We report the association of CDH1/E-cadherin mutations with cleft lip, with or without cleft palate (CLP), in two families with hereditary diffuse gastric cancer (HDGC). In each family, the CDH1 mutation was a splicing mutation generating aberrant transcripts with an in-frame deletion, removing the extracellular cadherin repeat domains involved in cell-cell adhesion. Such transcripts might encode mutant proteins with trans-dominant negative effects. We found that CDH1 is highly expressed at 4 and 5 weeks in the frontonasal prominence, and at 6 weeks in the lateral and medial nasal prominences of human embryos, and is therefore expressed during the critical stages of lip and palate development. These findings suggest that alteration of the E-cadherin pathway can contribute to human clefting.

In an attempt to correlate the TP53 mutation pattern of squamous cell carcinomas of the esophagus (ESCC) and life style factors of patients from the high risk area Rio Grande do Sul, Brazil, 135 ESCC were analyzed, after prescreening by p53 immunohistochemistry, by SSCP and DNA sequencing of TP53, exon 5-9. Forty-nine somatic TP53 mutations (and 1 case with p53 polymorphism) were identified as missense (n ‫؍‬ 39), frameshift (n ‫؍‬ 6), silent (n ‫؍‬ 1), amber (n ‫؍‬ 1) or intron border mutations (n ‫؍‬ 2) that cause splicing aberrations. They were preferentially found in exon 5 (36.7%) and exon 8 (32.7%). Several mutations were located in the mutation hot spot codons 248, 273 and 282, mainly at CpG sites. Transition mutations were observed in 53.1% (among them 50% G > A), transversion mutations in 34.7% (among them 47.1% G > T) and frameshifts in 12.2%, the latter 2 mainly in smokers and alcohol drinkers. Transitions were more prevalent in females than in males (p < 0.05). TP53 mutations, mainly transversions, were more frequently found in heavy smokers (p ‫؍‬ 0.03), with the same tendency after chronic alcohol consumption. Comparison with the worldwide IARC database disclosed differences in the TP53 mutation pattern of the Brazilian tumors, with a higher accumulation of TP53 mutations in exon 8 and a higher prevalence of transition mutations. Mutations at the reported hot spot codon 176 were missing. Although difficult because of the documented coexposure to various life style risk factors in most patients of this series, the hypothesis is proposed that besides smoking and alcohol drinking the commonly consumed hot mate tea in this high risk area for ESCC is responsible for this different pattern of TP53 mutations because of chronic hyperthermic irritation and inflammation in the esophagus with an endogenous formation of radicals or carcinogenic factors that lead to a higher prevalence of transition mutations.

SUMMARYEleven cases of involvement of the genital tract in paracoccidioidomycosis were collected in a retrospective study of the clinical records of 683 patients seen in Porto Alegre, Rio Grande do Sul, Brazil. These cases are herein summarily reported. Eighteen similar cases were gathered in review of the Brazilian literature. Obtained data are discussed.

We report a case of xanthogranulomatous cystitis (XC) in a 76-year-old man who presented with painless hematuria and a bladder mass on imaging studies. Xanthogranuloma is a chronic inflammatory condition that most commonly involves the kidney. XC is a rare condition of still unknown aetiology with only about 20 cases reported to date. The gold standard treatment is surgical resection. Consideration should be given to this entity in the differential diagnosis of urinary bladder masses.

