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P Hytiroglou

Publications and source records attributed to P Hytiroglou.

At least 19 recordsLinked to original sources
PubMed2003

Hepatic 'stem cell' malignancies in adults: four cases.

AIMS: Combined hepatocellular/cholangiocarcinomas have been explained by some investigators as bidirectional differentiation of neoplastic progenitor cell populations. The presence of hepatic progenitor cells has now been confirmed in humans, though whether they can give rise to malignant tumours has not been confirmed. We report four cases of small tumours identified in livers with features of chronic hepatitis which may suggest a role for malignant transformation of hepatic stem cells in hepatic malignancies. METHODS: Tumour samples were studied from four patients by histochemistry and immunohistochemistry. RESULTS: Two patients had chronic hepatitis B, one had chronic hepatitis C and chronic alcoholic liver injury, and one had non-B non-C chronic hepatitis. Stages of disease ranged from portal fibrosis to cirrhosis. All tumours contained undifferentiated cells with morphological and immunohistochemical features that would be expected of hepatic progenitor cells. These cells merged with both hepatocellular carcinoma and cholangiocarcinoma components as well as with mature appearing hepatocytes within the tumours. CONCLUSION: We suggest that these tumours are of hepatic progenitor cell origin, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells and that such a process may underlie development of some mixed hepatocellular/cholangiocarcinomas and dysplastic nodules.

Aged↗
PubMed2001

In situ hybridization and reverse transcription-polymerase chain reaction for cyclin D1 mRNA in the diagnosis of mantle cell lymphoma in paraffin-embedded tissues.

Mantle cell lymphoma (MCL) is characterized by the chromosomal translocation t(11;14), which involves rearrangement of the bcl-1 proto-oncogene to the immunoglobulin heavy chain gene and results in overexpression of cyclin D1 mRNA. In this study, we evaluated the diagnostic relevance of three methods that may be helpful in the diagnosis of MCL: in situ hybridization (ISH) and a stringent reverse transcriptase-polymerase chain reaction (RT-PCR) protocol for cyclin D1 mRNA, and immunohistochemistry for cyclin D1 protein. The study group included 37 paraffin-embedded specimens (25 from lymph nodes and 12 from extranodal tissues) from 30 patients. MCL diagnosis was performed according to the Revised European-American Classification of Lymphoid Neoplasms. Twenty-nine patients with non-MCL lymphoproliferative disorders comprised the control group. Biotin-labeled ISH was performed in 28 cases of MCL, 24 (86%) of which were found to be positive. As shown by ISH in extranodal tissues, cyclin D1 mRNA was present not only in neoplastic lymphoid cells, but in other cell types as well. For this reason, RT-PCR results were considered reliable for MCL diagnosis only on informative material (from tissues that do not normally express cyclin D1); this method was evaluated as positive in 16 of 18 (89%) MCL cases. Cyclin D1 immunopositivity was present in 20 of 29 (69%) MCL cases. No members of the control group were found to express cyclin D1 mRNA by either ISH or RT-PCR under the stringent conditions used. In conclusion, stringent RT-PCR for cyclin D1 expression can be helpful in MCL diagnosis in paraffin-embedded material from lymph nodes. ISH is a sensitive method for cyclin D1 mRNA detection; its sensitivity is superior to that of cyclin D1 immunohistochemistry and similar to that of the stringent RT-PCR used. ISH is very specific as well, clearly more specific than RT-PCR, because it allows the correlation of molecular findings with morphology. This method can be applied on all types of paraffin-embedded tissues and provides an accurate tool for MCL diagnosis.

Cyclin D1↗
PubMed2001

Cyclin D1 overexpression in multiple myeloma. A morphologic, immunohistochemical, and in situ hybridization study of 71 paraffin-embedded bone marrow biopsy specimens.

Cyclin D1 expression was evaluated by immunohistochemical analysis and biotin-labeled in situ hybridization (ISH) in a series of 71 decalcified, paraffin-embedded bone marrow biopsy specimens from patients with multiple myeloma (MM). Cyclin D1 messenger RNA (mRNA) overexpression was detected by ISH in 23 (32%) of 71 cases, whereas cyclin D1 protein was identified by immunohistochemical analysis in 17 (24%) of 71 specimens. All cases that were positive by immunohistochemical analysis also were positive by ISH. Statistically significant associations were found between cyclin D1 overexpression and grade of plasma cell differentiation and between cyclin D1 overexpression and extent of bone marrow infiltration. Our findings demonstrate the following: (1) ISH for cyclin D1 mRNA is a sensitive method for the evaluation of cyclin D1 overexpression in paraffin-embedded bone marrow biopsy specimens with MM. (2) ISH is more sensitive than immunohistochemical analysis in the assessment of cyclin D1 expression. (3) Cyclin D1 overexpression in MM is correlated positively with higher histologic grade and stage.

