Early Detection of Bilateral Testicular Metastases From Prostatic Adenocarcinoma Using 68Ga-PSMA Ligand PET/CT.

We present the case of a 76-year-old man with biochemical relapse after primary therapy for prostate cancer. Ga prostate-specific membrane antigen (PSMA) ligand PET/CT performed for localization of recurrent disease revealed bilateral metastases to the testes. Histopathologic evaluation after bilateral orchiectomy revealed testicular metastases. Metastases to the testes are rare and usually seen in advanced stages. Ga-PSMA ligand PET/CT is a highly sensitive and specific imaging method for the detection of primary and metastatic prostate cancer and has refined diagnostic approaches. This case highlights the potential of PSMA-targeted PET/CT for detection of prostate cancer metastases, even in very unusual localizations.

Lipoprotein lipase-facilitated uptake of LDL is mediated by the LDL receptor.

LPL mediates the uptake of lipoproteins into different cell types independent of its catalytic activity. The mechanism of this process and its physiological relevance are not clear. Taking into account the importance of the endothelial barrier for lipoprotein uptake, in vitro studies with primary aortic endothelial cells from wild-type and low density lipoprotein receptor (LDLR)-deficient (LDLR(-/-)) mice were performed. Addition of LPL almost doubled the uptake of LDL into wild-type cells. However, there was virtually no LPL-mediated change of LDL uptake into LDLR(-/-) cells. Upregulation of LDLR by lipoprotein-deficient serum/lovastatin in wild-type cells resulted in a 7-fold increase of LPL-mediated LDL uptake. Uptake of chylomicron remnants was not affected by LDLR expression. In proteoglycan-deficient cells, LPL did not increase the uptake of lipoproteins. The physiological relevance of this pathway was studied in mice that were both LDLR(-/-) and transgenic for catalytically inactive LPL in muscle. In the presence of LDLR, inactive LPL reduced LDL cholesterol significantly (13-24%). In the absence of LDLR, LDL cholesterol was not affected by transgenic LPL. Metabolic studies showed that in the presence of LDLR, LPL increased the muscular uptake of LDL by 77%. In the absence of LDLR, transgenic LPL did not augment LDL uptake. Chylomicron uptake was not affected by the LDLR genotype. We conclude that LPL-mediated cellular uptake of LDL, but not of chylomicrons, is dependent on the presence of both LDLR and proteoglycans.

Erdheim-Chester disease: a case report.

BACKGROUND: Erdheim-Chester disease (ECD) is a rare histiocytosis, histologically characterized by xanthogranulomatous inflammation. It may affect the bones, heart, lung, liver, kidneys, retroperitoneum, brain, and, rarely, the orbit. In the majority of patients, orbital infiltration is bilateral. CASE: A 61-year-old man presented with bilateral exophthalmos and progressive loss of visual function caused by chorioretinal folds and papillary swelling due to retrobulbar pseudotumor. The computed tomogram of the abdomen showed retroperitoneal thickening, leading to the interpretation of multifocal fibrosclerosis. This was further substantiated by an orbital biopsy revealing chronic fibrosing inflammation. Retrobulbar radiotherapy (20 Gy) and long-term systemic corticosteroid treatment followed. Although the retroperitoneal involvement decreased, no significant effect on orbital involvement was achieved. A second review of the orbital biopsy revealed foamy cell infiltration and the presence of a sclerotic process. Immunohistochemical examination demonstrated positive CD 68 stains, whereas S-100 and CD 1a were negative, thus confirming ECD. The histologic finding was comparable to a biopsy of the retroperitoneum. Endonasal decompression was performed but visual acuity (VA) decreased to 20/250 in the right eye and on finger counting in the left eye. The patient continues to be under therapy with prednisolone 20 mg/day and methotrexate 25 mg/week. CONCLUSIONS: The clinical orbital manifestation of ECD occurs in two different forms: one presenting as a mild impairment of visual function, while the second, clinical form, observed in our patient, is characterized by a progressive loss of VA despite therapeutic efforts such as immunosuppressive systemic therapy, radiation, and surgery. The described case illustrates that clinical findings in multifocal fibrosclerosis overlap with those observed in ECD.

Diagnostic impact of ornithine decarboxylase in meningiomas.

