Hepatocellular Carcinoma with Prominent Intracytoplasmic Inclusions: A Report of Two Cases.

Hepatocellular carcinoma (HCC) is the commonest primary malignant neoplasm of the liver in most countries with a notoriously poor prognosis. Variation in global incidence is well-recognized and the occurrence of HCC is linked to several established environmental, dietary, and lifestyle factors. HCC demonstrates morphological heterogeneity both within the same tumor and from patient to patient. Differing architectural patterns and cytological variants may be seen. Inclusion bodies are believed to represent organized structures of proteins which contribute to their pathogenesis and share several constituents like chaperones, p62, ubiquitin, and Valosin containing protein. The various hepatocyte cytoplasmic inclusions described in HCC include Mallory-Denk bodies (MDBs), hyaline bodies (HBs), glycogen, fat, fibrinogen, alpha 1 antitrypsin (AAT), and ground glass. MDBs are the most common inclusions seen in hepatocellular carcinomas. The two cases shared intracytoplasmic inclusions which are characterized by larger sizes and present in every section examined. These exhibited features of MDBs and HBs present in most tumor cells, further supporting close relationship.

Diverticular disease of the right colon.

BACKGROUND: The incidence of colonic diverticular disease varies with national origin, cultural background and diet. The frequency of this disease increases with advancing age. Right-sided diverticular disease is uncommon and reported to occur in 1-2% of surgical specimens in European and American series. In contrast the disease is more prevalent and reported in 43-50% of specimens in Asian series. Various lines of evidence suggest this variation may represent hereditary differences. The aim of the study is to report all cases of right sided diverticular disease underwent surgical resection or identified during pathological examination of right hemicoloectomy specimens METHODS: A retrospective review of all surgical specimens with right sided colonic diverticular disease selected from a larger database of all colonic diverticulosis and diverticulitis surgical specimen reported between January 1993 and December 2010 at the Pathology Department McMaster University Medical Centre Canada. The clinical and pathological features of these cases were reviewed RESULTS: The review identified 15 cases of right colon diverticulosis. The clinical diagnoses of these cases were appendicitis, diverticulitis or adenocarcinoma. Eight cases of single congenital perforated diverticuli were identified and seven cases were incidental multiple acquired diverticuli found in specimen resected for right side colonic carcinomas/large adenomas. Laparotomy or laparoscopic assisted haemicolectomies were done for all cases. Pathological examination showed caecal wall thickening with inflammation associated with perforated diverticuli. Histology confirmed true solitary diverticuli that exhibited in two cases thick walled vessels in the submucosa and muscular layer indicating vascular malformation/angiodysplasia. Acquired diverticuli tend to be multiple and are mostly seen in specimens resected for neoplastic right colon diseases. CONCLUSION: Single true diverticular disease of the right colon is usually of congenital type and affects younger age group and may be associated with angiodysplasia in some cases. Multiple false diverticuli are more seen in association with caecal carcinoma or large adenomas. These are usually asymptomatic and are more seen in older patients. However this study dose not reflects the true incidence of the disease in the general population.

Cutaneous angiomyxoma and pilomatricoma: a new combination.

Superficial angiomyxomas are rare benign tumors that typically present as a solitary lesion or as a component of Carney complex and rarely have been associated with other lesions. In this article, we report 3 cases of an unusual association of superficial angiomyxoma with pilomatricoma. This combination has never been described in the literature. The 3 patients presented with variable-sized pedunculated, asymptomatic skin papules overlying firm deeply situated nodules. Histopathologic examination demonstrated that the superficial pedunculated lesion is a superficial angimyxoma with underlying pilomatricoma. Thorough clinical examination failed to reveal any further lesions. We present a rare and unique combination of angiomyxoma and pilomatricoma. This combination may be incidental, representing collision tumors or etiologically related.

Nuclear expression of E-cadherin in solid pseudopapillary tumors of the pancreas.

