Langerhans cell histiocytosis

Langerhans cell histiocytosis
ICD-O-3 Morphology
9751/3: Langerhans cell histiocytosis
Effective 2010 and later
for cases diagnosed 2010 and later
Primary Site(s)
See Module 7
Most common sites of involvement: bone, lung, soft tissue, lymph nodes, bone marrow

Not Applicable
Module Rule
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
Letterer-Siwe disease (if disseminated or visceral involvement)
Malignant histiocytosis
Nonlipid reticuloendotheliosis [OBS]
Self-healing Langerhans cell histiocytosis (LCH) of the skin
This is a clonal neoplastic proliferation of Langerhans type cells that express CD1a, langerin and S100 protein, and shows 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.)

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
Genetics Data
X-linked androgen receptor gene assay (HUMARA)
CD45 (low expression)
S100 Protein expression
Chemotherapy (skin LCH associated with multisystem disease)
Observation (for all pediatric patients with skin only LCH)
Surgery (for localized lesions)
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)
C96.5 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)