A rare case of cancer-to-cancer metastasis: breast cancer to renal cell cancer : Case report and review of literature.

BACKGROUND: Cancer-to-cancer metastasis is very rare with less than 50 cases described in literature. This article reports a case of breast cancer with synchronous metastasis to clear cell renal cell cancer. CASE DESCRIPTION: A 79-year-old woman was diagnosed with a bilateral breast carcinoma. Sonographic staging investigation of the abdomen revealed a 6 cm wide expansion of the right kidney. Bilateral mastectomy and nephrectomy of the right kidney was performed. The histology revealed a clear cell renal cell carcinoma and in the center of the tumor a 0.5 cm metastasis of the breast cancer. The patient's comorbidities and performance status precluded chemotherapy und she received palliative radiotherapy, targeted monoclonal antibody therapy and antihormonal treatment. CONCLUSIONS: Even if cancer-to-cancer metastasis is a very rare phenomenon, the simultaneous or consecutive finding of a renal tumor in women with breast cancer should be carefully evaluated.

Graft Growth and Podocyte Dedifferentiation in Donor-Recipient Size Mismatch Kidney Transplants.

BACKGROUND: Kidney transplantation is the treatment choice for patients with end-stage renal diseases. Because of good long-term outcome, pediatric kidney grafts are also accepted for transplantation in adult recipients despite a significant mismatch in body size and age between donor and recipient. These grafts show a remarkable ability of adaptation to the recipient body and increase in size in a very short period, presumably as an adaptation to hyperfiltration. METHODS: We investigated renal graft growth as well as glomerular proliferation and differentiation markers Kiel-67, paired box gene 2 and Wilms tumor protein (WT1) expression in control biopsies from different transplant constellations: infant donor for infant recipient, infant donor for child recipient, infant donor for adult recipient, child donor for child recipient, child donor for adult recipient, and adult donor for an adult recipient. RESULTS: We detected a significant increase in kidney graft size after transplantation in all conditions with a body size mismatch, which was most prominent when an infant donated for a child. Podocyte WT1 expression was comparable in different transplant conditions, whereas a significant increase in WT1 expression could be detected in parietal epithelial cells, when a kidney graft from a child was transplanted into an adult. In kidney grafts that were relatively small for the recipients, we could detect reexpression of podocyte paired box gene 2. Moreover, the proliferation marker Kiel-67 was expressed in glomerular cells in grafts that increased in size after transplantation. CONCLUSIONS: Kidney grafts rapidly adapt to the recipient size after transplantation if they are transplanted in a body size mismatch constellation. The increase in transplant size is accompanied by an upregulation of proliferation and dedifferentiation markers in podocytes. The different examined conditions exclude hormonal factors as the key trigger for this growth so that most likely hyperfiltration is the key trigger inducing the rapid growth response.

Huge Congenital Segmental Dilatation of the Sigmoid Colon in a Neonate: A "Rarity to Meet" and a "Challenge to Treat".

Only ten cases of neonatal congenital segmental dilatation (CSD) of the colon have been described so far. We present a full-term female newborn with trisomy 21, ventricular septal defect, and gross abdominal distension. Plain abdominal radiographs revealed a huge cystic lesion occupying the left hemiabdomen. Upon laparotomy on day 4 a CSD of the distal sigmoid and proximal rectum was confirmed and resected. The proximal colon was exteriorized and the distal part closed as a Hartmann pouch. Histology confirmed a huge segmental dilatation of the sigmoid without dysganglionosis or pseudodiverticula, but normal intestinal architecture. After correction of the ventricular septal defect a low rectal end-to-end anastomosis could be performed at an age of 5 months. The postoperative course was uneventful. CSD of the sigmoid colon is extremely "rare to meet" and a "challenge to treat" in the newborn period, but clinical awareness of this entity prompts pediatric surgical success.

Heterogeneity of mitochondrial energy metabolism in classical triphasic Wilms' tumor.

Metabolic changes are observed in a variety of tumors. The nature of the changes in aerobic energy metabolism differs between tumor types. Therefore, immunohistochemical staining, enzymatic measurements and immunoblot analysis were used to determine alterations of oxidative phosphorylation (OXPHOS) in classic triphasic Wilms' Tumor (WT). Our studies revealed that the epithelial, stromal and blastemal elements of this tumor differ in their energy metabolism. Compared to unaffected kidney tissue, normal mitochondrial mass was observed in the epithelial and blastemal regions of WT, whereas the stroma showed a massive down-regulation of mitochondria, as indicated by low porin content, low citrate synthase activity, and reduced mtDNA copy number. All OXPHOS enzyme activities were reduced in all WT samples, with the exception of two epithelial-dominant cases, which showed up-regulation of complex III activity compared to control kidney tissues. Interestingly, our studies show that, even within a specific tumor entity, cell-type-specific alterations of aerobic energy metabolism can occur, although all cell types showed a clear tendency toward a reduced aerobic energy metabolism.

