Comparison of Multiparametric MRI-targeted and Systematic Biopsies for Detection of Cribriform and Intraductal Carcinoma Prostate Cancer.

Background Intraductal carcinoma (IDC) and invasive cribriform (Cr) subtypes of prostate cancer (PCa) are an indication of aggressiveness, but the evidence regarding whether MRI can be used to detect Cr/IDC-pattern PCa is contradictory. Purpose To compare the detection of Cr/IDC-pattern PCa at multiparametric MRI (mpMRI)-targeted biopsy versus systematic biopsy in biopsy-naive men at risk for PCa. Materials and Methods This study was a secondary analysis of a prospective randomized controlled trial that recruited participants with a clinical suspicion of PCa between April 2017 and November 2019 at five centers. Participants were randomized 1:1 to either the MRI arm or the systematic biopsy arm. Targeted biopsy was performed in participants with a Prostate Imaging Reporting and Data System score of at least 3. MRI features were recorded, and biopsy slides and prostatectomy specimens were reviewed for the presence or absence of Cr/IDC histologic patterns. Comparison of Cr/IDC patterns was performed using generalized linear mixed modeling. Results A total of 453 participants were enrolled, with 226 in the systematic biopsy arm (median age, 65 years [IQR, 59-70 years]; 196 biopsies available for assessment) and 227 in the mpMRI-targeted biopsy arm (median age, 67 years [IQR, 60-72 years]; 132 biopsies available for assessment). Identification of Cr/IDC PCa was lower in the systematic biopsy arm compared with the mpMRI arm (31 of 196 biopsies [16%] vs 33 of 132 biopsies [25%]; P = .01). No evidence of a difference in mean cancer core length (CCL) (11.3 mm ± 4.4 vs 9.7 mm ± 4.5; P = .09), apparent diffusion coefficient (685 µm2/sec ± 178 vs 746 µm2/sec ± 245; P = .52), or dynamic contrast-enhanced positivity (27 [82%] vs 37 [90%]; P = .33) for clinically significant PCa (csPCa) was observed between participants with or without Cr/IDC disease in the MRI arm. Cr/IDC-positive histologic patterns overall had a higher mean CCL compared with Cr/IDC-negative csPCa (11.1 mm ± 4.4 vs 9.2 mm ± 4.1; P = .009). Conclusion MRI-targeted biopsy showed increased detection of Cr/IDC histologic patterns compared with systematic biopsy. Clinical trial registration no. NCT02936258 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Scialpi and Martorana in this issue.

Primary amyloidosis of the bladder; a mimicker of bladder cancer.

Amyloidosis is a protein folding disorder characterized by the deposition of fibrillar proteins into solid organs or tissues. Primary localized amyloidosis of the bladder is very rare and can mimic bladder cancer in its presentation with hematuria, lower urinary tract symptoms or a mass on imaging. A case of localized amyloidosis of the bladder in a 48-year-old man with painless gross hematuria and evidence of bladder mass on ultrasound is presented. Amyloidosis is a rare but important non-malignant process of the bladder. We present a review of the literature and suggestions for management of this rare bladder disease.

Perineural invasion on biopsy is associated with upstaging at radical prostatectomy in Gleason score 3 + 4 = 7 prostate cancer.

This study assesses if perineural invasion (PNI) detected on biopsy with Gleason score (GS) 3 + 4 = 7 prostate cancer (PCa) is associated with upstaging/upgrading of disease after radical prostatectomy (RP). 154 patients with GS 3 + 4 = 7 PCa diagnosed from biopsy who underwent RP were assessed for PNI. The percentage of biopsy sites with PNI (%PNI) was also calculated. Pattern 4 morphologies (ill-defined glands [IDG], fused, cribriform, and glomerulations) were also assessed. Clinical information, GS and stage after RP were retrieved from the medical records. 45 % (69/154) of patients were upstaged (≥pT3) and 29 % (44/154) were upgraded to GS >3 + 4 = 7 after RP. 37 % (57/154) of patients had PNI which was associated with upstaging (RR 1.4; P = 0.04) but not upgrading (RR 0.9; P = 0.7). There was higher %PNI in upstaged patients (12.1 % ± 1.8 vs. 7.1 % ± 1.5, P = 0.03) with a significant correlation between %PNI and ≥pT3 (r = 0.178, P = 0.027). After multivariate analysis, only cribriform formations were significantly associated with upstaging (P = 0.009). The presence of PNI in biopsies with GS 3 + 4 = 7 PCa is associated with upstaging at RP but is a weaker predictor of ≥pT3 disease than cribriform morphology.

