At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation

Abstract Background Ewing sarcoma (ES) is the second most frequent sarcoma of bone, often affecting young patients and pursuing an aggressive clinical course. Among therapeutic choices, radio- and chemotherapy are employed in neoadjuvant setting, and they yield variable histological changes in neopl...

Full description

Saved in:
Bibliographic Details
Main Authors: Giorgia Arcovito, Giacomo Aringhieri, Virna Zampa, Luca Coccoli, Lorenzo Andreani, Alessandro Franchi
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Diagnostic Pathology
Subjects:
Online Access:https://doi.org/10.1186/s13000-025-01649-8
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850139442425102336
author Giorgia Arcovito
Giacomo Aringhieri
Virna Zampa
Luca Coccoli
Lorenzo Andreani
Alessandro Franchi
author_facet Giorgia Arcovito
Giacomo Aringhieri
Virna Zampa
Luca Coccoli
Lorenzo Andreani
Alessandro Franchi
author_sort Giorgia Arcovito
collection DOAJ
description Abstract Background Ewing sarcoma (ES) is the second most frequent sarcoma of bone, often affecting young patients and pursuing an aggressive clinical course. Among therapeutic choices, radio- and chemotherapy are employed in neoadjuvant setting, and they yield variable histological changes in neoplastic tissue, which mainly include necrosis and fibrosis. Cytodifferentiation is seldom observed in pediatric tumors such as nephroblastoma and rhabdomyosarcoma following treatment. Nevertheless, it represents an extremely rare phenomenon in ES. Case presentation In this study we present the clinico-pathologic and molecular features of two cases of ES undergoing neuroblastoma-like differentiation after treatment. Both tumors were primarily located in bone and presented the histologic and immunohistochemical features of classic ES in needle biopsies. They were treated with standard chemotherapy protocols followed by surgical resection. The resection specimens of the primary tumor of patient 1 and pleural metastases of patient 2 presented foci of eosinophilic fibrillary stroma resembling neuropil and containing cellular elements with wide granular eosinophilic cytoplasm, eccentric nuclei containing vesicular chromatin and prominent nucleoli, reminiscent of ganglion cells. These cells were positive for chromogranin, synaptophysin and CD56, while CD99 was negative. Molecular confirmation of EWSR1 rearrangement was provided in both cases by next generation sequencing and FISH analysis. Conclusions Evidence of neural differentiation in ES unravels interesting hints about its controversial histogenesis. Furthermore, awareness of this event must be increased to avoid misdiagnosis with neuroblastoma, which shows significant morphological overlap.
format Article
id doaj-art-4d99e954f50b4610bb477cf842f0bda8
institution OA Journals
issn 1746-1596
language English
publishDate 2025-04-01
publisher BMC
record_format Article
series Diagnostic Pathology
spelling doaj-art-4d99e954f50b4610bb477cf842f0bda82025-08-20T02:30:18ZengBMCDiagnostic Pathology1746-15962025-04-012011710.1186/s13000-025-01649-8At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiationGiorgia Arcovito0Giacomo Aringhieri1Virna Zampa2Luca Coccoli3Lorenzo Andreani4Alessandro Franchi5Section of Anatomic Pathology, Department of Translational Research and of New Technologies in Medicine and Surgery, University of PisaSection of Radiology, Department of Translational Research and of New Technologies in Medicine and Surgery, University of PisaDiagnostic and Interventional Radiology, University Hospital of PisaDepartment of Orthopedics and Trauma Surgery, University Hospital of PisaPediatric Hematology Oncology Unit, University Hospital of PisaSection of Anatomic Pathology, Department of Translational Research and of New Technologies in Medicine and Surgery, University of PisaAbstract Background Ewing sarcoma (ES) is the second most frequent sarcoma of bone, often affecting young patients and pursuing an aggressive clinical course. Among therapeutic choices, radio- and chemotherapy are employed in neoadjuvant setting, and they yield variable histological changes in neoplastic tissue, which mainly include necrosis and fibrosis. Cytodifferentiation is seldom observed in pediatric tumors such as nephroblastoma and rhabdomyosarcoma following treatment. Nevertheless, it represents an extremely rare phenomenon in ES. Case presentation In this study we present the clinico-pathologic and molecular features of two cases of ES undergoing neuroblastoma-like differentiation after treatment. Both tumors were primarily located in bone and presented the histologic and immunohistochemical features of classic ES in needle biopsies. They were treated with standard chemotherapy protocols followed by surgical resection. The resection specimens of the primary tumor of patient 1 and pleural metastases of patient 2 presented foci of eosinophilic fibrillary stroma resembling neuropil and containing cellular elements with wide granular eosinophilic cytoplasm, eccentric nuclei containing vesicular chromatin and prominent nucleoli, reminiscent of ganglion cells. These cells were positive for chromogranin, synaptophysin and CD56, while CD99 was negative. Molecular confirmation of EWSR1 rearrangement was provided in both cases by next generation sequencing and FISH analysis. Conclusions Evidence of neural differentiation in ES unravels interesting hints about its controversial histogenesis. Furthermore, awareness of this event must be increased to avoid misdiagnosis with neuroblastoma, which shows significant morphological overlap.https://doi.org/10.1186/s13000-025-01649-8Ewing sarcomaPost-treatment effectsCytodifferentiationNeuroblastoma
spellingShingle Giorgia Arcovito
Giacomo Aringhieri
Virna Zampa
Luca Coccoli
Lorenzo Andreani
Alessandro Franchi
At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
Diagnostic Pathology
Ewing sarcoma
Post-treatment effects
Cytodifferentiation
Neuroblastoma
title At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
title_full At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
title_fullStr At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
title_full_unstemmed At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
title_short At the crossroad between Ewing sarcoma and neuroblastoma: a report of two cases of Ewing sarcoma with post treatment neuroblastoma-like differentiation
title_sort at the crossroad between ewing sarcoma and neuroblastoma a report of two cases of ewing sarcoma with post treatment neuroblastoma like differentiation
topic Ewing sarcoma
Post-treatment effects
Cytodifferentiation
Neuroblastoma
url https://doi.org/10.1186/s13000-025-01649-8
work_keys_str_mv AT giorgiaarcovito atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation
AT giacomoaringhieri atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation
AT virnazampa atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation
AT lucacoccoli atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation
AT lorenzoandreani atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation
AT alessandrofranchi atthecrossroadbetweenewingsarcomaandneuroblastomaareportoftwocasesofewingsarcomawithposttreatmentneuroblastomalikedifferentiation