Parvovirus B19 detected in Rosai-Dorfman disease in nodal and extranodal manifestations.

Sinus histiocytosis with massive lymphadenopathy (SHML), also designated as Rosai-Dorfman disease (RDD), is a rare benign reactive lymphoproliferative disorder. It is defined by a characteristic histopathology with sinus histiocytosis and haemophagocytosis known as emperipolesis. In histiocytes S100 is strongly expressed, whereas CD1a staining typically is negative. The disease mainly manifests at a single lymph node; however, multilocular and extranodal affection can occur. Causative infectious agents, and virus infections in particular, have repeatedly been suspected, although until now the origin of the disease has been unclear. Four cases of RDD (two nodal sites and two extranodal upper respiratory tract sites) were analysed for parvovirus B19 (B19) infection by immunohistochemistry to detect B19 capsid proteins VP1/VP2. In all the four cases, huge numbers of B19-positive cells were partly detected. The positive cells were identified either as lymphocytes or, in one extranodal case, also as respiratory epithelial cells. This is the first report of B19 infection in RDD tissue, indicating that B19 may be associated with the pathogenesis of SHML.

Enhanced repair of articular cartilage defects in vivo by transplanted chondrocytes overexpressing insulin-like growth factor I (IGF-I).

Traumatic articular cartilage lesions have a limited capacity to heal. We tested the hypothesis that overexpression of a human insulin-like growth factor I (IGF-I) cDNA by transplanted articular chondrocytes enhances the repair of full-thickness (osteochondral) cartilage defects in vivo. Lapine articular chondrocytes were transfected with expression plasmid vectors containing the cDNA for the Escherichia coli lacZ gene or the human IGF-I gene and were encapsulated in alginate. The expression patterns of the transgenes in these implants were monitored in vitro for 36 days. Transfected allogeneic chondrocytes in alginate were transplanted into osteochondral defects in the trochlear groove of rabbits. At three and 14 weeks, the quality of articular cartilage repair was evaluated qualitatively and quantitatively. In vitro, IGF-I secretion by implants constructed from IGF-I-transfected chondrocytes and alginate was 123.2+/-22.3 ng/10(7) cells/24 h at day 4 post transfection and remained elevated at day 36, the longest time point evaluated. In vivo, transplantation of IGF-I implants improved articular cartilage repair and accelerated the formation of the subchondral bone at both time points compared to lacZ implants. The data indicate that allogeneic chondrocytes, transfected by a nonviral method and cultured in alginate, are able to secrete biologically relevant amounts of IGF-I over a prolonged period of time in vitro. The data further demonstrate that implantation of these composites into deep articular cartilage defects is sufficient to augment cartilage defect repair in vivo. These results suggest that therapeutic growth factor gene delivery using encapsulated and transplanted genetically modified chondrocytes may be applicable to sites of focal articular cartilage damage.

Outcome of cystic hygroma in fetuses with normal karyotypes depends on associated findings.

OBJECTIVE: To determine the associated diagnostic findings which are linked with adverse fetal outcome in nuchal cystic hygroma. STUDY DESIGN: Based on a series of 32 cases, we determined the sonographic morphology of the hygroma, associated structural anomalies, karyotypes and autopsy findings. Intrauterine fetal death, spontaneous abortion and abnormal karyotypes were assigned as adverse outcome parameters. RESULTS: The mean gestational age at diagnosis was 14.4 weeks (range 10-21). There were 18 nonseptated and 14 septated hygromas. Besides hygroma, associated sonographic detectable structural anomalies were observed in 17 cases (53.1%). The greatest number of associated sonographic anomalies were hydrops (31.3%), generalised skin oedema (6.3%) and pterygium colli (6.3%). Cytogenetic analysis revealed an abnormal karyotype in 13 of 26 (50%) invasive procedures. Turner syndrome and Trisomy 18 (both 15.4%) were the most frequent cytogenetic abnormalities. Autopsy was performed in 24 cases and 16 cases (66.7%) had an associated autopsy finding to hygroma colli. The most frequent associated autopsy findings were limb and craniofacial anomalies (both 25%). Only 3 (9.4%) mothers gave birth to healthy newborns. The overall fetal adverse outcome rate was 68.8% (22 cases). CONCLUSIONS: Fetuses with NCH are at high risk for adverse outcome and detailed prenatal diagnosis including invasive procedures should be offered. According to the presented autopsy findings, to determine fetal outcome in NCH cases with normal karyotypes, detailed sonography should be concentrated beside the exclusion of fetal heart defects and existence of hydrops fetalis, on the skeletal, urogenital and craniofacial anomalies, as these might cause severe morbidity.