The objective of this study was to investigate whether activity and protein expression of ornithine decarboxylase (ODC) the metabolism-rate limiting enzyme of the polyamine biosynthesis, which is involved in the regulation of cellular growth and differentiation, reflects the distinct histopathologic characteristics indicative of atypia and anaplasia in meningiomas as well as their impact in recurrences. The authors previously evaluated its value as a critical factor of tumor development in various brain tumors. Among 152 meningiomas, World Health Organisations (WHO) grade I meningiomas (n = 121) exhibited a low ODC activity, while meningiomas WHO grade II (n = 22) and WHO grade III (n = 9), respectively, showed a significantly increased ODC activity. Recurrent WHO grade I meningiomas exhibited the same low enzyme activity and immunohistochemical staining index for ODC positive tumor cells as their primary tumors, whereas raising ODC activity and protein expression in recurrent meningiomas paralleled malignant transformation. These results indicate that ODC reflects aggressive growth and malignization in meningiomas. Especially in recurrent meningiomas, the determination of its activity and protein expression by immunohistochemistry may provide a useful diagnostic tool to recognize malignant progression.

Ameloblastic fibrosarcoma or odontogenic carcinosarcoma: a matter of classification?

A biphasic odontogenic tumor with aggressive clinical behaviour is reported. The tumor arose posterior to the right mandibular third molar involving the angle of the mandible and the ascending ramus. Within a 5 years period the patient suffered from two episodes of local progression and final disease generalization occurred 6 years after initial surgical therapy. On histopathologic evaluation, both recurrences and the distant metastasis preserved the biphasic pattern seen in the primary tumor with both epithelial and mesenchymal components exhibiting clear cytological features of malignancy. There was no evidence of sarcomatous overgrowth within the progression of the tumor. By contrast, the proportion of the epithelial component was even enlarged in the second recurrence. Thus, both pathologic features and clinical behaviour clearly distinguishes this tumor from ameloblastic fibrosarcoma and demonstrates the clear morphological as well as clinical characteristics of a true malignant mixed type tumor with a definite sarcomatous and carcinomatous component. Thus, even though a very rare lesion, our case supports the consideration of the odontogenic carcinosarcoma as an individual entity.

Mice expressing only covalent dimeric heparin binding-deficient lipoprotein lipase: muscles inefficiently secrete dimeric enzyme.

Lipoprotein lipase (LpL) hydrolyzes triglycerides of circulating lipoproteins while bound as homodimers to endothelial cell surface heparan sulfate proteoglycans. This primarily occurs in the capillary beds of muscle and adipose tissue. By creating a mouse line that expresses covalent dimers of heparin-binding deficient LpL (hLpLHBM-Dimer) in muscle, we confirmed in vivo that linking two LpL monomers in a head to tail configuration creates a functional LpL. The hLpLHBM-Dimer transgene produced abundant activity and protein in muscle, and the LpL was the expected size of a dimer (approximately 110 kDa). Unlike the heparin-binding mutant monomer, hLpLHBM-Dimer had the same stability as nonmutated LpL. The hLpLHBM-Dimer transgene prevented the neonatal demise of LpL knockout mice; however, these mice were hypertriglyceridemic. Postheparin plasma LpL activity was lower than expected with the robust expression in muscle and was no longer covalently linked. Studies in transfected cells showed that Chinese hamster lung cells, but not COS cells, also degraded tandem repeated LpL into monomers. Thus, although muscle can synthesize tethered, dimeric LpL, efficient production of this enzyme leading to secretion, and physiological function appears to favor secretion of a noncovalent dimer composed of monomeric subunits.

[Lipoprotein lipase-mediated myopathy: implications for lipid metabolism and atherogenesis]. / Myopathische Veränderungen durch transgene Expression von Lipoproteinlipase. Implikationen für Stoffwechsel und Atherogenese.

BACKGROUND: Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. Various genetically modified mouse lines expressing either native or mutated LPL have been established, and the function of LPL in the metabolism and during lipoprotein transport has been characterized. Some of these animals showed an LPL-mediated myopathy or cardiomyopathy. Comparing the histological changes with metabolic data provides new insights in the function of LPL in metabolism and for atherogenesis. MATERIAL AND METHODS: Histological and electron microscopy specimens of muscle and heart from different LPL transgenic mouse lines have been evaluated and compared to metabolic data. RESULTS: Presence of LPL causes a myopathy and cardiomyopathy primarily by augmenting nonenzymatic selective cholesterol ester uptake. LPL-mediated fatty acid and lipoprotein uptake is not sufficient to harm muscle tissue. CONCLUSION: It is suggested, that LPL derived from endothelial cells and macrophages--besides other atherogenic mechanisms--can mediate cholesterol ester influx into the vessel wall and thereby promote proatherogenic modifications. Although due to its hydrolytic function, LPL is generally considered an antiatherogenic enzyme, endothelial LPL can locally facilitate atherogenesis.

Expression of somatostatin receptors in uveal melanomas.

