Article

Gastrointestinal Stromal Tumors in Children and Young Adults: A Clinicopathologic, Molecular, and Genomic Study of 15 Cases and Review of the Literature

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Journal of Pediatric Hematology/Oncology (Impact Factor: 0.9). 04/2005; 27(4):179-87. DOI: 10.1097/01.mph.0000157790.81329.47
Source: PubMed

ABSTRACT

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the intestinal tract that typically occur in adults over the age of 40 years. GISTs in younger patients are rare and not well characterized. The objective was to define the characteristics of GISTs in children and young adults (<30 years old). Clinicopathologic and molecular features, including KIT/PDGFRA genotype, in GISTs from 5 children and 10 young adults were analyzed. Gene expression analysis was performed on 5 gastric tumor samples from 2 children, 2 gastric tumors from young adults, and 10 gastric GISTs from older adults using an U133A Affymetrix platform (22,000 genes). All five pediatric GISTs occurred in girls, involved the stomach as multiple nodules, showed predominantly an epithelioid morphology, often involved lymph nodes, and lacked KIT or PDGFRA mutations. Although all five patients developed recurrence (four in the liver, three in the peritoneum, and two in both sites), four are still alive with disease. Of the 10 GISTs in young adults, half occurred in the small bowel and had spindle cell morphology, and one case had lymph node metastasis. KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. Seven patients developed recurrence, and at last follow-up two patients had died of disease. Gene expression analysis showed high expression of PHKA1, FZD2, NLGN4, IGF1R, and ANK3 in the pediatric and young adult versus older adult cases. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors. The distinct gene expression profile suggests avenues for investigation of pathogenesis and potential therapeutic strategies.

Download full-text

Full-text

Available from: Leonard H Wexler, Aug 21, 2014
  • Source
    • "It has been reported that adolescent and young adult (AYA) patients with malignant diseases have different molecular, epidemiological, and therapeutic outcomes in comparison with older patients14151617. In some neoplasms , such as breast cancer, soft tissue sarcoma, and colorectal cancer, AYA patients have inferior prognosis as compared to older patients181920. On the other hand, in acute lymphoblastic leukemia, the prognosis of AYA patients is inferior to that of children[21]. However, there Abstract Tyrosine kinase inhibitor (TKI) treatment has dramatically improved the outcome of chronic myelogenous leukemia in the chronic phase (CML-CP). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Tyrosine kinase inhibitor (TKI) treatment has dramatically improved the outcome of chronic myelogenous leukemia in the chronic phase (CML-CP). However, one study has reported a less favorable treatment outcome with TKIs in adolescents and young adults (AYA) when compared with older patients. In the present study, we retrospectively reviewed the response to TKIs in a Japanese population of 133 CML-CP patients divided into an AYA group (n = 19) and an older group (n = 114). At diagnosis, AYA patients presented with higher white blood cell counts and lower percentage of basophils, and with lower Hasford scores, but no difference was observed in EUTOS score. Probability of achieving complete cytogenetic response was not statistically different between the groups. However, the probabilities of achieving major and complete molecular responses were significantly lower in the AYA group compared to the older group (61 vs 87 % and 17 vs. 33 % at 24 months, respectively; P < 0.05). In addition, a 7-year event-free survival was significantly lower in the AYA compared to the older adults (58 vs. 80 %, P < 0.05). These results suggest that AYA Japanese patients with CML-CP tend to have an unfavorable outcome on treatment with TKI.
    Preview · Article · Jul 2015 · International journal of hematology
  • Source
    • "KIT mutations were identified in seven cases, four in exon 11 and three in exon 9. GISTs that occur in children are a separate clinicopathologic and molecular subset with predilection for girls, multifocal gastric tumors, and wild-type KIT/PDGFRA genotype. In contrast, GISTs in young adults are a more heterogeneous group, including cases that resemble either the pediatric or the older adult-type tumors [31]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Objective Gastrointestinal stromal tumor (GIST) is the most common sarcoma of the gastrointestinal tract. We report a case of gastrointestinal stromal tumor in a small intestine, initially suspected for leiomyosarcoma given that gastrointestinal stromal tumors in young patients are limited due to their rarity. Method A 30-year-old Caucasian ethnic Albanian female from Kosovo presented with abdominal pain, nausea and vomiting. Subsequently, the tumor was detected in the small intestine, as an infiltrating mass approximately 10 cm in diameter. The tumor has been resected en bloc and the duodenojejunal terminal-terminal anastomosis has been performed. Results The tumor was large, intramural mass, with fish-flesh to tan-brown appearance, as well as with foci of hemorrhage and necrosis. Histologically, the tumor showed transmural growth, deep infiltrative pattern and malignant feature, with dense cellularity, plump spindle cells, within variably hyalinized and edematous stroma. In addition, tumor was composed of frequent areas with epitheloid morphology. The immunohistochemistry results showed high expression of c-KIT (CD117), CD34 and Vimentin, whereas α-smooth muscle actin was focally positive. Desmin and S100 protein were negative. Conclusion Given, that GIST in young adults represents a more heterogeneous group, there should be made more efforts in investigating its pathogenesis and potential more specific treatment.
    Full-text · Conference Paper · Aug 2014
  • Source
    • "The natural history of these tumors nevertheless appears to be more indolent than adult GISTs, as patients can survive for many years with metastatic disease (Miettinen et al., 2005a). Interestingly, many of the characteristics of GISTs in the pediatric population (e.g., female predilection, predominance of gastric, multi-focal tumors of epithelioid morphology ) are not as clearly defined in the more heterogeneous group of young adult (i.e., 21–30 years) GIST patients (Miettinen et al., 2005a; Prakash et al., 2005; Agaram et al., 2008a; Rink and Godwin, 2009), suggesting that some but not all of the patients in this age group may more properly be considered with the pediatric group. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastrointestinal stromal tumors (GISTs) in adults are generally driven by somatic gain-of-function mutations in KIT or PDGFRA, and biological therapies targeted to these receptor tyrosine kinases comprise part of the treatment regimen for metastatic and inoperable GISTs. A minority (10-15%) of GISTs in adults, along with ∼85% of pediatric GISTs, lacks oncogenic mutations in KIT and PDGFRA. Not surprisingly these wild type (WT) GISTs respond poorly to kinase inhibitor therapy. A subset of WT GISTs shares a set of distinguishing clinical and pathological features, and a flurry of recent reports has convincingly demonstrated shared molecular characteristics. These GISTs have a distinct transcriptional profile including over-expression of the insulin-like growth factor-1 receptor, and exhibit deficiency in the succinate dehydrogenase (SDH) enzyme complex. The latter is often but not always linked to bi-allelic inactivation of SDH subunit genes, particularly SDHA. This review will summarize the molecular, pathological, and clinical connections that link this group of SDH-deficient neoplasms, and offer a view toward understanding the underlying biology of the disease and the therapeutic challenges implicit to this biology.
    Full-text · Article · May 2013 · Frontiers in Oncology
Show more