Endometrial Endometrioid Carcinomas Associated with Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor

Abstract

Three uterine tumors, each consisting of endometrioid carcinoma and Ewing's sarcoma/peripheral primitive neuroectodermal tumor (ES/pPNET) are described. The diagnosis of ES/pPNET in each case was first established in the hysterectomy specimen because each ES/pPNET was misinterpreted on the endometrial biopsy specimens as a high-grade homologous sarcoma. The ES/pPNET element in each case consisted of solid masses of small- to medium-sized round cells without Homer-Wright pseudorosettes, glial or ganglion cells, true rosettes with central lumens, or medulloepithelial tubules. Each ES/pPNET exhibited focal positive immunostaining for neuron-specific enolase, diffuse staining for vimentin, and strong cell membrane immunoreactivity for O13 (CD99), the last finding providing the first clue to the diagnosis of ES/pPNET in each case. The diagnosis in each case was confirmed by detection of EWS/FLI-1 fusion transcript through reverse transcription polymerase chain reaction. We also examined O13 immunoreactivity retrospectively in 40 cases of malignant mixed mullerian tumors (MMMT) with homologous or heterologous elements. O13 immunoreactivity was not observed in the malignant epithelium or in the homologous or heterologous sarcomas. The immunoreactivity of O13 in round cell endometrial sarcomas provides a clue to the diagnosis of ES/pPNET.

Endometrial endometrioid adenocarcinoma associated with primitive neuroectodermal tumour of the uterus: a poor prognostic subtype of uterine tumours

“…There are reports of uterine tumours with co-existent PNET and other tumour components, such as carcinoma [3,4,24]. Thus, the identification of a uniform, round, blue cell tumour component should arouse the search for a fibrillary background or rosette-like structures; immunohistochemistry including keratin, synaptophysin, and CD99 should be performed; tumours with primitive-like small blue cells lacking keratin expression but having expression of synaptophysin and CD99 indicate a neuroectodermal phenotype.…”

“…Noteworthy, it seems from the study of the published cases that the EWSR1 is more frequently found in younger (\50 years) patients. Only seven cases of endometrioid adenocarcinoma associated with PNET are described in the literature [4,9,18,24,29]. Three of these had an EWSR1 rearrangement, in three no molecular study was done, and in one no signal was obtained.…”

“…Of the 49 reported cases (including the present one), only 20 were evaluated for the EWSR1 rearrangement [4,7,19,24,26,27] and just 7 cases had a positive result: 2 of the 14 analysed by FISH, 4 of the 5 analysed by PCR and 1 of 1 analysed by IHC.…”

Ewing's Sarcoma Family of Tumors: Current Management

“…Individual members of this tumor family are defined along a gradient of limited neuroglial differentiation, with the poorly differentiated Ewing's sarcoma at one end and the more mature pPNETs at the other. With the availability of molecular tools to unambiguously confirm the presence of ews-ets gene rearrangements, the spectrum of Ewing's sarcoma-related neoplasms has recently been expanded to include rare CD99 MIC2 -positive extraskeletal tumors in various anatomic sites including the kidney [40][41][42][43][44], breast [41], gastrointestinal tract [45][46][47][48], prostate [49], endometrium [50], lung [44], adrenal gland [51], and meninges [52]. Although Ewing's family of tumors typically arise during adolescence, there is also an increasing number of adults being diagnosed with a CD99…”

Uterine Tumors with Neuroectodermal Differentiation. A Report of 4 Cases

“…Therefore, CD99 should be considered supportive but not diagnostic of Ewing sarcoma / pPNET. Sixteen of all reported cases have been subjected to molecular analysis of the EWSR1 gene, and EWSR1 gene rearrangement was detected in 4 of these cases [7,24,26,27]. Immunohistochemical analysis of FLI-1 expression was performed in only 2 of all the reported cases, in both cases with positive results (one case showed rearrangement of EWSR1 gene) [27].…”