Teratoma of the mediastinum: a case report

Abstract Introduction This case report illustrates a rare case of teratoma of the mediastinum which was continuous to the pericardium and caused extrinsic compression to the right atrium. Case presentation A 22-year-old Caucasian man with no complaints or comorbid conditions presented to our hospital with obliteration of the right cardiophrenic sinus by a mass. A non-invasive investigation demonstrated a tumoral mass which was continuous to the pericardium and caused extrinsic compression to the right atrium. The clinical suspicion was a pericardial or bronchogenic cyst. Surgical and anatomopathologic findings led to the diagnosis of a mature cystic teratoma with atrophic thymic tissue at the external teratoma surface. Conclusion We present an original report of a mature teratoma causing obliteration of the right cardiophrenic sinus with extrinsic heart compression. The diagnosis of this tumor is very difficult through non-invasive investigation.

"Exterritorial" lymphocytic hypophysitis within an ovarian teratoma during pregnancy: a possible sentinel lesion?

Pituitary tissue is rarely to be found among the constituents of ovarian teratomas (dermoid cysts). In some exceptional cases, however, such ectopic pituitary anlagen may even give rise to secondary organ-specific pathologies. Akin to those of the pituitary in its natural location, these tend to be adenomas. We describe a unique example of lymphocytic hypophysitis incidentally encountered in a mature left ovarian teratoma from a 30-year-old woman in the 19th week of pregnancy. Amidst various fully differentiated derivatives of all three embryonic layers, the cyst wall also included a miniature replica of the anterior pituitary lobe 0.5 cm in diameter. While a full set of adenohypophyseal hormone-producing cell types could be identified, there was characteristic pregnancy-related hyperplasia of lactotrophs. This was further overlaid by prominent mononuclear inflammation, including infiltration by T lymphocytes, follicular aggregates of B cells, and attendant destruction of parenchyma. There was no significant inflammatory reaction elsewhere. Discounting the non-standard location, the ensemble of the clinical setting and histology were felt to be indistinguishable from the classical paradigm of lymphocytic hypophysitis complicating pregnancy. To date, lymphocytic thyroiditis is the sole form of organ-specific inflammatory process within an ovarian teratoma on record. By analogy, we hypothesize that this ectopic manifestation of immune-mediated inflammation of pituitary parenchyma may possibly be read as a preclinical sentinel lesion of lymphocytic hypophysitis.

Teratoma of the nasal septum in a neonate: an endoscopic approach

Initial presentation of a white female newborn delivered after normal pregnancy demonstrated a white mass obstructing the left nare. Primary biopsy revealed a focus of fibrotic nasal mucosa that included squamous and respiratory epithelium. After endoscopic resection of the mass, histopathologic examination resulted in the diagnosis of a teratoma. According to our literature review, this is the first case of a teratoma arising from the nasal septum in a white. Worldwide, 3 additional cases have been reported, but none included endoscopic management. This case illustrates our protocol for an endoscopic approach to an obstructive nasal mass in a neonate and our experience in the management of this rare disease.

Inhibition of tumorigenicity of the teratoma PC cell line by transfection with antisense cDNA for PC cell-derived growth factor (PCDGF, epithelin/granulin precursor)

The PC cell line is a highly tumorigenic, insulin-independent, teratoma-derived cell line isolated from the nontumorigenic, insulin-dependent 1246 cell line. Studies of the PC cell growth properties have led to the purification of an 88-kDa secreted glycoprotein called PC cell-derived growth factor (PCDGF), which has been shown to stimulate the growth of PC cells as well as 3T3 fibroblasts. Sequencing of PCDGF cDNA demonstrated its identity to the precursor of a family of 6-kDa double-cysteine-rich polypeptides called epithelins or granulins (epithelin/granulin precursor). Since PCDGF was isolated from highly tumorigenic cells, its level of expression was examined in PC cells as well as in nontumorigenic and moderately tumorigenic cells from which PC cells were derived. Northern blot and Western blot analyses indicate that the levels of PCDGF mRNA and protein were very low in the nontumorigenic cells and increased in tumorigenic cell lines in a positive correlation with their tumorigenic properties. Experiments were performed to determine whether the autocrine production of PCDGF was involved in the tumorigenicity of PC cells. For this purpose, we examined the in vivo growth properties in syngeneic C3H mice of PC cells where PCDGF expression had been inhibited by transfection of antisense PCDGF cDNA. The results show that inhibition of PCDGF expression resulted in a dramatic inhibition of tumorigenicity of the transfected cells when compared with empty-vector control cells. These data demonstrate the importance in tumor formation of overexpression of the novel growth factor PCDGF.