Duodenal angiolipoma -- endoscopic diagnosis and therapy.

We report on two patients with upper gastrointestinal bleeding owing to duodenal angiolipomas, and their endoscopic diagnosis and therapy. In both cases the bleeding source was a pedunculated tumour. Diagnosis and definitive therapy was made by endoscopic snare polypectomy. After stopping the bleeding from the mucosal defect by injection therapy in one patient, the further course was uneventful in both. A colonic angiolipoma in one of the patients was also treated by polypectomy. Gastrointestinal angiolipomas are exceedingly rare, however, these case reports show that duodenal angiolipomas do exist and that they, as lipomas, may lead to substantial gastrointestinal bleeding and may be treated successfully by standard polypectomy techniques.

Adrenal metastases in 1635 patients with renal cell carcinoma: outcome and indication for adrenalectomy.

PURPOSE: Routine removal of the ipsilateral adrenal gland in patients with renal cell carcinoma who undergo nephrectomy has been a matter of dispute. In a retrospective study we screened for subgroups of patients with renal cell carcinoma from a large single center patient population who may have benefited from ipsilateral adrenalectomy. MATERIALS AND METHODS: Radical nephrectomy was performed in 1635 patients at a single institution between 1980 and 2000. A total of 1010 patients underwent radical nephrectomy plus ipsilateral adrenalectomy, whereas in 625 no simultaneous adrenalectomy was performed. Numerous clinical and histopathological parameters were investigated by univariate and multivariate statistical methods for their predictive value in regard to cancer specific survival. RESULTS: Metastases in the adrenal gland were found in 5.5% of patients (56 of 1010) undergoing nephrectomy with adrenalectomy. Of 30 patients with adrenal metastasis and preoperative computerized tomography/magnetic resonance imaging 23 were found to have histological evidence of cancer, approaching a false-negative rate of 23.3%. All patients with false-negative computerized tomography/magnetic resonance imaging had a primary tumor of greater than 4 cm. Patients with adrenal metastases predominately had pT3 or greater tumor stage (82%). Cancer specific survival rates (75% vs 73% for adrenalectomy vs no adrenalectomy) and postoperative complications rates (7% vs 8%) did not differ significantly between the 2 groups. The prognosis in patients with a solitary adrenal metastasis (18 of 56) was more favorable than in patients with additional metastatic sites (38 of 56). CONCLUSIONS: Adrenal metastases from primary renal cell carcinoma were found significantly more often in patients with advanced tumor stages. Ipsilateral adrenalectomy should be recommended for all resectable renal cell carcinoma with a primary tumor of greater than 4 cm or with nonorgan confined tumor stages (T3 or greater) since a false-negative rate of about 20% can be expected with current imaging techniques.

Inflammatory pseudotumor of the liver in a patient with congenital granulocytopenia and HCV infection.

Inflammatory pseudotumor (IPT) of the liver is a rare pathologic lesion. Although IPTs within the liver shows spontaneous regression, these lesions are frequently misdiagnosed as malignant on the basis of the clinical manifestation and the results of diagnostic imaging. With special regard to magnetic resonance imaging (MRI), differential diagnosis such as hepatocellular or cholangiocellular carcinoma (HCC/CCC) as well as regenerative liver lesions are discussed in a case of IPT with concomitant hepatitis C virus (HCV) infection and congenital granulocytopenia.

Immunohistochemical investigation on the pattern of vimentin expression in regenerated and intact monkey and human periodontal ligament.

