SUBMITTED 25 SEPT 22 1 REVISION REQ. 27 OCT 22; REVISION RECD. 17 NOV 22 2 ACCEPTED 18 DEC 22 3 ONLINE-FIRST: DECEMBER 2022 4 DOI: https://doi.org/10.18295/squmj.12.2022.064 5 6 Giant Mediastinal Myxoid Pleomorphic Liposarcoma 7 *Adil H. Al Kindi,1 Faiza A. Al Kindi,2 Marwa Al Riyami,3 Essam Khalil1 8 9 1Division of Cardiothoracic Surgery and 3Department of Pathology, Sultan Qaboos University 10 Hospital, Muscat, Oman; 2Radiology Department, Royal Hospital, Muscat, Oman. 11 *Corresponding Author’s e-mail: alkindi2001@gmail.com; adil.h.alkindi@gmail.com 12 13 Introduction 14 An 18 years old girl with no past medical history was experiencing progressive shortness of breath 15 for 3 months. At presentation, she was tachypneic, tachycardiac, hypotensive and was not able to 16 lie flat. 17 18 Her chest x-ray revealed abnormal contouring of the mediastinum (Figure 1A). Contrasted CT of 19 the chest showed a large heterogenous mass occupying the anterior mediastinum, right and left 20 hemithorax with posterior displacement of the heart and atelectasis of the lungs. (Figure B, C) The 21 patient underwent urgent surgical resection. The mass was exposed thorough a clam shell incision 22 exposing the anterior mediastinum and bilateral pleura (Figure 2A). The mass was yellow, 23 encapsulated and lobulated. It was resected en-block with intra-operative frozen section 24 confirming negative margins. The mass weighed 3208 grams and was 22 × 18 × 13 cms. (Figure 25 2B) 26 27 Post-operatively, the patient did well with complete resolution of her symptoms. The final 28 histopathology proved the mass to be high grade malignant pleomorphic myxoid liposarcoma. 29 (Figure 3 & 4). MDM2 and cyclin-dependent kinase 4 were both negative. She received adjuvant 30 chemotherapy and is now on close surveillance by the oncologist. 31 32 Consent was taken from the patient for the publication of the case and images. 33 34 Comment 35 Liposarcoma is a relatively uncommon malignant tumor of adipose tissue that can occur at 36 anybody site. 1 For rare instances it arises primarily in the mediastinum.2 The recent World Health 37 Organization (WHO) classification has classified adipocytic tumors into: 1) Benign 2) 38 Intermediate (locally aggressive) and 3) Malignant. Malignant tumors include: 1) Well 39 differentiated liposarcoma: lipoma-like, sclerosing, inflammatory 2) Dedifferentiated liposarcoma 40 3) Myxoid liposarcoma 4) Pleomorphic liposarcoma 5) Myxoid pleomorphic liposarcoma. 3, 2, 4 41 42 Myxoid pleomorphic liposarcoma is a new entity in this classification. Unlike other liposarcomas, 43 its most common anatomical site is in the mediastinum followed by the limbs and neck. 44 Histologically, it shows a mixture of both myxoid and pleomorphic liposarcoma.3 Mediastinal 45 liposarcoma may grow to substantial size before causing any symptoms. The most common 46 presentation is incidental finding on chest X-ray. Symptomatic patients may have cough, dyspnea, 47 dysphagia, and chest pain.5 48 49 Radiologically, the tumor appears inhomogeneous in CT scan with a difficulty to differentiate it 50 from other forms of sarcoma. MRI can differentiate lipoma from well differentiated liposarcoma 51 (WDL).6 In Lipoma, MRI shows high intensity in T1 and T2 weighted images as this represents 52 the uniform structure with fatty tissue. In contrast, high grade liposarcoma show low intensity in 53 T1 images. In addition, Liposarcomas tends to be larger and has more thick septa.7,8 As the entity 54 is rare, there are no randomized trials that assess different treatment modalities. Current practice 55 is based on case reports and series.4 Complete surgical resection remains the mainstay for the 56 treatment of myxoid pleomorphic liposarcoma.8 Wide resection with negative margins is the goal. 57 However, anatomical location plays an important role whether this is possible. Patients with huge 58 mediastinal mass that present late may pose high risk surgical candidates as the compression of 59 vital structures, such as the heart and the lung, may cause critical hemodynamic issues during 60 surgery.9 61 62 Myxoid pleomorphic liposarcoma has an aggressive clinical presentation with high recurrence rate 63 and distant metastasis following surgical resection Approximately 40% recur after surgery.8Thus, 64 discussion in a multidisciplinary tumor board is recommended to assess the need for adjuvant 65 radiotherapy with or without chemotherapy after surgical resection.9 Although 90% of mediastinal 66 WDL show 12q12-15 amplicon that represents amplified oncogenes MDM2 and CDK-4, no 67 genetic aberration has been associated with myxoid pleomorphic liposarcoma.3,9 68 69 In conclusion, primary mediastinal myxoid pleomorphic liposarcoma is a rare entity and tend to 70 present at an advanced stage. Recognition of the need for complete surgical resection followed by 71 adjuvant therapy is very important. 