PURPOSE: To investigate the distribution of somatostatin receptor (SSR) subtypes 2, 3, and 5 in uveal melanomas and their diagnostic and possible therapeutic value. METHODS: SSRs were investigated in 25 paraffin-embedded eyes with uveal melanomas and in 6 normal eyes without any disease, by using polyclonal antiserum directed to SSR2A, -2B, -3, and -5. Antigen expression was evaluated by a semiquantitative method. The expression pattern of SSR was correlated with the patients' ad vitam prognosis by use of the Kaplan-Meier survival curve. Six different human melanoma cell lines were incubated with octreotide and vapreotide, and a proliferation assay was performed by determining [(3)H]-TdR uptake. [111-Indium-DTPA-D-Phe1]-octreotide scintigraphy was performed in the eyes of four patients with known uveal melanomas. RESULTS: All uveal melanomas were positive for SSR2. SSR2A was expressed in 15 of 25, SSR2B in 23 of 25, SSR3 in 7 of 25, and SSR5 in 13 of 25 uveal melanomas. A Kaplan-Meier survival curve showed a significantly better ad vitam prognosis for patients with tumors expressing high levels of SSR2. Cell proliferation was inhibited up to 36% +/- 6% in three of six melanoma cell lines at a concentration of 10(-4) M octreotide or vapreotide. Eyes of two patients with uveal melanomas showed positive uptake of [111-Indium-DTPA-D-Phe1]-octreotide. CONCLUSIONS: SSR2, -3, and -5 are expressed in human uveal melanomas and patients with a high amount of SSR2 in the melanoma tissue have a better ad vitam prognosis. Because a melanoma cell proliferation assay showed an inhibitory effect of up to 36% +/- 6% using octreotide or vapreotide, somatostatin analogues may be beneficial in the treatment of patients with ocular melanomas.

Coinfection of the retina by Epstein-Barr virus and cytomegalovirus in an AIDS patient.

PURPOSE: To report an immunohistochemically proven case of a coinfection of the retina by Epstein-Barr virus and cytomegalovirus in a patient with acquired immunodeficiency syndrome (AIDS). DESIGN: Interventional case report. METHODS: Postmortem evaluation of retinal tissue of a 45-year-old female AIDS patient with atypical fibrinous iridocyclitis and vitritis in course of a cytomegalovirus retinitis in the left eye was performed for evidence of dual infection with cytomegalovirus and other herpes group viruses. Immunohistochemical examination with double-staining techniques and antibodies against Epstein-Barr virus and cytomegalovirus was used. RESULTS: In the retina of the left eye, cells reacting with antibodies against cytomegalovirus and cells stained with antibodies against Epstein-Barr virus were detected in the layer of ganglionic cells and the inner granular cell layer. CONCLUSION: Epstein-Barr virus coinfection should be taken into consideration in unusual cases of necrotizing cytomegalovirus retinitis in AIDS patients.

Inactive lipoprotein lipase (LPL) alone increases selective cholesterol ester uptake in vivo, whereas in the presence of active LPL it also increases triglyceride hydrolysis and whole particle lipoprotein uptake.

We have previously shown that transgenic expression of catalytically inactive lipoprotein lipase (LPL) in muscle (Mck-N-LPL) enhances triglyceride hydrolysis as well as whole particle lipoprotein and selective cholesterol ester uptake. In the current study, we have examined whether these functions can be performed by inactive LPL alone or require the presence of active LPL expressed in the same tissue. To study inactive LPL in the presence of active LPL in the same tissue, the Mck-N-LPL transgene was bred onto the heterozygous LPL-deficient (LPL1) background. At 18 h of age, Mck-N-LPL reduced triglycerides by 35% and markedly increased muscle lipid droplets. In adult mice, it reduced triglycerides by 40% and increased lipoprotein particle uptake into muscle by 60% and cholesterol ester uptake by 110%. To study inactive LPL alone, the Mck-N-LPL transgene was bred onto the LPL-deficient (LPL0) background. These mice die at approximately 24 h of age. At 18 h of age, in the absence of active LPL, inactive LPL expression did not diminish triglycerides nor did it result in the accumulation of muscle lipid droplets. To study inactive LPL in the absence of active LPL in the same tissue in adult animals, the Mck-N-LPL transgene was bred onto mice that only expressed active LPL in the heart (LPL0/He-LPL). In this case, Mck-N-LPL did not reduce triglycerides or increase the uptake of lipoprotein particles but did increase muscle uptake of chylomicron and very low density lipoprotein cholesterol ester by 40%. Thus, in the presence of active LPL in the same tissue, inactive LPL augments triglyceride hydrolysis and increases whole particle triglyceride-rich lipoprotein and selective cholesterol ester uptake. In the absence of active LPL in the same tissue, inactive LPL only mediates selective cholesterol ester uptake.