[Interstitial lung disease in infancy and early childhood]. / Nichtneoplastische Lungenerkrankungen des Säuglings und Kindesalters.

Diffuse interstitial lung disease of infancy (chILD) shows a spectrum of disease substantially different from that of adults. Established classification systems divide chILD into conditions that are more prevalent in infancy and conditions that occur at any age. The classification is based on a multidisciplinary approach including clinical, radiological, genetic, and histological findings. Lung biopsies become necessary if other diagnostic investigations have not identified a precise chILD or if severe or refractory respiratory distress of unknown cause is present. As the majority of pediatric lung biopsies will be received first by pathologists outside of specialist centers this review summarizes relevant clinical and histological findings of chILD.

Chronic progressive pulmonary paracoccidioidomycosis in a female immigrant from Venezuela.

Paracoccidioidomycosis (PCM) is a fungal infection caused by Paracoccidioides brasiliensis and P. lutzii. It is endemic to South and Central America. While PCM frequently remains latent, the disease can reactivate years after the initial infection. As the disease is rare outside the endemic area, and symptoms can mimic other pulmonary diseases, correct diagnosis can be challenging for clinicians in developed countries. In this report, we present the case of a 57-year-old female Venezuelan immigrant with PCM. She was initially misdiagnosed with sarcoidosis and treated with corticosteroids, leading to an exacerbation of the infection requiring intensive care. Because cultivation of Paracoccidioides sp. is slow and unsensitive, we opted for microscopic observation of fungal elements and molecular testing on a tissue biopsy and bronchoalveolar lavage (BAL) together with antibody detection. This allowed the diagnosis of PCM, enabling specific management. PCM and other imported mycoses should be considered as a differential diagnosis in patients originating from South and Central America displaying symptoms suggestive of sarcoidosis. The reviews of this paper are available via the supplemental material section.

Biocompatibility and Immunogenicity of Decellularized Allogeneic Aorta in the Orthotopic Rat Model.

IMPACT STATEMENT: The generation of a small-caliber arterial graft, utilizing a large vessel of a small animal, such as the aorta of the rat or rabbit, for clinical use in the peripheral arterial tree, can widen the options for arterial prostheses. This in vivo study demonstrated the ability of the decellularization protocol that was used to produce a noncytotoxic acellular small-caliber arterial graft, with sufficient biomechanical and biological integrity to withstand the demanding flow and pressure environment of the rat aorta. This work also demonstrated the superiority of the decellularized homograft over its intact counterpart, in terms of lower immunogenicity.

68Ga-DOTA-TATE PET/CT for Molecular Imaging of Somatostatin Receptor Expression in Metastasizing Epithelioid Hemangioendothelioma: Comparison With 18F-FDG.

Epithelioid hemangioendothelioma (EHE) is a rare tumor originating from vascular endothelial or pre-endothelial cells. It has the potential to metastasize. We present the case of a 51-year-old woman with metastasizing EHE who underwent both F-FDG and Ga-DOTA-TATE PET/CT for staging of disease and for evaluation of targeted radionuclide therapy potential. On Ga-DOTA-TATE PET scans, intense tracer accumulation was observed in metastases. Besides the increased glucose metabolism in EHE, this case highlights the potential of Ga-DOTA-TATE PET/CT for restaging of EHE and the option of targeted radionuclide therapy in this entity.

PSMA Expression in Tumor Neovasculature Endothelial Cells of Follicular Thyroid Adenoma as Identified by Molecular Imaging Using 68Ga-PSMA Ligand PET/CT.

The prostate-specific membrane antigen (PSMA) is expressed by both prostate cancer and other neoplasms. We report the case of a 65-year-old man with castration-resistant metastatic prostate cancer who underwent Ga-PSMA ligand PET/CT for restaging of disease. Ga-PSMA ligand accumulation was noted in a thyroid lesion, suspicious for thyroid malignancy on complementary ultrasound. Subsequent resection and histopathological analysis showed follicular thyroid adenoma with PSMA expression in tumor neovasculature endothelial cells, but not in thyroid epithelial cells. It is important to be aware that both malignant and benign thyroid neoplasms may show PSMA expression to avoid misinterpretation.

Testosterone-receptor positive hepatocellular carcinoma in a 29-year old bodybuilder with a history of anabolic androgenic steroid abuse: a case report.