Alterations of respiratory chain complexes in sporadic pheochromocytoma.

Succinate dehydrogenase (SDH) has been associated with carcinogenesis in hereditary pheochromocytoma (PC) and paraganglioma. We investigated if a similar association applies to sporadic pheochromocytoma. No genetic alteration was found in the SDHB, SDHC or SDHD genes of sporadic PC. However, in eight of nine sporadic PCs the SDH activity was, on average, reduced by 40%; moreover, the activities of the other oxidative phosphorylation (OXPHOS) complexes and citrate synthase were significantly lower compared to normal kidney tissue. Furthermore, immunohistochemical staining revealed a significant down-regulation of respiratory chain complexes. Since no pathogenic mutations were detected in the von Hippel-Lindau (VHL) gene, we can rule out that VHL deficiency is causing the general reduction of OXPHOS enzymes observed in the PCs investigated. In contrast to the single enzyme defects found in a subset hereditary PCs, a more generalized reduction of mitochondrial respiration seems to be present in most sporadic PCs. Strikingly, one of the nine PCs showed specific loss of complex I and a compensatory up-regulation of complexes II-V, which is a phenotype usually characteristic of oncocytic tumors.

Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors.

Oncocytic tumors, also called oxyphilic tumors, are characterized by hyperproliferation of mitochondria, which histologically presents as a fine granular eosinophilic cytoplasm. In accordance with the high mitochondrial density in oncocytomas, transcript levels of subunits of complexes of the oxidative phosphorylation (OXPHOS) system are increased. Hence, for a long time oncocytomas were presumed to have a highly active aerobic mitochondrial energy metabolism. Recently, detailed analysis of all OXPHOS complexes in a variety of oncocytomas revealed loss of complex I and compensatory up-regulation of the other complexes. In half of the oncocytoma cases examined the absence of complex I is caused by disruptive mutations in mitochondrial DNA encoding complex I subunits. The new data presented here on rare oncocytomas and the accompanying review of the literature clearly indicate that complex I deficiency in combination with up-regulation of mitochondria can be regarded as a hallmark of oncocytic tumor cells. Therefore, complex I of the respiratory chain has to be added to the growing list of mitochondrial tumor suppressors.

Diagnostic yield of touch imprint cytology of prostate core needle biopsies.

Touch imprint cytology may provide additional information to core needle biopsy interpretation according to previous reports. The aim of this study was to investigate the diagnostic yield of this method in the diagnosis of prostate carcinoma. For this purpose, 452 transrectal prostate needle biopsies were evaluated from 56 patients. All patients were clinically suspicious of having prostate carcinoma. Two touch imprints were prepared from each fresh biopsy cylinder. Results of the standard histology and of the touch imprint evaluation were compared. Histologically negative biopsy cylinders were further evaluated for prostate carcinoma by fine step serial sectioning. The standard histological examination showed adenocarcinoma in 27 patients. Touch imprint cytology revealed atypical cells suspicious of carcinoma in 38 patients. This group included all 27 patients with positive standard histology and further 11 patients with initially negative core biopsy. Following serial sectioning, in three out of these 11 samples, histological evidence of a carcinoma could be proven. Fine step serial sectioning of all 29 core biopsies negative for carcinoma by standard histological examination, 26 patients remained negative. All three core biopsies initially negative by standard histology but positive after serial sectioning had cytology findings suspicious of carcinoma. We conclude, that in problematic cases the additional use of touch imprint cytology and serial sectioning of prostate core needle biopsies significantly improve the diagnostic accuracy.

Loss of complex I due to mitochondrial DNA mutations in renal oncocytoma.

PURPOSE: Many solid tumors exhibit abnormal aerobic metabolism characterized by increased glycolytic capacity and decreased cellular respiration. Recently, mutations in the nuclear encoded mitochondrial enzymes fumarate hydratase and succinate dehydrogenase have been identified in certain tumor types, thus demonstrating a direct link between mitochondrial energy metabolism and tumorigenesis. Although mutations in the mitochondrial genome (mitochondrial DNA, mtDNA) also can affect aerobic metabolism and mtDNA alterations are frequently observed in tumor cells, evidence linking respiratory chain deficiency in a specific tumor type to a specific mtDNA mutation has been lacking. EXPERIMENTAL DESIGN: To identify mitochondrial alterations in oncocytomas, we investigated the activities of respiratory chain enzymes and sequenced mtDNA in 15 renal oncocytoma tissues. RESULTS: Here, we show that loss of respiratory chain complex I (NADH/ubiquinone oxidoreductase) is associated with renal oncocytoma. Enzymatic activity of complex I was undetectable or greatly reduced in the tumor samples (n = 15). Blue Native gel electrophoresis of the multisubunit enzyme complex revealed a lack of assembled complex I. Mutation analysis of the mtDNA showed frame-shift mutations in the genes of either subunit ND1, ND4, or ND5 of complex I in 9 of the 15 tumors. CONCLUSION: Our data indicate that isolated loss of complex I is a specific feature of renal oncocytoma and that this deficiency is frequently caused by somatic mtDNA mutations.