Nested and microcystic variants of urothelial carcinoma displaying immunohistochemical features of basal-like urothelial cells: an immunohistochemical and histopathogenetic study.

Nested/microcystic (NV/MV) urothelial carcinoma (UC) variants are associated with mild cytologic atypia and commonly present at high-stage disease. The histopathogenesis is investigated using urothelial basal cell markers. Archival 14 NV/MV and three inverted papilloma (IP) were immunostained for CD44, cytokeratin 5 (CK5), CK34bE12 and p63. Twenty consecutive cases of invasive high-grade UC including 14 superficial and 6 muscle-invasive UC cases were used as control. Immunostaining was scored as high for staining of full or more than 50% thickness of the epithelial nest or epithelium and low for lesser immunoreactivity and negative reactivity. All 14 NV/MV, 3 IP and 6 control cases showed a high score of immunoreactivity for CK5, CD44, CK34bE12 and focally for p63. The remaining control cases showed a high score of immunoreactivity for CK34bE12, while negative or low for CK5, CD44 and p63. In conclusion, immunoreactivity CK5 and CD44 commonly immunostained NV/MV and some invasive high grade UC. Other basal cell markers (CK34bE12 and p63) appear to be non specific or non sensitive. NV and MV and some UC likely represent a subset of UC displaying immunohistochemical features of urothelial basal cells. They had tendency of endophytic growth and early invasion despite the innocuous cytologic appearance.

Stimulated Raman histology as a method to determine the adequacy of renal mass biopsy and identify malignant subtypes of renal cell carcinoma.

INTRODUCTION: Renal tumor biopsy requires adequate tissue sampling to aid in the investigation of small renal masses. In some centers the contemporary nondiagnostic renal mass biopsy rate may be as high as 22% and may be as high as 42% in challenging cases. Stimulated Raman Histology (SRH) is a novel microscopic technique which has created the possibility for rapid, label-free, high-resolution images of unprocessed tissue which may be viewed on standard radiology viewing platforms. The application of SRH to renal biopsy may provide the benefits of routine pathologic evaluation during the procedure, thereby reducing nondiagnostic results. We conducted a pilot feasibility study, to assess if renal cell carcinoma (RCC) subtypes may be imaged and to see if high-quality hematoxylin and eosin (H&E) could subsequently be generated. METHODS/MATERIALS: An 18-gauge core needle biopsy was taken from a series of 25 ex vivo radical or partial nephrectomy specimens. Histologic images of the fresh, unstained biopsy samples were obtained using a SRH microscope using 2 Raman shifts: 2,845 cm-1 and 2,930 cm-1. The cores were then processed as per routine pathologic protocols. The SRH images and hematoxylin and eosin (H&E) slides were then viewed by a genitourinary pathologist. RESULTS: The SRH microscope took 8 to 11 minutes to produce high-quality images of the renal biopsies. Total of 25 renal tumors including 1 oncocytoma, 3 chromophobe RCC, 16 clear cells RCC, 4 papillary RCC, and 1 medullary RCC were included. All renal tumor subtypes were captured, and the SRH images were easily differentiated from adjacent normal renal parenchyma. High quality H&E slides were produced from each of the renal biopsies after SRH was completed. Immunostains were performed on selected cases and the staining was not affected by the SRH image process. CONCLUSION: SRH produces high quality images of all renal cell subtypes that can be rapidly produced and easily interpreted to determine renal mass biopsy adequacy, and on occasion, may allow renal tumor subtype identification. Renal biopsies remained available to produce high quality H&E slides and immunostains for confirmation of diagnosis. Procedural application has promise to decrease the known rate of renal mass nondiagnostic biopsies, and application of convolutional neural network methodology may further improve diagnostic capability and increase utilization of renal mass biopsy among urologists.

