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1 Enterprise Interest Nothing to declare

2 Sarcoma with CIC-DUX4 gene fusion: case report of kidney tumor location in a 12-year-old boy. Perret Cécile 1, Pierron Gaelle 2, Anne Mc Leer 3, Piolat Christian 4, Durand Chantal 5, Plantaz Dominique 1, Sartelet Hervé 2 1. Département d oncologie pédiatrique, CHU de Grenoble, Grenoble, France 2. Département de pathologie CHU de Grenoble, Grenoble, France 3. INSERM U830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France 4. Département de chirurgie, CHU de Grenoble, Grenoble, France 5. Département de Radiologie, CHU de Grenoble, Grenoble, France

3 Clinical data This patient consulted for fever and abdominal pain. The abdominal ultrasound revealed a tumor of the lower pole of the right kidney with a thrombus in the renal vein extending into the inferior vena cava. CT scan confirmed the tumor and revealed an infiltration of the perirenal fat. Chest CT scan showed bilateral multiple micro and macro pulmonary nodules.

4 Clinical data The patient received an emergency first line of chemotherapy, according to the SIOP protocol for stage 4 nephroblastoma Ultrasound and CT scan evaluation during preoperative chemotherapy showed a partial regression of the tumor and of the thrombus, allowing complete nephrectomy.

5 Nephrectomy The radical nephrectomy demonstrated a unifocal 6 cm tumor Histologically: Small round cells focally set in a myxoid stroma

6 CD99

7 Follow-up Diagnosis of Ewing sarcoma. In light of this diagnosis and of the lack of regression of the lung metastases, treatment was upgraded After two courses, the chest CT scan showed a discordant response with regression of some lesions and progression of others. Excision of lung metastases was decided to confirm the diagnosis.

8 Lung metastases The lung metastases presented the same histological aspect as the primary tumor with only focal necrosis. On fresh-frozen tissue, molecular analysis was performed by PCR (Curie Institut) and revealed CIC- DUX4 rearrangement.

9 FISH analyses FISH analyses of interphase nuclei was performed on formalin-fixed tissue: An absence of EWSR1 (EWSR1 probe Vysis, Downers Grove, IL, USA) translocation. A rearrangement of CIC-DUX4 (CIC-DUX4 dual probes Empire Genomics, Interchim, Montluçon, France) in 20 % of the nuclei Dr A Mc Leer Gambarotti et al Histopathology 2016, Choi et al Am J Surg Pathol 2013

10 Final Diagnosis Renal sarcoma with CIC-DUX4 gene fusion

11 Outcome The outcome of the disease was rapidly unfavorable CT scan performed after eight courses of chemotherapy showed the growth of previously noted metastases and revealed a new pulmonary nodule. A week later, a brain CT scan was performed because of frequent vomiting, and showed multiple brain metastases Unfortunately, the patient died a few days later.

12 Primary Ewing sarcoma of the kidney Primary Ewing sarcoma of the kidney is rare. Its diagnosis can be difficult Ewing sarcomas are poorly differentiated, highly cellular, round cell sarcomas CD99 expression is considered as a reliable marker Molecular analysis showed classical translocations: EWSR1-FLI1 Cases: no classical translocation Parham DM, Am J Surg Pathol Feb;25(2):

13 CIC-DUX4 Sarcoma Sarcoma with CIC-DUX4 gene fusion is a new group of undifferentiated soft tissue sarcoma recently described. The tumors have a membranous expression of CD99 These tumors more likely affect young adults with median age at diagnosis of 30 years. They have high rate of metastatic extension with lungs representing the most common location. They have been reported preferentially in soft tissue Renal location is rare Smith SC, Mod Pathol 2015 Jan;28(1):57-68.

14 CIC-DUX4 sarcoma of the kidney 1 9-year-old boy right kidney tumor Radical nephrectomy demonstrated a 10 cm tumor that invaded perirenal fat. Mangray S. Am J Surg Pathol Sep;40(9):

15 CIC-DUX4 sarcoma of the kidney 1 CD99 FISH analysis: CIC gene rearrangement was identified in 97% of the cells Genomic analysis: identified a variant of a CIC-DUX4 fusion Mangray S. Am J Surg Pathol Sep;40(9):

16 CIC-DUX4 sarcoma of the kidney 2 The case of a 29 year-old male patient with a primary CIC-DUX4 sarcoma of the kidney with lung metastasis. The patient developed an early local retroperitoneal recurrence associated with lung and liver metastases. The outcome of the disease was rapidly unfavorable. Bergerat S, Pathol Res Pract Feb;213(2):

17 Conclusion Primary renal CIC-DUX4 sarcoma is a new entity Its diagnosis is based on: The atypical morphology The membranous positivity of CD99 The search for the specific mutation (PCR, FISH)

18 Acknowledgement Allirot Camille 1, Bidaut Anne-Sophie 2, Perret Cécile 1, Bobillier-Chaumont Severine 1, Pierron Gaelle 3, Delattre Olivier 3, Saada-Sebag Geraldine 2, Anne mc Leer 2, Nika Eleni 2, Piolat Christian 4, Durand Chantal 5, Plantaz Dominique 1, 1. Département d oncologie pédiatrique, CHU de Grenoble, 2. Département de pathologie CHU de Grenoble, 3. INSERM U830, Laboratoire de génétique et biologie des cancers, Institut Curie, Paris, France 4. Département de chirurgie, CHU de Grenoble, 5. Département de Radiologie, CHU de Grenoble,

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