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Name
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 primary sites: bone, lung, soft tissue, lymph nodes
Common metastatic sites are the liver, and bone marrow
The most commonly involved bones include the craniofacial bones (head and neck, skull), femur, spine, pelvis, and/or ribs.
If unable to determine primary site, assign primary site C419
See also abstractor notes
Common metastatic sites are the liver, and bone marrow
The most commonly involved bones include the craniofacial bones (head and neck, skull), femur, spine, pelvis, and/or ribs.
If unable to determine primary site, assign primary site C419
See also abstractor notes
Coding Manual:
Hematopoietic Coding Manual (PDF)
Abstractor Notes
Langerhans cell histiocytosis, disseminated is part of the Langerhans cell and other dendritic cell neoplasms lineage table in the WHO 5th edition of Hematolymphoid Tumors. (See Appendix B in the Hematopoietic Manual, Table B11)
Reportability for Langerhans Cell Histiocytosis changed in 2021. For cases with diagnosis date before 2021, make sure you choose the "Help me code for diagnosis years" to 2020 or earlier.
Per the IARC/WHO Committee for ICD-O and included in the WHO Tumors of Hematopoietic and Lymphoid Tissues, Revised 4th Ed, Volume 2, only LCH disseminated/multisystem is now assigned /3 behavior (malignant). All other forms of LCH are no longer malignant (/3 behavior) and are not reportable except for benign Brain and CNS tumors (9751/1).
LCH, disseminated/multisystem is a combined pathological/clinical diagnosis. Microscopic (histological) confirmation of LCH may be done but may not document that the tumor is disseminated/ multisystem. The disseminated/multisystem diagnosis is based on clinical evaluation by the managing/treating physician and is based on multiple areas of involvement. Not all suspected sites of involvement need to be biopsied or surgically resected.
If the only information you have is a pathology report that has LCH, NOS with no clinical evaluation on the extent of involvement, do not abstract the case. Only reportable if benign Brain and CNS, See 9751/1)
Langerhans cell histiocytosis presents in several different forms
1. DISSEMINATED/MULTISYSTEM: Occurs in infants who present with fever, cytopenia, skin and bone lesions, and hepatosplenomegaly. Pulmonary disease in childhood is clinically variable. The skin, bone, and marrow are preferential sites of involvement. The liver and spleen are also common sites; however, they are typically metastatic and not the primary site. Involvement of bone marrow, liver, and lung are regarded as high-risk factors. (9751/3)
2. SOLITARY/UNIFOCAL form: Usually occurs in older children or adults who most commonly present with a lytic bone lesion eroding the cortex. Solitary lesions may occur at other sites as mass lesions or enlarged lymph nodes. Other sites include adjacent soft tissue (skull, femur, vertebra, pelvic bones, and ribs) and less commonly lymph nodes, skin and lung. (Only reportable if benign Brain and CNS, See 9751/1)
3. MULTIFOCAL/UNISYSTEM multifocal disease-Usually occurs in young children who present with multiple or sequential destructive bone lesions often associated with adjacent soft tissue masses. Skull and mandibular involvement are common. Diabetes insipidus follows cranial involvement. (Only reportable if benign Brain and CNS, See 9751/1)
Self-healing Langerhans cell histiocytosis (LCH) of the skin means that the disease regressed without treatment. This is a known phenomenon and is non reportable.
Reportability for Langerhans Cell Histiocytosis changed in 2021. For cases with diagnosis date before 2021, make sure you choose the "Help me code for diagnosis years" to 2020 or earlier.
Per the IARC/WHO Committee for ICD-O and included in the WHO Tumors of Hematopoietic and Lymphoid Tissues, Revised 4th Ed, Volume 2, only LCH disseminated/multisystem is now assigned /3 behavior (malignant). All other forms of LCH are no longer malignant (/3 behavior) and are not reportable except for benign Brain and CNS tumors (9751/1).
LCH, disseminated/multisystem is a combined pathological/clinical diagnosis. Microscopic (histological) confirmation of LCH may be done but may not document that the tumor is disseminated/ multisystem. The disseminated/multisystem diagnosis is based on clinical evaluation by the managing/treating physician and is based on multiple areas of involvement. Not all suspected sites of involvement need to be biopsied or surgically resected.