Unexpected diagnosis of metastatic breast carcinoma in an endomyocardial biopsy done for cardiac allograft rejection evaluation.

We report a case of a 75-year-old female post orthotopic heart transplantation, who presented to the emergency department with a six-week history of shortness of breath, hand tremor and ultimately delirium. She had lobular breast carcinoma more than 5 years prior to her heart transplant, treated by lumpectomy followed by anthracycline based chemotherapy. The reason for her heart transplant was heart failure that was suspected to be from anthracycline cardiomyopathy, however, her explanted heart actually showed cardiac sarcoidosis. She was placed on long-term immunosuppression with tacrolimus, mycophenolate mofetil and prednisone. Two years after her heart transplant, she underwent bilateral mastectomies for recurrent breast cancer. Her neurological workup, including brain imaging (CT, MRI, LP and EEG) did not show any structural abnormalities, ischemia, mass or neurosarcoidosis as cause for delirium. Tacrolimus was held due to renal dysfunction and hemolytic anemia, and then she developed signs of right heart failure so an endomyocardial biopsy was carried out for suspected allograft rejection. The biopsy did not show any evidence of cellular or antibody medicated rejection; however, it demonstrated infiltration by bland appearing cells with signet ring morphology cells many of which showed intracytoplasmic mucin. The cells were strongly positive with cytokeratins AE1/3, CK7 and mammaglobin. The morphology and immunoprofile were consistent with metastatic lobular breast carcinoma and this was thought to be the cause of her clinical presentation with delirium, hemolytic anemia and renal dysfunction as a paraneoplastic syndrome.

Evaluation of individual and cumulative sites of extrarenal tumor invasion in pT3a clear cell renal cell carcinoma.

INTRODUCTION: The Tumor-Node-Metastasis classification of renal cell carcinoma (RCC) for pT3a tumors includes sinus fat invasion (SFI), perinephric fat invasion (PFI), renal vein invasion (RVI), and/or pelvicaliceal system invasion (PSI). The purpose of this study was to determine the association between these patterns of invasion (assessed individually and cumulatively) with the development of metastases and cancer-specific mortality (CSM). MATERIALS AND METHODS: We identified 160 patients who underwent radical nephrectomy for pT3a clear cell RCC between 2011 and 2017. The association between individual patterns of invasion and metastases and cancer-specific survival were evaluated with multivariate logistic regression. Cox Hazard proportion ratios and Kaplan-Meier survival curves were generated for patterns of invasion (assessed individually and cumulatively). RESULTS: The number of individual invasive patterns was as follows: 97/160 (61%) presented with RVI, 91/160 with SFI (57%), 62/160 with PFI (39%), and 24/160 (15%) with PSI. At multivariate analysis, both PFI and RVI were associated with metastases (P < 0.001 and 0.028, respectively). PFI (hazard ratio [HR] 4.12, 95% confidence interval [CI] 2.14-7.92; P < 0.001), RVI (HR 2.44, 95% CI 1.18-5.01; P = 0.015), SFI (HR 2.13, 95% CI 1.05-4.34; P = 0.036) had higher CSM, while PSI (HR 1.43, 95% CI 0.65-3.16; p = 0.38) did not show increased CSM. Furthermore, cumulative analysis showed that multiple invasive patterns resulted in worse CSM (p < 0.001). CONCLUSIONS: In our study, PFI was associated with the most aggressive behavior while PSI was the most indolent. Furthermore, the presence of more than one pattern of invasion was associated with worse CSM. These results indicate that reporting of the individual location and cumulative amount of pT3a patterns of invasion in clear cell RCC is clinically relevant.

Oncocytic renal cell carcinoma with immunohistochemical properties of renal oncocytoma.

Renal oncocytoma (RO) is a characteristic benign renal tumor. The existence of malignant RO is controversial and anecdotal, partly due to a lack of specific markers for RO. With recent advances in immunohistochemistry, RO can be distinguished from other renal neoplasms with routine stains and with the aid of immunostaining. We report two cases of renal neoplasms with similar histopathological appearances. They were characterized by oncocytic cytoplasm, numerous intra-cytoplasmic vacuoles, uniform round to oval hyperchromatic nuclei with remarkably thick nuclear membranes and prominent nucleoli. The tumor cells were closely packed and disposed in an alveolar pattern. The neoplastic cells were diffusely reactive for CD117 and progesterone receptor, and diffusely or focally reactive for cytokeratin AE1/AE3, and focally reactive for cytokeratin 7, CD10, and racemase. The cells were non-reactive for renal cell carcinoma (RCC) antigen, vimentin, S100, and neuroendocrine markers. One tumor showed lymph node metastasis. Due to the remarkable cytological atypia, lymph node metastasis, and similar immunological features of RO, these two tumors likely represent a distinct subtype of RCC related to RO.

