Severe gastrointestinal cryptosporidiosis three years after multi-visceral transplantation.

BACKGROUND: Cryptosporidia are known to cause opportunistic gastrointestinal tract infections with variable severity. Such infections can be life-threatening in transplant recipients. We report the evolution of cryptosporidiosis in a multi-visceral transplant recipient with repeated endoscopic biopsies until specific therapy was instituted. CASE DESCRIPTION: A 40-year-old woman with a history of multi-visceral (stomach, duodenum, small bowel, liver, and pancreas) transplantation presented with severe acute diarrhea three years after transplantation. Endoscopic biopsies of the stomach, duodenum, and lower small bowel were performed and submitted for histologic examination to assess the possibility of rejection. Microscopic examination of the lower small bowel biopsy specimens revealed mild to moderate inflammation and the presence of microorganisms with features of Cryptosporidia in the intestinal crypts. No evidence of rejection was found. While waiting for the availability of nitazoxanide, the patient was initiated on metronidazole, but her diarrhea worsened. Eleven days later, new biopsies were obtained, revealing abundant Cryptosporidia in the lower small bowel and duodenal specimens and few Cryptosporidia in the gastric biopsy specimen. Nitazoxanide was soon administered, leading to clinical improvement. Six weeks later, new biopsies showed complete resolution of inflammation and the absence of microorganisms. CONCLUSION: Histological examination of biopsy specimens is crucial for the diagnosis of cryptosporidiosis, which can threaten the life of immunocompromised individuals. The importance of specific antiprotozoal treatment must be emphasized. HIPPOKRATIA 2022, 26 (3):121-123.

Radiological considerations and surgical planning in the treatment of giant parathyroid adenomas.

Giant parathyroid adenomas constitute a rare clinical entity, particularly in the developed world. We report the case of a 53-year-old woman where the initial ultrasonography significantly underestimated the size of the lesion. The subsequent size and weight of the adenoma (7 cm diameter, 27 g) combined with the severity of the hypercalcaemia raised the suspicion for the presence of a parathyroid carcinoma. This was later disproven by the surgical and histological findings. Giant parathyroid adenomas are encountered infrequently among patients with primary hyperparathyroidism, and appear to have distinct clinical and biochemical features related to specific genomic alterations. Cross-sectional imaging is mandated in the investigation of parathyroid adenomas presenting with severe hypercalcaemia as ultrasonography alone can underestimate their size and extent. This is important since it can impact on preoperative preparation and planning as well as the consent process as a thoracic approach may prove necessary for certain cases.

De novo autoimmune hepatitis associated with PTH(1-34) and PTH(1-84) administration for severe osteoporosis in a liver transplant patient.

De novo autoimmune hepatitis (AIH) is a rare graft dysfunction occurring in patients having undergone liver transplantation (LT) for causes other than AIH. We describe for the first time a case of de novo AIH associated with the administration of parathyroid hormone 1-34 [PTH(1-34)] and PTH(1-84) for severe osteoporosis. A 61-year-old woman was referred to our metabolic bone clinic due to severe osteoporosis, 3 years after LT for primary biliary cirrhosis. Initial treatment with PTH(1-34) led to asymptomatic hypertransaminasemia (two-fold the upper limit of normal), which normalized after drug discontinuation. A new flare of transaminases (three-fold the upper limit of normal) along with elevated alkaline phosphatase was observed after administration of PTH(1-84), which did not resolve after PTH(1-84) withdrawal. Subsequently, after exclusion of common causes of liver enzyme elevation, a liver biopsy was performed. Histological findings showed de novo AIH, which responded rapidly to treatment with methylprednisolone.

Significance of increased expression of decoy receptor 3 in chronic liver disease.

