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Acute pneumothorax is a frequent complication after percutaneous pulmonary radiofrequency (RF) ablation. In this study we present three cases showing delayed development of pneumothorax after pulmonary RF ablation in 34 patients. Our purpose is to draw attention to this delayed complication and to propose a possible approach to avoid this major complication. These three cases occurred subsequent to 44 CT-guided pulmonary RF ablation procedures (6.8%) using either internally cooled or multitined expandable RF electrodes. In two patients, the pneumothorax, being initially absent at the end of the intervention, developed without symptoms. One of these patients required chest drain placement 32 h after RF ablation, and in the second patient therapy remained conservative. In the third patient, a slight pneumothorax at the end of the intervention gradually increased and led into tension pneumothorax 5 days after ablation procedure. Underlying bronchopleural fistula along the coagulated former electrode track was diagnosed in two patients. In conclusion, delayed development of pneumothorax after pulmonary RF ablation can occur and is probably due to underlying bronchopleural fistula, potentially leading to tension pneumothorax. Patients and interventionalists should be prepared for delayed onset of this complication, and extensive track ablation following pulmonary RF ablation should be avoided. [ABSTRACT FROM AUTHOR]

Objective: The alpha(2)-Heremans-Schmid glycoprotein (AHSG; fetuin-A in animals) impairs insulin signaling in vitro and in rodents. Whether AHSG is associated with insulin resistance in humans is under investigation. In an animal model of diet-induced obesity that is commonly associated with hepatic steatosis, an increase in Ahsg mRNA expression was observed in the liver. Therefore, we hypothesized that the AHSG plasma protein, which is exclusively secreted by the liver in humans, may not only be associated with insulin resistance but also with fat accumulation in the liver.Research Design and Methods: Data from 106 healthy Caucasians without type 2 diabetes were included in cross-sectional analyses. A subgroup of 47 individuals had data from a longitudinal study. Insulin sensitivity was measured by a euglycemic-hyperinsulinemic clamp, and liver fat was determined by (1)H magnetic resonance spectroscopy.Results: AHSG plasma levels, adjusted for age, sex, and percentage of body fat, were higher in subjects with impaired glucose tolerance compared with subjects with normal glucose tolerance (P = 0.006). AHSG plasma levels were negatively associated with insulin sensitivity (r = -0.22, P = 0.03) in cross-sectional analyses. Moreover, they were positively associated with liver fat (r = 0.27, P = 0.01). In longitudinal analyses, under weight loss, a decrease in liver fat was accompanied by a decrease in AHSG plasma concentrations. Furthermore, high AHSG levels at baseline predicted less increase in insulin sensitivity (P = 0.02).Conclusions: We found that high AHSG plasma levels are associated with insulin resistance in humans. Moreover, AHSG plasma levels are elevated in subjects with fat accumulation in the liver. This is consistent with a potential role of AHSG as a link between fatty liver and insulin resistance. [ABSTRACT FROM AUTHOR]

Context: The effect of a lifestyle intervention to reduce liver fat content in nonalcoholic fatty liver disease in humans is influenced by genetics. We hypothesized that the amino acid exchange in human Gly388Arg (mouse homolog: Gly385Arg) in fibroblast growth factor receptor 4 (FGFR4), which regulates bile acid, lipid, and glucose metabolism, could determine hepatic lipid accumulation and insulin sensitivity. Mechanisms of this substitution were studied in mice under normal chow and high-fat diets., Design: In humans, the Gly388Arg polymorphism was studied for its relationship with changes in liver fat content and insulin sensitivity during 9 months of a lifestyle intervention. We also studied a knock-in mouse strain with an Arg385 allele introduced into the murine FGFR4 gene under normal chow and high-fat diets., Results: In humans, the FGFR4 Arg388 allele was not associated with liver fat content or insulin sensitivity in subjects who were overweight and obese before lifestyle intervention. However, it was associated with less decrease in liver fat content and less increase in insulin sensitivity during the intervention. In mice receiving normal chow, the FGFR4 Arg385 allele was associated with elevated hepatic triglyceride content, altered hepatic lipid composition, and increased hepatic expression of genes inducing de novo lipogenesis and glycolysis. Body fat mass and distribution, glucose tolerance, and insulin sensitivity were unaltered. The FGFR4 Arg385 allele had no effect on glucose or lipid metabolism under the high-fat diet., Conclusion: Our data indicate that the FGFR4 Arg388(385) allele affects hepatic lipid and glucose metabolism specifically during healthy caloric intake., (Copyright © 2019 Endocrine Society.)

