Utility of Phox2b immunohistochemical stain in neural crest tumours and non‐neural crest tumours in paediatric patients

Aims This study evaluated the utility of Phox2b in paediatric tumours. Previously, tyrosine hydroxylase ( TH ) was the most widely utilised sympathoadrenal marker specific for neural crest tumours with neuronal/neuroendocrine differentiation. However, its sensitivity is insufficient. Recently Phox2b has emerged as another specific marker for this entity. Methods and results Phox2b immunohistochemistry ( IHC ) was performed on 159 paediatric tumours, including (group 1) 65 neural crest tumours with neuronal differentiation [peripheral neuroblastic tumours ( pNT )]: 15 neuroblastoma undifferentiated ( NB ‐ UD ), 10 NB poorly differentiated ( NB ‐ PD ), 10 NB differentiating ( NB ‐D), 10 ganglioneuroblastoma intermixed ( GNB i), 10 GNB nodular ( GNB n) and 10 ganglioneuroma ( GN ); (group 2) 23 neural crest tumours with neuroendocrine differentiation [pheochromocytoma/paraganglioma ( PCC / PG )]; (group 3) 27 other neural crest tumours including one composite rhabdomyosarcoma/neuroblastoma; and (group 4) 44 non‐neural crest tumours. TH IHC was performed on groups 1, 2 and 3. Phox2b was expressed diffusely in pNT ( n = 65 of 65), strongly in NB ‐ UD and NB ‐ PD and with less intensity in NB ‐D, GNB and GN . Diffuse TH was seen in all NB ‐ PD , NB ‐D, GNB and GN , but nine of 15 NB ‐ UD and a nodule in GNB n did not express TH ( n = 55 of 65). PCC / PG expressed diffuse Phox2b ( n = 23 of 23) and diffuse TH , except for one tumour ( n = 22 of 23). In composite rhabdomyosarcoma, TH was expressed only in neuroblastic cells and Phox2b was diffusely positive in neuroblastic cells and focally in rhabdomyosarcoma. All other tumours were negative for Phox2b ( n = none of 44). Conclusion Phox2b was a specific and sensitive marker for pNT and PCC / PG , especially useful for identifying NB ‐ UD often lacking TH . Our study also presented a composite rhabdomyosarcoma/neuroblastoma of neural crest origin.