Lysosomal storage disorders affecting the heart: a review.

Lysosomal storage disorders (LSD) comprise a group of diseases caused by a deficiency of lysosomal enzymes, membrane transporters or other proteins involved in lysosomal biology. Lysosomal storage disorders result from an accumulation of specific substrates, due to the inability to break them down. The diseases are classified according to the type of material that is accumulated; for example, lipid storage disorders, mucopolysaccharidoses and glycoproteinoses. Cardiac disease is particularly important in lysosomal glycogen storage diseases (Pompe and Danon disease), mucopolysaccharidoses and in glycosphingolipidoses (Anderson-Fabry disease). Various disease manifestations may be observed including hypertrophic and dilated cardiomyopathy, coronary artery disease and valvular diseases. Endomyocardial biopsies can play an important role in the diagnosis of these diseases. Microscopic features along with ancillary tests like special stains and ultrastructural studies help in the diagnosis of these disorders. Diagnosis is further confirmed based upon enzymatic and molecular genetic analysis. Emerging evidence suggests that Enzyme replacement therapy (ERT) substantially improves many of the features of the disease, including some aspects of cardiac involvement. The identification of these disorders is important due to the availability of ERT, the need for family screening, as well as appropriate patient management and counseling.

Characteristics and outcomes in a prospective cohort of patients with histologically diagnosed aortitis.

OBJECTIVES: Our aim was to evaluate characteristics and prospective adverse aortic outcomes in a cohort of patients with non-infectious histological aortitis. METHODS: Patients with histological aortitis, diagnosed at the Ottawa Hospital after surgical repair of thoracic aortic aneurysms or dissections, consented to enrolment in a prospective observational cohort. Patients were assessed for an underlying inflammatory condition and followed prospectively with periodic clinical, laboratory and radiographic assessments. Aortic outcomes during follow-up included significant events, defined as new thoracic or abdominal aortic aneurysms, dissections, ruptures or other complications requiring aortic intervention, in addition to aortic branch ectasias, aneurysms and stenosis. RESULTS: Sixteen patients with histological aortitis from surgical procedures performed between 2010 and 2017 were included; nine had idiopathic and seven had secondary aortitis. Idiopathic patients were more likely to have smoked (100 vs 43%, P = 0.02) and had more associated arch or descending aortic aneurysms on pre-operative baseline imaging compared with secondary aortitis (6 vs 0, P = 0.01). At the median 3.6 years of follow-up, eight patients (50%) had 10 significant aortic events. The incidence of aortic dissection was higher in the first year post-surgery, compared with subsequent years, whereas incident aneurysms occurred throughout follow-up. Elevated inflammatory markers during follow-up trended towards association with accumulation of severe aortic damage. CONCLUSION: This is the first reported prospective study in patients with histological aortitis. Within the limitations of a small cohort, we report a high incidence of aortic complications. Studies with a larger sample size and longer follow-up are needed to corroborate these findings.

Sporadic clear cell renal cell carcinoma with diffuse cytokeratin 7 immunoreactivity.

