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

Histopathology. 2018 Mar;72(4):685-696. doi: 10.1111/his.13412. Epub 2017 Dec 21.

Abstract

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 (GNBi), 10 GNB nodular (GNBn) 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 GNBn 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.

Keywords: PHOX2B; immunohistochemical stain; neural crest tumours; neuroblastoma (peripheral neuroblastic tumour); small round blue cell tumours.

MeSH terms

  • Adrenal Gland Neoplasms / diagnosis*
  • Biomarkers, Tumor / analysis*
  • Child
  • Female
  • Homeodomain Proteins / analysis*
  • Humans
  • Immunohistochemistry / methods
  • Male
  • Staining and Labeling
  • Transcription Factors / analysis*

Substances

  • Biomarkers, Tumor
  • Homeodomain Proteins
  • NBPhox protein
  • Transcription Factors

Supplementary concepts

  • Neural crest tumor