Objective: The nitric oxide/cGMP/cGMP-dependent protein kinase type I (cGKI) signaling pathway regulates cell functions that play a pivotal role in the pathogenesis of type 2 diabetes. However, the impact of a dysfunction of this pathway for glucose metabolism in vivo is unknown., Research Design and Methods: The expression of cGKI in tissues relevant to insulin action was analyzed by immunohistochemistry. The metabolic consequences of a genetic deletion of cGKI were studied in mice that express cGKI selectively in smooth muscle but not in other cell types (cGKI-SM mice)., Results: In wild-type mice, cGKI protein was detected in hepatic stellate cells, but not in hepatocytes, skeletal muscle, fat cells, or pancreatic β-cells. Compared with control animals, cGKI-SM mice had higher energy expenditure in the light phase associated with lower body weight and fat mass and increased insulin sensitivity. Mutant mice also showed higher fasting glucose levels, whereas insulin levels and intraperitoneal glucose tolerance test results were similar to those in control animals. Interleukin (IL)-6 signaling was strongly activated in the liver of cGKI-SM mice as demonstrated by increased levels of IL-6, phospho-signal transducer and activator of transcription 3 (Tyr 705), suppressor of cytokine signaling-3, and serum amyloid A2. Insulin-stimulated tyrosine phosphorylation of the insulin receptor in the liver was impaired in cGKI-SM mice. The fraction of Mac-2-positive macrophages in the liver was significantly higher in cGKI-SM mice than in control mice. In contrast with cGKI-SM mice, conditional knockout mice lacking cGKI only in the nervous system were normal with respect to body weight, energy expenditure, fasting glucose, IL-6, and insulin action in the liver., Conclusions: Genetic deletion of cGKI in non-neuronal cells results in a complex metabolic phenotype, including liver inflammation and fasting hyperglycemia. Loss of cGKI in hepatic stellate cells may affect liver metabolism via a paracrine mechanism that involves enhanced macrophage infiltration and IL-6 signaling.

Background: The occurrence of ossifying fibromas (OFs) in childhood and adolescence has been described in the literature, along with different courses of the disease due to different growth rates., Case Report: In the case of the 15-year-old female patient presented here, an OF resulted in displacement of a maxillary third molar far into the maxillary sinus. It is assumed that the tumour originated coronal to the affected tooth 18. Radiographs document an initial rapid growth of this tumour over a period of 2 years, while its growth almost completely ceased in the next 2 years immediately prior to diagnosis and surgical treatment. The operation was complicated by unexpected profuse bleeding from the tumour tissue., Conclusion: The peculiarity of the OF in the case presented here is its similarity, in terms of clinical and radiological appearances, with a follicular cyst, its unusual place of origin that resulted in the migration of the tooth 18 into the maxillary sinus, its different growth dynamics, and the pronounced haemorrhage encountered as the tumour was surgically removed.

Purpose: Evaluation of bipolar radiofrequency (RF) ablation using internally cooled electrodes in an ex-vivo experiment., Materials and Methods: Bipolar RF ablations (n = 154) were performed in ex-vivo bovine liver. Both electrodes with a total length of the active tip of 4 cm were located on the same shaft of an internally cooled applicator. The power output was systematically varied between 20 and 100 watts (W). The energy application was continuous or modulated depending on the tissue resistance. In relationship to the maximum power output, the volume of coagulation was assessed., Results: In continuous energy application the induced volume of coagulation was increased at lower power outputs up to 33.7 cm (3) (20 watts). Parallel to an increased volume of coagulation, the required duration of energy application was increased up to a maximum of 51.6 minutes. Modulation of the power output as a function of the tissue resistance enabled application of a wide range of power outputs (40 - 75 watts) leading to a comparable extent of coagulation with a maximum of 14.9 cm (3) (10 min.), 16.8 cm (3) (15 min.), and 19.1 cm (3) (20 min.)., Conclusion: Continuous application of RF energy leads to an inverse relationship between volume of coagulation and power output. Modulation of the power output as a function of the tissue resistance enables application of a wider range of power outputs compared to continuous application of RF energy.

Objective: We sought to evaluate the relationship between parameters of bipolar radiofrequency (RF) ablation using internally cooled electrodes., Materials and Methods: Bipolar RF ablations (n = 24) were performed in ex vivo bovine liver using an internally cooled applicator with 2 electrodes located on the same shaft. The power-output was systematically varied (20-75 W). On the basis of our experimental data, mathematical functions were fitted and the goodness-of-fit was assessed by the parameter R., Results: The duration to induce an increase of tissue resistance and the amount of applied energy increased with a decreased power-output. The maximum short-axis was 4.5 cm (20 W) and required an application of 64 kilojoules (kJ). The volume of coagulation can be determined as a function of the duration of energy application (R = 0.954) and the amount of applied energy (R = 0.945)., Conclusion: The amount of applied energy and the duration of energy application can predict the volume of induced coagulation and may be useful to control internally cooled bipolar RF ablation.