AIMS: Clear cell renal cell carcinoma (CRCC) with diffuse immunoreactivity for CK7 is described. METHODS: All cases of CRCC, measuring 20 mm or less in diameter over a period of 10 years, were examined. Areas of regenerative epithelial cell nests (REC) were also examined. RESULTS: Fifteen specimens containing 29 nodules were diagnosed as CRCC due to the characteristic clear cytoplasm. Of these 29 nodules, 21 showed diffuse CK7 positivity while eight showed CK7 negativity. The CK7 positive CRCC measured less than 16 mm and contained varying proportions of tumour cells with chromophil cytoplasm. Architecturally, CK7 positive CRCC consisted of cysts and solid cell nests with tubulo-acinar formations or papillary formations. Immunostaining for AMACR, CD10 and RCC showed negative or focal reactivity in the CK7 positive CRCC, frequently positive reactivity in CK7 negative CRCC and negative reactivity in REC which also displayed strong CK7 reactivity. The ten patients with 21 CK7 positive CRCC developed no metastatic disease over a follow up time that ranged from 1 to 10 years (mean of 3 years). CONCLUSIONS: CRCC characterised by diffuse CK7 positivity represents a distinct type of CRCC with characteristic histopathological and immunohistochemical features.

Oncocytic papillary renal cell carcinoma with solid architecture: mimic of renal oncocytoma.

Papillary renal cell carcinoma (PRCC) can display extensive areas of solid and non-papillary architecture and extensive areas with oncocytic cytoplasm. Eleven oncocytic renal cell neoplasms (ORCN) with histopathological features posing a diagnostic problem between renal cell carcinoma (RCC) with oncocytic features and renal oncocytoma (RO) were identified. The neoplasms were well circumscribed or encapsulated tumors with solid and diffuse growth pattern. Very occasional papillae were seen in four and tumoral necrosis in two of 11. Six ORCN displayed a CD117+/progesterone receptor (PR)+ immunophenotype (feature shared by RO) and five tumors displayed a CD117-/PR- immunophenotype (feature shared by RCC). The CD117-/PR- ORCN also displayed alpha-methylacyl-coenzyme A racemase and RCC antigen reactivity as well as varying reactivity for cytokeratin 7, vimentin and CD10 (features of oncocytic PRCC). These five cases had tumor sizes ranging from 1 to 6 cm. Two patients in the latter group developed progression of the disease with metastases. In conclusion, oncocytic PRCC with solid architecture is a rare type of RCC. The carcinoma often poses differential diagnostic problems with RO and has similar immunohistochemical properties to the common type of PRCC. Cytogenetic and molecular studies have not been performed yet for this variant of RCC.

Primary prostatic central zone adenocarcinoma.

The central zone (CZ) of the prostate is embryologically, anatomically, and histologically distinct. High-grade prostatic intraepithelial neoplasia (HGPIN) and prostatic adenocarcinoma (PAC) are encountered in the CZ, but have not been well studied. Non-CZ PAC that spread into the CZ can mimic CZ PAC. We reviewed 300 consecutive radical prostatectomies performed for PAC to identify cases showing PAC and HGPIN in the CZ. There were nine PAC (3%) localized predominantly in the CZ, presenting as a single tumor nodule (8/9) and associated with 4.5+/-1.1 foci HGPIN in the CZ and with only 1.7+/-0.5 foci in the PZ. Of the 291 non-CZ PAC, 24 cases showed satellite tumor nodules in the CZ, and 92 cases demonstrated secondary contiguous spread to the CZ. As compared to the non-CZ PAC, CZ PAC tended to have lower tumor volume, but had higher Gleason scores (8.10+/-0.6 vs. 6.30+/-0.7, p<0.05), as well as a higher incidence of a ductal carcinoma component (6/9), higher rates of capsular penetration, positive resection margins (4/9), and seminal vesicle spread (2/9). The CZ HGPIN associated with CZ PAC demonstrated cells with prominent nucleoli and formed either slender papillary structures or cribriform/solid patterns. The correlating positive biopsy cores were from the mid portion or from base of prostate and contained foci of HGPIN in 4/7 cases. The CZ PAC is characteristically accompanied by more foci of HGPIN in the CZ than in non-CZ and is associated with high grade and high stage. Preoperative diagnosis of CZ PAC can be suspected due to the histopathological features in the biopsy and is important to improve the free surgical resection rate.

Invasive low-grade urothelial carcinoma in a bladder biopsy associated with high-stage disease and masquerading as schistosomiasis.

We present an interesting case of a 56-year-old Egyptian woman with high-grade urothelial carcinoma (HGUC) associated with schistosomiasis that appeared initially as low-grade (LGUC) disease on transurethral resection of the bladder tumor (TURBT). Areas of HGUC and tumor invasion were detected only after meticulous microscopic examination of the partial cystectomy specimen. Furthermore, there were no areas of squamous cell metaplasia identified. This case highlights one of the limitations of biopsy for determining cancer grade and stage. It also emphasizes that schistosomiasis may be associated with non-squamous cell forms of bladder cancer, the pathogenesis of which has not been fully elucidated.