BACKGROUND: Continuous use of anabolic androgenic steroid in high-doses is associated with substantial health risks, including hepatocellular adenoma. Malignant transformation from hepatocellular adenoma to hepatocellular carcinoma after anabolic androgenic steroid abuse has been rarely reported. The morphological distinction of adenoma from well-differentiated hepatocellular carcinoma is challenging and requires elaborated imaging techniques and histology. CASE PRESENTATION: We report about a 29-year old male professional bodybuilder who presented with mid-epigastric pain at the emergency unit. Ultrasound showed a severe hepatomegaly with multiple lesions. Contrast-enhanced ultrasound revealed a heterogeneous pattern with signs of hepatocellular carcinoma. CT scan of the abdomen confirmed multiple hypervascular lesions and central areas of necrosis without contrast enhancement. Subsequent diagnostics included fine needle aspiration (FNA) of suspicious lesions and mini-laparoscopy to establish the diagnosis of a ß-catenin and testosterone-receptor positive hepatocellular carcinoma embedded in multiple adenomas. The patient was subsequently treated by liver transplantation and remains tumor-free 27 month after surgery. CONCLUSION: Hepatocellular carcinoma occurring in association with anabolic androgenic steroid abuse should sensitize physicians and especially professional bodybuilders for the harmful use of high doses of steroids.

Gray scale and contrast-enhanced ultrasound imaging of malignant liver tumors of vascular origin.

OBJECTIVES: Malignant vascular tumors of the liver are rare. The aim of this study was to investigate the applicability of gray scale and contrast-enhanced ultrasonography in patients with epithelioid hemangioendothelioma (EHE) of the liver and hepatic angiosarcoma (HA) and to describe the clinical presentation. METHODS: We retrospectively analyzed all patients with epithelioid hemangioendothelioma or hemangiosarcoma of the liver from 1998 to 2011, who underwent ultrasound investigation. We describe the findings in gray scale and contrast-enhanced ultrasound and the clinical course of the disease of seven patients with EHE and five patients with HA. RESULTS: Ultrasound investigation in EHE showed mostly multiple hypoechoic irregular lesions close to the liver capsule and with a halo in some cases. Contrast enhancement revealed inhomogeneously and through all contrast phases vascularized tumors with a rim enhancement in 50%, with or without early wash out. All tumors had avascular parts. HA presented as multiple and irregular hypo-, iso- or hyperechoic lesions. After contrast enhancement, hypervascularization with individual patterns was evident in all patients. Of five, three had liquid parts. Patients with HA were significantly older (58 vs. 37 years, p = 0.014) and presented with lower thrombocyte counts (84 vs. 264, p = 0.0025) and with higher CEA levels (4.6 vs. 1.5, p = 0.03). CONCLUSION: EHE and HA are inhomogeneous tumors, explaining the high inter-individual variability and heterogeneity in ultrasound examination. The presence of multifocal lesions, heterogeneity and undefined margins may differentiate EHE or HA from hemangioma. A biopsy is essential in the diagnosis of vascular tumors.

Wheeze in preschool age is associated with pulmonary bacterial infection and resolves after antibiotic therapy.

BACKGROUND: Neonates with airways colonized by Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis are at increased risk for recurrent wheeze which may resemble asthma early in life. It is not clear whether chronic colonization by these pathogens is causative for severe persistent wheeze in some preschool children and whether these children might benefit from antibiotic treatment. We assessed the relevance of bacterial colonization and chronic airway infection in preschool children with severe persistent wheezing and evaluated the outcome of long-time antibiotic treatment on the clinical course in such children. METHODOLOGY/PRINCIPAL FINDINGS: Preschool children (n = 42) with severe persistent wheeze but no symptoms of acute pulmonary infection were investigated by bronchoscopy and bronchoalveolar lavage (BAL). Differential cell counts and microbiological and virological analyses were performed on BAL samples. Patients diagnosed with bacterial infection were treated with antibiotics for 2-16 weeks (n = 29). A modified ISAAC questionnaire was used for follow-up assessment of children at least 6 months after bronchoscopy. Of the 42 children with severe wheezing, 34 (81%) showed a neutrophilic inflammation and 20 (59%) of this subgroup had elevated bacterial counts (≥ 104 colony forming units per milliliter) suggesting infection. Haemophilus influenzae, Streptococcus pneumoniae and Moraxella catarrhalis were the most frequently isolated species. After treatment with appropriate antibiotics 92% of patients showed a marked improvement of symptoms upon follow-up examination. CONCLUSIONS/SIGNIFICANCE: Chronic bacterial infections are relevant in a subgroup of preschool children with persistent wheezing and such children benefit significantly from antibiotic therapy.

Grading of hypervascular hepatocellular carcinoma using late phase of contrast enhanced sonography - a prospective study.

