Silvia Christiansen

Prognostic value of Mdm2, p53 and p16 in patients with astrocytomas.

Surgical cure of gliomas infiltrating into the brain is practically impossible and their clinical course is primarily determined by the biological behavior of the tumor cell. The purpose of this study was to analyze retrospectively prognostic input of p53, Mouse double minute-2 (Mdm2) and p16 in 103 uniformly treated patients with astrocytic tumors. The expression of these molecules was measured by immunohistochemical procedure. Prognostic evaluation was performed with the multivariate proportional hazards model. The follow-up period lasted 19 (5–122) months for the survivors. We observed that 66% of gliomas showed mutated p53, while only 17% overexpressed Mdm2, the p53-regulatory molecule. Besides, almost 50% of gliomas lost p16 immunopositivity. Only p53 labeling showed a positive correlation with the grade of malignancy, according with the WHO classification. The association between mutated p53 and histological grade remained when prognostic variables were considered in a multivariate analysis. No association between p53 status and overall survival was found. On the other hand, Mdm2 overexpression and, unexpectedly, p16 immunopositivity were associated with a shorter survival in an univariate analysis. However, Cox-regression analysis showed that only Mdm2 in female patients was an independent prognostic factor, associated with shorter survival.In conclusion, our results suggest that Mdm2 could be a relevant marker in determining the evolution of glioma patients and could provide a more objective way to classify astrocytomas.

Histologically confirmed isolated IgG4-related hypophysitis: two case reports in young women

Summary IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis. Learning points IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis. It is more common in older men, but young women may also present this type of hypophysitis. Although involvement of other organs is frequent, isolated pituitary disease is possible. Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus. The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment. Glucocorticoids are recommended as first-line therapy.

[Eosinophilic gastroenteropathy: a pediatric series].

Eosinophilic gastroenteropathy (EoG) is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal (GI) mucosa. A chart review was performed searching for patients diagnosed between 2000 and 2010. EoG was diagnosed based on mucosal infiltration of 20 or more eosinophils/HPF in upper GI tract and more than 60 eosinophils/HPF in lower GI tract. Ten patients [median age: 10 mo. (r 2 mo.- 10 yr.)], 9 males, were diagnosed. Four presented with severe protracted diarrhea and weight loss, 2/10 abdominal distention and weight loss and 4/10 protein-losing enteropathy. Exclusive elemental or hypoallergenic diets were administered depending on the age of presentation with remission achieved in 4/10. Six required methylprednisolone to induce remission, 5 are still on budesonide. Due to the emergence of many cases of EoG in the last decade, we should increase our level of suspicion. Multicenter studies could contribute to define the best therapeutic approach for these patients.

Gender differences in macroprolactinomas: study of clinical features, outcome of patients and ki-67 expression in tumor tissue.

Prolactinomas in men are usually macroprolactinomas and other investigators have attributed bigger size of tumors in men to delay in diagnosis. A retrospective study of 71 macroadenomas (42 men) was carried out. Parameters studied were age, signs and symptoms at presentation, time of onset of symptoms, basal prolactin, estradiol, and total testosterone levels, tumor size and Ki 67 expression in tumor tissue. Male patients were older. Visual defects were significantly more prevalent in men. Hardy 4 stage tumors were found only in men. We found no significant correlation between tumor size and the patients age nor between tumor size and the onset of symptoms. Whereas basal E2 levels (21.2+/-12.9 vs. 33.3+/-43.3 pg/ml, p=n.s.) were very similar in male and female patients, testosterone levels were significantly higher in men (0.6+/-0.5 vs. 1.8+/-1.2 ng/ml, p=0.02). The rate of cell proliferation represented by Ki 67 was significantly higher in tumors in men (3.5+/-1.2 vs. 1.5+/-0.5%, p=0.0001). This is the first study focused in macroprolactinomas that shows that they are clinically and biologically more aggressive in men. Hypogonadism in men could appear later in the progression of prolactinomas and this might explain why men were older at the time of diagnosis. Furthermore, testosterone could be a source for E2 in situ aromatization giving male tumors an advantage in cell proliferation.

Carcinoma transicional de vejiga en adolescentes: un diagnóstico para tener en cuenta

Transitional cell carcinoma of the bladder has a high incidence in adults, but it is uncommon in children and adolescents. Hematuria is the most common symptom of presentation and vesical ecography the preferred diagnostic method. The diagnosis and treatment is performed with cystoscopy and endoscopic resection. We describe two patients: an 18 years old male, who presented with a pediculated tumor on the posterior bladder wall and a 15 years old female with a 1 cm long tumor on the posterior wall too; both were removed under endoscopic control. In both patients superficial transitional cell carcinoma was the final diagnosis and are disease free 3 and 5 years later. A review of the available literature was performed to clarify if this type of tumors must be considered malignant and try to define how long and by which way these patients must be controlled.