72 73 Authors’ Contribution 74 AHK performed the surgery of this case. EK assisted in the surgery. FAK prepared and reported 75 the radiological images. MR prepared the pathology of the patient and reported the pathological 76 images. AHK and EK drafted and edited the manuscript. All authors approved the final version of 77 the manuscript. 78 79 References 80 1. Dei Tos A. Liposarcoma: New entities and evolving concepts. Ann Diagn Pathol. 2000 81 Aug;4(4):252–66. doi: 10.1053/adpa.2000.8133 82 2. Suster DI, Suster S. Liposarcomas of the mediastinum. Mediastinum. 2020 Sep;4:27–27. 83 doi:10.21037/med-20-42 84 3. Choi JH, Ro JY. The 2020 WHO Classification of Tumors of Soft Tissue: Selected Changes 85 and New Entities. Adv Anat Pathol. 2021 Jan;28(1):44–58. 86 doi:10.1097/PAP.0000000000000284 87 4. Sugiura Y, Hashizume T, Fujimoto H, Nemoto E. A giant mediastinal liposarcoma weighing 88 3500 g resected with clam shell approach, a case report with review of literature. Int J Surg 89 Case Rep. 2017;41:292–5. doi:10.1016/j.ijscr.2017.10.055 90 5. Ortega P, Suster D, Falconieri G, Zambrano E, Moran CA, Morrison C, et al. Liposarcomas of 91 the posterior mediastinum: clinicopathologic study of 18 cases. Modern Pathology. 2015 May 92 5;28(5):721–31. doi:10.1038/modpathol.2014.152 93 6. Patnaik S, Malempati A, Uppin M, Susarla R. Rare mediastinal masses – imaging review. J 94 Cancer Res Ther. 2021;17(1):13. doi:10.4103/jcrt.JCRT_587_19 95 7. Nagano S, Yokouchi M, Setoguchi T, Ishidou Y, Sasaki H, Shimada H, et al. Differentiation 96 of lipoma and atypical lipomatous tumor by a scoring system: implication of increased 97 vascularity on pathogenesis of liposarcoma. BMC Musculoskelet Disord. 2015 Dec 98 22;16(1):36. doi:10.1186/s12891-015-0491-8 99 8. Mei X, Li M, Xia Y. A huge mediastinal, well-differentiated liposarcoma with heterogenous 100 smooth muscle differentiation: a case report. Int J Clin Exp Pathol. 2019;12(7):2763–6. 101 9. Nassif NA, Tseng W, Borges C, Chen P, Eisenberg B. Recent advances in the management of 102 liposarcoma. F1000Res. 2016 Dec 22;5:2907. doi:10.12688/f1000research.10050.1 103 104 Figure 1: A: Anteroposterior chest radiograph showing an abnormal contouring of the 105 mediastinum with a large lesion in the anterior mediastinum and the left lower hemithorax. Hilar 106 overlay sign is noted with both hilar shadows identified through the opacity of the abnormal 107 lesion. B & C: CT-scan Images of the chest with IV contrast, (B) Axial (C) Coronal , showing a 108 large heterogenous mass occupying the anterior mediastinum, right and left hemithorax with 109 posterior displacement of the heart and atelectasis of the lungs . The mass shows areas of low 110 density (*) likely representing fat content and other areas of high density (**) representing 111 calcification. 112 113 114 Figure 2: A: Clam-shell incision exposing the anterior mediastinum and bilateral pleura. B: The 115 mass was yellow, encapsulated and lobulated measuring was 22 × 18 × 13cms. 116 117 118 Figure 3: Microscopic examination showed an encapsulated multinodular malignant neoplasm 119 of variable cellularity (A). There were lipomatous areas showing atypical multivacuolated 120 lipoblasts (arrows) (B). Other areas showed myxoid stroma containing plump spindle to stellate 121 cells (C). There were highly cellular nodules formed of fascicles of pleomorphic spindle cells 122 with frequent mitotic figures (arrow) (D). 123 124 125 Figure 4: Areas of geographic coagulative type necrosis were seen (asterisk) (A). The tumor 126 cells in the lipomatous areas were strongly positive for s-100 (B) but this was negative in the 127 cellular pleomorphic areas (C). Tumor cells were negative for MDM2 and CDK4. CDK4 is 128 shown here (D). 129