Antigens, CD20↗
PubMed2000

Biliary cystadenocarcinoma with two types of tumour cells.

We report a rare case of biliary cystadenocarcinoma that occurred in the left hepatic lobe of a 62-year-old man and measured 20 cm in its greatest dimension. The neoplastic epithelium consisted of two types of cells: (1) cells with clear cytoplasm containing abundant mucin, and (2) cells with eosinophilic cytoplasm, which in some areas formed nodules with hepatocytoid features (polygonal cell shape, large nuclei with prominent nucleoli, and pseudoglandular structures). Histochemical stains revealed the presence of cytoplasmic mucin in the hepatocytoid areas, whereas immunohistochemical stains clearly showed a biliary phenotype (diffuse positive staining for "biliary type" cytokeratins, rare foci of positive staining with antibody to human hepatocytes (HEP-PAR1), absence of staining for alpha-fetoprotein, and no evidence of canalicular pattern of staining with polyclonal antibody to carcinoembryonic antigen). These findings indicate that areas reminiscent of hepatocellular carcinoma may occur in biliary cystadenocarcinomas. Histochemical and immunohistochemical stains are useful in reaching a definitive diagnosis in such cases.

Bile Duct Neoplasms↗
PubMed1999

Chemopreventive activity of very low dose dietary tannic acid administration in hepatoma bearing C3H male mice.

Tannins are plant polyphenols comprising a heterogeneous group of compounds. Tannic acid is a common tannin found in tea, coffee, immature fruits, etc. and it has also been used as a food additive. An increasing body of experimental evidence supports the hypothesis that tannins exert anticarcinogenic activity in chemically induced cancers in animal models. In the present study, tannic acid was administered in very low doses in the drinking water of C3H male mice divided into three groups (75 mg/l, 150 mg/l and 300 mg/l). These animals carry a genetic defect and show a high incidence of spontaneous liver tumors (> 50%) at an age older than 12 months. The results showed a decrease in the overall incidence of hepatic neoplasms (adenomas plus carcinomas): 53.3% of animals in the control group developed hepatic neoplasms versus 33.3% in the group given a low dose of tannic acid, 26.6% in the group given a medium dose and 13.3% in the high dosage group. The difference was more pronounced in the animals with carcinomas: 4.44% of mice who received tannic acid developed carcinomas versus 33.3% of those in the control group. Tannic acid administration did not affect the PCNA labeling index of normal hepatocytes. It is concluded that tannic acid dietary intake in low doses can exert a strong dose-dependent chemoprotective activity against spontaneous hepatic neoplasm development in C3H male mice, most probably through antipromoting mechanisms.

Adenoma↗
PubMed1999

Recurring fibro-obliterative venopathy in liver allografts.

Recurrent diseases in liver allografts are not uncommon. These occur most frequently in those transplanted for viral hepatitis B and C. We report an unusual case of recurrent process in two consecutive liver allografts received by a 37-year-old woman, who previously had an unremarkable past medical history but developed a rapidly progressive cholestatic liver failure. Histopathologic examination of the native liver showed fibroocclusive lesions of both terminal hepatic venules and portal vein branches. The exuberant fibroobliterative process created dense fibrosis with whorled appearance, and broad fibrous septa connecting adjacent central areas, and sometimes bridging portal to central areas. Dense portal fibrosis resulted in compression atrophy and loss of bile ducts. The first allograft, which failed within 3 months, showed histopathologic findings similar to that of the native liver. A liver biopsy that was performed 20 months after the second liver transplant again showed similar histopathology. The histopathologic features and clinical presentation of this patient suggest an unusual form of recurring progressive fibroobliterative venopathy causing liver failure.

Adult↗
PubMed1998

Telomerase activity in precancerous hepatic nodules.