Human parvovirus B 19 is known as a virus causing erythema infectiosum, arthropathy, transient aplastic crisis and intrauterine fetal death. Healthy hosts are able to clear the virus within weeks after infection. There are a few reports available in the literature regarding immunocompromised renal transplant recipients with persistent infection without seroconversion. Herein, we describe a 56-year old woman with a relapse of grade II follicular lymphoma who received a combined immunochemotherapy of rituximab, fludarabine and cyclophosphamide and subsequently developed a persistent parvovirus B19 infection. In the absence of serum immunoglobulin antibodies, PCR analysis of peripheral blood and bone marrow aspirate were positive for parvovirus B19. Treatment with IVIG treatment resulted in normalization of peripheral blood counts within 7 weeks.

Background: Distant metastases of solid tumors account for about 1% of all malign neoplasms. In about 30% of all patients who present with an oral metastasis, the distant primary tumour has not been diagnosed yet., Case Report: We report the case of a 71-year-old man who clinically demonstrated unilateral mental neuropathy as well as pathologic fracture of the mandible. Prostate carcinoma was identified as a primary tumor. Clinically, there was significant hypesthesia of the skin area innervated by the left inferior alveolar nerve. X-ray examination revealed an osteolytic lesion of the ascending ramus of the mandible as well as a pathologic fracture of the mandible. Further imaging showed an extensive neoplasm of the mandible and adjacent soft tissues and significant supraclavicular lymph node enlargement. The diagnosis of metastatic carcinoma of the prostate was histopathologically confirmed., Conclusion: Mental neuropathy without a dental focus indicates screening for an osseous metastasis. In cases of left-sided supraclavicular lymph node enlargement in men over 45 years, metastatic prostate carcinoma must be excluded.

Purpose: To evaluate the size and geometry of thermally induced coagulation by using multipolar radiofrequency (RF) ablation and to determine a mathematic model to predict coagulation volume., Materials and Methods: Multipolar RF ablations (n = 80) were performed in ex vivo bovine livers by using three internally cooled bipolar applicators with two electrodes on the same shaft. Applicators were placed in a triangular array (spacing, 2-5 cm) and were activated in multipolar mode (power output, 75-225 W). The size and geometry of the coagulation zone, together with ablation time, were assessed. Mathematic functions were fitted, and the goodness of fit was assessed by using r(2)., Results: Coagulation volume, short-axis diameter, and ablation time were dependent on power output and applicator distance. The maximum zone of coagulation (volume, 324 cm(3); short-axis diameter, 8.4 cm; ablation time, 193 min) was induced with a power output of 75 W at an applicator distance of 5 cm. Coagulation volume and ablation time decreased as power output increased. Power outputs of 100-125 W at applicator distances of 2-4 cm led to a reasonable compromise between coagulation volume and ablation time. At 2 cm (100 W), coagulation volume, short-axis diameter, and ablation time were 66 cm(3), 4.5 cm, and 19 min, respectively; at 3 cm (100 W), 90 cm(3), 5.2 cm, and 22 min, respectively; at 4 cm (100 W), 132 cm(3), 6.1 cm, and 27 min, respectively; at 2 cm (125 W), 56 cm(3), 4.2 cm, and 9 min, respectively; at 3 cm (125 W), 73 cm(3), 4.9 cm, and 12 min, respectively; and at 4 cm (125 W), 103 cm(3), 5.5 cm, and 16 min, respectively. At applicator distances of 4 cm (>125 W) and 5 cm (>100 W), the zones of coagulation were not confluent. Coagulation volume (r(2) = 0.80) and RF ablation time (r(2) = 0.93) were determined by using the mathematic model., Conclusion: Multipolar RF ablation with three bipolar applicators may produce large volumes of confluent coagulation ex vivo. A compromise is necessary between prolonged RF ablations at lower power outputs, which produce larger volumes of coagulation, and faster RF ablations at higher power outputs, which produce smaller volumes of coagulation., (Copyright RSNA, 2006.)