BACKGROUND: Outcome of patients with hepatocellular carcinoma is influenced by their histological grade. Invasive biopsy of the lesions is the gold standard in this regard. AIMS: We therefore analysed the diagnostic accuracy of contrast enhanced ultrasound for non-invasive grading of hypervascular hepatocellular carcinoma in liver cirrhosis. METHODS: According to the tumour perfusion kinetics on contrast enhanced ultrasound two grading groups were prospectively defined: well-differentiated hepatocellular carcinoma (US-G1) and higher grade hepatocellular carcinoma (US-G2/G3). Immediately after contrast enhanced ultrasound-grading, biopsies of hepatocellular carcinoma-lesions (n=95, 1.2-12.5 cm) were obtained and analysed for tumour grading (G). Descriptive statistics, sensitivity, specificity positive and negative predictive values, diagnostic likelihood ratios and interoperator reproducibility were calculated (κ). RESULTS: Histologically 77 (81.1%) patients had G2-G3 and 18 (18.9%) had G1 tumours. Higher grade hepatocellular carcinoma showed more often a washout in the portal or late phase (p<0.0001). The sensitivity, specificity, positive predictive values and negative predictive values of contrast enhanced ultrasound for grading of hepatocellular carcinoma for all patients were 94% (CI: 72-99%), 95% (CI: 88-99%), 81% and 99% and for patients with tumours<5 cm 100%(95% CI: 79-100), 96% (95% CI: 80-99), 92% and 100%. Positive and negative diagnostic likelihood ratios' were 18 and 26 and 0.06 and 0, respectively. κ=0.941 (p<0.001). CONCLUSIONS: Contrast enhanced ultrasound has a high diagnostic value and reproducibility for non-invasive grading of hypervascular hepatocellular carcinoma >1cm in patients with liver cirrhosis.

Contact endoscopy for the evaluation of the pharyngeal and laryngeal mucosa.

OBJECTIVES: Contact endoscopy is a noninvasive tool that allows in vivo and in situ examination of superficial mucosa. Its use for early diagnosis of cancerous lesions of the oropharynx and larynx has not been evaluated. The aim of the study was to validate contact endoscopy for the examination of pharyngeal and laryngeal mucosa. STUDY DESIGN: Prospective clinical study. METHODS: Superficial cells of the mucosa were stained with methylene blue and examined with contact endoscopes. The documented images were assessed by a cytopathologist and by an otolaryngologist independently for each patient. Biopsies for histopathological examination of the area were performed and correlated with contact endoscopic findings of both examiners. RESULTS: Of the 42 examined specimen, 32 (76.2%) showed benign changes in the histological analysis. Squamous cell carcinoma was revealed in 10 specimen (23.8%). Using contact endoscopy, the cytopathologist accurately identified 90.6% of the benign findings (29 of 32); however, only seven of 10 (70%) carcinomas were correctly categorized. In comparison, the otolaryngologist made a correct diagnosis in 93.75% (30 of 32) of the benign and in 90% (nine of 10) of the malignant cases. Thus, a sensitivity of 90% and a specificity of 93.75% can be achieved by contact endoscopy. CONCLUSIONS: Contact endoscopy offers valuable support for the evaluation of oropharyngeal, hypopharyngeal, and laryngeal mucosa. Contact endoscopy can be a useful contribution to rapid intraoperative evaluation of mucosal alterations for early diagnosis of tumors and might reduce diagnostic biopsy sampling. Even so, it does not replace biopsy sampling.

Losses of chromosome arms 4q, 8p, 13q and gain of 8q are correlated with increasing chromosomal instability in hepatocellular carcinoma.

OBJECTIVE: Chromosomal instability is a key feature in hepatocellular carcinoma (HCC). Array comparative genomic hybridization (aCGH) revealed recurring structural aberrations, whereas fluorescence in situ hybridization (FISH) indicated an increasing number of numerical aberrations in dedifferentiating HCC. Therefore, we examined whether there was a correlation between structural and numerical aberrations of chromosomal instability in HCC. METHODS AND RESULTS: 27 HCC (5 well, 10 moderately, 12 lower differentiated) already cytogenetically characterized by aCGH were analyzed. FISH analysis using probes for chromosomes 1, 3, 7, 8 and 17 revealed 1.46-4.24 signals/nucleus, which correlated with the histological grade (well vs. moderately,p < 0.0003; moderately vs. lower, p < 0.004). The number of chromosomes to each other was stable with exceptions only seen for chromosome 8. Loss of 4q and 13q, respectively, were correlated with the number of aberrations detected by aCGH (p < 0.001, p < 0.005; Mann-Whitney test). Loss of 4q and gain of 8q were correlated with an increasing number of numerical aberrations detected by FISH (p < 0.020, p < 0.031). Loss of 8p was correlated with the number of structural imbalances seen in aCGH (p < 0.048), but not with the number of numerical changes seen in FISH. CONCLUSION: We found that losses of 4q, 8p and 13q were closely correlated with an increasing number of aberrations detected by aCGH, whereas a loss of 4q and a gain of 8q were also observed in the context of polyploidization, the cytogenetic correlate of morphological dedifferentiation.