Mast Cell Sarcoma: An Aggressive and Potentially Under-Diagnosed Neoplasm That May Be Responsive to Targeted Therapy
Russell JH Ryan, Cem Akin, Mariana Castells, Martin K Selig, G Petur Nielsen, Judith A Ferry, Jason L Hornick. Massachusetts General Hospital, Boston, MA; Brigham and Women's Hospital, Boston, MA
Background: Mast cell sarcoma (MCS) is a rare, aggressive neoplasm composed of cytologically malignant mast cells presenting as a solitary mass. Previous descriptions of MCS are limited to 7 separate case reports, and the diagnostic features of this entity are not well known. Most mast cell neoplasms are dependent on signaling through the KIT kinase. The KIT D816V mutation detected in most cases of systemic mastocytosis (SM) confers resistance to imatinib. However, molecular testing of 4 previously reported cases of MCS did not detect the KIT D816V mutation.
Design: Three cases of MCS were retrieved from consultation files of 2 of the authors. Immunohistochemistry (IHC), electron microscopy, and KIT genotyping were performed according to clinically validated protocols.
Results: The patients with MCS included a 12 year-old female with a middle ear mass, a 19 year-old male with a lip mass and a remote history of infantile cutaneous mastocytosis, and a 77 year-old female with a mass of the right pelvic bone. All cases showed a characteristic morphology consisting of large epithelioid cells with distinct cell borders and bizarre multinucleated cells that do not closely resemble either normal mast cells or SM. All cases expressed mast cell tryptase and KIT by IHC. Electron microscopy performed on one case showed mast cell granules. Elevated serum tryptase levels were detected in all 3 patients. KIT sequencing was performed on 2 cases; one harbored an imatinib-sensitive KIT mutation (D419del), while no KIT mutation was detected in the other case. Both of these patients were treated with surgery and imatinib, among other therapies, and remained alive at 45 months (with disease) and 14 months (without evidence of disease). The elderly patient was treated with palliative radiation therapy, and died 4 months after diagnosis.
Conclusions: We report the first case series of MCS. None of the cases were correctly diagnosed as mast cell neoplasms on initial evaluation, suggesting that this entity may be under-recognized. The relatively favorable clinical course of the two imatinib-treated patients and the results of KIT sequencing in these and prior cases suggest that MCS may respond to KIT inhibitors.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 218, Wednesday Morning