Massive localized lymphedema (MLL) is a non-neoplastic benign soft tissue lesion that may be confused with sarcomas or other neoplastic proliferations both clinically and morphologically. Most occur ...in morbidly obese adults on the lower extremities. The objective of this article is to document a case of MLL in the retroperitoneal cavity which is a previously unreported site for this lesion, and to highlight its unusual clinical features.
The patient was a non-obese male who had undergone major abdominal surgery due to bladder extrophy 17 years ago. Abdominal ultrasonography detected a large incidental mass in the right renal sinus during his investigation for nephrolithiasis. The lesion extending from renal pelvis down to pelvis was resected and its histopathological findings were compatible with massive localized lymphedema.
Retroperitoneum has to be added to the list of locations that MLL can be found. Liposarcoma will be a challenging differential diagnosis when the lesion is encountered in an unusual site.
Noninvasive approaches for early detection of bladder cancer are actively being investigated. We recently developed a urine- based molecular assay for the detection and surveillance of bladder ...neoplasms (UroSEEK). UroSEEK is designed to detect alterations in 11 genes that include most common genetic alterations in bladder cancer. In this study, we analyzed 527 cases, including 373 noninvasive and 154 invasive urothelial carcinomas of bladder from transurethral resections or cystectomies performed at four institutions (1991-2016). Two different mutational analysis assays of a representative tumor area were performed: first, a singleplex PCR assay for evaluation of the TERT promoter region (TERTSeqS) and second, a multiplex PCR assay using primers designed to amplify regions of interest of 10 (FGFR3, PIK3CA, TP53, HRAS, KRAS, ERBB2, CDKN2A, MET, MLL, and VHL) genes (UroSeqS). Overall, 92% of all bladder tumors were positive for at least one genetic alteration in the UroSEEK panel. We found TERT promoter mutations in 77% of low-grade noninvasive papillary carcinomas, with a relatively lower incidence of 65% in high-grade noninvasive papillary carcinomas and carcinomas in situ; p = 0.017. Seventy-two percent of pT1 and 63% of muscle-invasive bladder tumors harbored TERT promoter mutations with g.1295228C>T alteration being the most common in all groups. FGFR3 and PIK3CA mutations were more frequent in low-grade noninvasive papillary carcinomas compared with high-grade noninvasive papillary carcinomas and carcinomas in situ (p < 0.0001), while the opposite was true for TP53 (p < 0.0001). Significantly higher rates of TP53 and CDKN2A mutation rates (p = 0.005 and 0.035, respectively) were encountered in muscle-invasive bladder tumors compared with those of pT1 stage. The overwhelming majority of all investigated tumors showed at least one mutation among UroSEEK assay genes, confirming the comprehensive coverage of the panel and supporting its potential utility as a noninvasive urine-based assay.
Abstract
Background
Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm seen in children and young adults, usually manifested by involvement of abdominal serosa. Here, we ...present an unusual case of primary DSRCT of kidney.
Case presentation
The patient was an 8-year-old girl with a large renal mass which was confused with primitive neuroectodermal tumor (PNET) in the needle biopsy. The tumor had a variegated histology revealing frequent pseudo-rosette formations, pseudopapillary architecture, rhabdoid, clear or pleomorphic cells in addition to typical small round cell morphology and desmoplasia. It showed immunohistochemical features of DSRCT, and
EWSR1
re-arrangement.
Conclusions
Proffering this diagnosis is particularly difficult for tumors of viscera because of the incognizance of the entity in these locations. Moreover, DSRCT is a great mimicker and may get easily confused with more common kidney malignancies of childhood such as Wilms tumor, PNET/EWS, rhabdoid tumor, clear cell sarcoma, and other small round cell tumors as well as renal cell carcinomas. The distinction is critical as the accurate therapeutic approach will require correct diagnosis.
Idiopathic nephrotic syndrome (INS) is a genetically heterogeneous group of disorders characterized by proteinuria, hypoalbuminemia, and edema. Because it typically results in end-stage kidney ...disease, the steroid-resistant subtype (SRNS) of INS is especially important when it occurs in children. The present study included 29 affected and 22 normal individuals from 17 SRNS families; genome-wide analysis was performed with Affymetrix 250K SNP arrays followed by homozygosity mapping. A large homozygous stretch on chromosomal region 12p12 was identified in one consanguineous family with two affected siblings. Direct sequencing of protein tyrosine phosphatase receptor type O (PTPRO; also known as glomerular epithelial protein-1 GLEPP1) showed homozygous c.2627+1G>T donor splice-site mutation. This mutation causes skipping of the evolutionarily conserved exon 16 (p.Glu854_Trp876del) at the RNA level. Immunohistochemistry with GLEPP1 antibody showed a similar staining pattern in the podocytes of the diseased and control kidney tissues. We used a highly polymorphic intragenic DNA marker—D12S1303—to search for homozygosity in 120 Turkish and 13 non-Turkish individuals in the PodoNet registry. This analysis yielded 17 candidate families, and a distinct homozygous c.2745+1G>A donor splice-site mutation in PTPRO was further identified via DNA sequencing in a second Turkish family. This mutation causes skipping of exon 19, and this introduces a premature stop codon at the very beginning of exon 20 (p.Asn888Lysfs∗3) and causes degradation of mRNA via nonsense-mediated decay. Immunohistochemical analysis showed complete absence of immunoreactive PTPRO. Ultrastructural alterations, such as diffuse foot process fusion and extensive microvillus transformation of podocytes, were observed via electron microscopy in both families. The present study introduces mutations in PTPRO as another cause of autosomal-recessive nephrotic syndrome.
