Pigmented apocrine hamartoma: A distinct and uncommon pigmented lesion with dendritic melanocytes and appraisal of terminology.

A 20-year-old female presented to a gynecologist with an irregular, darkly pigmented, vulvar lesion. Histopathologic sections of a biopsy specimen showed cystically dilated glands with apical snouts, pigmented secretion, and numerous dendritic melanocytes. The lesion was diagnosed as a pigmented apocrine hamartoma of the vulva. We report the fifth case of this uncommonly encountered entity and discuss the conflicting terminology in the literature of this rare, pigmented lesion.

The Interplay Between Human Leukocyte Antigen Antibody Profile and COVID-19 Vaccination in Waitlisted Renal Transplant Patients.

CONTEXT.­: Mass COVID-19 vaccination is mandated in vulnerable populations in our renal transplant waitlist cohort. However, the anti-human leukocyte antigen (anti-HLA) profile after COVID-19 vaccination is controversial, and the side effects are yet to be discerned. OBJECTIVE.­: To evaluate the status of HLA antibodies in waitlist renal transplant patients before and 3 weeks after each vaccination and if comorbidities are associated with the HLA antibody profile. DESIGN.­: A total of 59 waitlisted kidney transplant patients were included in this study. The anti-HLA antibodies were analyzed before and 6 months after their last COVID-19 vaccination. The mean fluorescence intensity change in the anti-HLA antibody levels was used to classify patients into 3 groups: high inducers, low inducers, and noninducers. RESULTS.­: There were significant HLA antibody profile changes after COVID-19 vaccination, showing 21 antibodies generated against HLA class I antigens and 7 against HLA class II antigens to their baseline. Compared with the noninducers, the high and low inducers showed a higher prevalence of COVID-19 infection, COVID-19 vaccine type, and background hypertension history. CONCLUSIONS.­: Our data suggest that COVID-19 vaccination propagates anti-HLA class I and II antibodies for waitlisted renal transplant patients. The clinical significance of these antibodies needs further study. Furthermore, comorbidities, such as history of COVID-19 infection and hypertension, supplemented this effect. Anti-HLA antibody monitoring may be warranted in vaccinated, waitlisted renal transplant patients with COVID-19 vaccinations, and a history of COVID-19 infection or hypertension.

Validation of next-generation sequencing-based chimerism testing for accurate detection and monitoring of engraftment in hematopoietic stem cell transplantation.

Allogenic hematopoietic stem cell transplantation (allo-HSCT) is a life-saving treatment for various hematological disorders. The success of allo-HSCT depends on the engraftment of donor cells and the elimination of recipient cells monitored through chimerism testing. We aimed to validate a next-generation sequencing (NGS)-based chimerism assay for engraftment monitoring and to emphasize the importance of including the most prevalent cell subsets in proficiency testing (PT) programs. We evaluated the analytical performance of NGS-based chimerism testing (AlloSeq-HCT and CareDx) with a panel of targeted 202 informative single-nucleotide polymorphisms (SNPs) (i.e., linearity and precision, analytical sensitivity and specificity, system accuracy, and reproducibility). We further compared the performance of our NGS panel with conventional short tandem repeat (STR) analysis in unfractionated whole blood and cell-subset-enriched CD3 and CD66. Our NGS-based chimerism monitoring assay has an impressive detection limit (0.3% host DNA) for minor alleles and analytical specificity (99.9%). Pearson's correlation between NGS- and STR-based chimerism monitoring showed a linear relationship with a slope of 0.8 and r = 0.973. The concordance of allo-HSCT patients using unfractionated whole blood, CD3, and CD66 was 0.95, 0.96, and 0.54, respectively. Utilization of CD3+ cell subsets for mixed chimerism detection yielded an average of 7.3 ± 7-fold higher donor percentage detection compared to their corresponding unfractionated whole blood samples. The accuracy of the NGS assay achieved a concordance of 98.6% on blinded external quality control STR samples. The reproducibility series showed near 100% concordance with respect to inter-assay, inter-tech, inter-instrument, cell flow kits, and AlloSeq-HCT software versions. Our study provided robust validation of NGS-based chimerism testing for accurate detection and monitoring of engraftment in allo-HSCT patients. By incorporating the cell subsets (CD3 and CD66), the sensitivity and accuracy of engraftment monitoring are significantly improved, making them an essential component of any PT program. Furthermore, the implementation of NGS-based chimerism testing shows potential to streamline high-volume transplant services and improve clinical outcomes by enabling early relapse detection and guiding timely interventions.

