NDT Advance Access originally published online on February 3, 2007
Nephrology Dialysis Transplantation 2007 22(5):1489-1490; doi:10.1093/ndt/gfl807
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Gastrointestinal stromal tumours (GIST) in kidney transplant recipients—a report of two cases
Email: abbas.agaimy{at}klinikum-nuernberg.deSir,
Gastrointestinal stromal tumours (GIST) represent the most common primary mesenchymal GI neoplasms. GISTs occur in the stomach (60%), small intestine (30%), duodenum (5%), colorectum (<5%) and oesophagus (<1%) [1]. The majority harbour activating mutation in KIT or PDGFRA [1]. No risk factors or predisposing conditions have been identified for GIST. About 10% of GIST occurs in patients with other solid malignancies [2] and rare cases have involved immunocompromised patients [3]. Epstein Barr-virus (EBV) and Kaposi sarcoma-associated Herpes virus (HHV8) were not detected in GISTs [4,5]. GISTs have not been described in renal transplant recipients.
We encountered two female patients aged 59 and 58 years, who presented with non-specific abdominal pain, 40 and 96 months after renal transplantation because of terminal diabetic nephropathy and unspecified glomerulonephritis, respectively. One patient had a low-risk epithelioid gastric GIST (3.5 cm; <5 mitoses/50 HPFs) (Figure 1A–C) and the other had a huge ruptured high-risk spindle GIST of small bowel (23 cm; 14 mitoses/50 HPFs) (Figure 1D–F). The first patient remained disease-free 68 months post-operatively. The second was a recent case. Both tumours stained strongly for CD117 (1:50, Dako) and variably for CD34 (1:200, Zymed), but were negative for smooth muscle actin, desmin, S100 and HHV8 (1:25, Novocastra). In situ hybridisation for EBV-encoded nuclear mRNAs (EBER-1 & EBER-2, Zytomed), performed in case 2, was negative.
|
The incidence and types of immune suppression-associated neoplasia in renal transplant recipients varies with extent of follow-up [6]. Kaposi sarcoma, skin cancer and lymphoproliferative disorders are most common and viral agents (HHV8, HPV and EBV, respectively) are detectable in most of these lesions [6,7]. Kaposi sarcoma and smooth muscle neoplasms are the main GIST mimics in transplant recipients [6,7]. Kaposi sarcoma shows a consistent nuclear staining for HHV8, combined with a cytoplasmic staining for endothelial markers (CD31 and factor VIII), but not for c-kit/CD117. Immune suppression-associated smooth muscle neoplasms consistently harbour EBV-infection and they show smooth muscle features, but they have not been evaluated for c-kit/CD117 expression [7].
Imatinib mesylate represents the only therapeutic option for patients with unresectable and metastatic GIST [1]. The use of this drug in organ transplant recipients and the potential interactions with immunosuppressive agents may represent a new challenge for nephrologists and oncologists. Interestingly, it has been demonstrated, in animal experiments, that imatinib prevents chronic allograft nephropathy through inhibition of the platelet-derived growth factor (PDGF) receptor [8].
In summary, we report for the first time the occurrence of GISTs in renal transplant recipients, showing that both spindle and epithelioid GISTs may rarely involve this group of patients. Absence of HHV8 and EBV in the current cases suggests a pathogenesis similar to sporadic GIST. GISTs should be considered in the differential diagnosis of mesenchymal neoplasia involving organ transplant recipients, to enhance their recognition in this unusual clinical setting.
Conflict of interest statement. None declared
Institute of Pathology
Nuremberg Clinic Centre
Nuremberg
Germany
References
- Miettinen M and Lasota J. (2006) Gastrointestinal stromal tumors. Review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 130:1466–1478.[Web of Science][Medline]
- Agaimy A, Wünsch PH, Sobin LH, Lasota J, Miettinen M. (2006) Occurrence of other malignancies in patients with gastrointestinal stromal tumors. Semin Diagn Pathol 23:120–129.[CrossRef][Web of Science][Medline]
- Padula A, Chin NW, Azeez S, Resetkova E, Andriko JA, Miettinen M. (2005) Primary gastrointestinal stromal tumor of the esophagus in an HIV-positive patient. Ann Diagn Pathol 9:49–53.[CrossRef][Medline]
- Su CC, Li CF, Liao YL, Lin CN, Lu JJ. (2005) Immunohistochemical and molecular assessment of human herpesvirus type 8 in gastrointestinal tumours. J Clin Pathol 58:856–859.
[Abstract/Free Full Text] - Lam KY. (1999) Oesophageal mesenchymal tumours: Clinicopathological features and absence of Epstein-Barr virus. J Clin Pathol 52:758–760.[Abstract]
- Yildirim Y, Ozyilkan O, Emiroglu R, Bemirhan B, Karakayali H, Haberal M. (2006) Early diagnosis of cancer in renal transplant patients: A single center experience. Asian Pacific J Cancer Prev 7:336–339.
- Deyrup AT, Lee VK, Hill CE, et al. (2006) Epstein-Barr-Virus-associated smooth muscle tumors are distinctive mesenchymal tumors reflecting multiple infection events. A clinicopathologic and molecular analysis of 29 tumors from 19 patients. Am J Surg Pathol 30:75–82.[CrossRef][Web of Science][Medline]
- Savikko J, Taskinen E, Von Willebrand E. (2003) Chronic allograft nephropathy is prevented by inhibition of platelet-derived growth factor receptor: tyrosine kinase inhibitor as a potential therapy. Transplantation. 75: pp. 1147–1153.[CrossRef][Web of Science][Medline]
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||