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01 August 2004

Other malignant neoplasms in patients with Gastrointestinal Stromal Tumors (GIST)

Włodzimierz Ruka, Piotr Rutkowski, Zbigniew I. Nowecki, Anna Nasierowska-Guttmejer, Maria Dębiec-Rychter

Med Sci Monit 2004; 10(8): LE13-14 :: ID: 11743

Abstract

Dear Editor,
Gastrointestinal stromal tumors (GIST) compose a recently defined pathological entity, which due to molecular identification of characteristic mutation in c-KIT membrane receptor gene (detected by CD117 immunostaining) and introduction of first effective molecular targeted anticancer agent – imatinib mesilate – tyrosine kinase inhibitor (e.g. c-KIT) has focused attention of oncologists over the world [1,2]. The results of new epidemiological studies suggest that GIST is the most common abdominal mesenchymal tumor with the frequency of 16–20 cases/1 million/year. However, the clinico-pathological features of GIST are not well described. There are some data regarding the associations between GIST and other malignant tumors. The single cases of coexistence of GIST and the renal cancer, cancer of the gall bladder, gastric cancer and lymphoma of the stomach were described [3]. GIST may also occur as a part of other tumors syndromes. The description of so called Carney’s triad includes the presence in one patient during his life: gastric GIST, paraganglioma and pulmonary chondromas [4]. GIST may also occur in association with neurofibromatosis type 1. The presence of other malignant neoplasms in the past history of GIST patients may be important issue. We analyzed the incidence of other malignant neoplasms in large group of patients with GIST. We performed a single-institution retrospective analysis of 180 consecutive patients (92 men and 88 women, median age 57 years; range: 19–82 yrs) with GIST treated between September 1999 and October 2003. All pathologic diagnoses were confirmed by positive immunostaining for CD117. During clinical examination all patients were interviewed for past history of other malignancies. Among the 180 GIST patients we found 18 patients with a history of other malignant neoplasms (10.0%). Two GIST patients suffered from more than one other malignancy. Most of these 18 GIST patients had gastric localization (72%), median age was 60 years, there were 8 men and 10 women; 5 cases were inoperable/metastatic (and treated with imatinib – 4 of them responded). Two women had a history of breast cancer (moreover one of them also suffered from chronic lymphocytic leukemia), 2 female patients were successfully treated for renal cell carcinoma, 2 men – for planoepithelial lung cancer and other 2 women – for invasive cancer of the uterine cervix. We also observed: 2 cases of gastric cancer, 2 cases of colon cancer, 1 case of gastric carcinoid, 1 case of the endometrial adenocarcinoma, 1 case of the uterine sarcoma and 1 case of seminoma (third neoplasm – primary spindle-cell bone sarcoma was diagnosed in this patient during imatinib treatment due to GIST liver metastases). In 2 patients treated primarily for GIST of the stomach multiple pulmonary chondromas were diagnosed (Carney’s triad). In 4 patients also benign soft tissue tumors (lipomas) were diagnosed. Six cases of non-GIST tumors occurred after diagnosis or simultaneously with GIST. The other metachronous tumors were resected and any patient relapsed. All of these non-GIST tumors were considered sporadic (no family history). Our data are supported by observation of Chacon et al. [5] on smaller cohort of GIST patients, who found also approximately 10% GIST patients with prior history of other solid cancers. A high ratio of other malignancies in GIST patients focused the attention of clinical oncologists on this problem and may imply a common genetic mechanism of their etiology. It is not possible to answer yet if it is the common genetic mechanism or random co-incidence in patients undergone special supervision during follow-up (however, most of these GIST tumors – 15/18 were in high potential of aggressiveness not like the cases found accidentally during the surgery from other indications). Moreover, the fact of this frequent coexistence does not deprive the patient of the possibility of the only effective treatment in unresectable/metastatic GIST – imatinib and it cannot be the exclusion criterion for treatment of recurrent GIST in case of other metachronous malignancy, which had been previously successfully treated.
REFERENCES:
1. DeMatteo RP: The GIST of targeted cancer therapy: a tumor(gastrointestinal stromal tumor), a mutated gene (c-kit), and a molecular
inhibitor (STI 571). Ann Surg Oncol, 2002; 9: 831–39
2. Miettinen M, Majidi M, Lasota J: Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur J Cancer, 2002; 38(Suppl.5): S39–S51
3. Antonini C, Forgiarini O, Chiara A et al: Stromal tumor of the ileum (GIST) at the same time as renal carcinoma. Description of the case and review of the literature. Pathologica, 1998; 90: 160–64
4. Carney JA: Gastric stromal sarcoma, pulmonary chondroma and extra-adrenal paragnaglioma (Carney triad): natural history, adrenocortical component and possible familial occurrence. Mayo Clin Proc, 1999; 74: 543–52
5. Chacon M, Roca E, Barugel M et al: Report of solid cancer in patients with gastrointestinal stromal tumours (GIST) Annual Meeing Proceedings American Society of Clinical Oncology, 2004; Abstract 9065,
page 830

Keywords: Piperazines - pharmacology, Antineoplastic Agents - pharmacology, Benzamides, Gastrointestinal Neoplasms - etiology, Neoplasms - etiology, Piperazines - pharmacology, Proto-Oncogene Proteins c-kit - immunology, Pyrimidines - pharmacology

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