How should I interpret a pathology report showing a FISH (fluorescence in situ hybridization) gain of the MAML2 probe on chromosome 11 in 36% of interphase cells?

Interpretation of FISH Gain of MAML2 Probe on Chromosome 11

This FISH finding of MAML2 gain in 36% of interphase cells is highly suggestive of mucoepidermoid carcinoma and should prompt immediate correlation with histopathology to confirm this diagnosis.

Understanding the Result

The pathology report shows a gain (not rearrangement) of the MAML2 probe in 36 out of 100 cells. This is a critical distinction:

• MAML2 rearrangement (translocation) is the classic finding in mucoepidermoid carcinoma, typically t(11;19)(q21;p13) creating a MECT1-MAML2 fusion gene 1
• MAML2 gain (increased copy number) represents a different genetic alteration—extra copies of the MAML2 locus without translocation

Determining if This is Abnormal

The 36% frequency exceeds typical laboratory cut-off values for abnormality. According to ACMG guidelines:

• FISH abnormality is determined when the percentage of cells with abnormal signal patterns exceeds the laboratory's established cut-off value at 95% confidence 2
• Most laboratories establish cut-offs using statistical methods (confidence interval around the mean or inverse beta function) from normal control populations 2
• A result of 36% positive cells is well above typical cut-offs (usually 5-10% for most probes), making this definitively abnormal 3

Clinical Context and Differential Diagnosis

Most Likely: Mucoepidermoid Carcinoma

• MAML2 alterations are highly specific for mucoepidermoid carcinoma, occurring in approximately 50% of cases 1
• While classic MAML2 rearrangement is more common, copy number gains can also occur in this tumor type 1
• MAML2-positive mucoepidermoid carcinomas tend to occur in younger patients (mean age 33 vs 60 years) and are restricted to low and intermediate grades 1

Important Distinction from Multiple Myeloma

The provided evidence discusses chromosome 11 centromere probes (D11Z1) used in multiple myeloma FISH panels 2, but these target the centromere, not the MAML2 locus at 11q21. Your report specifically mentions MAML2, indicating this is not a myeloma workup.

Prognostic Implications

If this represents mucoepidermoid carcinoma with MAML2 alteration, the prognosis is generally favorable:

• MAML2 rearrangement correlates with significantly better overall survival (p=0.023) and disease-free survival (p=0.027) in primary pulmonary mucoepidermoid carcinoma 1
• MAML2-positive tumors are typically low to intermediate grade 1
• Consider FLT1 immunohistochemistry, as absence of FLT1 expression combined with MAML2 alteration confers the most favorable outcome (p=0.009 for overall survival) 1

Critical Next Steps

1. Correlate with histopathology immediately: Review H&E sections for mucoepidermoid carcinoma features (mixture of mucous, intermediate, and epidermoid cells) 1

2. Determine anatomic site: MAML2 alterations are characteristic of mucoepidermoid carcinomas in salivary glands and lung 1

3. Consider additional IHC: FLT1 and HES1 expression may provide additional prognostic information 1

4. Verify the FISH probe used: Confirm whether this was a break-apart probe (detecting rearrangement) or enumeration probe (detecting copy number), as the interpretation differs 3, 4

Important Caveats

• This is a gain, not a rearrangement: The clinical significance of MAML2 copy number gain (versus translocation) is less well-established in the literature 1
• Laboratory-specific cut-offs matter: Confirm that 36% exceeds your specific laboratory's validated threshold, though this is almost certainly the case 2, 3
• Tissue type is critical: If this sample is from bone marrow or a hematologic specimen, the interpretation would be entirely different and potentially artifactual 2