An Incidental Finding of Gain of a Diminished Chromosome 12 Centromere in an Individual with Lymphocytosis: A Case Report and Clinical Implications in Cytogenetic Testing

TL;DR

A case report describes a rare chromosomal finding in a patient with lymphocytosis, highlighting challenges in cytogenetic testing and the need for further investigation.

Contribution

This is the first reported case of a mosaic 'partial trisomy 12' with an uncertain clinical impact.

Findings

An additional diminished CEN12 signal was observed in 70% of nucleated cells.

The signal was located on the centromere of one chromosome 16 homolog, not involving 12p or 12q.

The case presents a challenge to clinical cytogenetic diagnosis and highlights the need for orthogonal methods.

Abstract

Background: Fluorescence in situ hybridization (FISH) testing against chromosome 12 centromere (CEN12) is routinely included in the work-up of patients with suspected chronic lymphocytic leukemia (CLL) or monoclonal B-cell lymphocytosis (MBL). However, incidental findings can occur and be challenging. Methods: Interphase and metaphase FISH analyses with various probes, including CEN12 probes from different vendors, and conventional cytogenetics were applied. Results: A CLL FISH panel was performed at the clinician’s request on a peripheral blood specimen from a 55-year-old female with fluctuating leukocytosis and lymphocytosis for over six years. An additional diminished CEN12 FISH signal was observed in approximately 70% of the nucleated cells analyzed. Concurrent flow cytometry excluded a diagnosis of CLL or MBL, and karyotyping exhibited a normal female karyotype. Further studies excluded potential cross-hybridization due to limited specificity of the CEN12 probes and revealed the location of the additional diminished CEN12 signal on the centromere of one chromosome 16 homolog (CEN16), without other material from the short arm (12p) or long arm (12q) of chromosome 12 being involved. Conclusions: This is the first case with an “uncertain” trisomy 12 status, presenting a challenge to clinical cytogenetic diagnosis. Although the mechanism for this mosaic “partial trisomy 12” and its clinical impact remain unknown, this case highlights the importance of further investigation using orthogonal methods to clarify incidental findings during diagnostic practice.

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