Name

Langerhans cell histiocytosis, NOS

ICD-O-1 Morphology

9720/3: Malignant histiocytosis
Effective 1978 - 1991

ICD-O-2 Morphology

9720/3: Malignant histiocytosis
Effective 1992 - 2000

ICD-O-3 Morphology

9751/3: Langerhans cell histiocytosis
Effective 2010 and later

Reportable

for cases diagnosed 1978 - 2000, 2010 and later

Primary Site(s)

See Module 7
Most common sites of involvement: bone, lung, soft tissue, lymph nodes, bone marrow

Grade

Not Applicable

Module Rule

None

Alternate Names

Acute progressive histiocytosis X
Eosinophilic granuloma (if solitary lesion)
Hand-Schuller-Christian disease (if multiple lesions or visceral involvement))
Histiocytic medullary reticulosis [OBS]
Histiocytosis X [OBS]
Langerhans cell granulomatosis
Langerhans cell granulomatosis, unifocal
Langerhans cell histiocytosis, disseminated
Langerhans cell histiocytosis, generalized
Langerhans cell histiocytosis, mono-ostotic
Langerhans cell histiocytosis, multifocal
Langerhans cell histiocytosis, poly-ostotic
Langerhans cell histiocytosis, unifocal
Langerhans histiocytosis, NOS
LCH
Letterer-Siwe disease (if disseminated or visceral involvement)
Malignant histiocytosis
Nonlipid reticuloendotheliosis [OBS]
Self-healing Langerhans cell histiocytosis (LCH) of the skin

Definition

Langerhans cell histiocytosis (LCH) is a clonal neoplastic proliferation of Langerhans-type cells that express CD1a, langerin and S100 protein and show Birbeck granules by ultrastructural examination.

Abstractor Notes

(This neoplasm is reportable for cases diagnosed 2010 and later. Some of the terms were also reportable for earlier years.)

Note: Per the IARC/WHO Committee for ICD-O and included in the WHO Tumors of Hematopoietic Lymphoid Tissues, Revised 4th Ed, Volume 2, only LCH disseminated is now assigned /3 behavior (malignant). The following LCH types are assigned 9751/1: NOS, monostotic, polystotic. This change has not been approved by the United States and Canada. Continue to collect LCH diagnosis that include: NOS, monostotic, polystotic and assign 9751/3.

Langerhans cell histiocytosis presents in several different forms

1. SOLITARY form: bone and adjacent soft tissue (skull, femur, vertebra, pelvic bones, and ribs) and less commonly lymph nodes, skin, and lung.

2. MULTIFOCAL lesions: largely confined to bone and adjacent soft tissue.

3. MULTISYSTEM disease: skin, bone, and bone marrow are preferential sites of involvement. The liver and spleen are also common sites; however they are typically considered metastases and not the primary site.

TYPES of Langerhans disease:
1. UNIFOCAL disease-usually older children or adults who most commonly present with a lytic bone lesion, eroding the cortex. Solitary lesions at other sites present as mass lesions or enlarged lymph nodes.

2. UNISYSTEM multifocal disease-usually young children who present with multiple or sequential destructive bone lesions often associated with adjacent soft tissue masses. Skull and mandibular involvement is common. Diabetes insipidus follows cranial involvement.

3. MULTISYSTEM disease: infants who present with fever, cytopenia, skin and bone lesions, and hepatosplenomegaly. Pulmonary disease in childhood is clinically variable.

Involvement of bone marrow, liver, and lung are regarded as high-risk factors.

Self-healing Langerhans cell histiocytosis (LCH) of the skin means that the disease regressed without treatment. This is a known phenomenon and is reportable as 9751/3.

NOTE: Langerhans histiocytosis, unifocal (9752/1 in ICD-O-3 for 2001-2009) Langerhans cell histiocytosis, multifocal (9753/1), and Langerhans cell histiocytosis, disseminated (9754/3) are now grouped with the newly reportable Langerhans cell histiocytosis (9751/3).

Definitive Diagnostic Methods

Genetic testing
Histologic confirmation
Immunophenotyping

Genetics Data

TR genes are clonally rearragned
X-linked androgen receptor gene assay (HUMARA)

Immunophenotyping

CD1a expression
CD30 absent
CD45 expression
CD68 positive
HLA-DR positive
Langerin (CD207) expression
S100 Protein expression
Vimentin positive

Treatments

Chemotherapy
Hormone therapy
Immunotherapy
Other therapy
Radiation therapy
Surgery

Transformations to

There are no known transformations

Transformations from

There are no known transformations

Corresponding ICD-9 Codes

202.5 Letterer-Siwe Disease

Corresponding ICD-10 Codes

C96.0 Letterer-Siwe Disease
D76.0 Langerhans' cell histiocytosis, not elsewhere classifed

Corresponding ICD-10-CM Codes (U.S. only)

C96.0 Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis (effective October 01, 2015)
C96.5 Multifocal and unisystemic Langerhans-cell histiocytosis (effective October 01, 2015)
C96.6 Unifocal Langerhans-cell histiocytosis (effective October 01, 2015)

Signs and Symptoms

Easy bruising or bleeding
Painful bone lesion
Skin rash
Weight loss

Progression and Transformation

Progression from initial focal disease multisystem involvement can occur, mostly in infants
Systemic and (rarely) multifocal disease can be complicated by hemophagocytic syndrome

Epidemiology and Mortality

Age: most cases occur in childhood
Incidence: 5 per million population per year
Race: more common in whites of northern Europena descent, rare in blacks
Survival: Unifocal disease (99% or greater), Multisystem disease (66% mortality)

Sources

Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J (Eds):
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (Revised 4th edition)
IARC: Lyon 2017
Section: Histiocytic and dendritic cell neoplasms
Pages: 470-472

International Classification of Diseases for Oncology, Third Edition, First Revision. Geneva: World Health Organization, 2013.
Section: ICD-O-3.1 (2011) Morphological Codes
Pages: http://codes.iarc.fr/codegroup/2

National Cancer Institute
Section: General Information About Langerhans Cell Histiocytosis (LCH)
Pages: https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_178%20or%20http://www.cancer.gov/types/langerhans/patient/langerhans-treatment-pdq
Glossary