Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. A clinicopathologic, immunophenotypic and molecular analysis

Machado, Isidro; Yoshida, Akihiko; Morales, Gema Nieto; Abrahão-Machado, Lucas Faria; Navarro, Samuel; Cruz, Julia; Lavernia, Javier; Parafioriti, Antonina; Picci, Piero; Llombart‐Bosch, Antonio

doi:10.1016/j.anndiagpath.2017.11.011

Cited by 50 publications

(37 citation statements)

References 33 publications

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“…(1,3). Other tumors with similar but more variable morphology and behavior have been grouped in the so-called ‘Ewing-like’ tumors; they possess specific fusions such as CIC-DUX4, BCOR-CCNB3 , and EWSR1-NFATc2 (2,3,4). To date, the information known about NFATc2 rearranged bone tumors is limited to mainly single case reports and sporadic descriptions within Ewing family series of tumors many of them without clinicopathological information (5,6).…”

Section: Introductionmentioning

confidence: 99%

EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review

et al. 2019

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Background: The classification of bone neoplasms composed of small round cells is experiencing a transformation after the discovery of various gene fusion rearrangements that determine diagnosis, behavior, and response to therapy. Aim: We present herein four new cases of small round cell tumor of the bone that harbor NFATc2 rearrangements involving either EWSR1 or FUS genes. Materials and methods: We studied the clinical presentation, pathologic features, genetics (FISH, targeted RNA sequencing) and outcome in these four patients. We also reviewed the literature describing similar cases. Results: All our patients were male. The median age at diagnosis was 33.5 years. All tumors presented in long bones of the extremities as a large destructive mass with a mean size of 12.5 cm. All cases were hypercellular with prominent collagenous stroma and consisted of small to medium size round cells arranged in cords, thin trabeculae, and pseudoacinar structures. Most cases showed focal or diffuse membrane staining for CD99; whereas S100, synaptophysin and chromogranin were negative. EMA showed cytoplasmic staining in one case. Genetic studies identified EWSR1-NFATc2 fusion in three cases, and FUS-NFATc2 fusion in one case. The patients were treated with chemotherapy using Ewing sarcoma regimens and surgical excision was performed on three patients; necrosis was minimal. Follow-up is limited; after a median follow-up of 8.7 months one patient developed local recurrence and metastases to the lungs. Conclusion: Poorly differentiated round cell sarcoma with EWSR1/FUS-NFATc2 fusions are uncommon. The tumors have consistent clinical findings, morphology, and immunoprofile that in combination are distinctive and differ from that of Ewing sarcoma. Importantly, these tumors do not respond to Ewing sarcoma chemotherapy regimens.

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Section: Introductionmentioning

confidence: 99%

EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review

et al. 2019

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“…Staining for NKX2.2 (downstream target of EWSR1-ETS fusion gene), studied in 2 cases, was also variable. 10,20 The strong ETV4 positivity in one tumor suspected of harboring EWSR1-NFATC2 is unexpected for Ewing sarcoma, 20 but more typical of CIC-rearranged sarcoma. 20,21 Furthermore, cytokeratin positivity was found in 4 of 8 cases studied, compared with the 20% positivity in Ewing sarcoma.…”

Section: Discussionmentioning

confidence: 96%

“…[12][13][14] The amplification of fusion gene, varying from 4-fold to more than 15-fold, is a highly consistent feature of EWSR1-NFATC2 sarcomas. [10][11][12][13][14]20 Although copy number alterations can occur in Ewing sarcomas involving the region of chromosome 22q12, 22 the amplification of fusion gene in Ewing sarcoma is very rare. 23,24 It is tempting to speculate a gene dosage effect of amplified EWSR1-NFATC2 chimera on the tumor behavior.…”

Section: Discussionmentioning

confidence: 99%

Bone Sarcoma With EWSR1-NFATC2 Fusion: Sarcoma With Varied Morphology and Amplification of Fusion Gene Distinct From Ewing Sarcoma

et al. 2019

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Ewing sarcomas are typified by EWSR1 fusion to ETS gene family members. Tumors with fusion partners other than ETS family members and atypical histologic features pose significant diagnostic challenges and controversies as to their classification. In this article, we report a tumor with EWSR1-NFATC2 fusion in the left femur of a 43-year-old man and with unusual morphologic features that resemble undifferentiated high-grade sarcoma. Analysis together with reported cases in the literature shows that tumors with EWSR1-NFATC2 exhibit distinctive clinicopathologic features, including predilection for young male adults, highly variable histology that varies from round cell tumors frequently associated with nuclear irregularity, short spindle cells with nuclear pleomorphism, to myoepithelial tumor-like with or without myxohyaline matrix. They show variable positivity to CD99, frequent expression of cytokeratins, and consistent high-level amplification of EWSR1-NFATC2 fusion gene with distinctive gene expression profile. These tumors thus deserve classification separate from Ewing sarcoma.

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“…Further immune stains panels were used afterwards, as and when needed like CD20, CD3, CD30, BCL2, CD117, Ki-67, Tdt, synaptophysin, SMA, CD56, Melan A, HMB45, PAX5, Calretinin and WT1. However, many novel antibodies have also been used in other studies; like PAX7 21 , NKX2.2 18 , PHOX2B 20 , BCOR 27 , ETV4 28 and many more. Some of them claimed to be better and more specific than previously used.…”

Section: Discussionmentioning

confidence: 99%

“…The extent of positive IHC reaction was scored as focal (< 10%), patchy (10-50%) or diffuse (>50%). 18 and the final diagnosis was rendered.…”

Section: Methodsmentioning

confidence: 99%

Use of Immunohistochemistry in the differential diagnosis of Small Round Blue cell tumors.

Mudassar¹,

Baloch²,

Hameed

et al. 2020

TPMJ

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Objectives: Objective of the study is to differentiate and sub-categorize malignant small round blue cell tumors by using immune-histochemistry. Study Design: Descriptive Observational study. Setting: Meezan Private Lab, Faisalabad, Pakistan. Period: 5 years, from July 2014 to June 2019. Material & Methods: Sample Size: 126 cases of Round blue cells tumors. Sampling Technique: Non probability purposive sampling. Data Collection Procedure: 126 cases which fulfilled the inclusion and exclusion criteria were selected for the study. All these cases were subjected to immunohistochemistry. The IHC technique used was based on Peroxidase anti-peroxidase (PAP) method. Based on site and morphological clues, initially Leukocyte common antigen (LCA), Myogenin, Cytokeratin (CK), Desmin, chromogranin, Neuron specific enolase (NSE), S-100, Smooth muscle actine (SMA) and CD99 were used. Further immune stains panels were used afterwards, as and when needed like CD20, CD3, CD30, BCL2, CD117, Ki-67, Tdt, synaptophysin, SMA, CD56, Melan A, HMB45 and WT1. Results: Out of 126 cases of small round blue cell tumors, 35 (27.8 %) cases were diagnosed as diffuse large B cell lymphoma, 6 as Lymphoblastic lymphoma, 4 as Burkitt’s lymphoma, and 6 cases as NK/T cell lymphoma. Ewing’s sarcoma/PNET (12/126, 9.5%) was the 2nd highest in frequency, followed by Rhabdomyosarcoma, Synovial sarcoma, Malignant melanoma, and Germ cell tumor, which were all 9/126 each with 7.1 %. Conclusion: Immunohistochemistry is an important tool for appropriate and clear differential diagnosis of malignant small round blue cell tumors of childhood.

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Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. A clinicopathologic, immunophenotypic and molecular analysis

Cited by 50 publications

References 33 publications

EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review

EWSR1/FUS-NFATc2 rearranged round cell sarcoma: clinicopathological series of 4 cases and literature review

Bone Sarcoma With EWSR1-NFATC2 Fusion: Sarcoma With Varied Morphology and Amplification of Fusion Gene Distinct From Ewing Sarcoma

Use of Immunohistochemistry in the differential diagnosis of Small Round Blue cell tumors.

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