De novo lymphangiogenesis influences the course of different human diseases as diverse as chronic renal transplant rejection and tumor metastasis. The cellular mechanisms of lymphangiogenesis in human diseases are currently unknown, and could involve division of local preexisting endothelial cells or incorporation of circulating progenitors. We analyzed renal tissues of individuals with gender-mismatched transplants who had transplant rejection and high rates of overall lymphatic endothelial proliferation as well as massive chronic inflammation. Donor-derived cells were detected by in situ hybridization of the Y chromosome. We compared these tissues with biopsies of essentially normal skin and intestine, and two rare carcinomas with low rates of lymphatic endothelial proliferation that were derived from individuals with gender-mismatched bone marrow transplants. Here, we provide evidence for the participation of recipient-derived lymphatic progenitor cells in renal transplants. In contrast, lymphatic vessels of normal tissues and those around post-transplant carcinomas did not incorporate donor-derived progenitors. This indicates a stepwise mechanism of inflammation-associated de novo lymphangiogenesis, implying that potential lymphatic progenitor cells derive from the circulation, transmigrate through the connective tissue stroma, presumably in the form of macrophages, and finally incorporate into the growing lymphatic vessel.

Background and Objectives: Mucormycoses are seen with an increasing incidence in immunocompromised patients. Most common presentations are rhinocerebral and pulmonary. We here report the experience of a single center with mucormycoses in patients with hematologic malignancies., Results: Mucormycoses were diagnosed in six patients, (median age of 52 years; range, 26-74) treated between 2001-2004. Diagnoses included acute myeloid leukemia (AML) (n=3), acute lymphoblastic leukemia (n=1), chronic lymphocytic leukemia (n=1) and multiple myeloma (n=1). Mucormycosis was diagnosed in the neutropenic state following allogeneic hematopoietic cell transplantation (n=3) or intense chemotherapy (n=3). Sites of infections were rhinocerebral, facial and pulmonary involvement in one patient each and disseminated mucormycosis in three patients. The diagnosis was established by computed tomography followed by surgical interventions and histological diagnosis in 4 patients and post-mortem in two patients. Species identified were Rhizopus (n=3), Rhizomucor (n=2) and Absidia (n=1). Treatment responses were best if surgical resection was followed by aggressive antifungal chemotherapy. Five of six 6 patients died, all of complications of mucormycosis or their underlying disease. Only one patient with facial mucormycosis is still alive., Conclusions: This experience demonstrates that patient with mucormycoses have a high mortality rate and early recognition followed by aggressive surgical debridement, high dose antifungal therapy and attempts to correct the underlying immunocompromised state are crucial in the treatment of this fatal infection.

Preoperative localization of gastrinomas, especially of extrapancreatic origin, remains a challenge to the radiologist. Most patients with extrapancreatic gastrinomas undergo surgery without preoperative identification of the primary tumor. The appropriate imaging modality to localize gastrinomas is under continuing debate. We report a case of a duodenal gastrinoma with regional lymph node metastases that presented with Zollinger-Ellison syndrome. The small primary tumor was detected noninvasively by dual-phase multidetector thin-section computed tomography with adequate bowel distention and confirmed by endoscopy and histopathologic examination. The case illustrates that appropriate computed tomographic technique and scanning protocol are crucial for success in localizing extrapancreatic gastrinoma.

The prognosis of Fabry disease has changed since enzyme-replacement treatment was introduced. Therefore, early diagnosis is instrumental. We describe a family presenting with chronic renal failure and proteinuria in which classic skin and neurological features were absent and the diagnosis of Fabry disease was difficult and not established until a second family member developed renal abnormalities. A 35-year-old man was admitted because he was overweight and had hypertension, with a serum creatinine level of 1.3 mg/dL (115 micromol/L) and protein excretion of 870 mg/d. Because 1 brother, who died years ago at the age of 32 years of acute myeloid leukemia, also had chronic renal failure and proteinuria, the diagnosis of Fabry disease was entertained. In the index patient, acroparesthesia, hypohidrosis, pain, angiokeratomas of the skin, and cornea verticillata suggesting Fabry disease were absent. Conversely, renal biopsy showed typical globotriaosylceramide deposits, and leukocyte alpha-galactosidase (alpha-GLA) A activity was decreased. Analysis of the alpha-GLA gene showed the mutation E66K. The mutation also was found in another asymptomatic 30-year-old brother who also had chronic renal failure and proteinuria, but normal extrarenal findings. In the brother who died, Fabry disease, missed at autopsy because of cancer-related findings, could be confirmed after repeated review of histological slides. Mutation carriers also included the mother, a sister (both without abnormalities), and a nephew (with episodic pains in his feet). We conclude that familial chronic renal failure combined with proteinuria is suggestive of Fabry disease, and such specific mutations as E66K predominantly may affect the kidneys.