[Gender-related differences in pathological characteristics of upper urinary tract urothelial carcinoma: analysis of 597 cases].

OBJECTIVE: To assess the sex differences in pathologic characteristics of Chinese patients with upper urinary tract urothelial carcinoma (UUTUC). METHODS: Between January 2004 and December 2010, 597 patients (253 men and 344 women) underwent surgical management at Peking University First Hospital for pathologically proven UUTUC. We reviewed pathological data from these patients, and used univariate analysis to determine sex differences. RESULTS: Of the 597 consecutive cases, mean age was 67 years ranging from 20 to 94 years. Univariate analyses showed that female patients had less proportion of large tumor (P=0.017), local advanced tumor (P<0.001) and lymph node metastasis (P=0.022). No significant sex-related differences were found in the age, tumor grade, and tumor number. CONCLUSION: In Chinese UUTUC patients, female patients were more common. Females are less likely to have more advanced pathologic stage than males.

Transforming growth factor beta1 mediates apoptotic activity of angiotensin II type I receptor blocker on prostate epithelium in vitro.

BACKGROUND: The significant association of benign prostatic hyperplasia (BPH) and hypertension indicates a common pathophysiological factor for both diseases. Hyperactivity of the renin-angiotensin system (RAS) has been reported in BPH. Angiotensin II type I (AT1) receptor is the principal mediator of the RAS, and the antagonist, AT1 receptor blocker (ARB), can induce apoptosis in prostate epithelium cells and increase transforming growth factor beta1 (TGF-beta1) expression. We aimed to investigate the mechanism of inhibition of AT1 receptor in prostate epithelium cells and the role of TGF-beta1. METHODS: Human prostate epithelium cell lines were treated with different concentrations of ARB (losartan) (0, 0.1, 1, 10, 100, and 1,000 microM) for 24-72 hr. Cell proliferation was analyzed by cell proliferation assay. The location of AT1 receptor was shown by immunocytohistochemistry and immunocytofluorescence study. Analysis of apoptosis was by use of terminal transferase TdT-mediated dUTP-biotin end labeling (TUNEL) and caspase 3/7 activity assay. Mitochondrial outer-membrane permeabilization was measured by JC-1 staining. The level of TGF-beta1 was determined by enzyme-linked immunosorbent assay. RESULTS: Immunohistochemistry and immunofluorescence analysis showed AT1 receptor expressed in epithelium cells. Compared to control cultures, cultures treated with losartan for 24-72 hr showed a dose-dependent significant decrease in cell number, with apoptosis increased by 65.2%. Decreased cell number was reversed on treatment with anti-TGF-beta1 antibody. TUNEL staining showed increased apoptosis in prostate epithelium cells exposed to losartan. Caspase 3/7 activation was increased and mitochondrial membrane potential was downregulated. Expression of TGF-beta1 in cells treated with losartan was higher than that in untreated cells. CONCLUSIONS: The apoptotic effect of blockade of AT1 receptor on human prostatic epithelium cells may be mediated through an autocrine the production of TGF-beta1. Furthermore, this finding may have implications for medication options. Inc.

[Comparison and clinical significance of different imageological methods in the detection of transitional carcinoma of upper urinary tract: analysis of 234 cases].

