Diagnostic Utility of Antibody to Smoothelin in the Distinction of Muscularis Propria From Muscularis Mucosae of the Urinary Bladder
ABSTRACT Accurate recognition of urinary bladder muscularis propria (MP) invasion by urothelial carcinoma is crucial as it is the critical crossroad between conservative and aggressive management for the patient. It is now widely known that an inconsistent layer of muscularis mucosae (MM) muscle exists in the lamina propria, which can mimic the MP muscle, particularly when hyperplastic, making staging extremely challenging in some limited, unoriented, or highly cauterized specimens. Smoothelin is a novel smooth muscle-specific contractile protein expressed only by fully differentiated smooth muscle cells, and not by proliferative or noncontractile smooth muscle cells and myofibroblasts. We performed immunohistochemical staining in the bladder for smoothelin to: (a) evaluate its expression in MM and MP muscle in cystectomy specimens and by comparing the staining pattern with smooth muscle actin (SMA), (b) study MP variations in the bladder trigone and at the ureteric insertion in the bladder wall, and (c) assess the staining pattern of MM and MP in a representative group of transurethral resection of bladder tumor specimens. In contrast to SMA, which equitably stained both types of muscle fibers, smoothelin displayed striking differential immunoreactivity between MM and MP muscle. With smoothelin, the MM muscle (including hyperplastic forms) typically showed absent (19/42, 45%) or weak and focal (18/42, 43%) staining, whereas the MP muscle typically showed strong and diffuse staining (36/42, 86%). Smoothelin accentuated individual muscle fibers within groups of MP bundles only, a feature which was evident in both MM and MP stained by SMA. When only strong and diffuse immunoreactivity in muscle was set as a threshold for positivity, 100% specificity and positive predictive value of smoothelin for MP (vs. MM) was achieved in our study. Smoothelin staining confirmed the morphologic variations in MP muscle in the bladder wall of the trigone and at the ureteric insertion. In addition to the well-defined muscle layers of MM and MP, SMA staining revealed a continuous band of ill-defined haphazardly oriented compact spindle cells that were immediately subjacent to the urothelium in all cases. These spindle cells blended with the morphologically recognizable thin slender fascicles of the MM muscle. We designate this hitherto uncharacterized thin layer of SMA-positive [muscle-specific actin positive (6/6), Masson trichrome stain predominantly blue (5/6)] and smoothelin-negative cells as suburothelial band of myofibroblasts. In all 10 transurethral resection of bladder tumor sections, smoothelin staining was in agreement with the routine light microscopic presence and absence of MP muscle. In conclusion, the relatively distinct immunohistochemical staining pattern of smoothelin between MP and MM (including its hyperplastic forms) makes it a robust and attractive marker to be incorporated in the contemporary diagnostic armamentarium for the sometimes difficult area of staging bladder urothelial carcinoma.
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- "Despite these difficulties, accurate recognition of MD invasion is crucial for patient treatment according to the current guidelines. Immunohistochemical expression of the cytoskeletal protein Smoothelin is reported to be stronger in MD than in MM [13–15]. Therefore, additional immunohistochemistry using Smoothelin can be useful in differentiating both muscle layers. "
ABSTRACT: Urothelial cell carcinoma (UCC) with musculus detrusor (MD) invasion is treated by cystectomy. Subsequent pathologic evaluation of cystectomies does not reveal MD invasion (<pT2) in a subgroup of patients. Our objective was to identify features at diagnostic transurethral resection (TUR) predicting down-staging (<pT2) at cystectomy. Patients with pathologically confirmed MD invasion at TUR followed by cystectomy for UCC without (neo-) adjuvant therapy were included (N = 106). Slides of both TUR and cystectomy specimens were reviewed, and survival analyses were performed. In total, 27/106 (26 %) tumors were down-staged at cystectomy, of which 13 (12 %) had no residual tumor (pT0). There was no significant difference in age, gender, time interval between TUR and operation, number of slides sampled, and presence of TUR scar between down-staged (<pT2) and pT2 UCC. At review of TUR specimens (N = 52) with UCC initially diagnosed as pT2, MD invasion was not confirmed in eight cases (15 %). One case showed extensive histiocytic reaction misinterpreted as UCC; in four cases, muscularis mucosae had been considered MD, and in three cases, desmoplastic reaction mimicked MD. No histologic parameter at TUR was significantly associated with down-staging at cystectomy. Overall and disease-specific survival was not statistically different in down-staged and pT2 UCC. In conclusion, down-staging of UCC (<pT2) at cystectomy occurred in 26 %. At review of diagnostic TURs, MD invasion was not confirmed in 15 %. No clinical or pathologic parameter was predictive for down-staging at cystectomy. There was no difference in survival between down-staged and pT2-staged UCC.Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin 07/2012; 461(2):149-56. DOI:10.1007/s00428-012-1277-0 · 2.56 Impact Factor
Conference Paper: MotorMaster+ 2.0: Energy management for the pulp and paper industry[Show abstract] [Hide abstract]
ABSTRACT: MotorMaster+ 2.0 is designed to support energy management functions at medium and large sized industrial facilities. Version 2.0 contains many new design features and modifications that have been proposed by industrial users. This paper highlights the software enhancements that should be of interest to those in the pulp and paper industry and illustrates how MotorMaster+ is successfully being used by a large forest products companyPulp and Paper Industry Technical Conference, 1998. Conference Record of 1998 Annual; 07/1998
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ABSTRACT: Urothelial carcinoma (UCC) of the bladder demonstrates diverse morphologic features, often leading to diagnostic challenges in the discrimination between UCC and benign mimickers of neoplasia, and between primary UCC and secondary neoplasms involving the bladder. In situ lesions also provide diagnostic difficulty in some instances, most prominently in the distinction between normal, reactive urothelium and flat urothelial carcinoma in situ. The use of ancillary techniques, including panels of immunohistochemical markers, in distinguishing these entities has aided not only in the diagnosis of UCC, but has also provided insight into the molecular pathogenesis and prognostic value of numerous molecular pathways in UCC. This review focuses on some of the more commonly encountered biomarkers in UCC and their role in addressing key diagnostic and prognostic issues in this disease process.Advances in anatomic pathology 04/2009; 16(2):67-78. DOI:10.1097/PAP.0b013e318199f89e · 3.10 Impact Factor