Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support.
Ewing's sarcoma (ES)/peripheral neuroectodermal tumor (PNET) are malignant neoplasms affecting children and young adults. We performed a study to typify the histological diversity and evaluate antibodies that may offer diagnostic/prognostic support. In total, 415 cases of genetically confirmed paraffin-embedded ES/PNET were analyzed on whole sections and in tissue microarrays. This study confirms the structural heterogeneity of ES/PNET, distinguishing three major subtypes: conventional ES (280 cases); PNET (53 cases); and atypical ES/PNET (80), including large cells, vascular-like patterns, spindle pattern, and adamantinoma-like configuration. All cases presented positivity for at least three of the four tested antibodies (CD99, FLI1, HNK1, and CAV1). CAV1 appeared as a diagnostic immunomarker of ES/PNET being positive in CD99-negative cases. Hence, the immunohistochemical analysis confirmed the diagnostic value of all four antibodies, which together cover more than 99% of the tumors, independently of the histological variety. The univariate analysis for survival revealed atypical ES as the only histological parameter apparently associated with less favorable clinical outcome, particularly in the subgroup of patients treated with surgery. In conclusion, the diagnosis of atypical ES is a challenge for the pathologist and needs support from molecular techniques to perform an optimal differential diagnosis with other small round cell tumors.
Llombart-Bosch
Antonio
A
Department of Pathology, University of Valencia, Ave. Blasco Ibañez, 17, 46010, Valencia, Spain. antonio.llombart@uv.es
Machado
Isidro
I
Navarro
Samuel
S
Bertoni
Franco
F
Bacchini
Patrizia
P
Alberghini
Marco
M
Karzeladze
Apollon
A
Savelov
Nikita
N
Petrov
Semyon
S
Alvarado-Cabrero
Isabel
I
Mihaila
Doina
D
Terrier
Philippe
P
Lopez-Guerrero
Jose Antonio
JA
Picci
Piero
P
D000071443:12E7 Antigen; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000906:Antibodies; D015703:Antigens, CD / Q000096:biosynthesis; D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000378:metabolism / Q000473:pathology*; D018959:CD57 Antigens / Q000096:biosynthesis; D051242:Caveolin 1 / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D018241:Neuroectodermal Tumors, Primitive, Peripheral / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D051789:Proto-Oncogene Protein c-fli-1 / Q000096:biosynthesis; D012512:Sarcoma, Ewing / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
D000071443:12E7 Antigen; D000906:Antibodies; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C495540:CAV1 protein, human; D018959:CD57 Antigens; C061828:CD99 protein, human; D051242:Caveolin 1; D015815:Cell Adhesion Molecules; C078433:FLI1 protein, human; D051789:Proto-Oncogene Protein c-fli-1