MYB Gene Abnormalities t(6;9) in Adenoid Cystic Carcinoma Fine-Needle Aspiration Biopsy Using Fluorescence In Situ Hybridization2014-03-01 17:52:56
Archives of Pathology & Laboratory Medicine; 2014 March; DOI:doi.org/10.5858/arpa.2012-0736-OA
Jena B. Hudson and Brian T. Collins
Fine-needle aspiration (FNA) biopsy of salivary gland neoplasms can have a variety of overlapping appearances. Basaloid neoplasms can be a diagnostic challenge, and FNA cytomorphology alone cannot always provide a definitive diagnosis.
To examine the incidence and potential utility of detecting a MYB translocation by fluorescence in situ hybridization (FISH) in adenoid cystic carcinomas (AdCCs) and pleomorphic adenoma FNA smears with known surgical outcomes.
Patients who underwent FNA biopsy for surgically confirmed AdCCs and pleomorphic adenomas were identified. Fluorescence in situ hybridization, using commercially available fluorescent-labeled probes, hybridizing to MYB-telomeric and MYB-centromeric, was used to identify the MYB gene and to evaluate it for abnormalities and translocation. Using a fluorescent microscope, 4′,6-diamidino-2-phenylindole (DAPI)-stained, nonoverlapping cells were counted, and 10% or greater abnormal cells were considered positive.
The 10 AdCC and 13 pleomorphic adenoma FNA cases had FISH evaluations performed; 50% (5 of 10) of the AdCC cases showed a MYB abnormality by FISH; 40% (4 of 10) AdCCs showed a positive break-apart signal in most cells (48%-84%). One case (10%) of AdCC showed a trisomy MYB signal pattern without the break-apart translocation pattern. Of the 13 pleomorphic adenomas, none (0%) of the cases showed a MYB translocation or abnormality by FISH. MYB FISH abnormalities showed a 100% positive predictive value, 50% sensitivity, and 100% specificity, when differentiating AdCC from pleomorphic adenoma.
MYB gene abnormalities were present in 50% (5 of 10) of the AdCC cases. This corresponds to the reported prevalence in formalin-fixed, paraffin-embedded tissue for AdCC surgical resections. Using FISH testing for detecting MYB gene abnormalities in the salivary gland of FNA biopsies has the potential to provide additional, helpful ancillary information in diagnosing AdCC.
Adenoid cystic carcinomas (AdCCs) are infrequently encountered malignant neoplasms of the salivary glands that can present difficulties in specific preoperative diagnosis by fine-needle aspiration (FNA) biopsy. On aspirate smears, they frequently show small, round, bland nuclei without the typical features of malignancy noted in other carcinomas (nuclear enlargement, marked atypia, and pleomorphism). They can aggregate in small, 3-dimensional, tight groups with a background showing varying amounts of dense, matrixlike material. This general pattern overlaps with other benign and malignant basaloid-type salivary gland neoplasms, with the primary differential considerations being pleomorphic adenoma (PA) and, less-commonly, basal cell adenoma and basal cell carcinoma. These entities can often have indistinguishable, overlapping morphologic features, and although subtle differences can be noted, they are insufficient for a clear, definitive distinction on FNA biopsy. This typically results in a descriptive FNA biopsy diagnosis and is reported as a “basaloid neoplasm” with a comment detailing the differential diagnostic possibilities and limitations of definitive classification because of the morphologic appearance.
Currently, there are few ancillary studies available to assist in the differential diagnosis of salivary gland basaloid neoplasms on FNA biopsy. CD117 is a sensitive immunohistochemical marker for AdCC, but it can stain nearly 20% of benign PAs, the most common neoplasm of the salivary gland and the most frequent differential diagnosis for a basaloid neoplasm. Recently, cytogenetic abnormalities involving a t(6;9) (q22-23;p23-24) translocation have been described in adenoid cystic carcinoma of the salivary glands. The translocation involves the gene encoding the transcription factor MYB. Importantly, other salivary gland neoplasms, including PA, lack the MYB translocation, making a MYB gene abnormality specific to AdCC. These studies have been performed on formalin-fixed, paraffin-embedded, surgically excised neoplasms studied with fluorescent in situ hybridization (FISH) break-apart probes for the MYB gene.
Detecting a MYB translocation in a FNA biopsy specimen with the morphologic diagnosis of “basaloid neoplasm” could provide a more precise preexcision diagnosis of AdCC. The aim of this study was to examine the incidence and utility of detecting a MYB translocation in AdCC and PA FNA smears with known surgical outcomes.
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