Surgical treatment of hepatic tumors in children: lessons learned from liver transplantation

Purpose: Hepatectomy remains a complex operation even in experienced hands. The objective of the present study was to describe our experience in liver resections, in the light of liver transplantation, emphasizing the indications for surgery, surgical techniques, complications, and results. Methods: The medical records of 53 children who underwent liver resection for primary or metastatic hepatic tumors were reviewed. Ultrasonography, computed tomographic (CT) scan, and needle biopsy were the initial methods used to diagnose malignant tumors. After neoadjuvant chemotherapy, tumor resectability was evaluated by another CT scan. Surgery was performed by surgeons competent in liver transplantation. As in liver living donor operation, vascular anomalies were investigated. The main arterial anomalies found were the right hepatic artery emerging from the superior mesenteric artery and left hepatic artery from left gastric artery. Hilar structures were dissected very close to liver parenchyma. The hepatic artery and portal vein were dissected and ligated near their entrance to the liver parenchyma to avoid damaging the hilar vessels of the other lobe. During dissection of the suprahepatic veins, the venous infusion was decreased to reduce central venous pressure and potential bleeding from hepatic veins and the vena cava. Results: Fifty-three children with hepatic tumors underwent surgical treatment, 47 patients underwent liver resections, and in 6 cases, liver transplantation was performed because the tumor was considered unresectable. There were 31 cases of hepatoblastoma, with a 9.6% mortality rate. Ten children presented with other malignant tumors-3 undifferentiated sarcomas, 2 hepatocellular carcinomas, 2 fibrolamellar hepatocellular carcinomas, a rhabdomyosarcoma, an immature ovarian teratoma, and a single neuroblastoma. These cases had a 50% mortality rate. Six children had benign tumors-4 mesenchymal hamartoma, 1 focal nodular hyperplasia, and a mucinous cystadenoma. All of these children had a favorable outcome. Hepatic resections included 22 right lobectomies, 9 right trisegmentectomies, 8 left lobectomies, 5 left trisegmentectomies, 2 left segmentectomies, and 1 case of monosegment (segment IV) resection. The overall mortality rate was 14.9%, and all deaths were related to recurrence of malignant disease. The mortality rate of hepatoblastoma patients was less than other malignant tumors (P = .04). Conclusion: The resection of hepatic tumors in children requires expertise in pediatric surgical practice, and many lessons learned from liver transplantation can be applied to hepatectomies. The present series showed no mortality directly related to the surgery and a low complication rate. (C) 2009 Elsevier Inc. All rights reserved.

Mucinous ovarian tumors associated with pseudomyxoma peritonei of adenomucinosis type: immunohistochemical evidence that they are secondary tumors

Pseudomyxoma peritonei (PMP) is a clinical condition initially thought to be related to ovarian mucinous tumors; however, immunohistochemistry and molecular biology techniques have convincingly made the link to appendiceal mucinous neoplasms, resulting in changes in histologic and clinical approaches. The objective of this study was to compare the immunohistochemical profile of ovarian tumors associated with PMP and intestinal mucinous ovarian neoplasms without PMP. The study was retrospective and included 28 intestinal ovarian mucinous tumors selected from the files of the Division of Surgical Pathology of the University of Sao Paulo Medical School, from 1996 to 2005. Seven cases were associated with PMP of disseminated peritoneal adenomucinosis-type and all presented borderline histology. Immunohistochemical staining for mucin genes products (MUC1, MUC2, MUC5AC, and MUC6), CK7, CK20, CA19.9, and CA125 were performed in tissue microarrays. Of note, we detected differences in the expression of MUC2 and CK20 between cases with and without PMP. Comparisons of borderline histology with that of benign/malignant tumors also revealed differences in MUC2 and CK20. Our results confirm that there is a distinct profile of intestinal ovarian tumors associated with pseudomyxoma, particularly with respect to the expression of the gel-forming mucin MUC2. The profile of borderline tumors, even in cases without PMP, was distinct from that of other primary mucinous tumors of the intestinal type, suggesting that borderline histology may represent a secondary tumor or a less aggressive variant of PMP. An appendiceal origin seems the most probable for this group of neoplasias.

