Search Database ICD-O-3 Code Lists

Name

Aggressive NK-cell leukemia (ANKL)

ICD-O-3 Morphology

9948/3: Aggressive NK-cell leukemia
Effective 2001 and later

Reportable

for cases diagnosed 1978 and later

Primary Site(s)

C421
Primary site must be bone marrow (C421)

Coding Manual: Hematopoietic Coding Manual (PDF)

Abstractor Notes

Aggressive NK-cell leukemia (ANKL) is part of the Mature T-cell and NK-cell neoplasms lineage table in the WHO 5th edition of Hematolymphoid Tumors. (See Appendix B in the Hematopoietic Manual, Table B20)

The most commonly involved sites are the peripheral blood, bone marrow, liver, and spleen, but any organ can be involved.

Majority of patients are EBV+; however, EBV- can occur de novo, or evolve from NK-LGLL

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

Aggressive NK-cell leukaemia (ANKL) is a systemic malignant proliferation of NK cells, with an acute presentation, highly aggressive clinical course, and frequent association with EBV. (WHO 5th edition)

Definitive Diagnostic Methods

Bone marrow biopsy
Genetic testing
Immunophenotyping

Genetics Data

Chromosome 1q gain
Chromosome 7p loss
Chromosome 17p loss
del(6)(q21q25)
EBV+ (positive)

Immunophenotyping

CD2+ (expression/positive)
sCD3- (no expression/negative)
CD3+ (expression/epsilon positive)
CD5- (no expression/negative)
CD7+ (expression/positive)
CD11b+ (expression/positive)
CD16+ (expression/positive)
CD56+ (expression/positive)
CD57- (no expression/negative)
FASL+ (expression/positive)

Treatments

Chemotherapy
Hematologic Transplant and/or Endocrine Procedures
Radiation therapy

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)

C94.7 Other specified leukemias

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

C94.8 Other specified leukemias (effective October 01, 2015 - September 30, 2024)
C94.80 Other specified leukemias not having achieved remission (effective October 01, 2024)
C94.81 Other specified leukemias, in remission (effective October 01, 2024)
C94.82 Other specified leukemias, in relapse (effective October 01, 2024)

Signs and Symptoms

Anemia
Coagulopathy
Elevated serum lactate dehydrogenase level
Fever
Hepatosplenogemaly
Hemophagocytic syndrome
Multi-organ failure
Neutropenia
Thrombocytopenia

Diagnostic Exams

Blood chemistry studies
Bone marrow aspiration and biopsy
Cytogenetic analysis
Flow cytometry
Immunohistochemistry
Immunophenotyping
Peripheral blood smear

Progression and Transformation

Relapse is almost the rule in patients achieving remission with or without stem cell transplant.

Epidemiology and Mortality

Incidence: rare (more prevalent in Asian populations)
Age: median age 40
Sex: no male or female predilection
Survival: median survival time is months

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: Mature T- and NK-cell neoplasms
Pages: Part B: 677-679

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

PDQ® Adult Treatment Editorial Board. PDQ Peripheral T-Cell Non-Hodgkin Lymphoma Treatment. Bethesda, MD: National Cancer Institute. Updated <03/13/2025>. Available at: https://www.cancer.gov/types/lymphoma/hp/peripheral-t-cell-lymphoma-pdq. Accessed <03/31/2025>. [PMID: 37437079]
Section: Peripheral T-Cell Non-Hodgkin Lymphoma Treatment (PDQ®)–Health Professional Version
Pages: https://www.cancer.gov/types/lymphoma/hp/peripheral-t-cell-lymphoma-pdq#_2289
Glossary