Respiratory symptoms in a boy revealing carney triad

6. Jenkin RD, Boesel C, Ertel I, et al. Brain-stem tumors in childhood: tory function and radiosensitivity. Int J Radiat Oncol Biol Phys A prospective randomized trial of irradiation with and without adjuvant CCNU, VCR, and prednisone. A report of the Childrens 14. Grau C, Horsman MR, Overgaard J. Improving the radiation response Cancer Study Group. J Neurosurg 1987;66:227–233.
in a C3H mouse mammary carcinoma by normobaric oxygen or 7. Kretschmar CS, Tarbell NJ, Barnes PD, et al. Pre-irradiation carbogen breathing. Int J Radiat Oncol Biol Phys 1992; 22:415– chemotherapy and hyperfractionated radiation therapy 66 Gy for children with brain stem tumors. A phase II study of the 15. Suit HD, Marshall N, Woerner D. Oxygen, oxygen plus carbon Pediatric Oncology Group, Protocol 8833. Cancer 1993;72:1404– dioxide, and radiation therapy of a mouse mammary carcinoma.
8. Freeman CR, Perilongo G. Chemotherapy for brain stem gliomas.
16. Fatigante L, Ducci F, Cartei F, et al. Carbogen and nicotinamide combined with unconventional radiotherapy in glioblastoma 9. Allen J, Siffert J, Donahue B, et al. A phase I/II study of carboplatin multiforme: A new modality treatment. Int J Radiat Oncol Biol combined with hyperfractionated radiotherapy for brainstem gliomas. Cancer 1999;86:1064–1069.
17. van der Maazen RW, Thijssen HO, Kaanders JH, et al. Conven- 10. Moulder JE, Rockwell S. Hypoxic fractions of solid tumors: tional radiotherapy combined with carbogen breathing and Experimental techniques, methods of analysis, and a survey of nicotinamide for malignant gliomas. Radiother Oncol 1995;35: existing data. Int J Radiat Oncol Biol Phys 1984;10:695–712.
11. Collingridge DR, Piepmeier JM, Rockwell S, et al. Polarographic 18. Pickles T, Graham P, Syndikus I, et al. Tolerance of nicotinamide measurements of oxygen tension in human glioma and surrounding and carbogen with radiation therapy for glioblastoma [see peritumoural brain tissue. Radiother Oncol 1999;53:127–131.
comments]. Radiother Oncol 1996;40:245–247.
12. Cruickshank GS, Rampling R. Peri-tumoural hypoxia in human 19. Del Rowe J, Scott C, Werner-Wasik M, et al. Single-arm, open- brain: Peroperative measurement of the tissue oxygen tension label phase II study of intravenously administered tirapazamine around malignant brain tumours. Acta Neurochir Suppl (Wien) and radiation therapy for glioblastoma multiforme. J Clin Oncol 13. Hill SA, Collingridge DR, Vojnovic B, et al. Tumour radio- 20. Aquino-Parsons C, Lim P, Green A, et al. Carbogen inhalation in sensitization by high-oxygen-content gases: Influence of the cervical cancer: Assessment of oxygenation change. Gynecol carbon dioxide content of the inspired gas on PO2, microcircula- Respiratory Symptoms in a Boy Revealing Carney Triad Luc¸an Delemarre, MD,1 Daniel Aronson, MD, PhD,2 Rick van Rijn, MD, PhD,3 Hans Bras, MD, PhD,4 MD, PhD,5 and Arnauld Verschuur, MD, PhD * The association of gastrointestinal stromal cell tumor (GIST), the case of a 14-year-old male with respiratory symptoms resulting in paraganglioma, and pulmonary chondroma is known as the Carney the diagnosis Carney triad. Pediatr Blood Cancer 2008;50:399– triad, occurring predominantly in young adult females. We present Key words: Carney triad; chrondroma; GIST; paranganglioma CRP, hepatic and renal function, uric acid, and LDH. Cystic fibrosiswas ruled out. CT guided biopsy of the lung lesions, measuring 2 cm Gastrointestinal stromal cell tumors (GISTs) are mesenchymal and 1.7 cm, was performed. Histological analysis showed normal gastrointestinal tumors occurring predominantly in the middle-aged lung tissue. CT abdomen revealed an inhomogeneity of the left liver [1]. GISTs are rare in children, however, the exact incidence is lobe and a lesion in the stomach, with an extension in the peritoneal unknown [2]. In 1977, Carney [3] reported the triad of GIST,paraganglioma, and pulmonary chondroma, arising predominantly in young females. Paraganglioma are tumors derived from neural 1Department of Pediatric Oncology, Emma Children’s Hospital, crest cells located in the neck, mediastinum, and abdomen and may secrete catecholamines. We describe a 14-year-old male patient Netherlands; 2Department of Pediatric Surgery, Emma Children’s with respiratory symptoms, revealing a Carney triad.