Whipple's disease (WD) is a chronic systemic inflammatory disease of infectious origin caused by Tropheryma whipplei (TW). Abdominal pain and recurrent diarrhea are usually the main symptoms leading to the suspicion of a primary bowel disease. Systemic manifestations can mimic hematologic disorders. A 49-year-old man presented with fever, weight loss, long-standing arthralgia, and diarrhea. A duodenal biopsy was unremarkable. Bone marrow histology provided no evidence of a malignant hematological disorder but revealed noncaseating granulomas. TW was detected in the bone marrow trephine by polymerase chain reaction. This is the first report to describe TW-associated granulomatous myelitis as the initially recognized organ manifestation of WD, proven at the molecular level. This observation is relevant for the differential diagnosis of patients with systemic symptoms and granulomatous diseases affecting the bone marrow, emphasizing that WD should be considered in cases of unexplained granulomatous myelitis, even when small bowel biopsy specimens are negative.

Follicular dendritic cell sarcomas (FDCSs) are very rare and usually originate in lymph nodes. We report an exceedingly rare case with localization in the dorsal mediastinum and, for the first time, provide positron emission tomography (PET) data for this tumor. This report describes the case of a 76-year-old man with a clinically aggressive tumor in the dorsal mediastinum. Computed tomography scan revealed displacement of soft tissue and lymph nodes. PET showed that the tumor had a high proliferation rate. Investigation of the successfully removed tumor mass revealed reactivity of the tumor cells for follicular dendritic cell markers and desmosomes linking adjacent tumor cells at the ultrastructural level. Marked atypia, a high mitotic rate, and areas of coagulative necrosis were found. The tumor in our case revealed the typical features and thus was classified as FDCS. In contrast to previous reports in the literature, preoperative imaging, histology, and immunohistochemistry studies indicated at least an intermediate degree of malignancy. Nevertheless, the patient made a good postoperative recovery and remained apparently disease-free 2 years later.

Intravascular lymphoma is an uncommon and often overlooked form of non-Hodgkin's lymphoma characterized by extensive proliferation of lymphoid cells within the lumina of small and medium-sized vessels. Clinical symptoms of the disease are variable and often nonspecific, mostly neurologic in nature. With an aggressive course, intravascular lymphomatosis has a poor prognosis and is rarely diagnosed ante mortem. We describe here a 76-year-old woman with the clinical diagnoses of hemolytic anemia and progressive lethargy where intravascular lymphomatosis turned out as the underlying cause of the disease.

Background: Posttransplantation lymphoproliferative disorder (PTLD) of the iris is a rare entity with only ten cases having been published as yet. Its clinical aspect is typical. Therapy is multimodal and affords an interdisciplinary approach., Methods: A 7-year-old boy developed a lymphoproliferative mass of the iris with uveitis 4 years after heart transplantation and immunosuppression. A progressive, flesh-colored thickening of the iris with secondary angle closure glaucoma necessitated a diagnostic and therapeutic iridectomy. Morphological investigation of the iris specimen disclosed a polymorphic posttransplantation lymphoproliferative disorder (PTLD) and the presence of Epstein-Barr virus (EBV) within the tissue. The EBV load in peripheral blood monocytes was massively elevated, thus indicating a chronic EBV infection. After conservative treatment and radiation therapy, the iris mass quickly resolved. There was no evidence of systemic PTLD., Conclusions: PTLD is a well-known, EBV-induced entity that rarely affects the eye. EBV is principally detectable in specimens of iris PTLD. If conservative, antiviral treatment fails, the iris lesions can be treated by local radiation therapy with very good success. In the near future, patients with PTLD of the eye may benefit from immunologic treatment with ex vivo generation of virus-specific T-lymphocytes.

The rare hypocellular variants of acute leukemia (AL) previously also termed smouldering leukemia, almost always exhibit myeloid differentiation. Very rare cases of hypocellular AL with lymphoid differentiation have been reported, usually in children. This paper describes two cases (an 87-year-old woman and a 79-year-old man) in whom the blood findings were suggestive of AL. Paraffin-embedded bone marrow biopsy specimens revealed similar findings in both patients: there was severe hypocellularity, the cells of normal hemopoiesis were greatly reduced in number, and there was a diffuse increase in blast cells, which represented more than 50% of nucleated marrow cells. The blasts coexpressed TdT and CD34 and were negative for myeloperoxidase, CD117, CD68 and naphthol AS-D chloroacetate esterase. For the first time immunohistochemical Pax-5/CD34 doublestainings are provided, which revealed the blasts in one case to coexpress Pax-5 and CD34. All the blasts were CD79a-positive and 20% were also CD10-positive. In the other case, 20% of the blasts were CD79a-positive, 30% coexpressed Pax-5 and CD34 by doublestaining, and showed a clonal rearrangement of the immunoglobulin heavy chain gene. Thus a diagnosis of AL of lymphoid lineage, hypocellular variant, was made on the basis of immunohistochemical findings. The clinical course appears to be similar to that of hypocellular AML, as neither patient has developed overt leukemia during the one-year follow-up period.