BACKGROUND: Recent studies have demonstrated that telomerase, a reverse transcriptase linked to cellular "immortalization," is activated in a variety of malignant human tumors. This study was conducted to determine whether telomerase activity represents a marker of malignant transformation in precancerous (dysplastic) nodules arising in patients with cirrhosis. METHODS: Telomerase activity was evaluated in frozen tissue samples of 14 cirrhotic liver specimens and 30 large nodular lesions contained therein, including 13 large regenerative nodules/low grade dysplastic nodules, 10 high grade dysplastic nodules, and 7 hepatocellular carcinomas (HCCs). A modified telomeric repeat amplification protocol was used. RESULTS: There was a clear-cut difference in telomerase activity levels between HCC (positive or strongly positive) and cirrhotic liver samples (weakly positive or negative). The majority of large noncancerous nodules (86%) exhibited telomerase activity levels similar to HCCs. However, such activity was not limited to dysplastic lesions but also was detected in some large regenerative nodules. CONCLUSIONS: These findings suggest that telomerase activation is an early event in large nodule formation in cirrhosis, which may facilitate the action of other factors in the process of carcinogenesis. Telomerase activity in large hepatic nodules is not always indicative of malignant transformation.

Adult↗
PubMed1998

Coexistence of hereditary hemorrhagic telangiectasia and fibropolycystic liver disease.

This is a case report of a 43-year-old woman who received a transplant for end-stage liver disease due to hereditary hemorrhagic telangiectasia and fibropolycystic liver disease. This is an uncommon association of two autosomal-dominant conditions with defined genetic and molecular defects. The liver showed extensive vascular malformations of arteries and veins as well as telangiectasia and fibrosis. In addition, there were cystically dilated ducts containing inspissated bile and extensive von Meyenburg complexes. This case raises interesting questions about the possible relationship of these genes and their gene products, both of which are related to cell-matrix interactions and are strongly associated with blood vessels, one of them being expressed on endothelial cells and the other being developmentally important in blood vessels.

Adult↗
PubMed1998

Epithelioid hemangioendothelioma of the liver mimicking Budd-Chiari syndrome.

A case of epithelioid hemangioendothelioma of the liver in a 34-year-old man with clinical and radiologic findings suggestive of Budd-Chiari syndrome is reported. Despite clinical and radiologic findings, percutaneous liver biopsy was suspicious for epithelioid hemangioendothelioma. The patient underwent liver transplantation 2 months later, and histologic examination confirmed this diagnosis. Unusual histopathologic features included extensive areas of capillary-thin vascular structures with open lumina, lack of significant cytologic atypia in the majority of neoplastic cells, and areas with Budd-Chiari-like features in the hepatic parenchyma surrounding the tumor. The neoplastic cells were focally immunopositive for endothelial markers, such as factor VIII-related antigen and CD34 antigen. The unusual clinical presentation may have been due to tumor invasion and fibrous obliteration of terminal hepatic venules and sublobular veins. Epithelioid hemangioendothelioma should be considered when evaluating patients with clinical features of Budd-Chiari syndrome or veno-occlusive disease.

Adult↗
PubMed1998

Differential diagnosis of hepatocellular nodular lesions.

The great advances in radiologic imaging of the last two decades have focused attention on hepatic nodular lesions. Various entities with a nodular appearance are predominantly composed of hepatocytes or tumor cells of hepatocytic origin, including benign and malignant neoplasms as well as tumorlike lesions. Differential diagnosis of these nodules can often be difficult, especially in the limited material of a needle biopsy specimen. The histological features that can be of help in this regard are the focus of this review. In noncirrhotic livers, differential diagnoses include liver cell adenoma, focal nodular hyperplasia, large regenerative nodule, nodular regenerative hyperplasia, partial nodular transformation, compensatory hyperplasia, focal fatty change, and well-differentiated hepatocellular carcinoma. Poorly differentiated hepatocellular carcinoma must be distinguished from other malignant tumors, especially metastatic, poorly differentiated adenocarcinoma. In cirrhotic livers, the differential diagnoses include large regenerative nodule, focal fatty change, low-grade dysplastic nodule, high-grade dysplastic nodule, and hepatocellular carcinoma.

Adenoma↗
PubMed1997

Large-cell change of hepatocytes in cirrhosis may represent a reaction to prolonged cholestasis.

