Klaus A. Metz

Diagnostic Yield of Computed Tomography-Guided Coaxial Core Biopsy of Undetermined Masses in the Free Retroperitoneal Space: Single-Center Experience

The purpose of this study was to evaluate the diagnostic yield of core biopsy in coaxial technique under guidance of computed tomography (CT) for retroperitoneal masses. We performed a retrospective analysis of CT-guided coaxial core biopsies of undetermined masses in the non-organ-bound retroperitoneal space in 49 patients. In 37 cases a 15-G guidance needle with a 16-G semiautomated core biopsy system, and in 12 cases a 16-G guidance needle with an 18-G biopsy system, was used. All biopsies were technically successful. A small hematoma was seen in one case, but no relevant complication occurred. With the coaxial technique, up to 4 specimens were obtained from each lesion (mean, 2.8). Diagnostic accuracy in differentiation between malignant and benign diseases was 95.9%. A specific histological diagnosis could be established in 39 of 42 malignant lesions (92.9%). Correct subtyping of malignant lymphoma according to the WHO classification was possible in 87.0%. Benign lesions were correctly identified in seven cases, although a specific diagnosis could only be made in conjunction with clinical and radiological information. In conclusion, CT-guided coaxial core biopsy provides safe and accurate diagnosis of retroperitoneal masses. A specific histological diagnosis, which is essential for choosing the appropriate therapy, could be established in most cases of malignancy.

Diagnostic image quality of gadolinium-enhanced T1-weighted MRI with and without fat saturation in children with retinoblastoma

BackgroundGadolinium-enhanced T1-weighted MRI without fat saturation has been recommended for assessment of retinoblastoma.ObjectiveThe purpose of this study was to compare diagnostic image quality without and with fat saturation following gadolinium administration.Materials and methodsHigh-resolution gadolinium-enhanced T1-weighted sequences with and without fat saturation performed in children with subsequently histopathologically confirmed retinoblastoma were included. Image analysis (image quality [1 = poor, 2 = moderate, 3 = good], anatomical detail depiction, tumour extension) was performed by two neuroradiologists in consensus. Enhancement was scored and measured. Signal- and contrast-to-noise ratios were calculated. Image-assessed tumour invasiveness was compared to histopathological findings. Paired sample t-test was used for statistical analysis.ResultsThirty-six children (mean age, 19.0 ± 16.8 [SD] months) were included. Image quality and anatomical detail depiction were significantly better without fat saturation (P < 0.001). Tumour enhancement was rated higher with fat saturation (P < 0.001). Fat saturation improved detection of (post-)laminar optic nerve infiltration. Detection of choroidal invasion was improved without fat saturation. Combining both sequences was best in the assessment of tumour extension (sensitivity/specificity for (post-)laminar optic nerve infiltration, 75.0%/100.0%, and for choroidal invasion, 87.5%/85.7%).ConclusionCombined T1-weighted spin-echo imaging with and without fat saturation improved the image quality for assessment of invasiveness of retinoblastoma.

Immunohistochemical evidence of BMP-2, -4 and -7 activity in otospongiosis.

Conclusion. This study is the first to show that bone morphogenetic proteins (BMP)-2, -4 and -7 play a role in active phase otosclerotic bone remodelling (otospongiosis). Objectives. The role of BMPs in various tissue growth and repair mechanisms is an ongoing topic in the literature. BMP-2, -4 and -7 are known to be of major importance in bone formation and repair. Their role in otosclerotic bone transformation has not been analysed previously. The main goal of this study was to perform an immunohistological analysis of BMP-2, -4 and -7 in otoclerosis. Materials and methods. Parts of the stapedial footplates, collected during partial stapedectomies in 30 patients with clinical otosclerosis, were analysed for histological otosclerotic lesions after staining haematoxylin and eosin. Immunohistochemical analysis was performed using polyclonal IgG antibodies for BMP-2, -4 and -7, as well as biotinylated secondary antibodies, avidin-biotin-peroxidase complex reaction and alkaline phosphatase staining. Results. In all, 14 specimens contained otosclerosis; 3 of these were otospongiotic, 8 fibrotic, 2 sclerotic and 1 had both sclerotic and fibrotic lesions. Thus in total 14/30 specimens (47%) showed histological otosclerosis. Only the multiple osteoblasts and osteoclasts in those specimens exhibiting an otospongiotic phase showed distinct immunochemical staining for BMP-2, -4 and -7.

