Search Database ICD-O-3 Code Lists

Name

ALK-positive histiocytosis

ICD-O-3 Morphology

9750/3: Malignant histiocytosis
Effective 2001 and later

Reportable

1978-2009, 2026 and later; see Abstractor Notes

Primary Site(s)

See Module 7
Most common primary sites: central and peripheral nervous system, bone, lung, skin, breast, soft tissue

See also abstractor notes.

Coding Manual: Hematopoietic Coding Manual (PDF)

Abstractor Notes

This is a new reportable neoplasm for 2026. If the diagnosis is prior to 1/1/2026, it is not reportable.

ALK Histiocytosis is part of the Histiocyte/macrophage neoplasms lineage table in the WHO 5th edition of Hematolymphoid Tumors. (See Appendix B in the Hematopoietic Manual, Table B12)

ALK histiocytosis has multiple presentations

1. Multisystem with systemic hematopoietic involvement: Systemic involvement of the liver, spleen, and/or marrow, but additional sites can be involved, such as the skin and CNS

2. Multisystem (others): Tumorous involvement of two or more organ systems. Commonly involved sites include the central and peripheral nervous system, bone, lung, and skin

3. Single system: Tumorous involvement of one single organ system, with solitary or multiple lesions. Commonly involved sites include the central and peripheral nervous system, skin, breast, and soft tissue

Diagnostic Confirmation

None

Module Rule

None

Alternate Names

ALK-related histiocytosis
ALK-rearranged histiocytosis

Definition

ALK-positive histiocytosis is a histiocytic neoplasm lacking high-grade cytological atypia and characterized by ALK (anaplastic lymphoma kinase) immunoreactivity, usually due to ALK gene rearrangement. (WHO 5th edition)

Definitive Diagnostic Methods

Cytogenetics
Genetic testing
Histologic confirmation
Immunohistochemistry
Immunophenotyping

Genetics Data

ALK gene translocation, most commonly with exon 24 of KIF5B fused to exon 20 of ALK

Immunophenotyping

CD4+ (expression/positive)
CD14+ (expression/positive)
CD68+ (expression/positive)
CD163+ (expression/positive)
Lysozyme positive

Treatments

None

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)

C96.1 Malignant histiocytosis

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

C96.A Histiocytic sarcoma (effective October 01, 2015)

Signs and Symptoms

Anemia (severe)
Ataxia
Coagulopathy
Diplopia
Headaches
Hepatomegaly
Hypotonicity
Paroxysmal neurological symptoms
Seizures
Splenomegaly
Thrombocytopenia
Trigeminal neuralgia
Vomiting

Diagnostic Exams

Biopsy
Bone marrow aspiration and biopsy
Bone scan
CT (CAT) Scan
Cytogenetic analysis
Flow cytometry
Immunophenotyping
Molecular analysis
Neurological exam
PET (positron emission topography) scan
Physical exam and history

Progression and Transformation

None

Epidemiology and Mortality

Incidence: Rare
Age: Infants for multisystem systemic form
Age: Any for multisystem (and others) and single form
Sex: female dominance

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: 252-254

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
Glossary