1. LG Fibromyxoid Sarcoma Proliferative Myositis Solitary Fibrous Tumor
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, Kamal Peddinti, S. K. Doss, Sri Kiranmai Nanduru, Kanaka Durga NH Madasu, Vipin Chauhan, Aurobinda Samal, Vijender Bhandari, Arjun Singh, Santosh Pandey, Shipra Garg, Lata Kini, Sambit K. Mohanty
Department of Pathology and Laboratory Medicine, CORE Diagnostics, Gurgaon, India and Pathnsitu Biotechnologies, India.
Introduction and Aim:
TLE-1, a member of TLE family of genes that is homologous to Drosophilia co-repressor that encodes for human transcriptional co-repressors and is an important part of Wnt signaling pathway.
This is expressed in basal keratinocytes, endothelial cells, adipocytes and is involved in the developmental processes like lateral inhibition, segmentation, sex determination, hematopoiesis, and neuronal differentiation.
The TLE-1 antibody has been reported as useful adjunct in distinguishing synovial sarcoma (SS) from its potential morphological mimics including Ewing’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.
Table and Figures
Results:
Synovial sarcoma exhibited strong and diffuse positivity (20/40, 50%) and focal positivity (12/40, 30%).
Peripheral nerve sheath tumors (MPNSTs) 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%) , liposarcoma (4/7; 57%), pleomorphic undifferentiated sarcoma (3/17; 18 %) and malignant melanoma (1/3; 33%).
Only one case of sarcomatoid mesothelioma was included in study revealed strong diffuse staining.
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%), non-hodgkin lymphoma (1/7%; 14%), malignant melanoma (1/3; 33%). One case of inflammatory myofibroblastic tumor and angiomatous meningioma and two cases of neuroendocrine neoplasm showed focal labeling.
Sex cord stromal tumor, DFSP, malignant phyllodes tumor, myositis ossificans and haemangioendothelioma did not show either strong diffuse or focal labeling.
57.2%
Design:
184 cases were included in the study (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. The 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 TLE-1 in various soft tissue and other tumors and tumor like conditions.
Rhabdomyosarcoma
GIST
Liposarcoma
LG Fibromyxoid Sarcoma
Proliferative Myositis
Angiosarcoma
MPNST
Solitary Fibrous Tumor
Conclusions:
TLE-1 is a useful marker for SS, when used in conjunction with other immunostains and confirmed by molecular study, if available.
Promiscuity of TLE-1 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.