Langerhans Cell Histiocytosis

Updated by Mark Edson

BACKGROUND

What is the estimated annual incidence of Langerhans cell histiocytosis (LCH) in the U.S.?

~1,200 cases/yr of LCH in the U.S. It is likely underdiagnosed in the general population and is most common in children 1–3 yrs.

Is there a sex predilection in LCH?

Yes. Males are more commonly affected than females (3:2).

What is the cell of origin of LCH?

LCH results from dysregulation of the mononuclear cell line (not the skin Langerhans cell)

What are the diagnostic histopathologic characteristics of LCH?

Birbeck granules on electron microscopy and CD1a, S100, and CD207 (Langerin) positivity are typical for LCH.

What is the normal function of Langerhans cells? Where are they normally found?

Langerhans cells serve as antigen presenting cells to lymphocytes and are typically found in skin, mucosa, spleen, and lymphatics.

What organs are typically involved in LCH?

Bones (children) and lungs (adults), but LCH can present in any organ (e.g., liver, skin, etc.).

What defines low-risk groups vs. high-risk groups?

Low risk: unifocal lesion in bone, LN, GI tract, CNS

High risk: <2 yo with organ dysfunction (hepatosplenomegaly, pancytopenia); liver, spleen, BM involvement

How does LCH relate to other histiocytosis entities like eosinophilic granuloma, Letterer-Siwe Dz, Hand-Schuller-Christian Dz, and histiocytosis X?

Eosinophilic granuloma is an older term for focal LCH, while the eponyms represent multifocal Dz. Histiocytosis X is the older term for LCH. All are antiquated terms.

What is Hand-Schuller-Christian Dz?

Hand-Schuller-Christian Dz refers to the proliferation of histiocytes that results in exophthalmos, skull lesions, diabetes insipidus (DI), and hemangiomas (poor prognosis).

In what age group are widespread seborrheic rashes in the scalp/groin, +LAD, and liver involvement seen with LCH?

These Sx are seen in LCH pts <2 yo.

For what age group is DI a common presentation of LCH?

>2 yo (20%–50%). In this group, bone (pain +/– soft tissue mass), lung, oral mucous membrane, and cerebral involvement by LCH can be seen.

WORKUP/STAGING

Is bone scan useful for LCH? Why?

No. LCH bone lesions are usually purely lytic.

What type of workup is necessary?

LCH workup: H&P, labs, skeletal survey (lucency in the medullary cavity), and Bx

What is the appearance of LCH lesions on plain radiograph?

LCH lesions appear lytic or “punched-out” on plain radiograph.

What staging system is used for LCH?

There is no staging system. LCH is described as single-system (unifocal or multifocal involvement of an organ/body system) or multisystem (≥2 organ or body systems).

TREATMENT

What are the indications for RT in LCH?

No signs of local healing, relapse after surgery, if other local therapy (i.e., curettage) is not appropriate, potential compromise of critical structures from expansile bone lesions, pain relief, and DI

What is the largest series supporting RT for DI from LCH?

Mayo data (Kilpatrick SE et al., Cancer 1995): 45 pts. There was a 36% rate of DI improvement with RT.

Within how many days after Dx should RT be given for DI?

RT should be administered within 14 days of DI Dx. (Kilpatrick SE et al., Cancer 1995)

When is RT not indicated in LCH?

RT is not indicated for sclerotic LCH lesions and collapsed vertebral lesions (only indicated if such lesions are painful).

What data support the use of RT for localized osseous LCH lesions?

German meta-analysis (Olschwski T et al., Strahlenther Onkol 2006): LC was 96% and CR was 93% for single-system Dz with RT.

What are the commonly used doses and volumes for LCH?

DI: 15 Gy to pituitary/hypothalamus

Bone (small margin): 5–10 Gy

Adults: 15–24 Gy (in 2 Gy/fx)

When is chemo used in LCH?

Multisystem Dz (e.g., if fever, pain, severe skin involvement, failure to thrive, and organ dysfunction)

What systemic agents are used for LCH?

Prednisone (1^st-line), then vinblastine. Single-agent chemo is as good as multiagent chemo. Vincristine can also be used.

How are asymptomatic, organ-confined LCH lesions managed?

Asymptomatic LCH lesions are typically observed.

How is a symptomatic bony LCH lesion managed?

A symptomatic bony LCH lesion is typically managed by surgery (curettage, excision) and/or local injection of steroids.

How are symptomatic LCH skin lesions managed?

Symptomatic LCH skin lesions are managed by topical therapy with nitrogen mustard, steroids, or systemic therapy.

How is LCH of the eye, ear, spine, or weight-bearing bones managed?

LCH of these areas is managed by systemic steroids or local RT.

How is asymptomatic multifocal LCH Dz with organ dysfunction managed?

Such asymptomatic LCH Dz is typically observed.

How is symptomatic multifocal LCH Dz with organ dysfunction managed?

Symptomatic multifocal LCH Dz with organ dysfunction is managed by systemic therapy (as described above). If the pt is symptomatic due to organ failure, consider transplant (liver, lung).

What is the long-term OS for solitary LCH lesions?

The OS for solitary LCH lesions is ∼100%.

What is the long-term OS for multisystem LCH with organ dysfunction?

The long-term OS for multisystem LCH with organ dysfunction is 33%–54%.

What is the long-term OS for multisystem LCH without organ dysfunction?

The long-term OS for multisystem LCH without organ dysfunction is 82%–96%.