Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow

Jessica L. Hata, Hernan Correa, Chandra Krishnan, Adam J. Esbenshade, Jennifer O. Black, Dai H. Chung, Bret C. Mobley

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Context.-Neuroblastoma (NB) is the most common extracranial tumor of childhood. Although most cases have a distinctive histology, a subset of primitive cases require immunohistochemical studies to distinguish them from other small round blue cell tumors of childhood. Immunohistochemistry is also used to detect small amounts of tumor metastatic to the bone marrow and in posttreatment samples with obscuring fibrosis, calcification, or inflammation. The transcription factor PHOX2B is essential for the differentiation and survival of sympathetic neurons and chromaffin cells, and therefore is highly specific for the peripheral autonomic nervous system. Objective.-To determine the diagnostic utility of PHOX2B immunohistochemistry as a marker of primary, treated, and metastatic NB. Design.-Neuroblastoma tissue microarrays were stained with PHOX2B, CD57, and synaptophysin. Arrays containing rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor were stained with PHOX2B, and negative bone marrow samples were stained with PHOX2B and CD57. Results.-PHOX2B and CD57 were similar to synaptophysin in their ability to detect NB. PHOX2B and CD57 similarly showed robust staining in posttreatment NB and NB metastatic to the bone marrow. In contrast to the cytoplasmic staining pattern seen with synaptophysin and CD57, clear and strong nuclear PHOX2B permitted identification of individual tumor cells. PHOX2B staining was absent in all cases of rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor, and in the negative bone marrow. Conclusions.-PHOX2B and CD57 are useful markers of NB. PHOX2B is specific for NB in its differential diagnosis with other small round cell tumors, and its nuclear staining may be helpful for accurate bone marrow tumor quantification.

Original languageEnglish (US)
Pages (from-to)543-546
Number of pages4
JournalArchives of Pathology and Laboratory Medicine
Volume139
Issue number4
DOIs
StatePublished - Apr 1 2015
Externally publishedYes

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Neuroblastoma
Bone Marrow
Ewing's Sarcoma
Synaptophysin
Staining and Labeling
Neoplasms
Wilms Tumor
Rhabdomyosarcoma
Immunohistochemistry
Chromaffin Cells
Autonomic Nervous System
Peripheral Nervous System
Histology
Differential Diagnosis
Fibrosis
Transcription Factors
Inflammation
Neurons

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Medical Laboratory Technology

Cite this

Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow. / Hata, Jessica L.; Correa, Hernan; Krishnan, Chandra; Esbenshade, Adam J.; Black, Jennifer O.; Chung, Dai H.; Mobley, Bret C.

In: Archives of Pathology and Laboratory Medicine, Vol. 139, No. 4, 01.04.2015, p. 543-546.

Research output: Contribution to journalArticle

Hata, Jessica L. ; Correa, Hernan ; Krishnan, Chandra ; Esbenshade, Adam J. ; Black, Jennifer O. ; Chung, Dai H. ; Mobley, Bret C. / Diagnostic utility of PHOX2B in primary and treated neuroblastoma and in neuroblastoma metastatic to the bone marrow. In: Archives of Pathology and Laboratory Medicine. 2015 ; Vol. 139, No. 4. pp. 543-546.
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AU - Hata, Jessica L.

AU - Correa, Hernan

AU - Krishnan, Chandra

AU - Esbenshade, Adam J.

AU - Black, Jennifer O.

AU - Chung, Dai H.

AU - Mobley, Bret C.

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N2 - Context.-Neuroblastoma (NB) is the most common extracranial tumor of childhood. Although most cases have a distinctive histology, a subset of primitive cases require immunohistochemical studies to distinguish them from other small round blue cell tumors of childhood. Immunohistochemistry is also used to detect small amounts of tumor metastatic to the bone marrow and in posttreatment samples with obscuring fibrosis, calcification, or inflammation. The transcription factor PHOX2B is essential for the differentiation and survival of sympathetic neurons and chromaffin cells, and therefore is highly specific for the peripheral autonomic nervous system. Objective.-To determine the diagnostic utility of PHOX2B immunohistochemistry as a marker of primary, treated, and metastatic NB. Design.-Neuroblastoma tissue microarrays were stained with PHOX2B, CD57, and synaptophysin. Arrays containing rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor were stained with PHOX2B, and negative bone marrow samples were stained with PHOX2B and CD57. Results.-PHOX2B and CD57 were similar to synaptophysin in their ability to detect NB. PHOX2B and CD57 similarly showed robust staining in posttreatment NB and NB metastatic to the bone marrow. In contrast to the cytoplasmic staining pattern seen with synaptophysin and CD57, clear and strong nuclear PHOX2B permitted identification of individual tumor cells. PHOX2B staining was absent in all cases of rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor, and in the negative bone marrow. Conclusions.-PHOX2B and CD57 are useful markers of NB. PHOX2B is specific for NB in its differential diagnosis with other small round cell tumors, and its nuclear staining may be helpful for accurate bone marrow tumor quantification.

AB - Context.-Neuroblastoma (NB) is the most common extracranial tumor of childhood. Although most cases have a distinctive histology, a subset of primitive cases require immunohistochemical studies to distinguish them from other small round blue cell tumors of childhood. Immunohistochemistry is also used to detect small amounts of tumor metastatic to the bone marrow and in posttreatment samples with obscuring fibrosis, calcification, or inflammation. The transcription factor PHOX2B is essential for the differentiation and survival of sympathetic neurons and chromaffin cells, and therefore is highly specific for the peripheral autonomic nervous system. Objective.-To determine the diagnostic utility of PHOX2B immunohistochemistry as a marker of primary, treated, and metastatic NB. Design.-Neuroblastoma tissue microarrays were stained with PHOX2B, CD57, and synaptophysin. Arrays containing rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor were stained with PHOX2B, and negative bone marrow samples were stained with PHOX2B and CD57. Results.-PHOX2B and CD57 were similar to synaptophysin in their ability to detect NB. PHOX2B and CD57 similarly showed robust staining in posttreatment NB and NB metastatic to the bone marrow. In contrast to the cytoplasmic staining pattern seen with synaptophysin and CD57, clear and strong nuclear PHOX2B permitted identification of individual tumor cells. PHOX2B staining was absent in all cases of rhabdomyosarcoma, Ewing sarcoma, and Wilms tumor, and in the negative bone marrow. Conclusions.-PHOX2B and CD57 are useful markers of NB. PHOX2B is specific for NB in its differential diagnosis with other small round cell tumors, and its nuclear staining may be helpful for accurate bone marrow tumor quantification.

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