Hospital, Academic Medical Center Amsterdam, Amsterdam, TheNetherlands; 3Department of Radiology, Academic Medical Center Amsterdam, Amsterdam The Netherlands; 4Department of Pathology,Academic Medical Center Amsterdam, Amsterdam The Netherlands;5 A 14-year-old male presented with progressive coughing and Department of Pediatric Pulmonology, Wilhelmina Children’s dyspnea. On physical examination, incidental wheezing was heard.
Hospital, University Medical Center Utrecht, The Netherlands Asthma treatment resulted in only little improvement. A chest X-ray *Correspondence to: Arnauld Verschuur, Academic Medical Center revealed two lesions in the left lower lobe. Despite antibiotic Amsterdam/Emma Children’s Hospital F8-243, Meibergdreef 9, 1105 treatment for possible infectious causes, the radiological abnormal- AZ, Amsterdam, The Netherlands. E-mail: [email protected] ities persisted. Extensive work up showed a normal blood count, Received 31 May 2006; Accepted 31 August 2006 Fig. 2. MRI after intravenous ferucarbotran shows a decreased signalintensity of normal hepatic tissue (L) due to the specific uptake of thiscontrast media in hepatocytes. A hyperintense hepatic metastasis is seen Fig. 1. Contrast enhanced abdominal CT. Two distinct nodular lesions in segment II of the liver (encircled). The spleen (Sp) shows no lesions.
(asterisks) are seen protruding from the stomach (S). The liver (L),spleen (Sp), kidneys (K), and pancreas (P) show no lesions.
cavity (Fig. 1). Ultrasound showed an inhomogeneous lesion GISTs arise from the mucosa muscularis of the bowel wall. In between the left liver lobe and the stomach, of approximately pediatric GIST, epitheloid or mixed epitheloid and spindle 5 Â 2 cm, and the presence of a lymph node between the liver and the morphology seem to be more frequent than in adults [5,6].
pancreas. Laparoscopic biopsy resulted in the diagnosis GIST, Immunohistochemical staining is positive for KIT (CD117) in staining positive for CD117 and CD34. No Kit mutations were approximately 95% of GISTs, and for CD34 in approximately found in exon 9 and 11, nor PDGFRa exon 12 mutations. PET scanning showed uptake in the tumor region and was indicative for KIT is a transmembrane tyrosine kinase receptor for a growth regional lymph node metastasis and a lesion in the posterior factor called stem-cell factor (SCF). KIT function is critical to the mediastinum. Further work-up showed pathological midthoracic development of the interstitial cells of Cajal (ICC): stromal cells uptake of metaiodobenzyl guanidine (MIBG). Urine catecholamine which control gut motility [4,7]. Oncogenic activation of KIT plays levels were normal. Serum levels of alpha-fetoprotein and beta- an important role in the growth of GIST [7]. Several mutations of the HCG were low. Combining the CT scan, PET scan, and MIBG c-KIT gene, located on chromosome 4, have been described. Exon results, paraganglioma around the aortic arch were suspected.
