Molecular and Clinicopathological Findings in a Tonsillar Synovial Sarcoma. A Case Study and Review of the Literature

Synovial sarcoma (SS), 3–5% of which occurs in the head and neck region, has generally been regarded as high grade sarcoma. Recent analysis of clinical, morphological, and molecular characteristics of SS, however, identified low and high risk group of patients, resulting in important implications for the treatment of patients diagnosed with SS. We describe the case of a 31-year-old male who presented with biphasic SS with poorly differentiated areas (clinical stage IIA) in a palatine tonsil, an extremely rare site of SS. Molecular analyses revealed typical t(X;18) translocation of the SYT gene and a SYT/SSX1 fusion type. The tumor was surgically resected with free margins. Adjuvant radiotherapy or chemotherapy was not considered indicated. To date, the patient has remained free of tumor for 4 years after surgery. Literature review reveals that primary tonsillar HNSS has previously been documented only in three patients. In all of these patients the tumor was histologically biphasic; however only one published case and the case presented here showed areas of poor differentiation. We discuss the relevance of the presented findings with regard to prognostic and therapeutic considerations in SS in the head and neck region

Involvement of the PI3K/Akt pathway in myxoid/round cell liposarcoma

The molecular determinates involved in the progression of myxoid liposarcoma to increased cellularity/round cell change are poorly understood. We studied the PI3K/Akt pathway in myxoid and round cell liposarcomas using a tissue microarray composed of 165 tumors from 111 patients, and mutational analysis of PIK3CA in 44 cases. Activating PIK3CA mutations were found in 6/44 cases, 14%; mutations were more frequent in round cell vs. myxoid tumors (5/15, 33% vs. 1/29, 3%; p=0.013). Complete loss of PTEN, an alternative mechanism for PI3K/Akt activation, was found in 13/111 (12%) cases and was mutually exclusive with PIK3CA mutation. Strong IGF1R expression was demonstrated in 14/39 (36%) of round cell and 11/58 (19%) of myxoid tumors (p=0.062). Activation of the PI3K pathway was confirmed using immunohistochemical analysis for downstream targets phospho-S6 ribosomal protein and phospho-4EBP1. Phospho-4EBP1 was increased in round cell tumors compared to myxoid tumors (24/30, 80% vs. 25/44, 57%; p=0.038) or tumors with treatment effect (10/24, 42%; p=0.02). Phospho-S6 was highly expressed in both myxoid and round cell tumors (29/47, 62% and 14/30, 47%, respectively; p=0.2). In tumors with PIK3CA mutation, any IGF1R expression, or loss of PTEN expression, phospho-4EBP1 was more frequently elevated compared to tumors without a known activating event in the PI3K pathway (55/72; 76% vs. 3/8, 38%; p=0.033). These findings suggest that activation of the PI3K/Akt pathway via activating mutation of PIK3CA, loss of PTEN, or IGF1R expression play a role in round cell transformation. The PI3K/Akt pathway may therefore provide a therapeutic target in round cell liposarcoma