The expression of vimentin is well documented in the intact animal and human periodontal ligament (PDL), but there is limited information on the pattern of vimentin expression in the regenerated PDL. The aim of the present study was to investigate the pattern of vimentin expression in the regenerated and intact monkey and human PDL. A total of 12 chronic recession-type defects were created in three monkeys (Macaca fascicularis) and treated either with guided tissue regeneration (GTR), or with an enamel matrix protein derivative (EMD). After 5 months, the animals were sacrificed and specimens containing the defects and surrounding tissues were dissected free, decalcified in EDTA and embedded in paraffin. Sections were labelled immunohistochemically by using monoclonal antibody against vimentin (VIM 3B4). Twelve patients, each of whom displayed one deep intrabony defect scheduled for extraction were treated with GTR, EMD or combination of EMD+natural bone mineral (NBM). Following a healing period of 6 months, the teeth were extracted "en block" and immunohistochemically analysed according to the same protocol as described in monkeys. The results revealed that in both monkeys and humans the newly formed PDL was labelled similarly for vimentin to the intact (non-treated) PDL. In all specimens, the newly formed PDL was in continuation with the intact parts of PDL, thus suggesting that the mesenchymal cells capable of regenerating the attachment apparatus may have their origin in the intact PDL. In conclusion, the present findings indicate that (a) the reformed PDL displayed a similar expression of vimentin to the intact (original) PDL, and (b) the cells capable of regenerating new PDL and new cementum appear to be of mesenchymal origin and their source may be in the intact PDL.

[Expression of genes of potential importance in the response to chemotherapy in osteosarcoma patients]. / Expression von Genen mit möglicher prognostischer Bedeutung für das Ansprechen auf Chemotherapie bei Patienten mit Osteosarkom - Gene mit möglicher prognostischer Bedeutung beim Osteosarkom -

BACKGROUND: The prognosis of patients with osteosarcoma has considerably improved over the last 30 years, mainly due to developments in chemotherapy. However, almost half of the osteosarcomas do not respond to chemotherapy. Predictive markers for chemosensitivity at diagnosis are desirable. PATIENTS AND METHODS: In order to investigate the potential of some chemotherapy-associated genes with respect to their predictive value for chemosensitivity, the mRNA expression of 8 genes was evaluated in the osteosarcomas of 45 patients and correlated to the histological response to neoadiuvant chemotherapy. RESULTS: ERCC4, a member of the nucleotide excision repair system, showed a orrelation between expression and the histologically evaluated response to chemotherapy. The expression of the other investigated genes HER-2/neu, HSP 70, GST, DHFR, BCRP, ERCC1 and Mlh1 showed no significant correlation to response to chemotherapy. CONCLUSION: In our retrospective analyses, low expression of ERCC4 was shown to be related to poor response to chemotherapy. The potential value of ERCC4 as response predictor has to be investigated in a prospective study.

Prenatal diagnosis of sacrococcygeal teratoma: a review of cases between 1993 and 2000.

Sacrococcygeal teratoma is the most common fetal neoplasm with a reported incidence of 1 in 30,000 to 40,000 births. Affected fetuses carry a high perinatal mortality and morbidity. The aim of this retrospective study was to assess prenatal sonographic aspects and pathological details of our cases with sacroccocygeal teratoma. Over the last seven years we identified six cases by retrospective chart review in our institution. Four fetuses were electively aborted, in two of these four fetuses the diagnosis was made before the 16th week of gestation. Two caesarean sections were performed at 35 + 5 and 37 + 0 weeks of gestation, respectively. In those two cases the diagnosis was only made in the late second and third trimester. No case of neonatal mortality occurred. In one of the two resected sacroccocygeal teratomas potential malignancy was diagnosed. A multidisciplinary approach seems advisible for optimal perinatal management.

Haemorrhagic hypersensitivity pneumonitis due to naphthylene-1,5-diisocyanate.

Symptoms of hypersensitivity pneumonitis and massive pulmonary haemorrhage occurred in a 24-yr-old male shortly after occupational exposure to naphthylene-1,5-diisocyanate (NDI). The present examination was performed approximately 1-yr after the initial life-threatening haemoptysis and following an uneventful recovery after resection of the middle lobe, which had been identified bronchoscopically as the bleeding source. Histological re-examination of the lung was compatible with hypersensitivity pneumonitis. After a chamber challenge with NDI (5 parts per billion (ppb) for 10 min, 10 ppb for 110 min), rales were heard in both lungs, and a fall in vital capacity and partial pressure of arterial oxygen as well as a rise in body temperature were documented. Isocyanate-specific immunoglobulin-G antibodies could not be detected in the patient's serum, possibly due to the long period without exposure to isocyanates. The authors conclude that naphthylene-1,5-diisocyanate may cause immunological pulmonary haemorrhage. The underlying disease is consistent with hypersensitivity pneumonitis and may be triggered by low concentrations of the diisocyanate.