Study Type – Therapy (case series) 
Level of Evidence 4 What's known on the subject? and What does the study add? As PSA exhibits suboptimal specificity, different strategies have been proposed in order to decrease the number of negative biopsies. An empirical course of antibiotics has been proposed as a cost‐saving strategy to differentiate patients with benign cancer as it could potentially avoid unnecessary biopsies. Despite being limited by its non‐randomized open‐label design, our data suggest that no specific PSA reduction threshold can accurately discriminate prostate cancer. The empirical use of antibiotics for asymptomatic patients with elevated PSA levels should be discouraged. OBJECTIVES To compare the influence of a 4‐week course of empirical antimicrobial therapy or observation on the prostate‐specific antigen (PSA) levels of asymptomatic patients with a raised baseline PSA. To identify whether a decrease in PSA can predict the risk of prostate cancer (PCa) detection on prostate biopsy. PATIENTS AND METHODS Patients were referred to our ambulatory centre because of a raised PSA level (>2.5 ng/mL) with a normal digital rectal examination. A 12‐core prostate biopsy was indicated in these patients and they were offered antibiotic treatment with levofloxacin 500 mg daily for 30 days. Patients who did not agree to use antibiotics but who still showed interest in participating underwent simple observation, serving as controls. Total and free PSA levels at baseline and after 45 days were measured. Variation in PSA level was calculated. All patients underwent a 12‐core prostate biopsy 6 weeks after the initial visit. RESULTS In all, 245 men were enrolled, but 43 were lost due to follow‐up. A total of 145 patients who used antibiotics and 57 controls were included in the analysis. The median baseline PSA levels were 7.6 and 7.7 ng/mL in the antibiotic and control groups, respectively, with median follow‐up levels of 6.8 and 7.0 ng/mL. The follow‐up PSA level was significantly lower than the initial PSA level (P = 0.009). Mean absolute and percentage variation in PSA level were similar in both groups (P = 0.828 and 0.128, respectively). The overall PCa detection rate was 15.8%, and did not differ among the groups (P = 0.203). Regarding the percentage variation in PSA level, patients diagnosed with PCa tended to have their PSA level increased (22.4 vs –5.3%; P = 0.001). Indeed, a decrease of 20% in PSA was not predictive of a negative prostate biopsy (P = 0.41). The area under the receiver operating characteristic curve for percentage PSA variation as a predictor of PCa was 0.660. CONCLUSIONS PSA levels tend to fall when repeated after 45 days, regardless of antibiotic use. Despite being associated with the chance of PCa, no percentage PSA variation threshold value exhibits satisfactory discriminatory properties.

CBs collected by EUS-FNA and analysed by immunohistochemistry showed a high diagnostic yield in patients with mesenchymal neoplasms, even without on-site cytopathology.

The screening for additional human YjeF_N domain containing proteins beside the apolipoprotein A-I interacting protein (AI-BP), identified two other genes designated hYjeF_N2-15q23 (formerly human homologue of yeast edc3) and hYjeF_N3-19p13.11 comprising the human YjeF_N family. AI-BP is ubiquitously expressed, with a predominance of these tissues where the homologues were found to be restricted including brain, mammary gland, testes and ovaries. Immunohistochemistry of human testes and ovaries showed an expression of hYjeF_N3-19p13.11 only in Leydig cells and theca cells, respectively, indicating a role in steroid hormone metabolism. Interestingly, the protein was also strongly expressed in Leydig cell tumors and in thecofibromas. The identification of hYjeF_N2-15q23 in theca cells and granulosa cells in ovaries, in human spermatids of meiotic division part II and the apical membrane of Sertoli cells in testes suggest similar functions in oogenesis and sperm maturation which is strengthened by the identification of the spermatogenesis regulator HMGA1 as a conserved transcription factor. However, in contrast to AI-BP, both homologous proteins are unable to bind apoA-I. These results relate the human YjeF_N domain containing protein family to cholesterol processing and steroid hormone metabolism in spermiogenesis and oogenesis, and AI-BP may link this function to the HDL pathway.

We present the case of a 77-year-old female with a rare genital and anoperineal granulomatous cutaneous manifestation resembling cheilitis granulomatosa Miescher. The typical histological findings of epithelioid cell granulomas were localized in the vulva and anoperineal region; the latter manifestation has not yet been described. Based on our personal observations and a review of the literature, the clinical and histological features of vulvitis granulomatosa are described.