Diagnostic dilemma in pancreatic lymphoma. Case report and review.

SummaryNon-Hodgkins lymphoma predominantly involving the pancreas is a rare tumor of the gastrointestinal tract. Diagnosis can be difficult, since lymphoma may mimic carcinoma or pancreatitis. Lymphoproliferative diseases induced by immunosuppressive therapy frequently occur in the gastrointestinal tract of posttransplant patients. However, pancreatic involvement of posttransplant lymphoma is an exceptional condition. We present the case of a cyclosporin-treated renal transplant recipient with pancreatic lymphoma mimicking carcinomatous or inflammatory tumors. The diagnostic difficulties and treatment options of pancreatic lymphoma as well as lymphoproliferative disorders in immunosuppressed renal recipients are discussed in light of the current literature.

Signaling by way of type IB and II bone morphogenetic protein receptors regulates bone formation in otospongiosis.

Hypothesis: The main goal of this study was to perform an immunohistologic analysis of bone morphogenetic protein receptors (BMPR) in otospongiosis.

Novel SDHD Gene Mutation (H102R) in a Patient With Metastatic Cervical Paraganglioma Effectively Treated by Peptide Receptor Radionuclide Therapy

Case Report A 23-year-old woman was referred to our hospital as a result of loss of weight of 15 kg in the 8 months after the birth of a girl. Weight at admission was 70 kg, and height was 180 cm. Laboratory tests showed microcytic anemia and increased alkaline phosphatase, C-reactive protein, and ferritin. An ultrasound of the abdomen revealed multiple bilobar hepatic masses, which were confirmed by magnetic resonance imaging. Colonoscopy and endoscopy yielded no pathologic results. Histology from a biopsy of the largest liver tumor showed clusters of medium-sized cells with large nuclei, abundant cytoplasm, fibromuscular stroma, and high expressions of vimentin, synaptophysin, CD56, and chromogranin A. Therefore, the morphology and immunoprofile were suggestive of a neuroendocrine tumor. The Ki-67 proliferative index was 3% to 5%. The only relevant event in the past medical history of the patient was the resection of a cervical paraganglioma at age 16 years. The tumor was located at the right carotid artery bifurcation and had already grown around the external and internal carotid arteries. By means of a saphenous vein graft, the tumor was removed. Resection was described as removal in toto; however, the minimal distance to the resection margin was only 1 mm. Histologically, no evidence of malignancy,vascular invasion,ornecrosiswas identified.Six lymphnodeswere free of tumor cells. Laboratory tests from that time were not available. In view of the clinical history of the patient, a recurrence of a malignant paraganglioma was strongly suspected. Histologic sections of the original paraganglioma and the current hepatic metastasis biopsy (Figs 1 A and 1B, respectively; hematoxylin and eosin, original magnification 40) showed an identical morphology of tumor cells and a strong positive reaction to chromogranin A (Fig 1C, liver biopsy),which thus confirmed metastatic disease from a paraganglioma. Because a malignant course is most common in paragangliomas as a result of a mutation in the succinate dehydrogenase (SDH) SDHB gene, this gene was sequenced, but a mutation was not detected. However, the sequencing of the SDHD gene revealed a heterozygous missense mutation in exon 3 (c.305A G; p.H102R; Fig 2; electropherograms of the SDHD gene show the forward sequence in the upper panel and the reverse complement sequence in the lower panel with the missense mutation indicated by arrows). Metanephrine and normetane prine in urine were normal at 37 g/24 h (normal, 350) and 159 g/24 h (normal, 159), respectively, and in plasma (metanephrine 39 ng/L [normal, 90] and normetanephrine 123 ng/L [normal, 180]). Staging was completed with imaging studies. A bone scan showed multiple metastases in the axial skeleton, which were confirmed by magnetic resonance imaging of the spine. A lesion in L1 extended into the spinal canal with a 4-mm minimal distance to the spinal cord. As a result of the paraganglionic nature of the primary, I-metaiodobenzylguanidine (MIBG)–positron emission tomography (PET)/computed tomography (CT) was performed, which showed negligible lesional MIBG uptake (Fig 3B; I-MIBG-PET/CT maximum intensity projection). In contrast, all lesions were avid in Ga-DOTA-(0)-Phe(1)-Tyr(3)-octreotide (DOTATOC)–PET/CT (Fig 3A; Ga-DOTATOC-PET/CT maximum intensity projection), with remarkably high uptake in multiple hypervascularised liver metastases (maximum standard uptake value up to 149) and disseminated osteolytic-osteoblastic lesions in the spine (Fig 4B; from left to right: I-MIBG-PET, I-MIBG-PET/CT fusion, CT, GaDOTATOC-PET/CT fusion, Ga-DOTATOC-PET; the height of transversal sections is indicated by the lower line in Fig 3), at both scapulae and the pelvis. T1 and L1 were at risk of fracture as a result of the osteolyses. Moreover, local relapse was detected in the paravertebral region on the right side of C1 (14 21 mm; maximum standard uptake value of 69; Fig 4A; image sequence as in Fig 4B; the height of transversal sections is indicated by the upper line in Fig 3). Clinically, the patient had no neurologic deficits. After a diagnosis of risk of fracture, an anterior distraction device was implanted after corpectomy of T1. Histology from T1 confirmed the presence of metastatic paraganglioma.