Decreased CD44v6 expression in lamina propria lymphocytes of patients with inflammatory bowel disease.

Splice variants of the glycoprotein CD44 are transiently expressed on lymphocytes during T cell activation. Increased expression of CD44v6 on peripheral blood lymphocytes (PBL) of patients with inflammatory bowel disease (IBD) was described recently. The aim of this study was therefore to characterize CD44v6 expression on CD4(+) lamina propria lymphocytes (LPL) of patients with active IBD in comparison to controls. CD44v6 expression on CD4(+) LPL (n = 19) of controls and patients with active IBD (Crohn's disease n = 14, ulcerative colitis n = 15) was analyzed by flow cytometry and compared to that on autologous PBL. Thereby, in vitro regulation of CD44v6 on LPL and PBL via CD3 and CD2 and the costimulatory signal B7-1 was examined. In addition, the role of protein kinase C (PKC) in CD44v6 expression was tested. CD44v6 expression was increased in CD4(+) LPL (median, 45%) compared to PBL (median, 38%). Surprisingly, in IBD CD44v6 was downregulated on CD4(+) lamina propria T cells, irrespective of their state of inflammation (median, 28%). CD44v6 expression on LPL was not upregulated upon CD3 activation alone but following costimulation with B7-1. However, CD2-mediated T cell activation sufficiently induced upregulation of CD44v6 on LPL and PBL. In our study, downregulation of CD44v6 on LPL of patients with IBD was not due to defective PKC activation. Taken together, these data indicate that decreased CD44v6 expression on LPL in IBD might be a feature of an inappropriate costimulatory signal in T cell activation.

Lymphangioma of the pancreas and the duodenal wall: MR imaging findings.

Pancreatic lymphangiomas are rare benign tumours with a histogenesis not yet completely understood. Predominantly the cystic aspect of this lesion can complicate the differentiation from other neoplastic and non-neoplastic cystic tumours of the pancreas. We present a case of a middle-aged woman with a lymphangioma involving the duodenal wall and the pancreatic head. With special regard to MR imaging findings differential diagnosis is discussed.

Progesterone receptor expression in human prostate cancer: correlation with tumor progression.

BACKGROUND: The recent discovery of the classical estrogen receptor alpha (ERalpha) in metastatic and recurrent prostatic adenocarcinoma suggests that estrogens are implicated in prostate cancer progression. METHODS: To get more insight into estrogen signaling in prostate cancer tissue, the current study has examined the immunoprofile of the estrogen-inducible progesterone receptor (PR), and evaluated its relation to ERalpha gene expression. RESULTS: In primary tumors, the PR was detectable in 36% of primary Gleason grade 3 (5 of 14 cases), 33% of primary Gleason grade 4 (5 of 15 cases), and in 58% of primary Gleason grade 5 tumors (7 of 12 cases). None of the 41 primary tumors investigated revealed significant PR expression in more than 50% of tumor cells. Conversely, moderate to strong receptor expression was observed in 60% of metastatic lesions (9 of 15 cases), and in 54% of androgen-insensitive tumors (38 of 71 cases). Irrespective of grades and stages, the presence of the PR was invariably associated with high steady state levels of ERalpha mRNA, whereas the ERalpha protein was undetectable by immunohistochemistry (IHC) in a significant number of cases (58 of 97 cases). CONCLUSIONS: The progressive emergence of the PR during tumor progression obviously reflects the ability of metastatic and androgen-insensitive tumors to use estrogens through a ERalpha-mediated pathway. The present data provide a theoretical background for studying the efficiency of antiestrogens and antigestagens in the medical treatment of advanced prostate cancer.

Why do bilioduodenal plastic stents become occluded? A clinical and pathological investigation on 100 consecutive patients.

