Expression of TLE-1 and CD99 in Carcinoma: Pitfalls in Diagnosis of Synovial Sarcoma

Zaccarini, Daniel J.; Deng, Xiaobing; Tull, Jamie; Maciak, Charlene; Valente, Alfredo; Zhang, Shengle

doi:10.1097/pai.0000000000000436

Cited by 24 publications

(14 citation statements)

References 20 publications

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“…However, even strong membranous CD99 immunoreactivity is not specific for EwS [28,55]. Indeed, 40% of non-EwS cases examined in the current study (128/320 samples, representing 11 distinct tumor entities) exhibited a strong CD99 immunostaining (IRS >8).…”

Section: Discussioncontrasting

confidence: 50%

“…For almost three decades, the standard immunohistochemical marker for EwS has been the membranous glycoprotein CD99 [1,26], which shows a striking sensitivity but low specificity for EwS [27][28][29][30][31]. Since fusions of the FET family of genes comprising FUS, EWSR1, and potentially TAF15, with members of the ETS family of transcription factors (including FLI1, ERG, ETV1/4/6 and FEV) are largely pathognomonic for EwS [32][33][34], molecular identification of such fusions is the most reliable diagnostic test for EwS to date [24].…”

Section: Introductionmentioning

confidence: 99%

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High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

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Ewing sarcoma (EwS) is an aggressive cancer displaying an undifferentiated small-round-cell histomorphology that can be easily confused with a broad spectrum of differential diagnoses. Using comparative transcriptomics and immunohistochemistry (IHC), we previously identified BCL11B and GLG1 as potential specific auxiliary IHC markers for EWSR1-FLI1-positive EwS. Herein, we aimed at validating the specificity of both markers in a far larger and independent cohort of EwS (including EWSR1-ERG-positive cases) and differential diagnoses. Furthermore, we evaluated their intra-tumoral expression heterogeneity. Thus, we stained tissue microarrays from 133 molecularly confirmed EwS cases and 320 samples from morphological mimics, as well as a series of patient-derived xenograft (PDX) models for BCL11B, GLG1, and CD99, and systematically assessed the immunoreactivity and optimal cut-offs for each marker. These analyses demonstrated that high BCL11B and/or GLG1 immunoreactivity in CD99-positive cases had a specificity of 97.5% and an accuracy of 87.4% for diagnosing EwS solely by IHC, and that the markers were expressed by EWSR1-ERG-positive EwS. Only little intra-tumoral heterogeneity in immunoreactivity was observed for differential diagnoses. These results indicate that BCL11B and GLG1 may help as specific auxiliary IHC markers in diagnosing EwS in conjunction with CD99, especially if confirmatory molecular diagnostics are not available.

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Section: Discussioncontrasting

confidence: 50%

Section: Introductionmentioning

confidence: 99%

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Orth¹,

Hölting²,

Dallmayer

et al. 2020

Cancers

View full text Add to dashboard Cite

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“…9,10 Moreover, non-mesenchymal tumors have recently been shown to overexpress TLE1 by immunohistochemistry, including cutaneous neoplasms (eg, spindle cell melanoma), mesothelioma, and carcinomas. [10][11][12][13][14] As illustrated in the biopsy from our patient, a carcinoid tumor of the lung with spindle cell morphology raises a large differential diagnosis that requires resolution through ancillary studies. Carcinoid tumors of the lung are characterized by various growth patterns (eg, organoid, nested, trabecular) and demonstrate a range of morphologic appearances from epithelioid to oncocytic to spindled, among others.…”

Section: Discussionmentioning

confidence: 89%

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology—A Potential Diagnostic Pitfall