Non-choriocarcinomatous trophoblastic tumors (NCTTs) are seldomly diagnosed in male genital tract. As they have been recently described among the testicular germ cell tumor (TGCT) variants, ...pathologists’ familiarity with their morphology is limited. We searched our electronic hospital records covering the years 2000–2017 for post-chemotherapy retroperitoneal TGCT metastectomies. Slides of all cases with viable tumor were retrieved from the archives and reviewed. Cases suspected of N-CTT morphologies were subjected to immunohistochemistry. Twelve NCTTs were identified, 9 of which were unseen or misdiagnosed by the original pathologists: Cystic trophoblastic tumor (CTT) (
n
= 5), placental site trophoblastic tumor (
n
= 2), epithelioid trophoblastic tumor (ETT) (
n
= 4), and coinciding PSTT + ETT (
n
= 1). Eight of these were associated with mature teratoma components, and one case (ETT) contained embryonal carcinoma and yolk sac tumor in addition to teratoma. Ten patients were clinically N1 at the time of primary tumor detection and orchiectomy. One patient had burned-out primary testicular tumor. Six patients were clinical M1a at presentation, while one male was cM1b. Six patients had mildly elevated β-HCG (≤ 410 mIU/ml) just prior to retroperitoneal lymph node dissections (RPLND), while the others had normal β-HCG levels. All patients had follow-ups ranging from 8 to 118 months (mean 42.3 months). Three patients died of disease-related and two of unrelated causes. In conclusion, because NCTTs are rare and newly described tumor types, their diagnosis is difficult and most of them are missed in post-chemotherapy RPLNDs. The majority of patients exhibit normal or slightly elevated β-HCG levels. N-CTTs are usually accompanied by other components of TGCT, the most common being teratoma. Despite the high survival rate of the patients, our study points to the unpredictable evolution of NCTT cases, which may concur with a high-stage or progressive disease.
To evaluate the impact of a histologically inverted pattern on recurrence in patients with newly diagnosed non-invasive, low-grade papillary urothelial carcinoma of the urinary bladder.
A total of 81 ...patients with primary bladder non-invasive, low-grade papillary urothelial carcinoma diagnosed in a single tertiary-care centre who had at least 1-year follow-up after an initial resection were included. All slides from each case were reviewed to determine the growth pattern (exophytic versus endophytic, i.e. inverted) and other histological parameters. Clinical data were retrieved from hospital records.
Disease recurrence occurred in 41 (50.6%) patients. Cases with an inverted pattern showed a lower recurrence rate than those with pure exophytic tumours (37.5% versus 52.1%), a longer time to first recurrence (mean 34 versus 21.5 months) and fewer recurrence episodes (p=0.482, 0.564 and 0.051, respectively). All recurring inverted cases recurred only once during follow-up. No tumour with >80% inverted architecture recurred.
Our results suggest that non-invasive, low-grade papillary urothelial carcinoma of the bladder tends to have a better outcome in terms of disease recurrence if it shows an inverted growth pattern. To indicate the presence and percentage of the inverted pattern in low-grade urothelial carcinomas in the pathology report might be considered as an adjunct to help long-term patient management.
Introduction and Objectives
To investigate the additive role of prostate‐specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) independent from multiparametric ...magnetic resonance imaging (mpMRI) and clinical‐pathological parameters to predict pathological upgrading in patients with ISUP grade group (GG) 1 prostate cancer (PCa) at prostate biopsy.
Materials and Methods
A total of 41 patients who underwent robotic radical prostatectomy (RP) for GG1 disease at prostate biopsy with preoperative PSMA PET/CT and mpMRI images available for central review were included in the study. Univariate and multivariate logistic regression analyses were performed to determine the independent predictors of pathological upgrading (GG ≥ 2).
Results
Final RP pathology revealed upgrading in 26 patients (65.9%); to GG 2 disease in 25 cases and GG 4 disease in one case. International Society of Urological Pathology (ISUP) upgrading rates for prostate imaging‐reporting and data system (PIRADS)‐5, PIRADS‐4, and PIRADS ≤ 3 lesions were 78%, 74%, and 38%, respectively. Fourteen out of 15 (93.3%) patients with an SUVmax ≥ 5.6 and all patients with an SUVmax ≥ 6.5 (n = 10) had pathological upgrading. The upgrading rate in patients with SUV < 5.6 was 46.2% (12/26). Intraprostatic SUVmax ≥ 5.6 was found as the only independent predictor of pathological upgrading in multivariate analysis.