Diagnostic Accuracy of Intraocular Tumor Size Measured with MR Imaging in the Prediction of Postlaminar Optic Nerve Invasion and Massive Choroidal Invasion of Retinoblastoma

Purpose To assess the correlation of intraocular retinoblastoma tumor size measured with magnetic resonance (MR) imaging in the prediction of histopathologically determined metastatic risk factors (postlaminar optic nerve invasion and massive choroidal invasion). Materials and Methods The ethics committee approved this retrospective multicenter study with a waiver of informed consent. The study population included 370 consecutive patients with retinoblastoma (375 eyes) who underwent baseline MR imaging, followed by primary enucleation from 1993 through 2014. Tumor sizes (maximum diameter and volume) were measured independently by two observers and correlated with histopathologic risk factors. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of tumor size, and areas under the curve were calculated. Logistic regression analysis was performed to evaluate potential confounders. Results Receiver operating characteristic analysis of volume and diameter, respectively, yielded areas under the curve of 0.77 (95% confidence interval [CI]: 0.70, 0.85; P < .0001) and 0.78 (95% CI: 0.71, 0.85; P < .0001) for postlaminar optic nerve invasion (n = 375) and 0.67 (95% CI: 0.57, 0.77; P = .0020) and 0.70 (95% CI: 0.59, 0.80; P = .0004) for massive choroidal tumor invasion (n = 219). For the detection of co-occurring massive choroidal invasion and postlaminar optic nerve invasion (n = 219), volume and diameter showed areas under the curve of 0.81 (95% CI: 0.70, 0.91; P = .0032) and 0.83 (95% CI: 0.73, 0.93; P = .0016), respectively. Conclusion Intraocular tumor size shows a strong association with postlaminar optic nerve invasion and a moderate association with massive choroidal invasion. These findings provide diagnostic accuracy measures at different size cutoff levels, which could potentially be useful in a clinical setting, especially within the scope of the increasing use of eye-salvage treatment strategies. (©) RSNA, 2015 Online supplemental material is available for this article.