Jeffus,

Meena,

Lindberg

2023

Applied Immunohistochemistry &Amp; Molecular Morphology

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Tumors of the lung with a spindle cell morphology require consideration of many entities in the differential diagnosis, including metastases. Ancillary immunohistochemical stains but also molecular studies are typically required to arrive at the proper diagnosis. We present a case of a 71-year-old woman with multiple lung nodules, mediastinal lymphadenopathy, and a history of uterine cancer who underwent endobronchial ultrasound-guided fine needle aspiration and biopsy of the lung and mediastinal lymph nodes. A sampling of the lung lesion showed a cytologically bland neoplasm with spindle cell morphology, lacking necrosis or brisk mitotic activity. In conjunction with the cytomorphology, strong and diffuse Transducin-like enhancer of split 1 (TLE1) reactivity in the tumor cells initially raised the diagnosis of synovial sarcoma; however, subsequent results of additional testing showed strong and diffuse expression with AE1/AE3, CK 8/18, TTF-1, synaptophysin and chromogranin and focal or negative staining with a large number of other antibodies. This warranted a diagnosis of a carcinoid tumor. This is the first report of TLE1 staining in a carcinoid tumor of the lung. Therefore, when evaluating tumors of the lung with spindle cell morphology in which the differential diagnosis may include both carcinoid tumor and synovial sarcoma, TLE1 expression should be interpreted with caution and in conjunction with an expanded immunohistochemical staining panel.

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“…The high sensitivity and specificity are due to the predominance of epithelial and lymphoid tumours at this site, and their diagnosis as malignant usually does not represent a problem; however, mesenchymal lesions are considerably more difficult to classify [6]. Previous studies in the literature have shown that diagnostic accuracy of FNA is 63-95% for mesenchymal lesions [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23]. In our cohort, high diagnostic accuracy of 93.8% was observed in differentiating benign neoplasm from malignancies on cytomorphology.…”

Section: Discussionmentioning

confidence: 99%

Transthoracic Fine-Needle Aspiration Cytology of Pulmonary Spindle and Mesenchymal Neoplasms: A Pandora’s Box

et al. 2022

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Introduction: Pulmonary spindle cell and mesenchymal lesions are paradox for pathologists due to their rarity, overlapping morphology and differentials ranging from benign to malignant lesions, correct diagnosis is essential due to major treatment implications. This study highlights the role of fine-needle aspiration cytology (FNAC), clot core biopsy/cell block and immunohistochemistry in diagnosis of spindle-cell lesions in lung, thus playing a key role in patient management. Methods: It is a retrospective study of lung FNA with predominantly spindle and mesenchymal cells from 2015-2020 which were classified cytomorphologically into spindle, epithelioid, small round cell and biphasic and IHC panels are applied accordingly. Granulomatous lesions, FNA from mediastinum and chest wall were excluded. Results: 60 cases of lung FNA with spindle and mesenchymal cells were identified and included 6 benign and 54 malignancies which included 24 primary pulmonary and 30 metastases. Most common primary malignancies sarcomatoid carcinoma and most common metastasis was malignant peripheral nerve sheath tumour. FNA was paucicellular in 7 cases, was reported as benign in 7 cases and malignant in 46 cases. There were two false negative cases. One case of pulmonary blastoma was reported as inflammatory pseudotumour on cytology, other case of chondrosarcoma was reported as chondroid tumour. Sensitivity and specificity of FNA in distinguishing benign lesions and malignancies was 93.8% and 100% respectively. Conclusion: FNA along with clot core and IHC plays a pivotal role in the subsequent pathway taken for diagnostic or therapeutic management of these patients without the need for second sampling or trucut biopsies in a low resource setting.

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Expression of TLE-1 and CD99 in Carcinoma: Pitfalls in Diagnosis of Synovial Sarcoma

Cited by 24 publications

References 20 publications

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

High Specificity of BCL11B and GLG1 for EWSR1-FLI1 and EWSR1-ERG Positive Ewing Sarcoma

Expression of TLE1 in a Carcinoid Tumor of the Lung With Spindle Cell Morphology—A Potential Diagnostic Pitfall

Transthoracic Fine-Needle Aspiration Cytology of Pulmonary Spindle and Mesenchymal Neoplasms: A Pandora’s Box

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