Acute Management of Infected Chronic Thromboembolic Disease.

A 29-year-old man with chronic pulmonary emboli presented to the hospital with progressive pleuritic chest pain. He was in acute right ventricular failure and received intrapulmonary arterial tissue plasminogen activator. Massive hemoptysis developed, requiring emergent thromboendarterectomy. A clot was visualized in the main left pulmonary artery that had formed a bronchovascular fistula into the left upper lobe bronchus. Pathology of the clot revealed fibrinopurulent exudate and Gram-positive cocci. The left pulmonary artery was repaired with a pericardial patch, and the left upper lobe was oversewn with subsequent left upper lobectomy. The patient was discharged home on postoperative day 23.

Evaluation of tumor morphologies and association with biochemical recurrence after radical prostatectomy in grade group 5 prostate cancer.

We assessed Gleason pattern 5 (GP5) and other prostatic adenocarcinoma (PCa) morphologies to determine their association with biochemical recurrence (BCR). A search for grade group 5 PCa with radical prostatectomy (RP) yielded 49 patients. RPs were reviewed for %GP5 and morphologies (sheets, single cells, cords, small solid cylinders, solid medium to large nests with rosette-like spaces [SMLNRS], comedonecrosis, cribriform glands, glomerulations, intraductal carcinoma of the prostate [IDC-P], and prostatic ductal adenocarcinoma [PDCa]). Prevalence of morphologies was as follows: single cells 100%, cribriform glands 98.7%, cords 85.7%, IDC-P 77.6%, comedonecrosis 53.1%, sheets 49.0%, small solid cylinders 49.0%, PDCa 44.9%, glomerulations 34.7%, and SMLNRS 14.3%. From 28 patients who were treated with RP as monotherapy, 64.3% (18/28) had BCR. Comedonecrosis, sheets, small solid cylinders, IDC-P, and PDCa were significantly associated with BCR. Number of morphologies on RP and %GP5 were higher in patients with BCR (6.8 ± 2.1 versus 3.7 ± 2.9%; P < 0.001 and 26.9 ± 16.8 versus 11.4 ± 14.1%; P = 0.02) with area under ROC curve of 0.89 (confidence intervals [CI] 0.77-1.00). Sensitivity/specificity was 77.8/80.0% for predicting BCR when ≥ 5 morphologies were present and 0.79 (CI 0.60-0.99) with sensitivity/specificity of 66.7/80.0% for predicting BCR when ≥ 15% GP5 was present. Hazard ratio for BCR was higher with increasing number of morphologies (1.23, CI 1.02-1.49; P = 0.034) but not %GP5 (0.99, CI 0.97-1.02, P = 0.622). Our results indicate that GP5 morphologies may represent a biologically heterogeneous group and that an increasing number of PCa morphologies on RP is strongly associated with an increased risk of BCR.

Transforming the prostatic tumor microenvironment with oncolytic virotherapy.

Prostate cancer (PCa) was estimated to have the second highest global incidence rate for male non-skin tumors and is the fifth most deadly in men thus mandating the need for novel treatment options. MG1-Maraba is a potent and versatile oncolytic virus capable of lethally infecting a variety of prostatic tumor cell lines alongside primary PCa biopsies and exerts direct oncolytic effects against large TRAMP-C2 tumors in vivo. An oncolytic immunotherapeutic strategy utilizing a priming vaccine and intravenously administered MG1-Maraba both expressing the human six-transmembrane antigen of the prostate (STEAP) protein generated specific CD8+ T-cell responses against multiple STEAP epitopes and resulted in functional breach of tolerance. Treatment of mice with bulky TRAMP-C2 tumors using oncolytic STEAP immunotherapy induced an overt delay in tumor progression, marked intratumoral lymphocytic infiltration with an active transcriptional profile and up-regulation of MHC class I. The preclinical data generated here offers clear rationale for clinically evaluating this approach for men with advanced PCa.