Rationale and Objectives: To evaluate the efficiency of 4 radiofrequency (RF) systems by assessing the amount of delivered energy for each thermal induced lesion after perfusion mediated RF ablation and to compare the influence of perfusion mediation types on the energy efficiency., Methods: A total of 43 ablations in 16 male landrace pigs with 4 RF devices were performed strictly according to the manufacturers' instructions. Total absorbed energy was computed and then related to 3D volumetry obtained after histopathological evaluation. Sixteen ablations were performed under physiological liver perfusion and 27 ablations with occlusion of portal vein, hepatic artery, or both vessels. Energy efficiency values of the RF systems for different vascular occlusion techniques were compared and analyzed by a nonparametrical rank sum test., Results: Under physiological perfusion, the average energy delivered to produce 1-cm3 lesion size was calculated to 1650 +/- 929, 3097 +/- 389, 8312 +/- 2068, and 5493 +/- 2306 Watt x s/cm3 for the Berchtold, Radionics, Radiotherapeutics, and RITA system, respectively. After perfusion-mediated RF ablation, artery occlusion was not as effective as portal vein occlusion, which reduced the energy to 587 +/- 148, 869 +/- 276, and 903 +/- 394 Watt. s/cm3 for the Berchtold, Radionics, and Radiotherapeutics system, respectively. The occlusion of vessels, portal vein, and artery or portal vein alone increased the energy efficiency compared with physiological liver perfusion or occlusion of the artery (P = 0,003)., Conclusions: Under physiological liver perfusion the open perfused system and the internally cooled system provided the best efficiency values with lowest standard deviations. The energy efficiency was increased markedly for all systems after occlusion of the portal vein either alone or in combination with arterial occlusion. Occlusion of the hepatic artery did not improve the efficiency.

Efficient engulfment of the intact cell corpse is a critical end point of apoptosis, required to prevent secondary necrosis and inflammation. The presentation of "eat-me" signals on the dying cell is an important part of this process of recognition and engulfment by professional phagocytes. Here, we present evidence that apoptotic cells secrete chemotactic factor(s) that stimulate the attraction of monocytic cells and primary macrophages. The activation of caspase-3 in the apoptotic cell was found to be required for the release of this chemotactic factor(s). The putative chemoattractant was identified as the phospholipid, lysophosphatidylcholine. Further analysis showed that lysophosphatidylcholine was released from apoptotic cells due to the caspase-3 mediated activation of the calcium-independent phospholipase A(2). These data suggest that in addition to eat-me signals, apoptotic cells display attraction signals to ensure the efficient removal of apoptotic cells and prevent postapoptotic necrosis.

Background: Xanthogranulomatous cholecystitis is a macrophage-rich inflammatory condition of the gallbladder that occasionally presents with tumorlike appearance., Case Presentation: In the present case the inflammation involved all the layers of the gallbladder, the surrounding connective tissue, and part of the right lobe of the liver and right transverse colon. The clinical and radiological findings were suggestive of advanced carcinoma of the gallbladder. However, intraoperative frozen section investigation revealed xanthogranulomatous cholecystitis, for which simple cholecystectomy is the treatment of choice., Conclusions: The original cause of the condition is unclear in most cases. In the present case it is possible that rupture of the gallbladder in association with the patient's known history of trauma have initiated the process.

Primary lymphoma of the urinary bladder is a very rare tumour. A bladder tumour was found in a 57 year old man with obstructive dysuria. It was found by histological and immunohistohistochemical investigation to be an extranodal marginal zone B cell lymphoma. Lymphoepithelial lesions were absent, but were found in a clinically silent gastric lymphoma discovered four weeks later during staging investigations; this gastric lymphoma was negative for Helicobacter pylori by breath test and molecular biological analysis. Sequencing of the clonal immunoglobulin heavy chain gene in both tumours indicated the same precursor cell, of follicular or post follicular origin. In synopsis, the data suggested that this was a case of primary lymphoma of the bladder with involvement of the stomach. The application of a chromosome 3 specific alpha satellite probe revealed trisomy 3. A tumour with these characteristics arising as a lymphoma of the bladder with a metachronous involvement of the gastric mucosa has not been described previously.

