A shower of second hit events as the cause of multifocal renal cell carcinoma in tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic disorder characterized by seizures and tumor formation in multiple organs, mainly in the brain, skin, kidney, lung and heart. Renal cell carcinoma (RCC) occurs in ∼3% of TSC patients, and typically develops at age <50. Here we describe genetic findings in two TSC patients with multiple renal tumors, each of whom had the germline mutation TSC2 p.R905Q. The first (female) TSC patient had a left followed by a right nephrectomy at ages 24 and 27. Both kidneys showed multifocal TSC-associated papillary RCC (PRCC). Targeted, next-generation sequencing (NGS) analysis of TSC2 in five tumors (four from the left kidney, one from the right) showed loss of heterozygosity in one tumor, and four different TSC2 point mutations (p.E1351*, p.R1032*, p.R1713H, c.4178_4179delCT) in the other four samples. Only one of the 11 other tumors available from this patient had one of the TSC2 second hit mutations identified. Whole-exome analysis of the five tumors identified a very small number of additional mutated genes, with an average of 3.4 nonsilent coding, somatic mutations per tumor, none of which were seen in >1 tumor. The second (male) TSC patient had bilateral partial nephrectomies (both at age 36), with similar findings of multifocal PRCC. NGS analysis of TSC2 in two of these tumors identified a second hit mutation c.2355+1G>T in one sample that was not seen in other tumors. In conclusion, we report the first detailed genetic analysis of RCCs in TSC patients. Molecular studies indicate that tumors developed independently due to various second hit events, suggesting that these patients experienced a 'shower' of second hit mutations in TSC2 during kidney development leading to this severe phenotype.

Should active surveillance in prostate cancer patients be based on a single histological assessment?

INTRODUCTION: Active surveillance (AS) is always associated with a degree of uncertainty, whether or not prostate biopsy (TRUSBx) results indeed can be relied on for evaluation of cancer stage and histological grade, as the most commonly observed limitations of TRUSBx are undergrading, understaging and underestimating true prostate cancer (PCa) volume. We evaluated prostate cancer characteristics in men who could have been offered active surveillance based on clinical features and TRUSBx results, and compared them with the same patient's histology results following their radical prostatectomy (RP). Moreover, we assessed the level of consistency in reporting TRUSBx and RP specimens by the same pathologist on two separate occasions, as well as by another independent pathologist. MATERIAL AND METHODS: All patients who underwent RP between 2005 and 2008 had their medical records reviewed retrospectively. All histological specimens were prospectively re-evaluated by the same pathologist, as well as by a second to assess for intra- and interobserver variability, respectively. RESULTS: Eight out of a total of 124 patients who underwent RP could have been offered AS on the basis of initial microscopic reports. However, there was significant intra- and interobserver variability. The differences in the histological grade of the specimens obtained from TRUSBx and RP, reported by the same pathologist and by the second pathologist were apparent in 6 and 4 cases, and in 7 and 6 patients, respectively. CONCLUSIONS: We recommend that the decision about AS should be made after at least two pathologists have jointly reviewed and agreed on the TRUSBx histology results.

Degeneration of the symphysis pubis presenting as a submucosal urinary bladder tumour.

Urinary bladder sonography is a sensitive diagnostic technique used for visualizing urinary bladder tumours. The aim of our communication is to present a case of a pseudotumour of the urinary bladder originating from the symphysis pubis syndesmosis. A 58-year-old woman was seen by a urologist with symptoms of lower urinary tract infection. Urinary bladder sonography was performed, followed by magnetic resonance imaging. Sonographic images of the bladder showed an exophytic mass on the urinary bladder's anterior wall. A transurethral resection of the tumour was performed. A histopathological examination revealed a necrotic extramural mass, without traits of malignancy. The mass reappeared in the follow-up vesical sonography. Subsequently, its transurethral resection was repeated with the same histopathological findings. The next urinary bladder sonography revealed the presence of the mass again. Pelvic magnetic resonance imaging was performed, which showed advanced degenerative changes in the pubic symphysis syndesmosis that protruded into the bladder, imitating a urinary bladder tumour. To avoid unnecessary surgery, both radiologists and urologists should be made aware that there is a possibility of similar cases in patients. Magnetic resonance imaging enabled correct determination of the primary site of the growth, which, together with the histopathological examination results, influenced the choice of the implemented therapeutic procedures.

Clinical significance of surgical margin status in patients subjected to radical prostatectomy.

The aim of this study is to evaluate the clinical value of positive surgical margins (PSM) in patients subjected to radical prostatectomy (RP). The data of men who were subjected to RP from the 1st of January, 2001 to the 30th of May, 2010 were analyzed. Specimens with PSM were again evaluated to confirm the presence of positive margins. PSM were found in 64 (25%) out of 255 analyzed patients. Out of all clinical features, only biopsy Gleason score and clinical stage of the disease were found to be predictive of PSM. Biochemical recurrence (BR) was found in 42 (16.5%) men, among them 17 (26.6%) had PSM and 25 (13.1%) had negative margins. The risk of BR in those with "focal" PSM (<3 mm) did not differ from the risk of BR observed in patients without PSM. In contrast, the likelihood of BR was significantly greater in cases of PSM in which maximum longitude exceeded 3 mm. Reevaluation of the PSM specimens revealed equivocal margins status in six cases. PSM are not inevitably associated with BR. The risk of failure is influenced by their length. Reevaluation of the prostate specimen may lead to surgical margins status modification.

Incidental sonographic detection of mucosa-associated lymphoid tissue lymphoma of the urinary bladder found in a very young woman: report of a case.

We report a rare case of a mucosa-associated lymphoid tissue (MALT)-type lymphoma of the bladder, incidentally found on sonography in a 17-year-old girl during the workup of arterial hypertension. The diagnosis was established by a transurethral biopsy. Treatment consisted of transurethral resection of the bladder tumor and subsequent chemotherapy. To the best of our knowledge, this is the youngest patient with asymptomatic MALT-type lymphoma of the urinary bladder.

D-chiro-inositol affects accumulation of raffinose family oligosaccharides in developing embryos of Pisum sativum.

Developing garden pea embryos are able to take up exogenously applied cyclitols: myo-inositol, which naturally occurs in pea, and two cyclitols absent in pea plants: d-chiro-inositol and d-pinitol. The competition in the uptake of cyclitols by pea embryo, insensitivity to glucose and sucrose, and susceptibility to inhibitor(s) of H(+)-symporters (e.g. CCCP and antimycin A) suggest that a common cyclitol transporter is involved. Both d-chiro-inositol and d-pinitol can be translocated through the pea plant to developing embryos. During seed maturation drying, they are used for synthesis of mainly mono-galactosides, such as fagopyritol B1 and galactosyl pinitol A. Accumulation of d-chiro-inositol (and formation of fagopyritols), but not d-pinitol, strongly reduces accumulation of verbascose, the main raffinose oligosaccharide in pea seeds. The reasons for the observed changes are discussed.

Ectopic decidual reaction in the urinary bladder presenting as a vesical tumor.

A urinary bladder tumor in young pregnant women is a very rare finding. It may bring diagnostic problems despite use of advanced imaging techniques. We report on a case of an exceedingly rare occurrence of a decidual reaction in the urinary bladder of a pregnant young woman. To the best of our knowledge, it is the first such case reported in published medical data. The final diagnosis was possible only after histopathologic assessment of a specimen obtained during diagnostic cystoscopy, which showed typical decidual changes within detrusor muscle, without ectopic endometrium, which could suggest more frequent vesical endometriosis.