Conclusion
High prostatic PSMA uptake was found to be a very reliable predictor of pathological upgrading, but low PSMA uptake cannot exclude pathological upgrading. Intraprostatic PSMA uptake along with previously known mpMRI and biopsy‐related parameters should be considered when making a treatment decision in patients with GG1 PCa at prostate biopsy.
Activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene are the most common genetic alterations in urothelial carcinoma (UC) of the bladder and upper urinary tract. ...Although the cadherin 1 (CDH1) gene is commonly mutated in the clinically aggressive plasmacytoid variant of urothelial carcinoma (PUC), little is known about their TERT promoter mutation status. A retrospective search of our archives for PUC and UC with plasmacytoid and/or signet ring cell features (2007-2014) was performed. Ten specimens from 10 patients had archived material available for DNA analysis and were included in the study. Intratumoral areas of nonplasmacytoid histology were also evaluated when present. Samples were analyzed for TERT promoter mutations with Safe-SeqS, a sequencing error-reduction technology, and sequenced using a targeted panel of the 10 most commonly mutated genes in bladder cancer on the Illumina MiSeq platform. TERT promoter mutations were detected in specimens with pure and focal plasmacytoid features (6/10). Similar to conventional UC, the predominant mutation identified was g.1295228C>T. In heterogeneous tumors with focal variant histology, concordant mutations were found in plasmacytoid and corresponding conventional, glandular, or sarcomatoid areas. Co-occurring mutations in tumor protein p53 (TP53, 2 cases) and kirsten rat sarcoma (KRAS) viral proto-oncogene (1 case) were also detected. TERT promoter mutations are frequently present in PUC, which provides further evidence that TERT promoter mutations are common events in bladder cancer, regardless of histologic subtype, and supports their inclusion in any liquid biopsy assay for bladder cancer.
•Plasmacytoid bladder cancer frequently harbors hotspot TERT promoter mutations.•TERT promoter mutations are common events in bladder cancer, regardless of subtype.•Liquid biopsy assays for bladder cancer should include the TERT promoter region.
OBJECTIVEThe aim of this study is to compare systematic, cognitive fusion, in-bore, and software fusion prostate biopsies regarding rates of and risk factors for pathological upgrading. MATERIAL AND ...METHODSCharts of 291 patients with systematic biopsy (n = 105), magnetic resonance imaging- targeted cognitive fusion (n = 58), in-bore (n = 68), and software fusion biopsy (n = 60), and who subsequently underwent radical prostatectomy were retrospectively evaluated. The degree of similarity between the grade groups reported in the biopsy and radical prostatectomy pathology results was recorded. Analyses of the associated factors for concordance and discordance were performed with univariate and multivariate methods. RESULTSThe concordance rates were as follows: systematic biopsy = 42.8%, cognitive fusion-targeted biopsy = 50%, in-bore fusion-targeted biopsy = 61.8, and software fusion biopsy = 58.4%. The upgrade rate of systematic biopsy (46.6%) was higher than cognitive fusion-targeted biopsy (27.6%), in-bore fusiontargeted biopsy (26.4%), and software fusion-targeted biopsy (18.3%). The number of positive cores was significantly associated with grade group concordance for the systematic biopsy group (P = .040). Within the cognitive fusion-targeted biopsy cohort, number of positive cores was the only parameter that exhibited a significant association with grade group concordance in multivariate analysis (P = .044). Considering the in-bore fusion-targeted biopsy group, maximum tumor length was statistically significant (P = .021). In the software fusion-targeted biopsy group, low prostate volume was found to be the only significant predictor for grade group accordance (P = .021). CONCLUSIONMagnetic resonance imaging-targeted biopsy techniques showed higher concordance and lower upgrade rates compared to systematic biopsy. For systematic biopsy and cognitive fusion-targeted biopsy, the number of positive cores was associated with grade group concordance, while maximum tumor length in in-bore fusion-targeted biopsy and low prostate volume for in-bore fusion-targeted biopsy were associated with grade group concordance. Among the MRI-targeted biopsy methods, in-bore fusion-targeted biopsy and software fusion-targeted biopsy were more accurate than cognitive fusion-targeted biopsy in terms of grade group.
Our group and others have previously demonstrated the presence of
TERT
promoter mutations (
TERT-mut
) in 60–80% of urothelial carcinomas and some of their histologic variants. Five other genes have ...been frequently implicated in bladder cancer:
FGRF3
,
TP53
,
PIK3CA
,
HRAS
, and
CDKN2A
. In the current study, we sought to determine the prevalence of mutations in
TERT
and these five other genes in de novo papillary urothelial neoplasms of low malignant potential (PUNLMP) of the urinary bladder. A retrospective search of our archives for PUNLMP was performed and 30 de novo cases were identified and included in the study. We found mutations in
TERT (TERT-mut)
and
FGFR3
(
FGFR3-mut)
to be the most common alterations in the cohort (63 and 60%, respectively). The majority of the
TERT-mut
-positive tumors (84%) had a g.1295228C > T alteration with the remaining tumors demonstrating g.1295250C > T. Approximately one fourth of tumors had TP53 mutations. These findings support the potential utility of a uniform genetic mutation panel to detect bladder cancers of various subtypes.
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