Reduction of the tumorigenic potential of human retinoblastoma cell lines by TFF1 overexpression involves p53/caspase signaling and miR-18a regulation

Trefoil factor family (TFF) peptides have been shown to play a pivotal role in oncogenic transformation, tumorigenesis and metastasis by changing cell proliferation, apoptosis, migration and invasion behavior of various cancer cell lines. In the study presented, we investigated the effect of TFF1 overexpression on cell growth, viability, migration and tumorigenicity of different retinoblastoma (RB) cell lines. Transient TFF1 overexpression significantly increases RB cell apoptosis levels. Stable, lentiviral TFF1 overexpression likewise decreases RB cell viability, proliferation and growth and significantly increases apoptosis as revealed by WST‐1 assays, BrdU and DAPI cell counts. TFF1‐induced apoptosis is executed via cleaved caspase‐3 activation as revealed by caspase blockage experiments and caspase‐3 immunocytochemistry. Results from pG13‐luciferase reporter assays and Western blot analyses indicate that TFF1‐induced apoptosis is mediated through transcriptional activity of p53 with concurrently downregulated miR‐18a expression. In ovo chicken chorioallantoic membrane (CAM) assays revealed that TFF1 overexpression significantly decreases the size of tumors forming from Y79 and RB355 cells and reduces the migration potential of RB355 cells. Differentially expressed genes and pathways involved in cancer progression were identified after TFF1 overexpression in Y79 cells by gene expression array analysis, underlining the effects on reduced tumorigenicity. TFF1 knockdown in RBL30 cells revealed caspase‐3/7‐independent apoptosis induction, but no changes on cell proliferation level. In summary, the in vitro and in vivo data demonstrate for the first time a tumor suppressor function of TFF1 in RB cells which is at least partly mediated by p53 activation and miR‐18a downregulation.

Transretinale Biopsie beim intraokularen Lymphom

BACKGROUND Intraocular lymphoma is in most cases a diagnostic challenge. Gold standard is a diagnostic vitrectomy. Vitreous biopsy and transretinal biopsies are therefore employed. METHODS A retrospective analysis was undertaken of all cases of cytological or histological proven intraocular lymphoma between 2002 and the beginning of 2015 in our clinic. RESULTS The diagnosis of intraocular lymphoma could be established in 16 cases by cytological or histological analysis. Six patients had previously been treated with steroids in the assumption of uveitis. Five of 16 patients had a systemic or CNS lymphoma in their history. The diagnosis of intraocular lymphoma could be made on the basis of a vitreous biopsy in only in 3 cases. In 7 cases an additional vitrectomy with transretinal biopsy was needed. In 1 case a transretinal biopsy was performed initially and in 1 case a re-transretinal biopsy was needed to establish the diagnosis. Two patients underwent iris biopsy to diagnose a secondary metastatic intraocular lymphoma. One amaurotic eye was diagnosed with intraocular lymphoma after enucleation. DISCUSSION Due to the high relevance for the diagnosis intraocular lymphoma, when a vitreous biopsy was non-informative, a transretinal biopsy should always be considered in cases of retinal or subretinal involvement.

Primäres intraokuläres Lymphom: Relevanz der diagnostischen Vitrektomie

Primary intraocular lymphomas are rare tumours that can be further subdivided into primary vitreoretinal and the even rarer primary uveal lymphoma. The incidence of primary vitreoretinal lymphoma (PVRL) has increased during the last few decades. Differential diagnostic distinction between lymphoma and posterior uveitis is often difficult, so that adequate diagnosis and treatment is often delayed. This is fatal, because PVRL is often associated with primary central nervous lymphoma. To confirm the diagnosis, prior treatment of cytological or histological detection of lymphoma cells is the gold standard. Therefore, a diagnostic vitrectomy should be performed with vitreous biopsy and sometimes transretinal biopsy. Cytokine analysis, as well as flow cytometry and molecular tests, are only additional methods that can be employed in case enough tumour material is available. After the diagnosis has been made, an interdisciplinary treatment concept must be developed by oncologists and ophthalmologists together.