Karyotype Interpretation: 45,X,inv(16)(p13.3q22) 1/ 46,XX,inv(16)(p13.3q22) 99
This karyotype represents a patient with a predominant inv(16)(p13.3q22) abnormality in 99% of cells (indicating likely acute myeloid leukemia) with low-level 45,X mosaicism that is clinically insignificant and should not alter AML-directed management.
Primary Clinical Significance: AML with inv(16)
The inv(16) Abnormality Defines the Disease Entity
The inv(16)(p13.3q22) present in 99% of cells is diagnostic of AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22); CBFB-MYH11, which is classified as AML with recurrent genetic abnormalities 1
This genetic abnormality alone is sufficient for AML diagnosis regardless of blast percentage, as the presence of inv(16) defines a specific WHO disease entity 2
Chromosome analysis is mandatory at diagnosis for risk stratification in AML, and inv(16) is one of the most important prognostic markers 1
Prognostic Implications
Inv(16) is classified as favorable-risk cytogenetics in both pediatric and adult AML 1
This abnormality is part of core binding factor (CBF)-AML, which accounts for a significant proportion of pediatric AML cases and carries a better prognosis 1
FISH may be used to confirm the CBFB-MYH11 fusion gene, particularly where abnormalities recurrently associated with specific rearrangements are found, such as the association of inv(16) with trisomy 22 1
Required Additional Testing
Molecular workup should include screening for mutations in NPM1, FLT3, CEBPA, RUNX1, ASXL1, DNMT3A, and TP53, as these findings can further define the subtype and refine prognosis 1
FISH or molecular analysis is recommended for PML-RARA, CBFB-MYH11, or RUNX1-RUNX1T1 rearrangements to confirm the specific fusion gene 1
Additional FISH testing for KMT2A and MECOM gene rearrangements should be considered if no other entity-defining abnormality is confirmed 1
The 45,X Component: Clinically Insignificant
Low-Level Mosaicism Does Not Affect Management
The 45,X cell line represents only 1% of analyzed cells (1 out of 100 metaphases), which is extremely low-level mosaicism 3
In the context of a hematologic malignancy with inv(16) in 99% of cells, this single 45,X cell is most likely:
- An artifact of cell culture
- A secondary chromosomal loss during malignant transformation
- Unrelated to Turner syndrome phenotype
The presence of 45,X in only 1 cell does not meet criteria for mosaic Turner syndrome, which typically requires a significant proportion of cells with the 45,X line to have clinical significance 4
Why This is NOT Turner Syndrome
Turner syndrome requires clinical correlation with phenotypic features (short stature, ovarian dysgenesis, cardiac anomalies, etc.), and the diagnosis should not be made on a single 45,X cell in the context of AML 4
Most living Turner syndrome patients are mosaics with a substantial 45,X cell line, not a single cell among 100 analyzed 4
The inv(16) abnormality is the dominant and clinically relevant finding that drives all management decisions 1
Management Algorithm
Immediate Actions
Confirm AML diagnosis through bone marrow morphology, immunophenotyping, and molecular testing for CBFB-MYH11 fusion 1
Complete molecular profiling including NPM1, FLT3, CEBPA, RUNX1, ASXL1, DNMT3A, and TP53 mutations 1
Risk stratify as favorable-risk AML based on inv(16) cytogenetics 1
Treatment Approach
For patients aged <60 years with favorable-risk cytogenetics (inv(16)), standard induction chemotherapy consists of cytarabine (100-200 mg/m² continuous infusion for 7 days) combined with either idarubicin (12 mg/m² for 3 days) or daunorubicin (60-90 mg/m² for 3 days) 1
The 45,X finding should not influence treatment decisions, as the inv(16) abnormality is the sole determinant of risk stratification and therapy selection 1
HLA typing should be performed for potential allogeneic hematopoietic cell transplantation consideration, though favorable-risk AML may not require transplant in first remission 1
No Turner Syndrome Evaluation Needed
Do not pursue Turner syndrome workup (cardiac echo for coarctation, renal ultrasound, etc.) based on this single 45,X cell 4
If the patient has phenotypic features suggestive of Turner syndrome independent of this karyotype, that would be a separate clinical consideration unrelated to the AML diagnosis 4
Critical Pitfall to Avoid
The most important pitfall is misinterpreting the 45,X cell as clinically significant Turner syndrome and allowing it to distract from the primary diagnosis of favorable-risk AML with inv(16). The inv(16) abnormality in 99% of cells is the only finding that matters for prognosis, treatment selection, and clinical management 1.