Atypical hemorrhagic presentation of a fourth ventricle subependymoma: case report.

To present a case of a fourth ventricle subependymoma (SE) with a spontaneous acute subarachnoid intra-cisternal bleeding. A 33-year-old man was admitted with 5 days history of oppressive occipital headache and neck pain without additional neurological focus. Unenhanced computed tomography (CT) scan demonstrated an isointense mass located in the fourth ventricle with a spontaneously hyperdense acute extratumoral hemorrhage in the cisterna magna. Contrast-enhanced magnetic resonance imaging (MRI) revealed a well-delimitated non-enhanced tumor, hypointense on T1-weighted and hyperintense on T2-weighted images, involving the floor of the fourth ventricle and extending caudally into the cervical spinal canal via foramen magnum. Intraoperative, a large blood clot was removed and a macroscopically hypovascularlesion was completely excised from the right lateral recess and the floor of the fourth ventricle. Intra and postoperative immuno-histopathological examination revealed a SE. The patient has a normal postoperative course and was discharged in the fifth postoperative day. A 10-month postoperative MRI study confirmed a complete tumor resection. Symptomatic SEs should be surgically treated emphasizing the urgency in the presence of hemorrhage. The interest of this case is to demonstrate that infratentorial SEs although extremely rare, might present with acute subarachnoid bleeding.

Unusual Benign Paratesticular Tumor in an Infant Mimicking Rhabdomyosarcoma

Paratesticular tumors are extremely rare, with paratesticular rhabdomyosarcoma being the most common finding. A 6-month-old boy presented with an asymptomatic, right intrascrotal mass whereby the testicle was surrounded by a friable lipomatous tumor. Frozen section revealed an inflammatory process, negative for malignancy. Tumorectomy with vaginal resection was performed, maintaining the testicle and excretory ducts. Histopathologic findings showed a juvenile xanthogranuloma, a non-Langerhans histiocytosis commonly described in infants in the skin and skeletal muscle. The patient is doing well 2 years after surgery and is the first such case reported in the literature with successful conservative treatment.

Restricted diffusion in a ring-enhancing mucoid metastasis with histological confirmation: case report.

We present a case of restricted diffusion in a ring-enhancing cerebellar metastasis in a 58-year-old man. Diffusion imaging showed restriction with low apparent diffusion coefficient values within the cavity. Diagnosis of abscess was suggested based on radiological findings. A suspicious lung nodule was found in the systemic evaluation, and histological examination of the brain lesion confirmed metastatic adenocarcinoma with mucoid content confirmed by further specific pathological tests. We discuss the reason of diffusion findings and the importance of the correct interpretation of this technique in a clinical situation. Our case confirms previous hypothesis about restricted diffusion related to mucoid content in metastasis.

Low-impedance Baseline Values Predict Severe Esophagitis

Objectives: The aim of the study was to determine whether esophageal baseline impedance (BI) values in children could be predictive of esophagitis. Materials and Methods: Multichannel intraluminal impedance (MII) tracings of children 3 to 17 years of age suspected of having gastroesophageal reflux and esophagitis, who had also undergone upper endoscopy with multiple esophageal biopsies, were reviewed. Patients with eosinophilic esophagitis were excluded. Esophagitis was assessed by macroscopic and microscopic parameters. Esophageal histology was reported by 2 blinded independent pathologists unaware of the MII results. Mean BI was automatically calculated in the different MII channels (ch) by the specific software without removing any episode of increased/decreased BI. BI results were plotted against macroscopic and histological scores for each channel. Results: Tracings of 87 children, 53 boys, were evaluated. Mean age was 7.4 years: 45 had histologic esophagitis, 8 macroscopic. Histologic mild esophagitis (grade 1) was observed in 30, and 15 had moderate to severe esophagitis (grade 2–3). Ten had grade 3 esophagitis. Eight had macroscopic esophagitis as well. Results: in channel 6 of the MII, all 10 patients with grade 3 esophagitis and the 8 with macroscopic esophagitis had a BI <900 &OHgr;/s (positive predictive value 100% and negative predictive value 100%), whereas none of those having a biopsy score of 0 to 2 or no endoscopic evidence of esophagitis had a mean BI below 2000 &OHgr;/s. Conclusions: The evaluation of the BI measured in channel 6 gave us 100% prediction of grade 3 and macroscopic esophagitis. BI on channel 6 may be useful to predict severe esophageal mucosa inflammation and could potentially be used for follow-up evaluation, rather than repeating an upper endoscopy. In addition, it would seem that grade 3 esophagitis even in the absence of macroscopic esophagitis affects the integrity of the esophageal epithelium.

Immune-mediated rippling muscle disease and myasthenia gravis

Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies.