ABSTRACT
Context: Ewing sarcoma (ES) are malignant small round cell tumors (MSRCT) characterized by rearrangements of EWSR1 gene. Although gold standard for diagnosis is detection of specific fusion genes by molecular testing, these ancillary tests are costly and only available in limited number of settings. There is a persuasive evidence for reliability of NKX2.2 immunohistochemistry (IHC) as a surrogate marker for EWSR1 gene rearrangement in ES. Aims: The aim of this study is to correlate the NKX2.2 immuno-expression with genetically confirmed ES cases and also to assess the reliability and accuracy of NKX2.2 along with combined positivity of NXX2.2 and CD99 in diagnosing ES and differentiating it from other relevant histological mimics. Settings and Design: The present study is a retrospective study conducted over a period of 6-year duration in a tertiary cancer care center. Methods and Material: We evaluated NKX2.2 immunoexpression in 35 genetically confirmed cases of ES and also in pertaining differential entities (n = 58) of ES including rhabdomyosarcoma (n = 20), lymphoblastic lymphoma (n = 14), Wilms tumor (n = 10), poorly differentiated synovial sarcoma (n = 4), small-cell osteosarcoma (n = 4), neuroblastoma (n = 5), and mesenchymal chondrosarcoma (n = 1). CD99 was performed in the category of MSRCTs showing NKX2.2 positivity to evaluate combined specificity for the diagnosis of ES. Results: Of the 35 genetically confirmed cases of ES, 29 cases (83%) showed NKX2.2-positive expression (83% sensitivity). Compared to ES, NKX2.2 was positive in only 05% cases (3/58 cases) of non-ES MSRCT. Only two of five cases of neuroblastomas and one case of mesenchymal chondrosarcoma showed NKX2.2 positivity. CD99 positivity was seen in 100% of ES and in the single case of mesenchymal chondrosarcoma. All five cases (100%) of neuroblastoma were negative for CD99. Conclusions: The presented study, which is the first from an Indian oncology center, showed NKX2.2 IHC is quite reliable in diagnosis of ES in the right clinicopathological context. With remarkable sensitivity and specificity of NKX2.2 IHC for diagnosis of ES, we propose that combined positivity of CD99 and NKX2.2 IHC can obviate or minimize the need of EWSR1 gene rearrangement molecular testing for diagnosis of ES.
ABSTRACT
Objective:To investigate the value of friend leukemia integration-1 (FLI1) and NKX2.2 in the diagnosis of pediatric extraskeletal Ewing′s sarcoma (E-EWS), and the differential diagnosis of other pediatric small round cell tumors.Methods:Clinical data of children with E-EWS and other small round cell tumors diagnosed in the Department of Pathology of Xi′an Children′s Hospital and Xijing Hospital, Air Forth Medical University from January 2014 to December 2020 were retrospectively analyzed.Expression levels of FLI1 and NKX2.2 were examined by immunohistochemical staining.Results:(1)A total of 27 cases of E-EWS and 145 cases of other small round cell tumors were included, including 40 cases of poorly differentiated and undifferentiated neuroblastoma, 34 cases of rhabdomyosarcoma, 30 cases of metanephric Wilms tumor, 25 cases of lymphoma, 10 cases of malignant rhabdomyosarcoma, 2 cases of myeloid sarcoma, 1 case of desmoplastic small round cell tumor, 1 case of BCOR-rearranged sarcoma, 1 case of CIC-rearranged sarcoma and 1 case of melanotic neuroectodermal tumor of infancy.(2)The sensitivity, specificity, positive and negative predictive value of FLI1 in E-EWS were 88.9%(24/27 cases), 5.5%(8/145 cases), 14.9%(24/161 cases) and 72.8% (8/11 cases), respectively, and those of NKX2.2 in E-EWS were 92.6%(25/27 cases), 97.9%(142/145 cases), 89.3% (25/28 cases) and 98.6%(142/144 cases), respectively.The sensitivity, specificity, positive and negative predictive value of combined FLI1 and NKX2.2 were 85.2%, 97.9%, 88.5%, and 97.3%, respectively.Conclusions:NKX2.2 is sensitive and specific for the differential diagnosis of E-EWS from other pediatric small round cell tumors, showing a high diagnostic utility.FLI1 has high sensitivity but poor specificity for diagnosing E-EWS.The combination of detecting FLI1, NKX2.2 and other antibodies and genetic analysis is recommended to prevent misdiagnosis.
ABSTRACT
Purpose To investigate the expression of CYP4 A11 and CYP4 A22 in triple-negative breast carcinoma (TNBC) and its relationship with clinicopathological features and M2 tumor-associated macrophages (TAMs). Methods 72 cases of TNBC with clinical and pathological data were collected. The expression of CYP4 A11 and CYP4 A22 in the carcinoma cells and the expression of CD68 and CD163 of the TAMs were detected by immunohistochemically and analyzed with image processing software. The relationship between the expressions of CYP4 A11 and CYP4 A22 with clinicopathologic features and its correlation of the M2 state of TAMs was studied. Results Both the immunohistochemically staining scores of CYP4 A11 and CYP4 A22 were higher in cancer tissues than that in breast tissues (P<0.001, P<0.001). The higher expression of CYP4 A11 was associated with tumor diameter increase (P<0.001), lymph node metastasis (P<0.001), higher clinical stage (P<0.001) and higher Ki-67 index (P=0.011). Both the positive rates of CD68 and CD163 in the high expression group of CYP4 A11 were higher than those in the low expression group of CYP4 A11 (P=0.021, P<0.001). The higher expression of CYP4 A22 was associated with lymph node metastasis (P<0.001), higher clinical stage (P=0.006), higher recurrence rate (P<0.001), and higher Ki-67 index (P=0.040).The positive rates of CD163 in the high expression group of CYP4 A22 was higher than that in the low expression group of CYP4 A22 (P<0.001). Conclusion Both the expression of CYP4 A11 and CYP4 A22 may be associated with M2 polarization state of TAMs, high proliferative activity and lymph node metastasis in the TNBC.