Large-cell change of hepatocytes (LCC), also called liver cell dysplasia of large-cell type, is a set of cytologic changes comprising nuclear and cytoplasmic enlargement, nuclear pleomorphism, and multinucleation. This entity is encountered frequently on histologic or cytologic examination of specimens obtained from livers with a variety of chronic diseases and originally was thought to have a premalignant nature. Accumulating evidence, however, now suggests that LCC is merely a reactive change. Having often observed LCC in liver specimens with chronic biliary tract disease, that is, in livers where cholestasis preceded hepatocyte injury, we surmised that LCC may be a result of prolonged cholestasis. To determine whether there was any association between LCC and cholestasis, we examined microscopically a series of 400 nodules from 40 consecutive adult cirrhotic livers, resected on transplantation, and graded LCC and cholestasis semiquantitatively. LCC was present diffusely in cirrhotic nodules of 25 specimens (62.5%). Nine additional specimens (22.5%) had focal mild LCC. Usually, LCC and cholestasis occurred together, in the same cirrhotic nodules and in the same areas of nodules. There was a statistically significant association between the presence and grade of LCC and those of cholestasis (p < 0.0001; chi-square test). Within etiological categories of cirrhosis (chronic hepatitis; n = 28; alcoholic liver disease; n = 6; biliary disease: n = 6), the significance was maintained. We conclude that, in cirrhosis of different etiologies, LCC may represent a reactive change that results from prolonged cytoplasmic cholestasis.

Adult↗
PubMed1997

Lamellar fibrosis in the fibrolamellar variant of hepatocellular carcinoma: a role for transforming growth factor beta.

Transforming growth factor-beta (TGF-beta) is a pluripotent regulatory molecule, found in at least five different isoforms. It is produced in many different organs. In the liver, TGF-beta is expressed in non-parenchymal cells, but not in hepatocytes. This growth factor is known to induce fibrosis in the course of a variety of pathologic processes. Recently, TGF-beta has also been identified in hepatocellular carcinoma (HCC) cells, and the suggestion has been made that this growth factor may play a role in hepatocarcinogenesis. In this study, we report the findings of immunohistochemical stains for TGF-beta, performed on paraffin sections of 14 human HCCs of the usual type and 11 examples of the fibrolamellar variant (FLC). TGF-beta was detected in tumor cells of 3 HCCs (21%) and 9 FLCs (82%). Compared with the HCCs, the FLCs displayed a more diffuse and intense staining pattern for TGF-beta. Our findings suggest that lamellar fibrosis, which is a histologic hallmark of FLC, may be due to the action of TGF-beta produced by tumor cells.

Carcinoma, Hepatocellular↗
PubMed1997

Microanatomy of the vasa vasorum of the human thoracic aorta: a study utilizing a polyester resin casting technique.

We have studied the vasa vasorum of the human thoracic aorta using a polyester resin casting technique, coupled with the tissue clearing method of Spalteholz. We found that the vasa vasorum originated from intercostal arteries. They ramified and formed networks within the aortic adventitia and the outer layers of the media. Venous networks were identified in the adventitia as wall. In addition to being a usefull research tool, the methodology utilized in this study produces specimens that can be used in teaching vascular anatomy to medical students.

Adult↗
PubMed1996

Low proliferative activity in macroregenerative nodules: evidence for an alternate hypothesis concerning human hepatocarcinogenesis.

UNLABELLED: Macroregenerative nodules are commonly thought to be hyperplastic lesions, deriving both their large size and premalignant potential from an increased proliferative rate. We have previously suggested an alternate model of macroregenerative nodule development in which neither size nor premalignant potential of macroregenerative nodules would depend on increased proliferation. We tested this hypothesis by examining the proliferative activity in macroregenerative and surrounding cirrhotic nodules. METHODS: Eighteen macroregenerative nodules, including five type I and 13 type II, were immunostained for proliferating cell nuclear antigen (PCNA). Type II macroregenerative nodules included ten with diffuse large (7) or small (3) liver cell dysplasia only and eight containing nodule-in-nodule lesions. Five nodule-in-nodule lesions met the histologic criteria for hepatocellular carcinoma. PCNA labeling indices (PCNA-LIs; percentage positive hepatocyte nuclei/500 randomly counted cells) were determined in macroregenerative nodules and the four largest adjacent cirrhotic nodules. Nodule-in-nodule lesions were assessed separately from the background macroregenerative nodule. RESULTS: 4/5 type I and 12/13 type II macroregenerative nodules (exclusive of NIN lesions) had PCNA-LIs lower than the mean of surrounding cirrhotic nodules. All nodule-in-nodule lesions, whether atypical or overtly malignant, had PCNA-LIs greater than any surrounding nodules. In conclusion, macroregenerative nodules have PCNA-LIs indistinguishable from, and often lower than, surrounding cirrhotic nodules. Increased proliferative activity only occurs with the development of atypia and transition to hepatocellular carcinoma. CONCLUSION: Macroregenerative nodules derive neither their size nor their premalignant potential from on-going rapid proliferation, a finding consistent with our alternate hypothesis of macroregenerative nodule development.

Carcinoma, Hepatocellular↗