11 mutations, occurring in 20%–92% of GIST may lead to a A partial resection of the stomach according to Billroth I was clinically more aggressive GIST. Mutations of exon 9, 13, or 17 are performed. A tumor with a maximum diameter of 6 cm with clear rare [4,7], especially in pediatric GISTs [5,8–10]. In KIT negative margins was removed and multiple metastases were seen on the liver GISTs platelet derived growth factor alpha (PDGFRa) may be surface. Biopsy of two lesions showed GIST. Two of the eight lymph activated or mutated. Chromosome gains and losses have also been nodes in the omentum minor were GIST metastases. MRI with ferucarbotran (Resovist1, Schering) confirmed the presence of the In a population of 200 adult GIST patients, the 5-year disease- liver lesions: 20 in total with a largest diameter of 0.6 cm (Fig. 2).
specific survival rate ranged from 35% for the entire population to The two lesions in the left lower lobe were resected, ensuing 54% after complete surgical resection [1]. Despite complete clinical improvement. Histological analysis confirmed the hypoth- surgical resection, recurrent GISTs developed in 40% of the esis of pulmonary chondromas as part of the Carney triad. On patients. The response of unresectable or recurrent GISTs to exploration of the mediastinum, the lesion earlier reported on MIBG chemotherapy or radiotherapy is poor [1]. Clinical outcome in and PET scan could not be found. Treatment was started with pediatric GIST patients was reported in small series. Pediatric imatinib mesylate (Glivec1, Novartis), 340 mg/m2/day, q.i.d. orally.
GISTs might be biologically and clinically different from adult Repeated liver MRI showed stable disease. Imatinib dose was raised GISTs [2,9–13]. Imatinib is a promising adjuvant therapy for GISTs to 440 mg/m2/day, with minor response and cystic alterations of the [14]. Imatinib inhibits KITand PDGFRa by interfering with the ATP liver metastasis (follow-up 12 months). A second dose increase to binding site of the receptor tyrosine kinase domain. Adult patients 570 mg/m2/day b.i.d. resulted in a good partial response.
with unresectable or metastatic GISTs show response rates of 40–54%. The 1-year survival rate of adult patients with advanced GIST has risen to approximately 90% [1]. Patients with exon 11 mutationsmight have a better response to imatinib. GISTs without demonstrable KIT mutations typically do not respond [4,7] Carney The clinical presentation of GISTs varies, from nonspecific signs and symptoms such as abdominal pain to gastrointestinal bleeding.
In a report of 79 cases with the Carney triad, 85% were female Most GISTs are localized in the stomach and small intestine [4–6].
patients with an average age of 20 years (ranging from 7 to 48 years); 22% of patients had all three tumors. Fifty-eight patients presented 5. Prakash S, Sarran L, Socci N, et al. Gastrointestinal stromal tumors with a GIST. Seventy-six percent of patients had pulmonary in children and young adults. J Pediatr Hematol Oncol 2005;27: chondroma, most being asymptomatic. The 47% of patients with paraganglioma presented with a mass or signs of catecholamine 6. Durham MM, Gow KW, Shehata BM, et al. Gastrointestinal excess [15]. Thirty-two of Carney triad patients had a local stromal tumors arising from the stomach: A report of three children.
recurrence of the GIST. In general, the chondromas exhibited slow 7. Duensing A, Heinrich MC, Fletcher M, et al. Biology of gastro- growth or became stable; pulmonary surgery was curative in 44% of intestinal stromal tumors: KIT mutations and beyond. Cancer patients. Most paraganglioma were resected. After a follow-up period ranging from 1 to 49 years (median: 20 years), a survival rate 8. Kerr J, Hicks MJ, Nuchtern JG, et al. Gastrointestinal auto- of 81% of the 79 patients was found.
nomic nerve tumors in the pediatric population. A report of four Only a few cases of the Carney triad in children have been cases and a review of literature. Cancer 1999;85:220–230.
described [15,16]. The cause of the Carney triad is unknown.
