[Show abstract][Hide abstract] ABSTRACT: To describe the first reported case of a patient with multiple endocrine neoplasia type 2A and a gastrointestinal stromal tumor, as well as the second reported case of metastatic medullary thyroid cancer to the ovary.
We present the clinical, imaging, surgical, and pathologic findings of the study patient and review the relevant literature.
A 57-year-old woman with a clinical diagnosis of multiple endocrine neoplasia type 2A presented with a new mass in the right lower quadrant. Surgical exploration identified a 5-cm pedunculated small-bowel mass approximately 25 cm from the ileocecal junction, as well as bilaterally firm ovaries. Bilateral oophorectomy revealed medullary thyroid cancer in both ovaries and fallopian tubes. Pathology of the resected mass revealed a gastrointestinal stromal tumor of uncertain malignant potential, mitotic rate of 1/50 per high-power field, with positive staining for c-kit and smooth muscle actin and negative staining for CD34 and S-100.
This case is the first description of a gastrointestinal stromal tumor in a patient with multiple endocrine neoplasia type 2A, potentially representing a new paraganglioma/gastrointestinal stromal tumor syndrome. This case also highlights the possibility of the ovary as a metastatic site for medullary thyroid cancer.
Endocrine Practice 11/2008; 14(7):898-901. DOI:10.4158/EP.14.7.898 · 2.81 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The interstitial cells of Cajal (ICC) form a complex cell network within the gastrointestinal tract wall where they function as a pacemaker system. Expression of the kit proto-oncogene is essential for the development of this system. The aim of our study was to examine the hypothesis that gastrointestinal stromal tumors differentiate toward cells with an ICC phenotype. Ultrastructurally, 58 stromal tumors were characterized and found to share many features with ICC. Seventy-eight stromal tumors were immunophenotyped, particularly with regard to the kit receptor. All 78 tumors revealed strong, homogeneous immunoreactivity for the kit receptor as did ICC of adjacent and control gastrointestinal walls. Focal hyperplasia and hypertrophy of kit receptor positive cells were also observed in the gastrointestinal wall adjacent to the tumors. CD34 immunoreactivity observed in interstitial cells surrounding Auerbach's ganglia suggests that a subpopulation of ICC is CD34 positive and may explain why 56 of 78 stromal tumors were CD34 positive. Thirty control tumors, including gastrointestinal leiomyomas and leiomyosarcomas, were all negative for the kit receptor. We conclude that gastrointestinal stromal tumors show striking morphological and immunophenotypic similarities with ICC and that they may originate from stem cells that differentiate toward a pacemaker cell phenotype. We propose that the noncommittal name "gastrointestinal stromal tumor" be replaced by gastrointestinal pacemaker cell tumor.
American Journal Of Pathology 06/1998; 152(5):1259-69. · 4.59 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract and arises from the interstitial cells of Cajal. It is characterized by expression of the receptor tyrosine kinase CD117 (KIT). In 70-80% of GIST cases, oncogenic mutations in KIT are present, leading to constitutive activation of the receptor, which drives the proliferation of these tumors. Treatment of GIST with imatinib, a small-molecule tyrosine kinase inhibitor, inhibits KIT-mediated signaling and initially results in disease control in 70-85% of patients with KIT-positive GIST. However, the vast majority of patients eventually develop resistance to imatinib treatment, leading to disease progression and posing a significant challenge in the clinical management of these tumors. Here, we show that an anti-KIT monoclonal antibody (mAb), SR1, is able to slow the growth of three human GIST cell lines in vitro. Importantly, these reductions in cell growth were equivalent between imatinib-resistant and imatinib-sensitive GIST cell lines. Treatment of GIST cell lines with SR1 reduces cell-surface KIT expression, suggesting that mAb-induced KIT down-regulation may be a mechanism by which SR1 inhibits GIST growth. Furthermore, we also show that SR1 treatment enhances phagocytosis of GIST cells by macrophages, indicating that treatment with SR1 may enhance immune cell-mediated tumor clearance. Finally, using two xenotransplantation models of imatinib-sensitive and imatinib-resistant GIST, we demonstrate that SR1 is able to strongly inhibit tumor growth in vivo. These results suggest that treatment with mAbs targeting KIT may represent an alternative, or complementary, approach for treating GIST.
Proceedings of the National Academy of Sciences 02/2013; 110(9). DOI:10.1073/pnas.1222893110 · 9.67 Impact Factor
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