Is Langerhans Cell Histiocytosis a Cancer?

Langerhans cell histiocytosis is not definitively a type of cancer. Many experts treat it as an autoimmune disorder. This disease causes the body to produce too many of a type of white blood cells, which congeal into tumors called granulomas.

Langerhans cell histiocytosis (LCH) is a disorder in which people produce too many Langerhans cells or histiocytes, a form of white blood cell that helps protect the body from infection. In Langerhans cell histiocytosis, Langerhans cells grow out of control and build, causing tumors called granulomas to form. 

Langerhans cell histiocytosis primarily affects children, but it can also occur in adults. 

There are four variants of Langerhans cell histiocytosis with different degrees of severity:

• Hashimoto-Pritzker disease: a congenital self-healing form
• Hand-Schüller-Christian disease: an intermediate chronic form with multiple lesions characterized by diabetes insipidus, bulging of the eye, and localized lesions in the bone
• Eosinophilic granuloma: a less severe form, characterized by solitary or few, and chronic lesions of bone or other organs
• Letterer-Siwe disease: a severe, acute, disseminate form 

Symptoms of Langerhans cell histiocytosis vary depending on the body part affected and how much of the body is involved. The disease can affect nearly every organ, including skin, bones, bone marrow, lymph nodes, liver, lungs, gastrointestinal tract, spleen, thymus, central nervous system, and hormone glands. 

Symptoms of Langerhans cell histiocytosis based on the organ affected include: 

• Skin 
  • Red, scaly papules in skin folds
  • Infants with skin presentation on the scalp may be misdiagnosed with cradle cap
  • Skin symptoms usually improve without treatment
• Bone 
  • Often affects the skull, lower limbs, ribs, pelvis, and vertebrae 
  • Pain
  • Swelling
  • Limited motion
  • Inability to bear weight
• Lymph nodes
  • Cervical lymph nodes (in the neck) are commonly affected
  • Pain of the affected lymph node
• Liver 
  • Usually associated with more severe disease
  • Buildup of fluid in the abdomen (ascites)
  • Yellowing skin and eyes (jaundice) 
  • Low levels of protein
  • Prolonged clotting time
• Central nervous system (CNS) and hormones
  • Rare but severe
  • Alters hormonal function, and some patients develop diabetes insipidus
• Lung
  • Most frequently involved organ in adults
  • Chronic cough
  • Difficulty breathing/shortness of breath
  • Chest pain
  • Collapsed lung (pneumothorax) 

The cause of Langerhans cell histiocytosis is unknown, however, mutations in the BRAF gene have been identified in the Langerhans cells of about half of patients. These are not inherited gene changes. 

Smoking is strongly associated with developing Langerhans cell histiocytosis. 

Risk factors for Langerhans cell histiocytosis may include: 

• Personal or family history of thyroid disease 
• Family history of cancer 
• Parental exposure to solvents 
• Perinatal infections 
• Parental occupational exposure to metal, granite, or wood dust 
• Ethnicity and race  
• Low socioeconomic status 
• Lack of childhood vaccinations 

Langerhans cell histiocytosis is diagnosed with the following tests: 

• Bronchoscopy with biopsy
• Skin biopsy
• X-ray
• Skeletal X-rays survey
• Bone marrow biopsy
• Complete blood count
• Pulmonary function tests 
• Liver function tests
• Magnetic resonance imaging (MRI) and computerized tomography (CT) scanning of the head to check for abnormalities of the hypothalamus and the pituitary gland
• Fluorodeoxyglucose (FDG) positron-emission tomography (PET) scanning for bone lesions

Treatment for Langerhans cell histiocytosis varies and depends on the variant of the condition, its severity, and the body part(s) affected. In some cases, LCH will go away on its own. 

When needed, treatments for Langerhans cell histiocytosis may include surgery, chemotherapy, radiation therapy, and/or medications.

Treatment for Langerhans cell histiocytosis with asymptomatic isolated skin involvement includes: 

• Topical steroids
• Oral methotrexate
• Oral hydroxyurea
• Oral thalidomide
• Topical nitrogen mustard
• Psoralen and long-wave ultraviolet A radiation (PUVA) or UVB
• Chemotherapy
• Radiation therapy

Treatment for Langerhans cell histiocytosis with skeletal involvement includes: 

• Curettage or curettage plus injection of methylprednisolone may also be used
• Low-dose radiation therapy
• Chemotherapy
• Bracing or spinal fusion
• Bisphosphonate therapy

Treatment for Langerhans cell histiocytosis with central nervous system (CNS) involvement includes: 

• Chemotherapy
• BRAF V600E inhibitor therapy
• Rituximab
• Tretinoin
• IVIG

Treatment of high-risk Langerhans cell histiocytosis multisystem disease (spleen, liver, and bone marrow involving one or more sites) includes:

• Chemotherapy
• Targeted therapy (BRAF inhibitors)