. 2022 Mar 12;139(17):2601–2621. doi: 10.1182/blood.2021014343

Table 3.

Summary of organ manifestations of LCH in adults

Organ/organ system	Clinical and radiographic features
Bones	Lytic osseous lesions seen in 30-50% of cases may occur as single-system or multisystem disease.¹⁵^,⁴¹ Frequently involves the skull and dental sites; other sites include the pelvis, vertebrae, ribs, and extremities.⁵¹^,⁵⁵¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (FDG-PET/CT) is highly sensitive for bone lesion detection and is superior to other imaging studies like CT and MRI.³⁸^,⁶⁸^,⁶⁹ On FDG-PET/CT, LCH bone lesions are lytic, involve the cortex, and have a “punched-out” appearance.
Skin	Isolated skin involvement with LCH in adults is uncommon (5-10%) and tends to occur more commonly as part of multisystem disease (20-50%).⁴¹^,⁴⁴ Most commonly presents as an erythematous papular rash with scaling and crusting, located on the chest, back, abdomen, limbs, scalp, or groin. Rarely can involve mucosa of the oral cavity, genitalia, or perianal region.⁴⁰^,⁴⁷^,⁵³
Endocrine	Most commonly presents as DI (25%) and may precede LCH diagnosis by years.⁵⁴^,⁶⁵ Anterior pituitary dysfunction can be seen in ∼20% of cases.⁶¹^,⁶² Pituitary endocrinopathies can occur without corresponding abnormal imaging studies.⁶¹^,⁶³^,⁶⁶^,⁷⁵ Most endocrinopathies may not be reversible despite systemic LCH treatments.⁵⁴
Nervous system and orbit	Seen in 15-20% of cases¹⁵; can occur as focal mass lesions in the pituitary stalk, hypothalamus, or pineal gland. Infiltration of the brain parenchyma is rare, most often in the cerebellum or brainstem, leading to ataxia and dysarthria.⁴⁶^,⁴⁸ Neurodegenerative LCH is a rare manifestation with 2 components: 1) LCH-associated abnormal CNS imaging (LACI) with T2 hyperintense lesions and atrophy predominantly involving the posterior fossa,⁸¹ and 2) LCH-associated abnormal CNS symptoms (LACS) manifesting as neuropsychological impairment and gait ataxia.⁶⁰ There may be a lag of 10-20 y between the diagnosis of LCH and LACI/LACS.⁶⁰ Orbit involvement is very rare.⁴⁹
Pulmonary	PLCH can occur in 40-50% of cases, mostly presenting as single-system disease; 60-70% have respiratory symptoms, 10% may present as pneumothorax.³³ Decreased diffusing capacity for carbon monoxide is the most common abnormality (80-90%) in combination with changes of either obstructive, restrictive, or mixed physiologic abnormalities; lung function tests may be normal in 10% of cases.³³ Standard chest radiographic features of PLCH include upper and middle field predominant reticulonodular changes, and HRCT of the chest may show nodular or cystic lesions (Figure 1). In advanced stages of disease, cystic lesions predominate. These findings on HRCT are diagnostic of PLCH in a smoker; however, every attempt should be made for tissue acquisition unless considered unsafe. Bronchoscopy may be normal or show inflammatory changes. Bronchoalveolar lavage is rarely diagnostic of PLCH.⁸⁰ PLCH lung nodules can be hypermetabolic on FDG PET-CT, which does not allow differentiation from other malignant lesions. Thick-walled cysts may also demonstrate FDG uptake.⁵⁸^,⁶⁸
Liver and spleen	Liver involvement can occur in 10-15% of cases,⁴¹ seen more commonly in multisystem LCH.³⁷ May manifest in 2 forms: 1) early-stage disease with parenchymal infiltration (hepatomegaly, tumorous nodules, mild cholestasis) and 2) late-stage sclerosing cholangitis-like disease (severe cholestasis) that can quickly progress to end-stage liver failure and be lethal.⁵⁰ Magnetic resonance cholangiopancreatography may show irregularities of intrahepatic bile ducts and is the recommended initial test (Figure 1).⁵⁰ Liver biopsy may be negative for LCH and may show fibrosis or nonspecific inflammation. Spleen involvement occurs in 10-15% of patients and may coexist with liver disease.⁴⁴^,⁴⁸
Bone marrow and lymph nodes	Bone marrow involvement by LCH can occur, but the frequency is unknown.⁵⁶ Presence of peripheral blood count abnormalities may point toward bone marrow infiltration by LCH or another myeloid neoplasm. Isolated LCH of lymph nodes is uncommon,⁷² although it can occur as part of multisystem disease in 10-30% of cases.⁶^,¹⁵^,⁴⁴
Gastrointestinal and cardiovascular	Gastrointestinal involvement is rare and may present with diarrhea, abdominal discomfort, or an incidental polyp on colonoscopy.⁴³^,⁷¹^,⁷⁷ Although the encasement of arterial structures has been reported,⁴⁵ cardiovascular involvement is very rare and raises suspicion for an LCH/ECD overlap.