Background: Cystic carcinomas of the neck without evidence of a primary tumor are diagnostically challenging lesions. Differentiation between a cystic lymph node metastasis of an occult primary tumor and a carcinoma arising in a branchiogenic cyst is frequently not possible even with histological examination. In order to clarify the diagnosis, an intensive search for a primary lesion in the upper aerodigestive tract must be carried out., Diagnosis: An occult carcinoma might be situated in Waldeyer's ring, especially in the tonsillar crypts. These tumors tend to produce cystic metastases in the jugulodigastric region. Therefore, multiple biopsies have to be taken from the tissue of Waldeyer's ring. In the case of a positive histological result, adequate therapy of both the primary and the metastasis can be carried out. The diagnosis of a malignant branchiogenic cyst is only permissible after a primary lesion has been thoroughly excluded.

Rituximab, a chimeric anti-CD20 monoclonal antibody, has been approved for systemic treatment of relapsed or refractory CD20-positive B-cell non-Hodgkin's lymphoma. As cutaneous B-cell lymphoma (CBCL) also expresses the CD20 molecule, three patients with histologically and immunohistochemically confirmed CBCL without systemic involvement were treated with low-dose intralesional rituximab in a pilot study. Single doses applied ranged from 10 to 30 mg per lesion, according to lesion extent, with a cumulative dose of up to 350 mg. Injections were given two or three times weekly for 3-5 weeks, with a second cycle after 6 weeks in one patient with incomplete remission. Complete and lasting remission was achieved in each patient; this has persisted for up to more than 1 year. The observed adverse events were of grade 1 severity. Results suggest that intralesional rituximab may be a safe and effective new therapy modality for CBCL.

Background: Although numerous antibodies suitable for use on paraffin wax embedded sections are available for the subtyping of acute leukaemia (acute myelogenous leukaemia (AML) and acute lymphoblastic leukaemia (ALL)) in bone marrow biopsy sections, unequivocal identification of the cell line involved is sometimes impossible., Methods: Forty eight formalin fixed, paraffin wax embedded bone marrow biopsy specimens that had been decalcified in EDTA were investigated, including 42 thought to exhibit ALL on the basis of bone marrow smears. Five specimens exhibited AML and one biphenotypic leukaemia, as diagnosed immunohistochemically in bone marrow biopsies. Immunostaining was performed with antibodies against relatively specific B and T cell antigens. The blasts were investigated for rearrangements of the immunoglobulin heavy chain (IgH) and the T cell antigen receptor (TCR) genes., Results: Amplifiable DNA was obtained from all 48 specimens. An IgH gene rearrangement was detected in 20 of 23 c-ALL specimens. Four of seven T cell ALL (T-ALL) specimens had a TCR-gamma gene rearrangement, and the one B cell ALL (B-ALL) specimen exhibited a clonal IgH gene. Three of four cases of unclassifiable ALL could be assigned to the B cell lineage on the basis of gene rearrangement analysis. Seven cases originally diagnosed in smears as ALL were rediagnosed as AML (n = 5) or biphenotypic leukaemia (n = 2) because of immunohistochemical reactivity for myeloperoxidase or lysozyme. Two of these AML cases and two of three cases of biphenotypic leukaemia exhibited a monoclonal IgH gene rearrangement., Conclusions: Acute leukaemia can be subtyped in bone marrow sections with a limited panel of antibodies suitable for use on paraffin wax embedded sections (against CD3, CD10, CD20, CD79a, myeloperoxidase, and lysozyme). In patients with ALL and a diagnostically equivocal immunophenotype, gene rearrangement analysis might indicate whether the B or T cell lineage is involved.

Paragangliomas of the glomus caroticum are relatively rare, but highly vascularized neoplasmas, which develop from chemoreceptors. They can be develop at any age, but most often in the third or fourth decade of life. Paragangliomas grow very slowly and are most always of benign origin. There is a familial predisposition, and an autosomal-dominant transmission is presumed. They are commonly located in the jugular region; in rare cases a polytopic manifestation is found. We describe the case of a 47-year-old male patient who was referred to our department because of a progressive swelling of the neck on both sides. Contrast-enhanced computed tomography had displayed soft tissue tumors in the jugular regions. We performed an operative exploration, which showed a highly vascularized tumor. Histopathologic analysis revealed the diagnosis of a paraganglioma. An angiography of the neck and thoracic region, furthermore, revealed an additional paraganglioma in the anterior mediastinum. Using a surgical approach via lateral cervicotomies and thoracotomy the paragangliomas were extirpated. Our case report demonstrates the rare polytopic manifestation of paragangliomas. This perivascular neoplasms have to be removed before haemodynamic complications develop. The extent of this tumors is clearly illustrated by use of an angiography. Because of the familial predisposition, clinical and radiological examinations of relatives are mandatory.