Gangliocytes in neuroblastic tumors express alarin, a novel peptide derived by differential splicing of the galanin-like peptide gene.

In neuroblastic tumors a relationship of differentiation of the tumor to galanin receptor expression and antiproliferative and apoptotic effects upon activation of galanin receptors in neuroblastoma cells was reported. To elucidate the expression of other components of the galanin peptide family in neuroblastic tumors, RT-PCR analysis of a variety of human neuroblastic tumor tissues was performed. Ganglioneuroma tissues revealed the presence of a splice variant of the galanin-like peptide (GALP) mRNA, which results in exclusion of exon 3 and a frame shift after the signal peptide sequence of GALP. This generates a peptide of 25 amino acids, which we have termed alarin because of the N-terminal alanine and the C-terminal serine. The novel neuropeptide alarin does not reveal significant homology to other peptides. Immunohistochemistry with antibodies directed against synthetic alarin peptide detected specific cytoplasmic granular staining in ganglia of human ganglioneuroma and ganglioneuroblastoma, as well as differentiated tumor cells of neuroblastoma tissues. Undifferentiated neuroblasts of these tumor tissues did not show alarin-like immunoreactivity and alarin-specific mRNA. Our findings indicate that alarin expression is a feature of ganglionic differentiation in neuroblastic tumor tissues.

Cervicomediastinal thymic cyst: report of a case.

Congenital thymic cysts are rare. Consequently, they are often misdiagnosed and not included in the preoperative differential diagnosis of neck masses. We report the case of a 7-year-old boy with a large cervicomediastinal thymic cyst to increase the awareness of this unusual entity. We discuss the clinical features, presentation, and pathogenesis of thymic cysts.

Galanin and galanin receptors in human cancers.

The increasing interest in peptides and peptide receptors in cancer is based on the possibility of receptor targeting, because peptide receptors are often expressed in different human tumors. The neuropeptide galanin has also been suggested to be involved in the development of neuroendocrine tumors based on the development of estrogen-induced tumors in estrogen-sensitive rats. This study summarizes our current knowledge on the expression of galanin peptide and galanin receptors in different human neuroendocrine tumors. The expression of both, peptide and corresponding receptor, seems to be a common feature of human gliomas, pheochromocytomas, pituitary and neuroblastic tumors. The co-expression of galanin and its receptors supports a role for galanin in tumor cell pathology via autocrine/paracrine mechanisms.

The pT1a and pT1b category subdivision in renal cell carcinoma: is it reflected by differences in tumour biology?

OBJECTIVE: To assess systematically the possible differences in pathology between pT1a and pT1b renal cell carcinomas (RCCs), as the sixth edition of the Tumour-Nodes-Metastasis (TNM) system implemented a subdivision of category pT1 into pT1a (<4 cm) and pT1b (4-7 cm), based on clinical outcome analysis and the approach to therapy. PATIENTS AND METHODS: Conventional histopathology and immunohistochemical expression of several biomarkers were analysed in 66 patients with pT1a and 29 with pT1b RCCs, using a tissue microarray technique. RESULTS: After 2 years of follow-up, none of the 66 patients with pT1a and three of the 29 with pT1b tumours developed progressive disease. The tumour was grade 3 in four (6%) pT1a and 11 (38%) pT1b RCCs. Immunohistochemically, pT1a RCCs were characterized by strong expression of p27 (79%), bcl-2 (67%), MUC1 (87%), insulin-like growth factor (IGF)-I (71%) and CD10 (88%), as well as moderate expression of IGF-I receptor (43%) and low expression of epidermal growth factor receptor (EGFR, 20%). During progression to category pT1b, expression of p27 significantly decreased (54%) and EGFR expression increased (38%). Moreover, membranous staining patterns of MUC1 and CD10 changed from apical to circumferential in clear cell RCCs. p53 (pT1a 23%, pT1b 28%), E-cadherin (10% and 17%), MIB-1 (1.2% and 1.5%) and Skp2 (2% and none) expression seemed to be of minor importance. CONCLUSION: This is the first study to show that the subdivision of category pT1 implemented in the latest issue of the TNM system is reflected by differences in conventional histopathology and expression of biomarkers.

