1. Department of Laboratory Medicine, CORE Diagnostics, Gurgaon, India
TRANSDUCING-LIKE ENHANCER OF SPLIT (TLE-1): Promiscuous Staining Patterns in Soft Tissue and Other Neoplasms, A Diagnostic Pitfall
Samriti Arora, Anurag Sharma, Shivani Sharma, Vipin Chauhan, Aurobinda Samal, Vijender Bhandari, Arjun Singh, Santosh Pandey, Shipra Garg, Bonnie Balzer, Lata Kini, Sambit K. Mohanty
Department of Laboratory Medicine, CORE Diagnostics, Gurgaon, India
Introduction
TLE-1 is the member of TLE family of genes that is homologous to Drosophilia corepressor groucho, that encodes for human transcriptional co-repressors and is an important part of Wnt signalling pathway.
TLE-1 is expressed in basal keratinocytes, endothelial cells, adipocytes and is involved in the developmental processes like lateral inhibition, segmentation, sex determination, haematopoiesis and neuronal differentiation.
The TLE-1 antibody has been reported as useful adjunct in distinguishing Synovial sarcoma (SS) from its potential morphological mimics including Ewings’s sarcoma/primitive neuroectodermal family of tumors(EWS/PNET), peripheral nerve sheath tumors, smooth muscle neoplasms, etc.
TLE1 expression has also been observed in various soft tissue neoplasms, which raises the concern for misdiagnosis.
As the specificity of TLE1 in the morphologic mimics of SS has not been extensively studied, we sought to explore the pattern of TLE1 labeling in various soft tissue and other neoplasms and tumor-like lesions.
Results
Discussion
Synovial sarcoma exhibited strong and diffuse positivity (20/40, 50%) and focal positivity (12/40, 30%).
Peripheral nerve sheath tumors and EWS/PNET showed strong diffuse positivity (4/15; 27%, 3/25, 12% respectively) and focal positivity in (5/15; 33%, 4/25; 16% respectively).
Strong diffuse positivity was seen in smooth muscle neoplasms (6/14; 43%), rhabdomyosarcoma (1/6; 17%), GIST (1/5, 20%), solitary fibrous tumors (3/4; 75%), fibroblastic/myofibroblastic tumors (2/7; 29%), angiosarcoma (1/4; 25%), epithelioid sarcoma (1/2; 50%), carcinoma and carcinomas with sarcomatoid dedifferentiation (1/9; 11%), and sarcomatoid mesothelioma (1/1;100%), liposarcoma (4/7; 57%), pleomorphic undifferentiated sarcoma (3/17; 18 %), malignant melanoma (1/3; 33%).
Low-grade fibromyxoid sarcoma, non-hodgkin lymphomas, neuroendocrine neoplasms and inflammatory myofibroblastic tumor did not show a strong and diffuse positivity
Focal positivity was seen in smooth muscle neoplasms (5/14; 36%), rhabdomyosarcoma (2/6; 33%), GIST(1/5; 20%), fibroblastic and myofibroblastic tumor (2/7; 29%), angiosarcoma (1/4; 25%), low-grade fibromyxoid sarcoma (1/4; 25%) carcinomas and carcinomas with sarcomatoid dedifferentiation (5/9;56%), liposarcoma (2/7; 29%), pleomorphic undifferentiated sarcoma( 1/17; 6%), inflammatory myofibroblastic tumor (1/1; 100%), non-hodgkin lymphoma (1/7%; 14%), and malignant melanoma (1/3; 33%) neuroendocrine neoplasms (2/2;100%), angiomatous meningioma (1/1; 100%)
Solitary fibrous tumor, epitheloid sarcoma, and sarcomatoid mesothelioma did not show focal positivity for TLE1.
57.2%
Design
The diagnosis of184 cases that were included in the study were: group I: Synovial sarcoma (40], group II: close morphologic mimics of SS (EWS/PNET (25), peripheral nerve sheath tumors (15), smooth muscle neoplasms (14), rhabdomyosarcoma (6), gastrointestinal stromal tumors (5), solitary fibrous tumors (4), angiosarcoma (4), fibroblastic/myofibroblastic tumors (7), low-grade fibromyxoid sarcoma (4),dermatofibrosarcoma protuberance (3), epithelioid sarcoma (2), myositis ossificans (1), carcinoma and carcinomas with sarcomatoid dedifferentiation (9), and sarcomatoid mesothelioma (1), and group III: other tumors (liposarcoma [7], pleomorphic undifferentiated sarcoma [17], inflammatory myofibroblastic tumor [1], ovarian sex-cord stromal tumor [4], hemangioendothelioma [1], malignant phyllodes tumor [1], neuroendocrine neoplasms [2], non-Hodgkin’s lymphoma [7], malignant melanoma [3], and angiomatous meningioma [1]).
Immunhistochemistry was performed on 4 µm section using monoclonal TLE-1 antibody (clone IF5) at dilution 1: 60.
Nuclear positivity was scored as 1+/2+/3+ and percentage of positive cells was scored as [0, 1(1-25%), 2(25-50%), 3(51-100%). “Focal positivity” was defined as 2+ or 3+ intensity in >25% positive cells. “Strong diffuse “ positivity was defined as 3+ intensity in >50% positive cells.
Table: Expression pattern of TLE1 in various soft tissue and other tumors and tumor like conditions.
Conclusion
TLE1 is a useful marker for SS, when used in conjunction with other immunostains and confirmed by molecular study, if available.
Promiscuity of TLE1 as depicted in the present study warrants awareness of its staining pattern in various soft tissue and other neoplasms to avoid potential diagnostic pitfalls.
Further studies with a larger cohort and varieties of cases are needed to substantiate the current findings.