Background: Slight, diffuse or focal lymphocyte proliferation is relatively common in bone marrow biopsy specimens. It may be impossible to determine whether this represents a reactive lymphocytosis or low grade non-Hodgkin lymphoma (NHL) on the basis of routine investigations alone., Aim: To investigate the supplementary use of molecular biological techniques in this situation., Methods: 529 formalin fixed, paraffin embedded bone marrow biopsy specimens from the iliac crest were subjected to histological and immunohistochemical staining to determine the number and nature of the lymphocytes present. The cases were divided into three groups according to the lymphocyte count: normal (< 10% of nucleated bone marrow cells), slightly increased (10-30%), and markedly increased (> 30%). All of the last group could be diagnosed as NHL from the morphological findings alone. The clonality of rearrangements of the IgH and TCR gamma genes was investigated by polymerase chain reaction (PCR)., Results: Monoclonality was observed in 7.5% of the 372 cases with a normal lymphocyte count, in 50% of the cases with a modest increase in lymphocyte numbers (suggesting a diagnosis of low grade NHL not detected by immunostaining), and in 77% of the cases with markedly increased lymphocyte numbers., Conclusions: If PCR is used in addition to the immunohistochemical investigation of bone marrow biopsies, considerably more cases of NHL can be identified, making this of particular use in staging and detection of recurrences.

We describe a case of granulomatous mycosis fungoides, tumor stage, mimicking sarcoidosis in an 82-year-old man with a 2-year history of skin disease. The final diagnosis was established after one of seven biopsy specimens showed a nongranulomatous histologic picture of patch-stage mycosis fungoides. Monoclonality was proven for the lymphocytic population by T-cell-receptor rearrangement studies. The unusually extensive granulomatous inflammation with huge giant cells surrounded by CD1a-positive cells in the other six biopsy specimens was suggestive of the histopathology of granulomatous slack skin, another rare granulomatous cutaneous T-cell lymphoma. Because both a clinical and histologic overlap between granulomatous mycosis fungoides and granulomatous slack skin have been reported in the literature, we conclude that they may belong to the spectrum of a single disease.

Giant cell tumour (GCT) of bone is a locally aggressive tumour with a high rate of recurrence if not completely excised. The present study was undertaken to clarify whether flow cytometric, immunohistochemical and morphometric studies can be a useful tool to assess the prognosis of patients with GCT. DNA flow cytometry, cell cycle studies and immunohistochemical investigations with antibodies against CD 68, CD 34, p53 and Ki67 were performed on paraffin embedded tissue of 10 cases of GCT. As a further possible prognostic parameter angiogenesis within the tumour was investigated using an automatic image analysis system. Histologically 4 cases were grade 1 tumours and 6 cases grade 2. Among the Grade 1 cases, all were diploid. Of the Grade 2 cases, 4 were diploid and 2 were aneuploid. Both of the patients with an aneuploid tumour developed a loval recurrence. All GCT revealed large numbers of CD 68 positive giant cells, but mononuclear tumour cells exhibiting CD 68 immunoreactivity were also present. Corresponding to the immunohistochemical findings with MIB-1 the flow cytometric DNA histogram revealed high proliferation rates (mean value 14.9%). None of the tumours exhibited p53 immunoreactive cells. All cases showed high content of vessels with on the average relative vessel area of 7.7%. No correlation between clinical outcome and vascular parameters (number of vessels, vessel area, perimeter) was found. Our findings suggest that DNA flow cytometry is useful in predicting tumour behaviour in some cases. GCT exhibits extensive angiogenesis, but none of the vascular parameters investigated was found to be of prognostic value.

Mast cells are now known to derive from CD34+ haemopoietic stem cells in the bone marrow. However, it has not yet been established whether the various types of mastocytosis, which involve tumour-like proliferation of mast cells, are true neoplastic disorders or reactive/hyperplastic conditions. In this study, tissue specimens (five bone marrow, two spleen, one skin) from female patients with histologically confirmed mastocytosis were investigated with a recently developed polymerase chain reaction assay for the determination of clonality of female cells using the human androgen receptor gene (HU-MARA). Mast cells purified to near homogeneity from hysterectomy specimens served as a control. The findings in bone marrow and skin either were not reproducible, or indicated polyclonality. However, both spleen specimens exhibited monoclonality. In addition, DNA analysis by flow cytometry was performed and revealed a diploid chromosome content with proliferation indices of under 8% in all the specimens. This is the first molecular biological study to indicate that mastocytosis is indeed neoplastic in nature.