Marijana Coric

MAGE‐A10 cancer/testis antigen is highly expressed in high‐grade non‐muscle‐invasive bladder carcinomas

Bladder cancer is a common urinary malignancy and a prevalent cause of cancer‐related death. Current therapies of early stage non‐muscle‐invasive bladder cancer (NMIBC) are frequently associated with undesirable toxicities and recurrence. Active antigen‐specific immunotherapy may provide a valid therapeutic option for patients with NMIBC. Cancer‐testis antigens (CTA) expressed in various tumour types and in a limited range of healthy tissues may represent potential targets for specific immunotherapy. MAGE‐A10 is probably the most immunogenic antigen of the MAGE‐A family. We evaluated the expression of MAGE‐A10 in NMIBC. Seventy‐nine patients undergoing surgical treatment for NMIBC were enrolled in the study. MAGE‐A10 gene expression was assessed by quantitative real‐time polymerase chain reaction. Immunohistochemistry was performed on paraffin‐embedded sections. MAGE‐A10 gene was specifically expressed in one‐third of NMIBC (n = 24: 32.43%). Gene expression was correlated with high tumour grade. MAGE‐A10 protein was exclusively detectable in nuclei of tumour cells. More importantly, MAGE‐A10 protein was also more frequently detectable in high‐grade tumours (p = 0.0001) and in stage T1 tumours invading subepithelial tissue or lamina propria (p = 0.01). A strong correlation between MAGE‐A10 staining score and tumour grade and stage could accordingly be observed. These data indicate that MAGE‐A10 expression is a feature of aggressive NMIBC and might be used as a novel target for specific immunotherapy of these cancers.

Anderson-Fabry Disease in Kidneys from Deceased Donor

Anderson‐Fabry disease (AFD) is a rare, X‐linked lysosomal storage disease that leads to progressive intracellular accumulation of globotriaosylceramide in visceral organs and the vascular endothelium. We report two patients with end‐stage renal disease who received renal allograft from deceased female donor who died from heart failure. A 62‐year‐old women received a renal allograft in July 2006. Except for low‐range proteinuria, renal function was normal until 6 months after transplantation when serum creatinine increased from 120 to 150 μmol/L. A renal biopsy was performed. Based on the specific pathological finding, AFD in donor was suspected. In order to prove the diagnosis, the other recipient also underwent renal biopsy 3 months later. This was 45‐year‐old female with stable graft function and nonnephrotic proteinuria. Light microscopic findings included a ‘foamy’ appearance of affected cells with swelling and vacuolization of podocytes. Electron microscopic finding show mesangial cells and podocytes filled with dense lysosomal granules appearing as myelin figures and ‘zebra bodies’. Changes were less intensive than in the biopsy of the first recipient. The donor was 54‐year‐old Italian women who died on the Adriatic coast after heart attack. This is the first case of AFD found in a kidney allograft from deceased donor.

Testicular germ cell tumor composed of placental site trophoblastic tumor and teratoma

We present a case of a 24-year-old man with a right testicular mass, 2.5 cm in largest diameter. Before orchiectomy, the serum level of beta-human chorionic gonadotropin (hCG) was elevated, whereas that of alpha-fetoprotein was normal. Histologic examination showed a malignant germ cell tumor with a unique and hitherto unpublished combination of placental site trophoblastic tumor and teratoma. Testicular tubules adjacent to the tumor contained intratubular germ cell neoplasia. All cells of placental site trophoblastic tumor were immunohistochemically cytokeratin 7, 18, and pancytokeratin positive and cytokeratin 20, S-100 protein, alpha-fetoprotein, placental alkaline phosphatase, p63, OCT3/4, Nanog, and calretinin negative. Ten percent of the placental site trophoblastic tumor stained with hCG, 30% with epithelial membrane antigen and human placental lactogen, and 80% with inhibin antibodies. FISH study showed a gain on the short arm of chromosome 12 in the placental site trophoblastic tumor, proving that this component is of germ cell origin. The patient is alive and well 3 years after the orchiectomy without additional treatment.

Pancreatic analogue solid pseudopapillary neoplasm arising in the paratesticular location. The first case report

We describe the first pancreatic analogue of solid pseudopapillary neoplasm arising in paratesticular location. It was a tumor arising in 32-year-old man adhering closely to the testis. The tumor had several morphologic components. The greatest was represented by signet ring cells which gradually changed into solid, non-signet ring cell areas, often being mixed together. It also formed distinct trabeculae and pseudopapillae frequently adhering to cystic areas of the tumor. Immunohistochemically, the tumor had an identical profile to its pancreatic counterpart. The tumor cells reacted diffusely with S100 protein, β-catenin, cyclin D1, Fli-1, vimentin, CD10, galectin-3, and neuron-specific enolase and focally with synaptophysin. CD56 and E-cadherin reacted only in those parts of the tumor, which formed pseudopapillae. Cytokeratin antibody AE1-AE3 was strongly positive in the areas of trabecular formation of the tumor. The mutational analysis of exon 3 of the CTNNB1 gene confirmed mutation in this exon.

Do we need more intensive enzyme replacement therapy for Anderson-Fabry disease?

tive state and only certain stimuli (eg. the mechanical stretch during skin expansion) are capable of activating these genes. During skin expansion, such genes could be activated, initiating sequential nuclear regulation. This regulation promotes cell proliferation, increased collagen synthesis, and enhanced vascularization, thus yielding the excess skin formed in the skin expansion process. In conclusion, skin expansion is an interesting model system for skin regeneration study and microarray analysis of conventional expanded skin could allow for determination of the genes regulating skin regeneration. If our hypothesis is correct and if the identified genes can be modulated (up-regulated or down-regulated) via gene therapy, our research would be of significant value to the wound healing and regeneration medicine as it has the potential to completely regenerate skin. Thus, the scarless wound healing would no longer be a myth but a reality.

