Case presentation

1. Case presentation • 13y/o M who developed weight loss, increased LFTs and hyperbilirubinemia

2. Case presentation (cont.) • On liver US: hepatic mass replacing most of left hepatic lobe and involving the periphery of the right hepatic lobe.

3. Dermoplastic small round cell tumor (DSRCT) Karen Estrella H. PGY-2 September 2010

4. Objectives: • Introduction • Characteristics of the disease • Differential diagnosis • Clinical findings • Diagnosis • Treatment • Prognosis

5. Introduction • Soft tissue sarcomas represent 10% of all children cancers. • DSRCT: very rare type of sarcoma • 1st described in 1989 in MSKCC • male:female ratio = 5:1 • Mean age of appearance: 21y/o • Associated with aggressive features and a poor prognosis.

6. Introduction (cont.) • Tumor cells co-express epithelial, mesenchymal and neuronal markers and are thought to originate from a mesothelial or submesothelial progenitor cell with the potential to undergo multilineage differentiation. • Also called "mesothelioblastoma". • Frequently rises from the peritoneum, but also seen in other surfaces: pleura, ovaries, tunica vaginalis, liver, CNS.

7. Differential diagnosis • Ewing sarcoma • Rhabdomyosarcoma • Neuroblastoma • Synovial sarcoma • Lymphoma • Ectomesenchymoma • Wilms’ tumor • Carcinoid tumor • Neuroendocrine carcinomas • Merkel cell carcinoma • Small cell mesothelioma in adults

8. Clinical findings • Regional • Usually: abdominal mass with peritoneal and omental implants • Crampy abdominal pain, constipation, weight loss • Abdominal distention, jaundice, ascitis • Other reported sites of disease include pleura, ethmoid sinuses, scalp, hand, posterior cranial fossa, pancreas, ovary, paratesticular and kidney. • Liver metastases are common at diagnosis and relapse; other distant sites include lymph nodes, lung, bone and bone marrow.

9. Diagnosis CT SCAN

10. Diagnosis PET SCAN

11. Histology • MACRO: • Solid, firm, multilobulated gray-white masses where cystic areas can also be found. • MICRO: • small cells that can be round, ovoid or spindled usually grouped in clumps, cords, nests or sheets. • Immunohistochemical markers : • Epithelial: cytokeratin • Mesenchymal: desmin, vimentin. • Neural: neuron-specific enolase, synaptophysin. • CD99, a marker associated with the Ewing’s sarcoma family positive in 23% of cases .

12. Histology (cont.) • The most specific diagnostic tool is the presence of translocation between EWS and WT-1 gene: • t(11;22)(p13;q12) • detected by RT-PCR and FISH • it encodes a binding protein, thought to have roles in both transcription and splicing • Related with oncogenenic factors such as: • IGF-1 receptor, PDGFα, PAX2-2, WT-1, ENT4, TALLA-1 and IL-2/15Rβ • CCN2 (connective tissue growth factor): associated with dissemination

13. Treatment • Options include debulking surgery, chemotherapy w/ or w/o stem cell transplantation, radiotherapy, and recently introduced molecularly targeted therapies. • Resection of > 90% of tumor + removal of parietal and visceral peritoneum, omentectomy, splenectomy and even removal of diaphragm.

14. Treatment (cont.) *No standard therapeutic regimen described since no modality is clearly superior to any other.

15. Treatment (cont.) • Chemotherapy (P6 chromosomes): Alkylating sensitive. • Cyclophosphamide, doxorubicin, vincristine, ifosfamide, etoposide, for 7cycles. • On cycle 4: CT scans for evaluation, consider adding: • cisplatin, carboplatin, topotecan, temozolamide, vinorelbine and irinotecan. • Invariably relapse: theory of “cancer stem cells”

16. Vincristine Vinorelbine Cyclophosphamide Doxorubicin Ifosfamide Etoposide Topotecan Irinotecan Temozolamide

17. Treatment (cont.) • Molecular targeted therapies: • Leflunomide (SU101) is a platelet-derived growth factor (PDGF) receptor inhibitor that acts by blocking PDGF-stimulated receptor autophosphorylation and subsequent cell-cycle progression. • Sunitinib is a multikinase inhibitor that targets VEGFR 1, 2 and 3, PDGFR- α, PDGFR -ß, KIT, FLT-3, RET and CSF-1. • ENT4, a direct transcriptional target of EWS/WT1

18. Prognosis • Sx+RT+P6 chemotherapy: had a 3-year survival of 55% (29/66), compared to 27% in those patients who did not receive all three therapies.

19. Case presentation (cont.) • Diagnosis was done: 2 yrs ago, • 09/08: laparoscopic bx, BMA • Infiltration to the mesenterium in the portahepatis, peripancreatric tissue and a heterogeneous mass in LUQ. • Adenopathy in the aorto-caval space, left iliac chain, left hemipelvis, and a pelvic mass in cul de sac • Infiltration of mesenterium in RLQ and superior to bladder. • Placement of percutaneousbiliary drains • Cycle 1

20. Case presentation (cont.) • 10/08: cycle 2, later bacteremia with E. faecium • 11-12/08: cycle 3-4 • 01/09: exploratory laparotomy with removal of DSRCT, distal pancreatectomy, splenectomy, resection of large rectal mass with coloproctosotomy, appendectomy and ileostomy • 02/09: abdominal abscess, which required sacral and left flank drains • Cycle 5 • Increased output from sacral drain: vesicorrectal fistula • Placement of suprapubic catheter, and G-tube • 03/09: cycle 6 • 04/09:cycle 7

21. Case presentation (cont.) • 11/09: disease progression • 12/09: septisemia due to K. pneumonia ESBL • 07/10: worsening coagulopathy and jaundice, replacement of biliary drains, restart of chemotherapy • 08/10: fungemia

22. References • http://seer.cancer.gov/publications/childhood/softtissue.pdf • http://sarcomahelp.org/dsrct.html • http://www.cancerindex.org/clinks2d.htm#2208 • http://www.dsrct.org/ • http://www.ncbi.nlm.nih.gov/pubmed/15868593 • http://www.wjgnet.com/1007-9327/15/4212.pdf • http://www.drugdevelopment-technology.com/projects/erbitux/images/2s_Cancer_Cell_Cycle.gif