Alternative lengthening of telomeres and ATRX/DAXX loss can be reliably detected in FNAs of pancreatic neuroendocrine tumors

BACKGROUND Pancreatic neuroendocrine tumors (PanNETs) frequently use the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. ALT is strongly correlated with α thalassemia‐mental retardation, X linked (ATRX), and death domain‐associated protein 6 (DAXX) alterations and a poor prognosis in patients with primary PanNET. Because fine‐needle aspiration (FNA) is a noninvasive way to sample tumors, the authors evaluated whether they could accurately detect ALT and loss of ATRX/DAXX in a primary PanNET cohort of FNAs. METHODS All preoperative FNA cytology cases (2005‐2016) with adequate remnant FNA cell block material were assessed for ALT by telomere‐specific fluorescence in situ hybridization and for ATRX and DAXX protein expression by immunohistochemistry. For 21 patients who underwent tumor resection, the resected specimen also was assessed to determine the concordance between the FNA and surgical specimens. RESULTS In the primary PanNET cohort of 65 FNAs, ALT was detected in 15 specimens (23%). Although all ATRX‐negative and DAXX‐negative tumors were ALT‐positive, 3 of 14 (21%) ALT‐positive tumors did not exhibit nuclear loss of either ATRX or DAXX. The ALT‐positive tumors were associated with larger radiographic size (4.9 vs 2.4 cm, on average; P < .05) and higher grade (P < .05). Overall, there was 100% concordance in ALT status and ATRX/DAXX immunohistochemistry results between the FNA and surgical specimens. CONCLUSIONS Both ALT and loss of ATRX/DAXX can be accurately performed on FNA specimens with adequate material. Because ALT is a fundamental mechanism of pathogenesis, the ability to determine ALT in small biospecimens has implications for the design of clinical trials. Cancer Cytopathol 2017;125:544–51. © 2017 American Cancer Society. Pancreatic neuroendocrine tumors commonly rely on the alternative lengthening of telomeres pathway for telomere maintenance, which correlates with ATRX/DAXX alterations and poor outcomes in primary pancreatic neuroendocrine tumors. The authors found that both telomere‐specific fluorescent in situ hybridization for alternative lengthening of telomeres and ATRX/DAXX immunohistochemistry can be accurately performed on fine needle aspiration specimens with adequate material.