’s care is comprehensive.