Embryonal tumor with abundant neuropil and true rosettes: Morphological,immunohistochemical, ultrastructural and molecular study of a case showing features of medulloepithelioma and areas of mesenchymal and epithelial differentiation

Embryonal tumors are a group of malignant neoplasms that most commonly affect the pediatric population. Embryonal tumor with abundant neuropil and true rosettes is a recently recognized rare tumor. It is composed of neurocytes and undifferentiated neuroepithelial cells arranged in clusters, cords and several types of rosettes in a prominent neuropil‐rich background. We describe a new case of this tumor. The patient, a 24‐month‐old female infant, was referred to the Meyer Children's Hospital with a history of right brachio‐crural deficit associated with occasional episodes of headache and vomiting. Computed tomography scan and MRI revealed a large bihemispheric mass. The patient underwent two consecutive surgeries. The resultant surgical resection of the tumor was macroscopically complete. The postoperative period was uneventful. On light microscopy the tumor showed a composite morphology: embryonal tumor with abundant neuropil and true rosettes (specimen from the first surgery); medulloepithelioma with mesenchymal and epithelial areas (specimen from the second surgery). The immunohistochemistry evidenced the heterogeneous (neuronal, mesenchymal and epithelial) immunoprofile of tumoral cells. By real‐time polymerase chain reaction (RT‐PCR), the PTEN gene expression in the tumor was lower than in the five non‐neoplastic brain tissues used as control. Mutation analysis did not show any variation in INI‐1 and PTEN sequence while P53 analysis showed the presence of homozygote P72R variation. Fluorescent in situ hybridization analysis showed polysomy of chromosome 2 while amplification of N‐MYC was not detected. Owing to the rarity of embryonal tumor with abundant neuropil and true rosettes, each new case should be recorded to produce a better clinical, pathological and molecular characterization of this lesion.     

Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy

Santi R, Cetica V, Franchi A, Pepi M, Cesinaro A M, Miracco C, Paglierani M, De Giorgi V, Delfino C, Difonzo E M, Pimpinelli N, Bianchi S, Sardi I, Santucci M & Massi D
(2011) Histopathology 58 , 455–466
Tumour suppressor gene TP53 mutations in atypical vascular lesions of breast skin following radiotherapy Aims: Atypical vascular lesions (AVL) occurring at the site of radiotherapy represent an uncommon but well‐documented complication in the setting of breast‐conserving therapy for breast carcinoma. Although the biological behaviour of AVL has been regarded as benign, it has been suggested that AVL may represent a precursor of angiosarcoma. A better understanding of the biology of AVL is essential in order to assess appropriate patient management. The aim of the present study was to investigate alterations of tumour suppressor gene TP53 in a series of radiation‐induced AVL and angiosarcomas (AS). Methods and results: Direct sequencing analysis of the TP53 gene showed the presence of at least one variation in 10 of 12 (83.3%) AVL and in seven of eight (87.5%) AS. The most common alteration in both categories was the P72R polymorphism in exon 4. One angiosarcoma sample carried a pathogenetically relevant disruptive mutation c.592delG, a frameshift deletion in exon 6, causing a premature stop codon. Conclusions: The presence of TP53 alterations suggests that its mutational inactivation may be implicated in the pathogenesis of radiation‐associated vascular proliferations. The common mutational pathway suggested by our data supports the hypothesis that AVL and AS are biologically related entities, most probably representing the extremes of a morphological continuum.     

Surgical Treatment of Postinfarction Left Ventricular Free Wall Rupture

Abstract Background: Left ventricular free wall rupture (LVFWR) is still one of the often fatal complications of acute myocardial infarction. Surgical repair is mandatory even with high operative mortality. The optimal surgical technique is controversial since the results depend on type of rupture. We present our mid‐term surgical experience according to the status of the left ventricular tear and type of surgical repair. Methods: From January 1997 to December 2007, 19 consecutive patients with LVFWR were treated at our institution. The mean age was 72 ± 8 ranging from 53 to 81 years; there were eight males and 11 females. According to the intraoperative findings, patients were divided into two groups: group 1 (eight patients), where no macroscopic tear of the LVFW could be detected with blood oozing from infarcted zone (Oozing type LVFWR); and group 2 (11 patients), where a macroscopic defect of the epicardium, with free communication between left ventricular cavity and pericardial space, was identified (Blow‐out type LVFWR). The patch covering and glue technique was applied for group 1 patients, while closure of the ventricular tear either by direct suture or by patch repair was used for group 2 patients. Results: The interval between diagnosis of LVFWR and surgery was 2.9 ± 1.1 hours. However, reevaluation of echocardiographic studies showed an early missed diagnosis of LVFWR in three patients of group 1 and in eight of group 2. Thus, the mean interval between initial signs of rupture and surgery was 9 ± 8 hours and 21 ± 15 hours, respectively, for oozing and blow‐out type rupture. On arrival in the operating room, four patients were on cardiopulmonary resuscitation, while four were in cardiogenic shock. The hospital mortality was 12% (one death) in group 1 and 36% (four deaths) in group 2 mainly due to multiorgan failure. Fourteen patients were discharged with a mean follow‐up of 3.8 ± 3.5 years. During follow‐up, one patient in group 1 died after 7.5 years. No recurrence of free wall rupture or aneurysm formation was demonstrated in all cases. At last follow‐up, all survivors showed excellent clinical results with a preserved left ventricular function. Patients with oozing type LVFWR and patch covering technique repair showed an absence of left ventricular‐restricted motion at the echocardiographic study. Conclusion: In patients with LVFWR, early diagnosis and surgical treatment are crucial for successful outcome when excellent results can be achieved with a simple glued patch covering technique.     