OBJECTIVE: To determine the diagnostic value of multislice CT urography (MSCTU) in patients with transitional cell carcinoma (TCC) of upper urinary tract by comparing other imageology methods used. METHODS: Two hundred and thirty four cases of transitional cell carcinoma of upper urinary tract, in which 82 cases were diagnosed pathologically with pelvic carcinoma and 152 cases with ureteral carcinoma, between June 2004 and September 2006 in our institute were enrolled in a retrospective study. Most of them underwent urological ultrasound, intravenous urogram (IVU), retrograde pyelography and MSCTU. We compared the positive rate (PR) and diagnostic rate (DR) of these methods used by chi-square test. RESULTS: Among the 234 cases, 215 patients underwent urologic ultrasound, in which 152 cases were detected to be abnormal, with the PR of 70.7%; Meanwhile, 58 cased were diagnosed by this examination, with the DR of 27.0%. IVU was performed in 193 patients and 132 cases were found to be abnormal, and the PR was 68.4%, 65 cases were diagnosed by IVU and the DR was 33.7%. And 132 patients underwent retrograde pyelography, by which 115 cases of lesion were detected, with the PR of 87.1%; In the meantime, 93 cases were diagnosed, with the DR of 70.5%. MSCTU was performed in 226 cases and 220 cases were found to be abnormal, and the PR was 97.3%; 214 cases were diagnosed by MSCTU, with the DR of 94.7%. The DR of detecting TCC of retrograde pyelography had statistically significant difference with that of ultrasound and IVU (P<0.001). As compared with retrograde pyelography, MSCTU had statistically significant superiority (P<0.001). CONCLUSION: To shorten the diagnosis time and mitigate the sufferings, patients with hematuria supposed to be TCC of upper urinary tract should be recommended to undergo MSCTU first.

Aberrant methylation of the 8p22 tumor suppressor gene DLC1 in renal cell carcinoma.

Epigenetic mechanisms involving DNA methylation and chromatin remodeling are important in silencing tumor suppressor genes (TSG) in various malignancies, including renal cell carcinoma (RCC). DLC1 (deleted in liver cancer 1)/ARHGAP7 is a recently identified 8p22 candidate TSG. Frequent methylation of the DLC1 promoter with resultant gene silencing has been reported in several tumors, but not in RCC yet. We examined DLC1 promoter methylation in 34 primary RCCs and the corresponding non-malignant tissues, and the correlation of DLC1 methylation with the clinicopathological characteristics of RCC patients. Although DLC1 methylation and downregulation were only detected in one of seven RCC cell lines using methylation-specific PCR (MSP) and semi-quantitative reverse-transcription PCR, we found that the DLC1 promoter was methylated in 35% (12/34) of primary RCC tumors, which was further confirmed by direct sequencing of MSP products and high-resolution bisulfite genomic sequencing. In contrast, only one of the 34 (3%) non-malignant renal tissues had weak methylation. Aberrant DLC1 methylation appeared to be a relatively early event during renal tumorigenesis since 33% of the RCC tumors with pT1 (TNM staging) showed methylation, which is similar to other late stage tumors. Thus, our results demonstrated that DLC1 methylation occurs in a subset of RCC tumors and may play a role in renal carcinogenesis.

Angiotension II receptor 1 blocker modifies the expression of apoptosis-related proteins and transforming growth factor-beta1 in prostate tissue of spontaneously hypertensive rats.

OBJECTIVE: To assess whether angiotensin II (Ang II), important in hypertension and highly expressed in benign prostatic hyperplasia (BPH), is involved in prostate growth, by analysing changes in the histological composition, tissue apoptotic status and level of transforming growth factor-beta1 (TGFbeta1) induced by an Ang II type 1 receptor blocker, losartan, in the prostates of spontaneously hypertensive (SH) rats. MATERIALS AND METHODS: We assessed four groups of six rats each: normotensive Wistar-Kyoto counterparts of SH rats; untreated SH rats; SH rats given low-dose losartan (10 mg/kg/day for 10 weeks); and SH given high-dose losartan (30 mg/kg/day for 10 weeks). We evaluated the histological composition and expression of TGFbeta1 and apoptosis-related proteins, i.e. Bax and the 116-kDa poly (adenosine diphosphate-ribose) polymerase (PARP), by Western blotting in the rat prostate ventral lobes. RESULTS: Compared with Wistar-Kyoto rats, untreated SH rats had a significantly increased epithelium component in the prostate (P < 0.01), but with losartan treatment, SH rats showed less of the epithelium component than untreated rats (P < 0.01 for both low- and high-dose losartan). Western-blot analysis showed a significantly increased level of Bax in high-dose losartan-treated rats (P < 0.01). The expression of 116 kDa PARP was also decreased in these rats (P < 0.01), which suggests increased caspase-3 activity. In addition, TGFbeta1 levels were significantly elevated in high-dose losartan-treated rats (P < 0.01). CONCLUSION: These results show that losartan can induce apoptosis of prostate epithelium and increase the TGFbeta1 expression in SH rats, suggesting that Ang II stimulation might be involved in the pathogenesis of BPH, which might correlate with the regulation of TGFbeta1 expression.