Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases.
More than 85% of Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET), or "Ewing family of tumors" (EFTs), have the translocation, t (11;22) (q24;q12), with others having variant translocations. Identification of these by cytogenetic and/or molecular genetic techniques is specific for EFT and is increasingly recognized as the "gold standard" for diagnosis. However, these techniques are not universally available. We therefore studied a large group of genetically confirmed EFTs to more completely understand the morphologic and immunophenotypic spectrum of this rare sarcoma. Sixty-six cytogenetically, FISH or RT-PCR proven-EFTs were retrieved. In 56 cases, immunohistochemistry (IHC) was performed for pan-cytokeratins (PanCK), high molecular weight cytokeratins (HMWCK), desmin (DES), CD99, CD117, and FLI1 protein using heat-induced epitope retrieval and the Dako Envision system. The cases arose chiefly in children and young adults (median 18 years; range, 3-65 years) of both sexes (male, 32; female, 31; unknown, 3) in a variety of bone (N = 39) and soft tissue (N = 27) sites. Histologically, 46 cases (73%) showed only typical features of ES, 9 cases (16%) showed features of PNET, 3 cases (5%) showed "adamantinoma-like" features, 3 cases (5%) corresponded to "atypical Ewing sarcoma," 3 cases (5%) showed principally intersecting fascicles of spindled cells, and 2 cases had abundant hyalinized matrix. IHC results were as follows: PanCK (18 of 56, 32%), HMWCK (3 of 55, 5%), DES (1 of 56, 2%), CD99 (52 of 52, 100%), CD117 (13 of 54, 24%), and FLI1 (44 of 47, 94%). HMWCK was expressed only in "adamantinoma-like" EFTs, none of which expressed DES. In conclusion, most, but not all, EFTs can be accurately diagnosed using time-honored morphologic criteria and ancillary immunohistochemistry. However, genetic confirmation remains essential for the diagnosis of unusual morphologic variants of EFT, including "adamantinoma-like," spindled, sclerosing, and clear cell/anaplastic variants. Therefore, to exclude or confirm the diagnosis of Ewing's sarcoma in round cell sarcomas having a variety of patterns but not specifically conforming to a tumor of known lineage (eg, rhabdomyosarcoma), cytogenetics, and/or molecular analysis is required.
Folpe
Andrew L
AL
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322, USA. afolpe@emory.edu
Goldblum
John R
JR
Rubin
Brian P
BP
Shehata
Bahig M
BM
Liu
Wendy
W
Dei Tos
Angelo P
AP
Weiss
Sharon W
SW
D000071443:12E7 Antigen; D000293:Adolescent; D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000032:analysis; D015815:Cell Adhesion Molecules / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003893:Desmin / Q000032:analysis; D005260:Female; D018260:Gelsolin / Q000032:analysis; D006801:Humans; D016130:Immunophenotyping; D007633:Keratins / Q000032:analysis; D008297:Male; D008840:Microfilament Proteins; D008875:Middle Aged; D019009:Proto-Oncogene Proteins c-kit / Q000032:analysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000032:analysis; D012509:Sarcoma / Q000473:pathology; D012512:Sarcoma, Ewing / Q000235:genetics / Q000276:immunology* / Q000473:pathology*; D015534:Trans-Activators; D014178:Translocation, Genetic
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D003893:Desmin; C098179:FLII protein, human; D018260:Gelsolin; D008840:Microfilament Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D015534:Trans-Activators; D007633:Keratins; D019009:Proto-Oncogene Proteins c-kit