BACKGROUND AND STUDY AIMS: The main complication associated with biliary stenting is stent occlusion. This study tested the hypothesis that bilioduodenal reflux may play a crucial role in stent clogging. PATIENTS AND METHODS: Plastic stents in 100 consecutive patients with various biliary disorders were investigated macroscopically and cytologically. RESULTS: In 37 patients with elective stent extraction, the only risk factor for stent occlusion was the duration of stenting. Plant material was found as a consequence of duodenobiliary reflux in 38 of the 89 stents with any stent content. In patients who had two stents, the stent content was identical in eight of 14 cases. CONCLUSIONS: In addition to other mechanisms of biliary stent occlusion, duodenobiliary reflux appears to play an important role. A stent design capable of at least partly preventing this type of reflux might be of clinical benefit.

Rare pseudotumors of the urinary bladder in childhood.

We report two cases of inflammatory pseudotumors of the urinary bladder, one case of a chronic granulomatous pseudotumor (CGT) and one case of a pseudosarcomatous myofibroblastic (fibromyxoid) tumor (PMT). Both tumors resembled malignancies such as rhabdomyosarcomas regarding clinical appearance and imaging findings and represent rare urinary bladder tumors. The imaging findings on unenhanced and contrast-enhanced MRI as well as histological specimen are presented. Final diagnosis was made following elective surgery. Differential diagnosis of urinary bladder tumors as well as the imaging findings of these clinically comparable cases are discussed. Awareness of these benign lesions may prevent patients from inappropriate therapies such as chemotherapy or radiation therapy.

Course and outcome of a pregnancy with a giant fetal cervical teratoma diagnosed prenatally.

We report the course and outcome of a pregnancy involving a giant fetal neck teratoma which was diagnosed at 23 weeks of gestation. Sonographic surveillance of the fetal neck revealed continuing growth of the tumor with development of polyhydramnios. Three-dimensional ultrasound provided additional detailed information on the external extent of the lesion. Color Doppler ultrasound showed intense arterial and venous flow with low resistance indices. Cesarean section under general anesthesia was planned in close cooperation with the neonatologist, pediatric surgeon and anesthesiologist because the size of the neck mass precluded vaginal delivery. Cesarean section was performed at 34 weeks of gestation following preterm rupture of the membranes. Orotracheal intubation was not successful because of compression of the airway and a tracheostomy could not be performed because of the risk of severe fetal hemorrhage from the tumor. The neonate died from respiratory insufficiency 66 min after birth.

Malignant odontogenic myxoma of the maxilla: case with cytogenetic confirmation.

An odontogenic myxoma of the maxilla with an aggressive clinical course is presented. The tumour arose in a 53-year-old patient, recurred two times after extended maxillectomy and ultimately caused the patient's death by uncontrollable local disease with infiltration of the cranial cavity. Microscopically, the tumour showed histological features of a low grade malignant myxosarcoma with cellular areas, enhanced mitotic activity and nuclear pleomorphism. Cytogenetic analysis revealed an unexpectedly aberrant hypertetraploid chromosome complement, that was considered as incompatible with the usual karyotypic patterns of benign tumours.

[Interferon alpha-2a in the treatment of diffuse thoracic angiomatosis in adulthood--a ase report]. / Interferon alpha-2a zur Therapie einer diffusen thorakalen Angiomatose im Erwachsenenalter--Ein Fallbericht.

A diffuse angiomatosis affecting thoracal organs is a rare, frequently fatal disorder occurring mainly in childhood. The definite diagnosis is usually made by autopsy. A specific treatment does not exist. In the case report presented here we describe the course of an 37-year old patient presenting initially with dyspnea and hemoptysis. Radiological investigations showed a mass lesion in the anterior superior mediastinum, bihilar masses and a periesophageal mass with soft tissue density and a pericardial effusion. Bilateral interstitial infiltrations were also present. CT-guided mediastinal biopsies and bronchial mucosal biopsies were nonspecific. Open-lung biopsy revealed the diagnosis of an extensive diffuse angiomatosis affecting mediastinum, pericardium and pleura. During the 18-month monotherapy with interferon-alpha 2a the patient showed significant improvements of clinical as well as laboratory and radiological parameters. The presented case confirms the experience of several authors, that the diagnosis of a diffuse thoracal authors can only be made by open lung biopsy or autopsy. The presented case also underlines the possibility of a palliative therapy of aggressive angiomatous diseases with interferon-alpha 2a.