Microvascular injury in persistent gastric ulcers after yttrium-90 microsphere radioembolization for liver malignancies.

Yttrium-90 microsphere radioembolization ((90)Y MRE) is a therapy for liver malignancies by permanently implanting (90)Y-containing microspheres into tumors via hepatic artery. The etiology of persistent gastric ulcerations in patients presenting months after treatment remains unclear. Three patients who presented with gastric ulceration 4 to 13 months after (90)Y MRE were examined by esophagogastroduodenoscopy and biopsies. Pathological examinations showed multiple (90)Y microspheres scattered within the lamina propria and submucosa. Most of the microspheres were distributed in a linear fashion, consistent with an intravascular location; however, the vascular lumen and endothelial cells were not present. The microspheres were surrounded by fibrotic tissue infiltrated by chronic inflammatory cells and rare neutrophils. Epithelial granulation without pititis and miniaturized glands with intervening fibrosis were noted, compatible with chronic ischemic changes. These findings suggest that the persistent gastric ulceration is a result of localized ischemic injury in response to (90)Y MRE-induced vascular damage.

Congenital anomalies and rhabdoid tumor associated with 22q11 germline deletion and somatic inactivation of the SMARCB1 tumor suppressor.

The most common microdeletion in humans involves the 22q11 region. Congenital anomalies associated with 22q11 loss include cardiac and facial defects. Less frequent is the co-presentation of malignant rhabdoid tumors that are highly aggressive childhood malignancies typically found in renal or extra-renal soft tissues and central nervous system. A newborn patient presented with multiple congenital anomalies consistent with 22q11 deletion syndrome including cleft lip and palate, ear tags and ventricular septal defects co-presenting with an axillary rhabdoid tumor. Comparative genomic hybridization revealed a 2.8 Mb germline deletion in the 22q11.2 region containing genes required for normal fetal development and the SMARCB1 tumor suppressor gene. Analysis of tumor DNA revealed a somatic deletion of exon 7 in the second allele of SMARCB1. Expression of SMARCB1 was absent, while tumor markers including MYC, GFAP, and CLAUDIN-6 were upregulated. The presence of tandem oriented BCRL modules located within interspersed low copy repeat elements throughout the 22q11 distal region may predispose this area for microdeletions through nonalleleic homologous recombination.

Diagnostic use of antibody to smoothelin in the recognition of muscularis propria in transurethral resection of urinary bladder tumor (TURBT) specimens.

Accurate recognition of muscularis propria invasion by urothelial carcinoma is vital as it serves as a crossroad between conservative and aggressive clinical management. Recently, there has been attention to the hyperplastic pattern of muscularis mucosae which may mimic the muscularis propria. We have earlier shown that smoothelin, a marker of terminally differentiated smooth muscle cells, is relatively specific for muscularis propria (positive staining) and is variably negative to weak in muscularis mucosae. The earlier study was based on cystectomy specimen slides in which the bladder cancer was not present. Pathologic staging in transurethral resection of urinary bladder tumor (TURBT) specimens is complicated by limited, unoriented, or highly cauterized samples. Herein, we test the capability of smoothelin to recognize muscularis propria in TURBT specimens to further substantiate its diagnostic applicability in routine practice. Representative sections from 70 TURBTs were immunostained with smoothelin, and muscularis propria was evaluated in H&E slides and the corresponding smoothelin immunohistochemistry slides using double-blinded analysis. In 31/70 (44%) cases, muscularis propria was involved by invasive carcinoma. Cautery artifact was present in 46/70 (66%) cases, which did not seem to affect smoothelin immunohistochemistry staining of the muscularis propria. Muscularis propria was present by H&E in 48/70 (69%) cases and 48/70 (69%) cases had muscularis propria by smoothelin immunohistochemistry-based 2 (+) or 3 (+) positivity in larger muscle bundles with round regular contours. Desmoplastic response to invasive carcinoma stained negatively for smoothelin. The sensitivity, specificity, positive predictive value, and negative predictive value of smoothelin based on comparison with morphology in TURBT specimens was 98%, 95%, 98%, and 95%, respectively. This study confirms the relatively high sensitivity and specificity for smoothelin in MP, including in TURBT specimens. Immunoreactivity is retained despite the presence of thermal tissue injury, desmoplasia, or involvement by carcinoma. Our data confirm the use of smoothelin in the accurate distinction between muscularis propria and muscularis mucosae or desmoplastic reactions, thereby facilitating appropriate pathologic stage designation in often challenging TURBT specimens.

Diagnostic utility of antibody to smoothelin in the distinction of muscularis propria from muscularis mucosae of the urinary bladder: a potential ancillary tool in the pathologic staging of invasive urothelial carcinoma.

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.