CONTEXT: Solid pseudopapillary tumors of the pancreas are rare and have recently been shown to harbor mutations of the beta-catenin gene with resultant nuclear localization of beta-catenin protein to the nucleus. Moreover, there is a close relationship between beta-catenin and E-cadherin. OBJECTIVE: To explore the protein expression of E-cadherin in a series of solid pseudopapillary tumors of the pancreas. PARTICIPANTS: Eighteen cases of solid pseudopapillary tumors of the pancreas. DESIGN: The cases were studied using a tissue microarray that was constructed as follows: for each case, 4 to 14 cores measuring 1.0 mm each were drilled from the blocks. Tissue cores from normal pancreas were used as controls and for orientation purposes. MAIN OUTCOME MEASURES: The slides were stained with the following commercially available antibodies: CD10, CD56, vimentin, alpha-1-antitrypsin, alpha-1-antichymotrypsin, neuron-specific enolase, chromogranin, synaptophysin, beta-catenin and E-cadherin. RESULTS: All the tumors were CD10, vimentin, alpha-1-antitrypsin and alpha-1-antichymotrypsin diffusely positive (50% or more of the tumor cells staining) and CD56 showed focal positivity in all cases with 5-10% of tumor cells displaying immunolabeling. All cases were negative for chromogranin and synaptophysin. All 18 cases displayed cytoplasmic and nuclear localization of beta-catenin protein. Similarly, E-cadherin protein was localized to the nucleus in all 18 cases, with loss of the characteristic membranous decoration of cells. CONCLUSION: This study is the first demonstration of aberrant nuclear localization of E-cadherin protein in solid pseudopapillary tumors of the pancreas. Whilst the exact mechanism is not know and nuclear E-cadherin is not related to tumor aggression, this staining pattern may be of diagnostic value in concert with beta-catenin staining.

Altered expression and localization of N-myristoyltransferase in experimentally induced rat model of ischemia-reperfusion.

N-myristoyltransferase (NMT) catalyzes the attachment of myristate onto the amino-terminal glycine residue of select polypeptides. In the present study, we investigated the expression and activity of NMT in rat heart after ischemia and reperfusion. Western blot analysis of rat heart samples indicated a prominent immunoreactive band of 66 kDa probed with human NMT antibody. Both the expression and activity of NMT were increased by ischemia-reperfusion. Immunohistochemical studies showed cytosolic localization of NMT in normal rat heart and predominant nuclear localization after ischemia followed by reperfusion. The pre-ischemic perfusion and post-ischemic reperfusion of hearts with a cell-permeable calpain inhibitor (N-Ac-Leu-Leu-methioninal) suppressed the increase in calpain expression and reversed the localization of NMT from nucleus to cytoplasm. This is the first study demonstrating the expression and alteration of NMT localization in cardiac ischemia and pertaining to a possible role of co-translational modification of proteins in cardiac functions and injury.

Calmodulin-dependent cyclic nucleotide phosphodiesterase in an experimental rat model of cardiac ischemia-reperfusion.

In the present study, we investigated the activity and expression of calmodulin-dependent cyclic nucleotide phosphodiesterase (CaMPDE) and the effects of calpains in rat heart after ischemia and reperfusion. Immunohistochemical studies indicated that CaMPDE in normal heart is localized in myocardial cells. Rat ischemic heart showed a decrease in CaMPDE activity in the presence of Ca2+ and calmodulin; however, in ischemic-reperfusion tissue a progressive increase in Ca2+ and calmodulin-independent cyclic nucleotide phosphodiesterase (CaM-independent PDE) activity was observed. Perfusion of hearts with cell-permeable calpain inhibitor suppressed the increase of Ca2+ and CaM-independent PDE activity. Protein expression of CaMPDE was uneffected by hypoxic injury to rat myocardium. The purified heart CaMPDE was proteolyzed by calpains into a 45 kDa immunoreactive fragment in vitro. Based on these results, we propose that hypoxic injury to rat myocardium results in the generation of CaM-independent PDE by calpain mediated proteolysis, allowing the maintenance of cAMP concentrations within the physiological range.