If the only information you have is a pathology report that has LCH, NOS with no clinical evaluation on the extent of involvement, do not abstract the case. Only reportable if benign Brain and CNS, See 9751/1)
Langerhans cell histiocytosis presents in several different forms
1. DISSEMINATED/MULTISYSTEM: Occurs in infants who present with fever, cytopenia, skin and bone lesions, and hepatosplenomegaly. Pulmonary disease in childhood is clinically variable. The skin, bone, and marrow are preferential sites of involvement. The liver and spleen are also common sites; however, they are typically metastatic and not the primary site. Involvement of bone marrow, liver, and lung are regarded as high-risk factors. (9751/3)
2. SOLITARY/UNIFOCAL form: Usually occurs in older children or adults who most commonly present with a lytic bone lesion eroding the cortex. Solitary lesions may occur at other sites as mass lesions or enlarged lymph nodes. Other sites include adjacent soft tissue (skull, femur, vertebra, pelvic bones, and ribs) and less commonly lymph nodes, skin and lung. (Only reportable if benign Brain and CNS, See 9751/1)
3. MULTIFOCAL/UNISYSTEM multifocal disease-Usually occurs in young children who present with multiple or sequential destructive bone lesions often associated with adjacent soft tissue masses. Skull and mandibular involvement are common. Diabetes insipidus follows cranial involvement. (Only reportable if benign Brain and CNS, See 9751/1)
Self-healing Langerhans cell histiocytosis (LCH) of the skin means that the disease regressed without treatment. This is a known phenomenon and is non reportable.
Diagnostic Confirmation
This histology can be determined by positive histology (including peripheral blood) with or without genetics and/or immunophenotyping. Review the Definitive Diagnostic Methods, Immunophenotyping and Genetics Data sections below, and the instructions in the Hematopoietic Manual for further guidance on assigning Diagnostic confirmation.
Module Rule
None
Alternate Names
Definition
Langerhans cell histiocytosis (LCH) is a clonal neoplasm of myeloid dendritic cells that have a Langerhans cell phenotype (CD1a and CD207 expression) and lack high-grade cytological features. (WHO 5th edition)
Multisystem LCH (MS-LCH): Occurs in two or more organ systems. Commonly there is bone, skin, liver, and spleen involvement, with additional extraosseous involvement, including lymph node involvement, visceral mass lesions, and cystic pulmonary nodules. MS-LCH with bone marrow, spleen, or liver involvement is considered high-risk.
In both SS-LCH and MS-LCH, the most commonly involved bones include the craniofacial bones, femur, spine, pelvis, and/or ribs.
Multisystem LCH (MS-LCH): Occurs in two or more organ systems. Commonly there is bone, skin, liver, and spleen involvement, with additional extraosseous involvement, including lymph node involvement, visceral mass lesions, and cystic pulmonary nodules. MS-LCH with bone marrow, spleen, or liver involvement is considered high-risk.
In both SS-LCH and MS-LCH, the most commonly involved bones include the craniofacial bones, femur, spine, pelvis, and/or ribs.
Definitive Diagnostic Methods
Cytogenetics
Genetic testing
Histologic confirmation
Immunohistochemistry
Immunophenotyping
Immunophenotyping
CD1a+ (expression/positive) (membranous)
CD45+ (low expression/positive)
CD68 (Golgi dot-like staining)+ (expression/positive)
CD207 (Langerin granular cytoplasmic)+ (expression/positive)
S100 (nuclear and cytoplasmic)+ (expression/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
Same Primaries
Corresponding ICD-10 Codes (Cause of Death codes only)
C96.0 Letterer-Siwe Disease
Corresponding ICD-10-CM Codes (U.S. only)
C96.0 Multifocal and multisystemic (disseminated) Langerhans-cell histiocytosis (effective October 01, 2015)
Signs and Symptoms
Diagnostic Exams
Biopsy
Bone marrow aspiration and biopsy
Bone scan
BRAF testing
CT (CAT) scan
Liver function test
Flow cytometry
PET (positron emission topography) scan
Immunophenotyping
Molecular analysis
Physical exam and history
Ultrasound exam
Urinalysis
Water deprivation test
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
Sources
WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. Lyon (France): International Agency for Research on Cancer; 2024. (WHO classification of tumours series, 5th ed.; vol. 11). https://publications.iarc.who.int/637.
Section: Histiocytic/dendritic cell neoplasms
Pages: Part A: 230-233
Section: Histiocytic/dendritic cell neoplasms
Pages: Part A: 230-233
International Classification of Diseases for Oncology, 3rd edition (including revisions). Geneva: World Health Organization, 2001, 2011, 2020.
Section: ICD-O-3.2 (2020) Morphological Codes
Pages: http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577
Section: ICD-O-3.2 (2020) Morphological Codes
Pages: http://www.iacr.com.fr/index.php?option=com_content&view=category&layout=blog&id=100&Itemid=577
PDQ® Pediatric Treatment Editorial Board. PDQ Langerhans Cell Histiocytosis Treatment. Bethesda, MD: National Cancer Institute. Updated <01/06/2025>. Available at: https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq. Accessed <02/28/2025>. [PMID: 26389240]
Section: Langerhans Cell Histiocytosis Treatment (PDQ®)–Health Professional Version
Pages: https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_178%20or%20http://www.cancer.gov/types/langerhans/patient/langerhans-treatment-pdq
Section: Langerhans Cell Histiocytosis Treatment (PDQ®)–Health Professional Version
Pages: https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq#section/_178%20or%20http://www.cancer.gov/types/langerhans/patient/langerhans-treatment-pdq