Primary signet ring stromal tumor of the testis: a study of 13 cases indicating their phenotypic and genotypic analogy to pancreatic solid pseudopapillary neoplasm

Primary signet ring stromal tumor of the testis (PSRSTT) is an extremely rare tumor described only twice in the literature. Pancreatic-analogue solid pseudopapillary neoplasm (SPN) of the testis is a recently reported entity with morphological overlap with PSRSTT. We reviewed our files to find all cases of PSRSTT to better characterize this entity. We studied 13 cases of PSRSTTs using histological, immunohistochemical (IHC), and molecular genetic methods and compared the results with pancreatic SPN. Grossly, the size of PSRSTTs ranged from 0.5 to 2 cm (mean 1.1). Microscopically, PSRSTTs predominantly showed a proliferation of low-grade epithelioid cells containing characteristic cytoplasmic vacuole dislodging the nucleus (signet ring cells) separated by fibrous septa into trabeculae and nests. The immunoprofile was characterized by immunoreactivity for β-catenin, cyclin D1 (nuclear positivity for both antibodies), CD10, vimentin, galectin-3, claudin 7, α-1-antitrypsin, CD56, and neuron-specific enolase and negativity for chromogranin, inhibin, calretinin, SF-1, NANOG, OCT3/4, and SALL4. In some cases, the IHC panel was restricted because of a limited amount of tissue. Molecular genetic analysis revealed mutations within exon 3 of the CTNNB1 encoding β-catenin in all analyzable cases. Based on histological similarities between pancreatic SPN and PSRSTT and their identical IHC and molecular genetic features, we assume that both neoplasms share the same pathogenesis, and thus, PSRSTT can be considered as a testicular analogue of pancreatic SPN.

Expression of bone morphogenetic proteins 4, 6 and 7 is downregulated in kidney allografts with interstitial fibrosis and tubular atrophy

AbstractPurpose Bone morphogenetic proteins (BMPs) are pleiotropic growth factors. This paper investigates the connection between the expression pattern of BMPs in kidney allograft tissue versus the cause of allograft dysfunction.Methods The expression pattern of BMP2, BMP4, BMP6 and BMP7 in 50 kidney allografts obtained by transplant nephrectomy is investigated. Immunohistochemical staining is semiquantitatively evaluated for intensity to identify the expression pattern of BMPs in normal and allograft kidney tissues.ResultsThe expression of BMP4 is unique between different tubular cell types in grafts without signs of fibrosis. This effect is not found in specimens with high grades of interstitial fibrosis and tubular atrophy (IFTA). In samples with IFTA grades II and III, the BMP7 expression is reduced in a significant fraction of specimens relative to those without signs of IFTA. The expression pattern of BMP6 indicates that its activation may be triggered by the act of transplantation and subsequent reperfusion injury. The expression of BMP2 is strong in all types of tubular epithelial cells and does not differ between the compared allografts and control kidney specimens.ConclusionThe intensity and expression pattern of BMP4, BMP6 and BMP7 in transplanted kidney tissue are found to be dependent upon the length of the transplanted period, the clinical indication for transplant nephrectomy and signs of IFTA in kidney tissue.

Appendiceal Carcinoid and Mucinous Cystadenoma in Renal Transplant Recipients: Case Reports

There is an increased incidence of tumors among renal transplant patients, which are associated with immunosuppression. Carcinoids are rare neuroendocrine tumors that arise from the enterochromaffin cells. Although appendiceal carcinoid tumors are the commonest malignant neoplasms affecting the appendix, and mucinous cystadenoma is the commonest benign appendiceal neoplasm, they have not been reported in immunosuppressed patients. We present two renal transplant recipients who developed combined appendiceal carcinoid and mucinous cystadenoma.

Posttransplant Lymphoproliferative Disorder in the Wall of a Lymphocele: A Case Report

Posttransplant lymphoproliferative disorder (PTLD) is a well-known complication of renal transplantation with increased incidence after introduction of more powerful immunosuppressive drugs. Presenting symptoms are nonspecific; some patients may be entirely asymptomatic. Herein we have reported a case of PTLD arising in the lymphocele wall presenting with B-symptoms and deterioration of graft function. A 62-year-old-female with end-stage renal disease secondary to Balkan endemic nephropathy and positive Epstein-Barr virus (EBV) serology before transplantation received a renal transplant from a deceased donor. Six months after transplantation she was admitted to the hospital with a 1-week history of malaise, weight loss, anorexia, night sweats, and febrile episodes. Multisliced computed tomography demonstrated a cystic structure at the renal hilus. Graft function deteriorated, so the patient underwent puncture of the lymphocele. Urgent graftectomy was necessary to stop the bleeding. Pathohistology demonstrated EBV-positive, CD20-positive PTLD. The patient received 6 cycles of chemotherapy and continued on hemodialysis. We concluded that a high index of suspicion for PTLD should be maintained when evaluating lymphoceles arising in the later posttransplantation period. Irrespective of their imaging features, biopsy should be performed to exclude PTLD.

IgA-dominant extracapillary proliferative glomerulonephritis following Escherichia coli sepsis in a renal transplant recipient

Postinfectious glomerulonephritis (PIGN) generally occurs in association with staphylococcal infection. We present the first reported case of IgA‐dominant PIGN after Escherichia coli infection in a renal‐transplant recipient. A 65‐year‐old patient with stable allograft function and E. coli urosepsis was treated with ciprofloxacin for 2 weeks with excellent response. One week later he developed proteinuria 16 g/day. Renal biopsy finding revealed IgA‐dominant PIGN. He received steroid pulses and intravenous imunoglobulins without effect and had started with hemodialysis.