A Ressonância Magnética no Diagnóstico Pré-Natal de Anomalias do SNC. A Propósito de 8 Casos Clínicos

A ressonância magnética nuclear (RMN) é um meio complementar de diagnóstico que só recentemente começou a ser utilizado na investigação de patologia fetal. São enormes as suas potencialidades sobretudo no esclarecimento de dificuldades de diagnóstico suscitadas pela ecografia e perante situações de risco acrescido de anomalias congénitas do sistema nervoso central. Os autores efectuaram uma avaliação retrospectiva de oito casos, em que foi realizada RMN cerebral fetal no Centro de Ressonância Magnética de Caselas, entre Março de 1999 e Agosto de 2001. Foi efectuado estudo anatomopatológico nas situações de interrupção da gravidez (5 casos). Os outros casos tiveram acompanhamento pós-natal em consulta de Neuropediatria. A RMN confirmou o diagnóstico ecográfico nas duas situações variantes do normal. Não foi concordante com a ecografia no caso de suspeita de teratoma encefálico – a RMN revelou tratar-se duma malformação artério-venosa do seio da dura-mater com trombose ao nível da tórcula. Nos restantes cinco casos confirmou e caracterizou melhor as lesões detectadas na ecografia. A RMN teve implicações na conduta obstétrica: tranquilizou os pais em 2 casos de suspeita ecográfica e permitiu um melhor aconselhamento, ao definir melhor a gravidade das lesões observadas na ecografia.

Pneumatose Cólica Tratada com Metronidazol e Oxigenoterapia Hiperbárica: um Caso de Sucesso

A pneumatose intestinal, caracterizada pela presença de gás na parede do cólon, é uma condição incomum com um espectro de apresentação variável. Pode ser idiopática ou secundária a outras doenças. A tomografia computorizada é o método de diagnóstico com maior sensibilidade. Na ausência de sinais e sintomas sugestivos de complicações, como a perfuração e a peritonite, a pneumatose intestinal pode ser tratada de forma conservadora. Apresenta-se o caso de uma mulher de 59 anos com pneumatose cólica secundária a teratoma ovárico benigno. Após a cirurgia, manteve-se sintomática e foi tratada com sucesso com metronidazol e oxigenoterapia hiperbárica.

Severe childhood encephalopathy with dyskinesia and prolonged cognitive disturbances: evidence for anti-N-methyl-d-aspartate receptor encephalitis.

Aim We report four cases of acquired severe encephalopathy with massive hyperkinesia, marked neurological and cognitive regression, sleep disturbance, prolonged mutism, and a remarkably delayed recovery (time to full recovery between 5 and 18mo) with an overall good outcome, and its association with anti-N-methyl-d-aspartate (anti-NMDA) receptor antibodies. Method We reviewed the four cases retrospectively and we also reviewed the literature. Results Anti-NMDA receptor antibodies (without ovarian teratoma detected so far) were found in the two children tested in this study. Interpretation The clinical features are similar to those first reported in 1992 by Sebire et al.,(1) and rarely recognized since. Sleep disturbance was not emphasized as part of the disorder, but appears to be an important feature, whereas coma is less certain and difficult to evaluate in this setting. The combination of symptoms, evolution (mainly seizures at onset), severity, paucity of abnormal laboratory findings, very slow recovery, and difficult management justify its recognition as a specific entity. The neuropathological substrate may be anatomically close to that involved in encephalitis lethargica, in which the same target functions (sleep and movement) are affected but in reverse, with hypersomnolence and bradykinesia. This syndrome closely resembles anti-NMDA receptor encephalitis, which has been reported in adults and is often paraneoplastic.

Reprogramming of human fibroblasts to induced pluripotent stem cells under xeno-free conditions

The availability of induced pluripotent stem cells (iPSCs)has created extraordinary opportunities for modeling andperhaps treating human disease. However, all reprogrammingprotocols used to date involve the use of products of animal origin. Here, we set out to develop a protocol to generate and maintain human iPSC that would be entirelydevoid of xenobiotics. We first developed a xeno-free cellculture media that supported the long-term propagation of human embryonic stem cells (hESCs) to a similar extent as conventional media containing animal origin products or commercially available xeno-free medium. We also derivedprimary cultures of human dermal fibroblasts under strictxeno-free conditions (XF-HFF), and we show that they can be used as both the cell source for iPSC generation as well as autologous feeder cells to support their growth. We also replaced other reagents of animal origin trypsin, gelatin, matrigel) with their recombinant equivalents. Finally, we used vesicular stomatitis virus G-pseudotyped retroviral particles expressing a polycistronic construct encoding Oct4, Sox2, Klf4, and GFP to reprogram XF-HFF cells under xeno-free conditions. A total of 10 xeno-free humaniPSC lines were generated, which could be continuously passaged in xeno-free conditions and aintained characteristics indistinguishable from hESCs, including colonymorphology and growth behavior, expression of pluripotency-associated markers, and pluripotent differentiationability in vitro and in teratoma assays. Overall, the resultspresented here demonstrate that human iPSCs can be generatedand maintained under strict xeno-free conditions and provide a path to good manufacturing practice (GMP) applicability that should facilitate the clinical translation of iPSC-based therapies.