9. Li P, Wei J, West AB, et al. Epitheloid gastrointestinal stromal Molecular analysis of GIST in a female patient with the Carney triad tumor of the stomach with liver metastases in a 12-year-old girl: showed wild-type KIT and PDGFRa genes [17]. The occurrence of Aspiration cytology and molecular study. Pediatr Dev Pathol 2002; multiple tumors in young patients suggests an inherited condition [15,18]. In 2002, Carney et al. [19] described a new syndrome in 10. Terada R, Ito S, Akama F, et al. Clinical and histopathological features of colonic stromal tumor in a child. J Gastroenterol 2000; 12 patients with paraganglioma and gastric stromal sarcoma that was inherited in an autosomal dominant manner, with incomplete 11. Haider N, Kader M, Dermott M, et al. Gastric stromal tumors in penetrance. In summary, we described the uncommon case of a boy children. Pediatr Blood Cancer 2004;42:186–189.
with respiratory symptoms leading to the diagnosis of Carney Triad.
12. Hughes JA, Cook JV, Said A, et al. Gastrointestinal stromal tumor of the duodenum in a 7-year-old boy. Pediatr Radiol 2004;34:1024–1027.
13. Cypriano MS, Jenkins JJ, Pappo AS, et al. Pediatric gastrointestinal stromal tumors and leiomyosarcoma. Cancer 2004;101:39–50.
The authors thank Niek Hofstee, MD, (Department of Pediatrics, 14. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the Twenteborg Hospital Almelo, The Netherlands) for helping with the tyrosine kinase inhibitor ST1571 in a patient with a metastaticgastrointestinal stromal tumor. N Engl J Med 2001;344:1052– care of this patient; and Jean-Franc¸ois Emile, MD, PhD (Depart- ment of Pathology, University Hospital Ambroise Pare´, Boulogne, 15. Carney JA. Gastric stromal sarcoma, pulmonary chondroma, and France) for performing the DNA analysis.
extra-adrenal paraganglioma (Carney triad): Natural history,adrenocortical component, and possible familial occurrence. MayoClin Proc 1999;74:543–552.
16. Raafat F, Salman WD, Roberts K, et al. Carney’s triad: Gastric leiomyosarcoma, pulmonary chondroma and extra-adrenal para- 1. DeMatteo RP, Lewis JJ, Leung D, et al. Two hundred gastro- ganglioma in young females. Histopathology 1986;10:1325–1333.
intestinal stromal tumors. Recurrence patterns and prognostic 17. Diment J, Tamborini E, Casali P, et al. Carney triad: Case report and factors for survival. Ann Surg 2000;231:51–58.
molecular analysis of gastric tumor. Hum Pathol 2005;36:112– 2. Price VE, Zielenska M, Chilton-MacNeill S, et al. Clinical and molecular characteristics of pediatric gastrointestinal stromal 18. Boccon-Gibod L, Boman F, Boudjemaa S, et al. Separate occur- tumors (GISTs). Pediatr Blood Cancer 2005;45:20–24.
rence of extra-adrenal paraganglioma and gastrointestinal stromal 3. Carney JA, Sheps SG, Go VLW, et al. The triad of gastric tumor in monozygotic twins: Probable familial Carney syndrome.
leiomysarcoma, functioning extra-adrenal paraganglioma and Ped Developmental Pathology 2004;7:380–384.
pulmonary chondroma. N Engl J Med 1977;296:1517 –1518.
19. Carney JA, Stratakis CA. Familial paraganglioma and gastric 4. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal sarcoma: A new syndrome distinct from the Carney triad.
stromal tumors. J Clin Oncol 2004;22:3812–3825.

Source: http://www.sarcoma.nl/carneytriad/wp-content/uploads/2012/05/Delemarre-Carney-case-PBC-2006.pdf