sirolimus and Intestinal-Obstruction

Perivascular epithelioid cell tumors (PEComas) include different morphological entities originating from perivascular epithelioid cells. Their clinical behavior is not predictable, and there are no strict histologic criteria for malignancy, although larger tumors with infiltrative growth, hypercellularity, cellular atypia, atypical mitoses, and necrosis generally have a malignant course. Pediatric PEComas are rare, with less than 40 cases reported, mostly in children older than 5 years. We describe a case of malignant PEComa of the ligamentum teres in a 2-year-old girl, characterized by the occurrence of local relapse after primary treatment with chemotherapy and surgery and poor response to imatinib mesilate and temsirolimus used after further analyses confirmed p70S6K expression involved in the mTOR pathway. The girl was eventually treated with a debulking surgical procedure and is now alive with disease 6 years after diagnosis. Literature data of children affected by PEComas were also analyzed, trying to identify pathologic characteristics that could predict their course and therapeutic options. Histologically, they may be differentiated in 3 prognostic categories: (1) benign, lacking unfavorable morphological markers; (2) with uncertain malignant potential, carrying 1 unfavorable marker; and (3) malignant, with at least 2 unfavorable markers. In the literature, 9% of cases occurred as a second malignancy probably because of genomic instability related to treatment. Their different biology and the potential value of targeted therapies remain to be explored. The indolent evolution in our patient was similar to that reported in some other cases in the literature. In terms of treatment, the present case suggests a minor response to temsirolimus compared with the adult population.

Topics: Abdominal Neoplasms; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Benzamides; Biopsy; Child, Preschool; Combined Modality Therapy; Diagnostic Errors; Etoposide; Female; Humans; Imatinib Mesylate; Intestinal Obstruction; Ligaments; Liver Neoplasms; Neoplasm Recurrence, Local; Peritoneal Neoplasms; Perivascular Epithelioid Cell Neoplasms; Piperazines; Protein Kinase Inhibitors; Pyrimidines; Radiography; Sarcoma, Clear Cell; Sirolimus; X Chromosome Inactivation

Encapsulating peritoneal sclerosis is a serious complication of peritoneal dialysis and can occur even after transplant. The gut is partially or totally enveloped by a thick fibrous membrane that leads to the formation of multiple sections containing intestinal loops contracted and reduced in volume. Exacerbation after renal transplantation is a very rare but sometimes dramatic condition. We report a patient who developed intestinal obstruction due to encapsulating peritoneal sclerosis 1 year after a deceased-donor kidney transplant. Treatment included laparotomy, small-bowel lengthening by release of adhesions, and high doses of corticosteroids. The patient received immunosuppressive therapy with a combination of low-dose cyclosporine, everolimus, and prednisone, unchanged except for a temporary steroid increase in the postoperative period. We report success with this combined surgical plus medical therapy, with no recurrence after 81 months of follow-up.

Topics: Adult; Calcineurin Inhibitors; Cyclosporine; Drug Therapy, Combination; Everolimus; Female; Glucocorticoids; Humans; Immunosuppressive Agents; Intestinal Obstruction; Kidney Transplantation; Peritoneal Dialysis; Peritoneal Fibrosis; Prednisone; Sirolimus