Comparative study of eosinophil chemotaxis, adhesion, and degranulation in vitro in ulcerative colitis and Crohn's disease

BACKGROUND: Eosinophils have been identified in tissues from patients with Crohn's disease (CD) and ulcerative colitis (UC) but whether they contribute to IBD pathogenesis is unknown. This study aimed to investigate the functional activity and morphological aspects of peripheral-blood eosinophils from IBD patients compared to those from healthy volunteers (HVs). METHODS: Eosinophils from HVs and CD and UC patients were purified using a Percoll gradient and then a immunomagnetic cell separator. Functional activity in inactivated and previously activated cells was investigated by measuring adhesion to fibronectin and chemotaxis to fMLP, and degranulation was measured by release of eosinophil peroxidase (EPO). Cell morphology was investigated using electron microscopy. RESULTS: Eosinophil adhesion to human fibronectin in both inactivated and PAF-stimulated and PMA-stimulated eosinophils was markedly higher in patients with CD than in either patients with UC or HVs. Similarly, the chemotactic response was markedly higher in eosinophils isolated from CD patients than in those isolated from UC patients or HVs. Baseline EPO release was higher in eosinophils isolated from UC patients than in those isolated from HVs or CD patients. Stimulation with fMLP or PMA did not further increase EPO release in cells from UC or CD patients. Comparable expression of MAC- 1 and VLA-4 adhesion molecules was observed on the surfaces of eosinophils from all groups, and an greater number of granules was noted in the eosinophils from UC patients than in those from CD patients. CONCLUSIONS: Our results indicate that peripheral-blood eosinophils are potentially primed and activated in IBD patients. Whether the differences in the morphology and functional responses of eosinophil from UC and CD patients reflect differences in disease phenotype remains to be elucidated.     

Endothelial protein C receptor plasma levels increase in chronic liver disease, while thrombomodulin plasma levels increase only in hepatocellular carcinoma

INTRODUCTION: Thrombomodulin (TM) and endothelial protein C receptor (EPCR) are two transmembrane endothelial receptors involved in the protein C pathway, that regulates coagulation and inflammation processes. We postulated that soluble thrombomodulin and EPCR are plasmatic markers of progression to hepatocellular carcinoma (HCC) and prognostic indicators in cirrhotic patients. MATERIALS AND METHODS: Plasma levels of TM and EPCR were measured in 104 patients affected by different stages of liver diseases (66 patients with HCC, and 38 without HCC), and in 52 healthy controls. RESULTS: EPCR levels were higher in patients than in controls (239+/-1.8 ng/mL vs. 127+/-1.5 ng/mL, p<0.0001). TM levels were higher in patients with HCC than in those without (42.1+/-2.0 ng/mL vs. 28.3+/-2.1 ng/mL; p=0.039), while EPCR levels were similar in the two groups. No association between TM and clinical outcome was found, while high levels of EPCR were associated with death and thrombosis of the portal vein. CONCLUSIONS: We surmise a possible role for high levels of TM as a marker of HCC development in patients with cirrhosis, whereas high levels of EPCR are a possible marker of worse HCC prognosis, being a sign of endothelial damage of large vessels.     

Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide-triggered murine fetal resorption

Genital tract bacterial infections could induce abortion and are some of the most common complications of pregnancy; however, the mechanisms remain unclear. We investigated the role of prostaglandins (PGs) in the mechanism of bacterial lipopolysaccharide (LPS)-induced pregnancy loss in a mouse model, and we hypothesized that PGs might play a central role in this action. LPS increased PG production in the uterus and decidua from early pregnant mice and stimulated cyclooxygenase (COX)-II mRNA and protein expression in the decidua but not in the uterus. We also observed that COX inhibitors prevented embryonic resorption (ER). To study the possible interaction between nitric oxide (NO) and PGs, we administered aminoguanidine, an inducible NO synthase inhibitor. NO inhibited basal PGE and PGF(2alpha) production in the decidua but activated their uterine synthesis and COX-II mRNA expression under septic conditions. A NO donor (S-nitroso-N-acetylpenicillamine) produced 100% ER and increased PG levels in the uterus and decidua. LPS-stimulated protein nitration was higher in the uterus than in the decidua. Quercetin, a peroxynitrite scavenger, did not reverse LPS-induced ER. Our results suggest that in a model of septic abortion characterized by increased PG levels, NO might nitrate and thus inhibit COX catalytic activity. ER prevention by COX inhibitors adds a possible clinical application to early pregnancy complications due to infections.