Flat Intraurothelial Neoplasia Exhibiting Diffuse Immunoreactivity for CD44 and Cytokeratin 5 (Urothelial Stem Cell/Basal Cell Markers): A Variant of Intraurothelial Neoplasia Commonly Associated With Muscle-invasive Urothelial Carcinoma.

BACKGROUND: Immunoreactivity for CD44 and cytokeratin (CK)5 (urothelial stem/basal cell markers) are decreased/negative in the common type of intraurothelial neoplasia including urothelial carcinomas (UC) in situ. Recent studies also reveal that a majority of muscle-invasive UC are basal-like UC with large areas of positive CD44/CK5 immunoreactivity. In addition, approximately 80% of muscle-invasive UC develop de novo as nonpapillary invasive UC. In this study, we investigate the CD44/CK5 immunoreactivity of the flat intraurothelial neoplasia (FIUN) associated with nonpapillary invasive UC. MATERIALS AND METHODS: Consecutive cases of nonpapillary UC were submitted for immunostaining. Immunostaining for CK5/CD44 was scored as high for staining of >25% thickness of urothelium and low for lesser immunoreactivity. RESULTS: In total, 109 consecutive cases were grouped into: in situ UC [carcinoma in situ (CIS)] (n=11), pT1 (n=14), and pT2-4 (n=84) with surface urothelium available for study. Forty-four cases including CIS (n=9), pT1 (n=12), and pT2-4 (n=23) showed FIUN with low/negative CD44/CK5 reactivity; 40 cases showed strong CK20 reactivity. Sixty-two cases including CIS (n=2), pT1 (n=2), and pT2-4 (n=58) showed extensive FIUN exhibiting high CD44/CK5 reactivity; 30 cases showed reactive CK20. FIUN lesions with high CD44/CK5 reactivity scores were associated with mild (urothelial dysplasia) to moderate atypia (CIS) and were rarely preceded by papillary UC. Most invasive UC associated with FIUN with high CD44/CK5 reactivity also exhibited extensive CD44/CK5 reactivity. The remaining 3 cases showed only reactive urothelium. Of interest, 4 cases with FIUN showed negative CD44/CK5/CK20 reactivity. CONCLUSIONS: Existence of CD44/CK5-immunoreactive (or basal-like) FIUN is consistent with the recent distinction of basal and luminal subtypes of UC. This type of FIUN is often associated with UC with progression to high-stage disease not preceded by recurrent papillary UC.

A case series of surgically diagnosed idiopathic aortitis in a Canadian centre: a retrospective study.

BACKGROUND: Idiopathic aortitis became recognized relatively recently, and the body of knowledge concerning this condition is scarce. We aimed to determine the frequency of idiopathic aortitis in aortic specimens, the clinical, laboratory and radiologic characteristics at diagnosis and during follow-up, and the approach to investigation, treatment and monitoring taken by the treating physicians. METHODS: We identified cases of aortitis diagnosed on pathological specimens of the aorta between Jan. 1, 2003, and July 31, 2013, at The Ottawa Hospital by reviewing the hospital's pathology database. Charts of identified patients were reviewed, and data on patient demographic characteristics, clinical features, laboratory and imaging tests, treatment and outcomes were analyzed. RESULTS: A total of 684 aortic specimens were analyzed during the study period; 47 cases of aortitis were identified, 32 of which were idiopathic. Twenty-one patients (66%) had complete imaging of branch vessels at baseline, 16 (76%) of whom had additional aortic or branch vessel lesions. Twelve patients (38%) received corticosteroids postoperatively. Over a mean follow-up period of 47.5 months, among the 12 patients (38%) who had complete imaging of branch vessels at least once, new aortic or branch lesions were diagnosed in 5 (42%); 3/32 patients (9%) required additional vascular surgery; and a new systemic condition was diagnosed in 2/32 (6%). INTERPRETATION: Idiopathic aortitis is commonly discovered incidentally on examination of the pathological specimen following ascending aortic aneurysm repair. No guidelines exist for the investigation, treatment and follow-up of this condition, resulting in great variability of practice. Good-quality prospective studies are needed to address the many unanswered clinical questions regarding idiopathic aortitis and to allow formulation of more definitive recommendations.