No abstract

No abstract

Inflammation suppresses phasic contractile activity in vivo. We investigated whether inflammation also suppresses in vitro phasic contractile activity and, if so, whether this could in part be due to the alteration of specific slow wave characteristics and morphology of the interstitial cells of Cajal (ICC). Circular muscle strips were obtained from normal and inflamed distal canine colon. Inflammation was induced by mucosal exposure to ethanol and acetic acid. The amplitudes of spontaneous, methacholine-induced, substance P-induced, and electrical field stimulation-induced contractions were smaller in inflamed muscle strips than in normal muscle strips. Inflammation reduced the resting membrane potential and the amplitude and duration of slow waves in circular muscle cells. Inflammation did not affect the amplitude of inhibitory junction potentials but did decrease their duration. Ultrastructural studies showed expansion of the extracellular space between circular muscle cells, reduction in the density of ICC and associated neural structures, damage to ICC processes, vacuolization of their cytoplasm, and blebbings of the plasma membrane. We conclude that inflammation-induced alterations of slow wave characteristics contribute to the suppression of phasic contractions. These alterations may, in part, be due to the damage to ICC. Inflammation impairs both the myogenic and neural regulation of phasic contractions.

Thrombospondin-1 (TSP-1), a trimeric high molecular weight glycoprotein, is one of the major secreted proteins of human platelets and an extracellular matrix component of a variety of cells including vascular endothelial cells and tumor cells. TSP-1 has been shown to be highly expressed in human malignant tissues and present in higher than normal levels in the plasma of cancer patients. TSP-1 has also been shown to promote hematogenous tumor spread, tumor cell adhesion and invasion, and angiogenesis. Overall these studies provide compelling evidence for the conclusion that TSP-1 plays an important role in tumor progression.

- -The ultimate goal for a pathologist is to render a specific diagnosis that provides diagnostic, prognostic, and therapeutic information to guide patient care. Immunohistochemistry is integral to the diagnosis and management of soft tissue tumors.

Histiocytic sarcoma, a rare malignant neoplasm showing morphologic and immunophenotypic features of histiocytes, is characterized typically by extranodal presentation and a dismal clinical course, particularly in patients with disseminated disease. A history of hematolymphoid disorder can be identified in a subset of patients, suggesting transdifferentiation of a preexisting hematolymphoid neoplasm in its pathogenesis. The differential diagnosis of histiocytic sarcoma includes various lymphomas, other histiocytic and dendritic cell neoplasms, carcinomas, melanomas, and pleomorphic sarcomas. Given its rarity and histologic overlap with diverse mimics, the diagnosis of histiocytic sarcoma can be extremely challenging. Recognition of morphologic clues, as well as judicious application of immunohistochemical markers to confirm its histiocytic lineage and to exclude mimics, is crucial for the diagnosis. Recent molecular studies by targeted next-generation sequencing identified recurrent alterations in the mitogen-activated protein (MAP) kinase pathway and chromatin regulators in the pathogenesis of histiocytic sarcoma and may suggest possible therapeutic targets.

No abstract

Initial diagnosis of submucosal gastrointestinal stromal tumors (GISTs) is often made from material obtained by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Although 95% of GISTs are positive for KIT by immunohistochemical analysis on surgical specimens, we have observed several cases of GIST that were negative for KIT on the cell block but subsequently positive on the surgical resection. DOG1 has been found to be a specific and sensitive marker for GISTs on surgical material. We compared KIT and DOG1 staining in 52 GIST cell blocks and in 44 cell blocks of other intra-abdominal spindle cell neoplasms. We found that DOG1 was the more sensitive marker, with positivity in all 52 GIST cell blocks. KIT was positive in 46 (88%) of the GIST cases, with sensitivity dependent on the FNA method. Both markers were highly specific: KIT was negative in all 44 non-GIST cases, whereas DOG1 showed weak positivity in only 1 leiomyosarcoma.