Quelle attitude face à une masse médiastinale antérieure chez l'adulte [Management of anterior mediastinal masses in adults].

The discovery of an anterior mediastinal mass requires careful management with specific consideration of the pathology. More than 50% of all mediastinal masses seen in adults are in the anterior mediastinum. The most frequent diagnoses are thymoma, lymphoma, teratoma and benign thyroid tumours. 60% of cases are malignant. Often the clinical and radiological findings do not allow a definitive diagnosis and a histological diagnosis is often required to select the optimal treatment modality. The choice of biopsy technique depends on the localization of the lesion, clinical factors, and the availability of special techniques and equipment. Biopsy may be obtained by trans-thoracic puncture under computed tomography or ultrasound guidance, or by a surgical approach (mediastinotomy or thoracoscopy).

Progenitor cell therapy for heart disease.

Many cell types are currently being studied as potential sources of cardiomyocytes for cell transplantation therapy to repair and regenerate damaged myocardium. The question remains as to which progenitor cell represents the best candidate. Bone marrow-derived cells and endothelial progenitor cells have been tested in clinical studies. These cells are safe, but their cardiogenic potential is controversial. The functional benefits observed are probably due to enhanced angiogenesis, reduced ventricular remodeling, or to cytokine-mediated effects that promote the survival of endogenous cells. Human embryonic stem cells represent an unlimited source of cardiomyocytes due to their great differentiation potential, but each step of differentiation must be tightly controlled due to the high risk of teratoma formation. These cells, however, confront ethical barriers and there is a risk of graft rejection. These last two problems can be avoided by using induced pluripotent stem cells (iPS), which can be autologously derived, but the high risk of teratoma formation remains. Cardiac progenitor cells have the advantage of being cardiac committed, but important questions remain unanswered, such as what is the best marker to identify and isolate these cells? To date the different markers used to identify adult cardiac progenitor cells also recognize progenitor cells that are outside the heart. Thus, it cannot be determined whether the cardiac progenitor cells identified in the adult heart represent resident cells present since fetal life or extracardiac cells that colonized the heart after cardiac injury. Developmental studies have identified markers of multipotent progenitors, but it is unknown whether these markers are specific for adult progenitors when expressed in the adult myocardium. Cardiac regeneration is dependent on the stability of the cells transplanted into the host myocardium and on the electromechanical coupling with the endogenous cells. Finally, the promotion of endogenous regenerative processes by mobilizing endogenous progenitors represents a complementary approach to cell transplantation therapy.

18F-fluorodeoxyglucose PET/CT findings in pleural effusions of patients with known cancer. A cytopathological correlation.

Aim: Pleural effusion is common in cancer patients and to determine its malignant origin is of huge clinical significance. PET/CT with 18F-FDG is of diagnostic value in staging and follow-up, but its ability to differentiate between malignant and benign effusions is not precisely known. Patients, methods: We examined 50 PET/CT from 47 patients (29 men, 18 women, 60±16 years) with pleural effusion and known cancer (24 NSCLC, 7 lymphomas, 5 breasts, 4 GIST, 3 mesotheliomas, 2 head and neck, 2 malignant teratoma, 1 colorectal, 1 oesophageal, 1 melanoma) for FDG uptake in the effusions using SUVmax. This was correlated to cytopathology performed after a median of 21 days (interquartile range -3 to 23), which included pH, relative distribution (macrophages, neutrophils, eosinophils, basophils, lymphocytes, plasmocytes), and absolute cell count. Results: Malignant cells were found in 17 effusions (34%) (6 NSCLC, 5 lymphomas, 2 breasts, 2 mesotheliomas, 2 malignant teratomas). SUV in malignant effusions were higher than in benign ones [3.7 (95%CI 1.8-5.6) vs. 1.7 g/ml (1.5-1.9), p = 0.001], with a correlation between malignant effusion and SUV (Spearman coefficient r = 0.50, p = 0.001), but not with other cytopathological or radiological parameters (ROC area 0.83±0.06). Using a 2.2-mg/l SUV threshold, 12 PET/CT studies were positive and 38 negative with sensitivity, specificity, positive and negative predictive values of 53%, 91%, 75% and 79%, respectively. For NSCLC only (n = 24), ROC area was 0.95±0.04, 7 studies were positive and 17 negative with a sensitivity, specificity, positive and negative predictive values of 83%, 89%, 71 and 94%, respectively. Conclusion: PET/CT may help to differentiate the malignant or benign origin of a pleural effusion with a high specificity in patients with known cancer, in particular NSCLC.