Kit (CD117) immunoreactivity is rare in renal cell and upper urinary tract transitional cell carcinomas.

OBJECTIVE: To investigate the presence of Kit (CD117), a transmembrane tyrosinase-kinase receptor, in primary and metastatic renal cell carcinomas (RCCs) and upper urinary tract transitional cell carcinomas (TCCs). MATERIALS AND METHODS: In human neoplasia, overexpression of Kit has been related to cell proliferation, differentiation, adhesion and control of apoptosis. If present, Kit may provide a suitable target for tumour therapy. Formalin-fixed and paraffin-embedded specimens of 180 primary and 58 metastatic RCCs and 54 upper urinary tract TCCs were immunostained for Kit (CD117) using a tissue microarray technique. RESULTS: In RCCs, immunoreactivity for CD117 was detected in only two of 23 (9%) chromophobe tumours, whereas all 137 conventional and 20 papillary subtypes, and metastatic RCC tissues, lacked CD117 immunoreactivity. In TCCs, CD117 expression of <10% cancer cells was found in two of 53 (4%) cases. Stromal mast cells served as a positive control and showed specific immunostaining. CONCLUSION: Kit immunoreactivity is infrequent in both RCCs and upper urinary tract TCCs. Thus, routine screening of tumour tissues for Kit by immunohistochemistry appears to be cost-ineffective and cannot be recommended. Moreover, the lack of substantial Kit immunoreactivity in both primary and metastatic carcinomas does not provide a rationale to investigate imatinib mesylate therapy in clinical trials including patients with advanced disease.

HER2 protein overexpression and gene amplification in upper urinary tract transitional cell carcinoma: systematic analysis applying tissue microarray technique.

OBJECTIVES: To investigate HER2 (c-erbB-2) protein overexpression and HER2 gene amplification in upper urinary tract transitional cell carcinoma (TCC) with respect to its association with tumor grade and stage, as well as the prognostic significance. METHODS: A total of 53 consecutive TCC specimens were analyzed immunohistochemically (HercepTest) and with fluorescence in situ hybridization applying a tissue microarray technique. RESULTS: Overall, HER2 immunoreactivity (expression) was detected in 28 of 53 TCC specimens and tended to be stronger in high-stage (8 [36%] of 22 pT1 versus 20 [65%] of 31 pT2-T3; P = 0.06) and high-grade (11 [39%] of 28 low-grade versus 17 [68%] of 25 high-grade; P = 0.054) tumors. Weak overexpression (HercepTest score 2+) was seen in 9 cases (17%) and was associated with angioinvasion (P = 0.02) and had independent prognostic significance with respect to metastasis-free survival (risk ratio 9.6; P = 0.03). Low HER2 amplification was present in four TCC specimens (9%), with HER2/chromosome 17 ratios of 2.03, 2.77, 2.91, and 3.39, and polysomy of chromosome 17 was present in another 3 cases (7%). HER2 amplification and/or polysomy of chromosome 17 prevailed in high-stage (0 [0%] of 20 pT1 versus 7 [27%] of 26 pT2-T3; P = 0.01) and high-grade (1 [4%] of 24 low-grade versus 6 [27%] of 22 high-grade; P = 0.04) tumors, but lacked independent prognostic significance. Of nine TCC specimens with weak HER2 overexpression (HercepTest score 2+), 3 (33%) showed low HER2 amplification and two others had polysomy of chromosome 17. CONCLUSIONS: HER2 overexpression and HER2 gene amplification were infrequent in our series. Thus, only a small number of patients with upper urinary tract TCC might benefit from HER2-targeted (Herceptin) cancer therapy.

Analysis of insulin-like growth factors and insulin-like growth factor I receptor expression in renal cell carcinoma.

The expression of insulin-like growth factors I (IGF-I) and II (IGF-II) and insulin-like growth factor-I receptor (IGF-IR) was studied in 137 clear cell, 23 chromophobe, and 20 papillary renal cell carcinomas (RCCs) using a tissue microarray technique. IGF-I immunoreactivity was detected in 110 (82.1%) of 134 clear cell, 8 (36%) of 22 chromophobe, and 3 (15%) of 20 papillary RCCs (P < .001). IGF-IR immunoreactivity was detected in 39 (29.5%) of 132 clear cell, 9 (41%) of 22 chromophobe, and 19 (95%) of 20 papillary RCCs (P < .001). In contrast, all tumors lacked IGF-II expression. Expression of IGF-I and IGF-IR was not related to tumor stage, grade, or prognosis. The IGF system is expressed differentially among different tumor types. The expression of IGF-I together with its receptor, IGF-IR, provides evidence for the existence of an autocrine-paracrine loop of tumor cell stimulation in RCC and makes this type of cancer a candidate for therapeutic strategies aimed to interfere with the IGF pathway.