Lingual alveolar soft part sarcoma with absent TFE3 rearrangement

Abstract Background Lingual ASPS is extremely rare and aggressive tumor. rearrangement is typically detected in ASPS patients using FISH analysis. Aim To present the clinical, histopathological, and radiological features of lingual Alveolar Soft Part Sarcoma. Method A 30‐year‐old male presented with a painless, slowly growing mass of the tongue. Initial impression was of benign vascular lesion. Later, the patient became symptomatic as the mass progressed in size, which necessitated further investigations. Result A lip‐split, mandibulotomy was performed for the excision of the tumor and revealed an alveolar soft part sarcoma with PAS‐positive, diastase resistant intracytoplasmic granules. However, molecular analysis using FISH was negative for TFE3 rearrangement. Patient underwent partial glossectomy with postoperative radiotherapy. Conclusion Clinical and pathological correlation of ASPS is very useful to reach a proper diagnosis.


| INTRODUCTION
Alveolar soft part sarcoma (ASPS) is a very rare and aggressive malignant neoplasm of uncertain histogenesis. 1 It comprises less than 1% of all soft tissue sarcomas, most commonly arising in lower extremities. Head and neck neoplasms occur in 27% of ASPS cases, and 25% of those cases arise in the tongue. Typically, ASPS of the tongue presents with a painless, slowly growing mass, and is more likely to occur in females between 15 and 35 years old. 2 Here, we describe the clinical, radiological, and histological features of alveolar soft part sarcoma (ASPS) of the tongue.

| CASE
A 30-year-old male presented with a painless swelling on the left base of the tongue surface, first noted 3 months back. The mass was slowly progressing in size. There were no other associated symptoms. Clinical examination revealed a nontender swelling on the left posterior part of tongue. The mass was firm in consistency, oval in shape, and had an intact mucosal covering, not associated with ulceration, and was not attached to any underlying tissue. Since the possibility of tongue cancer could not be ruled out in the presence of alarming compressive symptoms, incisional biopsy was planned. During the procedure, a significant bleeding was encountered which was difficult to be controlled with diathermy, local anesthesia, pressure packing and surgicel. Thus, it was decided to abort the procedure after hemostasis was completely secured, and the patient was extubated without any complications. Following   Figure 1). In addition to histopathological pattern, IHC studies are helpful to rule out differential diagnosis of ASPS such as granular cell tumor, paraganglioma, metastatic renal carcinoma (RCC) and alveolar rhabdomyosarcoma (ARMS). 6 Recently, it was proposed that the unbalanced translocation, del (17) t(X,17) (p11,p25), which results in the formation of ASPL-TFE3 transcript fusion detected on tumor cell, could specifically explain the tumorigenesis of ASPS. 7 Immunohistochemical reactivity for TFE3 in ASPS usually stains weak to moderately positive. 7 Sharain et al compared TFE3 rearrangement immunohistochemistry results between two laboratories. 8 The overall sensitivity of TFE3 immunohistochemistry to detect TFE3-rearranged neoplasms was 85% in laboratory A, and 70% in laboratory B. The difference in detection rate could be attributed to different fixation or processing techniques used by each laboratory, yet the presence or absence of immunohistochemical reactivity was not sufficient alone to confirm the diagnosis of ASPS since the specificities of IHC in lab A and lab B were 57% and 95% respectively. Also, a discordance between molecular and immunohistochemistry findings was reported in certain neoplasm in term of TFE3 rearrangement. 8 Although FISH analysis remained extremely sensitive and specific to detect Xp11.23 translocation associated with ASPS and Renal cell carcinoma (RCC), the possibility of chromosomal abnormalities could not be ruled out by FISH analysis alone. 9 In fact, a recent clinicalpathological review of 13 ASPS cases failed to show TFE3 rearrangements in four cases using FISH. 10 Our case was negative for TFE3 rearrangement, but the correlated clinical and pathological features confirmed the diagnosis of primary Alveolar soft part sarcoma. Exploring the sensitivity of FISH testing to detect TFE3 fusion gene in ASPS cases could be difficult due to the rarity of reported cases and inability to identify the fusion partner of TFE3 at certain circumstances. 11 Also, the possibility of unknown fusion variant could not be ruled out by molecular tests. 11

| CONCLUSION
Lingual ASPS is an extremely rare tumor. To the best of our knowledge, this is the first case to report ASPS of the tongue in Saudi Arabia. Clinically and radiologically, ASPS can be misdiagnosed as hemangioma. The nature of tumor location and behavior made the diagnosis and management of this case more challenging. Therefore, F I G U R E 3 imaging findings of ASPS. A, Axial contrast enhanced computed tomography demonstrates a homogenous well defined hypervascular lesion in left posterior tongue (white arrow). B, Sagittal enhanced T1 weighted image demonstrates a tongue mass with homogenous pattern of contrast en-hancement with flow void structures (white arrows). C, Axial unenhanced T2 weighted image demonstrates a hyperintense tongue mass with flow voids (white long arrow) and areas of slightly higher intensities (black short arrows) due to tumor necrosis careful evaluation of any hypervascular growing mass of the tongue should be done.
Histologic findings provide a reliable diagnostic method. Although molecular methods provide a great support to the diagnosis of ASPS, the absence of TFE3 fusion gene does not always rule out ASPS. Preoperative embolization for ASPS might be useful to avoid the risk of extensive bleeding during surgery.

ETHICS STATEMENT
Informed consent was obtained to publish this report.