Letter to the Editor
Gastrointestinal stromal tumors associated with other primary neoplasms
Tumores de la estroma gastrointestinal asociados a otras neoplasias primarias
Elena Romera Barba
, Juan Castañer Ramón-Llín, Francisco Javier Espinosa López, José Luis Vazquez Rojas
Corresponding author
Servicio de Cirugía General, Hospital Universitario Santa Lucía, Cartagena, Murcia, Spain
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(B) CT scan: cecum stenosing lesion with regional lymph nodes. (C) Gastroscopy: 3<span class="elsevierStyleHsp" style=""></span>cm submucosal lesion in the gastric body. (D) CT scan: 3<span class="elsevierStyleHsp" style=""></span>cm submucosal lesion on the posterior face of the gastric body.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">The <span class="elsevierStyleItalic">gastrointestinal stroma tumors</span> (GIST) are the most common neoplasms of the gastrointestinal tract with a mesenchymal origin, although they represent only 2% of all malignant neoplasms of the gastrointestinal tract.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> They originate from interstitial cells of Cajal, and although they can be located at any level, more than 60% appear at gastric level. They have a characteristic immunohistochemical profile, positive for CD117 (c-kit, tyrosine kinase receptor), CD34 and vimentin. 80% of cases have mutations in <span class="elsevierStyleItalic">c-kit</span>, a gene encoding a protein receptor from the tyrosine kinases (KIT) family, which activates it and results in tumor development.</p><p id="par0010" class="elsevierStylePara elsevierViewall">GIST association with other primary malignancies has rarely been described in medical literature, although it appears in up to 20% of cases.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1–4</span></a> We present three cases treated in our site.</p><p id="par0015" class="elsevierStylePara elsevierViewall">The first case is a 75-year-old woman who was diagnosed, through a study of anaemia, of right sided colon neoplasia (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A). The extension assessment CT (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B and D) showed a 3<span class="elsevierStyleHsp" style=""></span>cm submucosal tumor on the posterior face of the gastric body, indicative of GIST, diagnosis which was confirmed after performing a gastroscopy (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>C). A formal right hemicolectomy and an atypical gastric resection were performed by laparotomy. The anatomical pathology reported a low grade conventional invasive adenocarcinoma pT3N0(0/15) M0 and GIST 3<span class="elsevierStyleHsp" style=""></span>cm with 2 mitosis/50<span class="elsevierStyleHsp" style=""></span>hpf and free resection margins. The patient was referred to Oncology, deciding not to give any adjuvant treatment.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The second case, a 69-year-old man who was attended due to rectal bleeding. A colonoscopy was performed, finding sigma neoplasm. The extension assessment CT showed a 1.3<span class="elsevierStyleHsp" style=""></span>cm submucosal tumor in the front of the gastric body, indicative of GIST, diagnosis which was confirmed after performing a gastroscopy. A sigmoidectomy and atypical gastric resection plus resection of Meckel's diverticulum, found incidentally were performed by laparotomy. The anatomical pathology reported an infiltrating conventional colon adenocarcinoma pT3N0(0/18) M0, 1.3<span class="elsevierStyleHsp" style=""></span>cm GIST with 3 mitosis/50<span class="elsevierStyleHsp" style=""></span>hpf and well-differentiated neuroendocrine carcinoma in Meckel's diverticulum. The patient was referred to Oncology, deciding not to give any adjuvant treatment.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The third case was a 59-year-old woman diagnosed after an episode of upper gastrointestinal bleeding, of a 4.5<span class="elsevierStyleHsp" style=""></span>cm gastric body GIST. An atypical resection of the tumor was performed in June 2011. The anatomical pathology confirmed the diagnosis. A control CT at 9 months detected an 8<span class="elsevierStyleHsp" style=""></span>mm lesion in the left upper lobe. After performing a CT-guided core needle biopsy (CNB), which proved negative, the patient was referred to Thoracic Surgery. An upper lobectomy was performed in July 2012. The anatomical pathology reported an 8<span class="elsevierStyleHsp" style=""></span>mm bronchioloalveolar carcinoma. In the control CT scan at 3 months, a lesion was observed in the left breast. In November 2012, a superolateral quadrantectomy<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>left axillary lymphadenectomy were performed after completing the study with a mammography and CNB. The anatomical pathology reported a pT1cN1a infiltrating ductal carcinoma (2/15) M0. Later, she started adjuvant treatment with chemotherapy, radiation and hormone therapy.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Most GISTs occur sporadically, although familial cases are due to inheritable mutations in <span class="elsevierStyleItalic">KIT</span> or <span class="elsevierStyleItalic">PDGFRA</span> genes. Furthermore, there are syndromes with predisposition to develop GIST and other tumor types, as type I neurofibromatosis (tumors of the nerve sheath), Carney triad (pulmonary paraganglioma and chondroma) and Carney-Stratakis syndrome (paraganglioma).<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Several studies have shown that 14–20% of GIST patients develop other cancers, either synchronously or metachronously.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,5</span></a> Most cases involve silent gastric GIST diagnosed during surgery or preoperative assessment of another neoplasia.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">2,4,6,7</span></a> The most frequent association is gastric adenocarcinoma (47%), prostate (9%), leukaemia/lymphoma (7%), breast carcinoma (7%), renal (6%), lung (5%), gynaecological tumors (5%) and carcinoid tumor (3%).<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,6,8</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">It is unclear whether this is a coincidence or whether there is a causal relationship. The clinical application of Imatinib in the treatment of GIST has significantly changed its prognosis, increasing patient survival. As a result, they have more time to develop secondary neoplasms.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">1</span></a> Furthermore, the presence of silent gastric GIST is more common after a certain age, which is consistent with the development of other neoplasms.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Furthermore, it is possible that the existence of genetic instability or alteration in DNA repair mechanisms may result in a <span class="elsevierStyleItalic">KIT</span> mutation, resulting in GIST, but also in other oncogenes, favouring the emergence of other neoplasms.<a class="elsevierStyleCrossRefs" href="#bib0055"><span class="elsevierStyleSup">1,4</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, the association of GIST and other primary neoplasms are more common than what had been previously considered, but there are still no data to support a causal association. More studies to clarify the genetic and molecular mechanisms of carcinogenesis and the association between GIST and other synchronous or metachronous tumors are needed.<a class="elsevierStyleCrossRefs" href="#bib0095"><span class="elsevierStyleSup">9,10</span></a> In any case, this potential association should be considered in the approach of patients with gastrointestinal GIST regarding disease staging, surgery and, primarily, during follow up.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Romera Barba E, Castañer Ramón-Llín J, Espinosa López FJ, Vazquez Rojas JL. Tumores de la estroma gastrointestinal asociados a otras neoplasias primarias. Med Clin (Barc). 2015;145:370–371.</p>" ] ] "multimedia" => array:1 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1223 "Ancho" => 1398 "Tamanyo" => 229526 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Colonoscopy: caecal pole tumor. (B) CT scan: cecum stenosing lesion with regional lymph nodes. (C) Gastroscopy: 3<span class="elsevierStyleHsp" style=""></span>cm submucosal lesion in the gastric body. (D) CT scan: 3<span class="elsevierStyleHsp" style=""></span>cm submucosal lesion on the posterior face of the gastric body.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0055" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Survival of patients with multiple primary malignancies: a study of 783 patients with gastrointestinal stromal tumor" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R.K. Pandurengan" 1 => "A.G. Dumont" 2 => "D.M. Araujo" 3 => "J.A. Ludwig" 4 => "V. Ravi" 5 => "S. 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