BACKGROUND/AIMS: Considerable evidence has indicated that apoptosis plays an important role in hepatocyte death in chronic liver disease. However, the cellular and molecular mechanisms underlying liver regeneration in these diseases are largely unknown. Plausibly, certain molecules expressed to counteract apoptosis might provide survival advantage of certain liver cells. Therefore, we investigated a possible expression of decoy receptor 3 of the tumour necrosis factor receptor family in chronic liver diseases since decoy receptor 3 is known to inhibit apoptosis mediated by pro-apoptotic tumour necrosis factor family ligands including Fas ligand. METHODS: A series of liver biopsies from patients with different stages of fibrosis were subjected to immunohistochemistry and in situ hybridization. RESULTS: Both decoy receptor 3 protein and mRNA were mainly expressed in biliary epithelial cells and infiltrating lymphocytes in the diseased livers. Most noticeably, intense decoy receptor 3 expression was observed in newly developing biliary ductules in regenerative nodules as well as dysplastic nodules of cirrhotic livers. In addition, decoy receptor 3 secretion in hepatocellular carcinoma cells in culture was via the activation of mitogen-activated protein kinases. CONCLUSION: Decoy receptor 3 was specifically expressed in chronic liver diseases and hepatocellular carcinoma cells, and decoy receptor 3 might facilitate the survival of liver cells by exerting its anti-apoptotic activity during the progression of liver cirrhosis and hepatocarcinogenesis.

Middle ear adenoma/carcinoid tumour: a case report and review of the literature.

UNLABELLED: Middle ear adenoma, a rare benign tumour with glandular and neuroendocrine differentiation, originates from the epithelial lining of the middle ear. CASE REPORT: We report a case of a 52-year-old woman, who presented with progressive hearing loss and fullness in the left ear for 3 months. Clinical examination revealed a mass in the left middle ear. Histological examination revealed tumour cells forming gland-like and cribriform structures, as well as compact groups. The nuclei were round and uniform, without atypia or mitotic activity. On immunohistochemical staining, the tumour cells were positive for epithelial (cytokeratins, epithelial membrane antigen) and neuroendocrine (neuron specific enolase, synaptophysin, chromogranin and pancreatic polypeptide) markers. CONCLUSION: Middle ear adenoma is a benign tumour that is treated by complete surgical removal. Follow-up of the patient is essential in order to detect possible recurrence. The immunohistochemical staining of the present case supports the suggestion that this tumour is best described by the term neuroendocrine adenoma of the middle ear.

Solitary fibrous tumor of the tongue: case report and literature review.

Solitary fibrous tumor (SFT) is an uncommon spindle cell neoplasm with unpredictable behavior. It was originally described in the pleura, but is now known to occur in various locations. SFT of the tongue is rare, with only four cases on record. An SFT of the anterolateral part of the left side of the tongue, which occurred in a 48 year-old man is recorded. The tumor was resected and the patient remains free of recurrence 3 years postoperatively.

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.

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.

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.

Malignant fibrous histiocytoma of the spine causing spinal neural foramen widening.

A case with a clinical picture of a chronic low back pain radiating to both lumbar regions caused by malignant fibrous histiocytoma is reported. Radiological, surgical and histopathological findings and treatment of this rare case are discussed.

Prevention of blood-transfusion-induced impairment of anastomotic healing by leucocyte depletion in rats.

OBJECTIVE: To find out what effect whole blood and leucocyte-depleted blood transfusions had on the healing process of intestinal anastomoses in rats. DESIGN: Experimental study. SETTING: Teaching hospital, Greece. SUBJECTS: 100 Wistar rats in five groups of 20 each. INTERVENTIONS: Small and large bowel anastomoses were made and the five groups were given normal saline, homologous whole blood, heterologous whole blood obtained from PVG rats, homologous leucocyte-depleted blood or heterologous leucocytedepleted blood during the operation. MAIN OUTCOME MEASURES: Bursting pressures of anastomoses on the third and seventh postoperative days and infective complications. RESULTS: The groups given whole blood transfusions had significantly more anastomotic abscesses than controls (p = 0.003 compared with heterologous, p = 0.05 compared with homologous for the small bowel, and p = 0.007 for the large bowel). The pressure measurements indicated a significant reduction in anastomotic strength in the same groups compared with the control group (p = 0.0001/p = 0.001 on the third postoperative day, and p = 0.00001/p = 0.0004 on the seventh postoperative day for small and large bowel, respectively). There was no reduction in anastomotic strength in the leucocyte-depleted blood groups. CONCLUSIONS: Transfusion of leucocyte-depleted blood does not seem to impair intestinal anastomotic healing and carries an acceptable incidence of postoperative complications.

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.

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.

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.

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.

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.

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.

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.