Langerhans cell histiocytosis (LCH)

LCH is confirmed with a biopsy. A doctor removes a small piece of tissue from an affected area, such as bone, skin, a lymph node or the liver. A pathologist looks at it under a microscope and uses stains that pick out LCH cells, such as CD1a and langerin (CD207). The sample can also be tested for the BRAF V600E gene change. When LCH is widespread, this change can often be found in a blood sample too.

Next come tests to find out where else LCH may be. These usually include a complete blood count, blood chemistry and liver tests, and a urine test. Imaging may include X-rays, a bone scan, CT, MRI, PET scans and ultrasound. If a person is very thirsty and passes a lot of urine, a water deprivation test checks for diabetes insipidus. A bone marrow sample, breathing tests or a look inside the airways or gut (bronchoscopy or endoscopy) may be added, depending on the signs.

For children, care is usually led by a pediatric oncologist, a doctor who treats childhood cancers, working with other specialists. The signs of LCH can also be caused by more common conditions. St. Jude notes that crusty patches on a baby's scalp may be mistaken for cradle cap. In adults, the National Cancer Institute says diagnosis often comes many months or even years after symptoms start.

Treatment depends on where LCH is and how much of the body it affects. A single bone lesion may need only a biopsy or scraping out of the lesion (curettage), sometimes with a steroid shot, and then careful watching. In babies, LCH that affects only the skin can go away on its own, but it needs close checks because it can spread.

When LCH is in many bones or several organs, children usually get about 12 months of chemotherapy. The standard mix is vinblastine and prednisone, a steroid. Children with risk-organ disease also take a pill called 6-mercaptopurine in the later months. If LCH does not respond or comes back, doctors may switch to other chemotherapy medicines such as cytarabine, cladribine or clofarabine. Adults are often treated with other medicines, such as cytarabine or cladribine. For adults whose LCH is only in the lungs, stopping smoking is the first treatment.

Targeted medicines that block BRAF or MEK, such as vemurafenib, dabrafenib, cobimetinib and trametinib, are increasingly used when LCH comes back or does not respond. In the United States, cobimetinib was approved in October 2022 for adults with histiocytic neoplasms, a group that includes LCH. For children with LCH, these medicines are usually given off-label, which means outside an approved use, based mostly on observational studies. They usually bring active LCH under control quickly. But LCH often comes back when they are stopped, and there are no guidelines yet on how long treatment should last.

A donor stem cell transplant, also called an allogeneic transplant, has been used for a small number of children whose LCH is in the liver, spleen or bone marrow and keeps growing despite chemotherapy. It can bring lasting control for some of them. It also carries serious risks, including infection, graft-versus-host disease and death from complications. Targeted medicines now offer another option for these children. Experts have not settled exactly who should have a transplant, when, or which conditioning (the treatment given before transplant) works best.

Outlook depends most on where LCH is and how many body systems it affects. The National Cancer Institute says people with LCH in one body system, or in several systems but not the liver, spleen or bone marrow, do not usually die of LCH. For them, the bigger concerns are LCH coming back and long-term effects such as diabetes insipidus.

When LCH reaches the liver, spleen or bone marrow, it is harder to treat. In children, how well LCH responds in the first 6 to 12 weeks of treatment tells doctors more than the child's age does. Care teams watch this early response closely and add other treatment when the response is poor. Whether the BRAF change is present, and whether this is a first diagnosis or a return of LCH, also play a part.

A study looked at everyone recorded with LCH in England's national cancer registry from 2013 to 2019. Nearly all the children were alive five years later. Survival was lower in adults, and lowest in people over 60. These numbers count deaths from any cause, not only from LCH. People living in poorer areas also did less well. These are group results. They cannot tell any one family how their child, or one adult, will do.