Alessandro Del Gobbo

Helicobacter pylori-negative Russell body gastritis: case report.

Russell body gastritis is an unusual form of chronic gastritis characterized by the permeation of lamina propria by numerous plasma cells with eosinophilic cytoplasmic inclusions. Very few cases have been reported in the literature; the majority of which have shown Helicobacter Pylori (H. pylori) infection, thus suggesting a correlation between plasma cell presence and antigenic stimulation by H. pylori. We present a case of Russell body gastritis in a 78-year-old woman who was undergoing esophagogastroduodenoscopy for epigastric pain. Gastric biopsy of the gastroesophageal junction showed the presence of cells with periodic acid-Schiff-positive hyaline pink bodies. Giemsa staining for H. pylori infection was negative, as well as immunohistochemical detection. The cells with eosinophilic inclusions stained positive for CD138, CD79a, and κ and lambda light chains, which confirmed plasma cell origin. In particular, κ and lambda light chains showed a polyclonal origin and the patient was negative for immunological dyscrasia. The histological observations were confirmed by ultrastructural examination. The cases reported in the literature associated with H. pylori infection have shown regression of plasma cells after eradication of H. pylori. Nothing is known about the progression of H. pylori-negative cases. The unusual morphological appearance of this type of chronic gastritis should not be misinterpreted during routine examination, and it should be distinguished from other common forms of chronic gastritis. It is mandatory to exclude neoplastic diseases such as gastric carcinoma, lymphoma and plasmocytoma by immunohistochemistry and electron microscopy, which can help with differential diagnosis. The long-term effects of plasma cells hyperactivation are still unknown, because cases of gastric tumor that originated in patients affected by Russell body gastritis have not been described in the literature. We are of the opinion that these patients should be scheduled for endoscopic surveillance.

The oncofetal protein IMP3: a novel biomarker and triage tool for premalignant atypical endometriotic lesions

OBJECTIVE To determine whether the oncofetal protein IMP3 is detectable in endometriomas with or without histological atypia and whether IMP3 staining can be used as a triage tool to identify foci of atypical endometriosis in doubtful cases. DESIGN Retrospective study. SETTING Academic department and referral center for endometriosis. PATIENT(S) A consecutive series of 516 women who underwent excision of 874 endometriomas. INTERVENTION(S) Histological review by three expert pathologists and immunohistochemical staining for IMP3. MAIN OUTCOME MEASURE(S) Test performance of IMP3 immunohistochemistry versus first-round histology. RESULT(S) The prevalence of atypical endometriosis was 1.7% (95% confidence interval [CI], 0.9%-3.3%) based on the number of women and 1.0% (95% CI, 0.5%-1.9%) based on the number of cysts. Three cases of atypical endometriosis were identified at first-round histological examination. Immunohistochemistry detected seven of the eight cases diagnosed as preneoplastic atypia at second-round histology and one case diagnosed as reactive atypia at second-round histology. The sensitivity of first-round histology was 33.3%, compared with 88.9% of IMP3 immunohistochemistry. CONCLUSION(S) Immunohistochemical staining for IMP3 expression is a simple, inexpensive, and sensitive test that can be used in routine clinical practice as a triage tool to discriminate between cytological/structural atypia and confounding benign conditions.

The Oncofetal Protein IMP3: A Useful Marker to Predict Poor Clinical Outcome in Neuroendocrine Tumors of the Lung

Introduction: We evaluated the expression of the oncofetal protein IMP3 in a series of neuroendocrine tumors of the lung, correlating our results with proliferating index Ki67 and with the expression of the two most studied stem cell markers in lung cancer, Nanog and Oct3/4. Methods: A total of 74 patients with a diagnosis of neuroendocrine tumor including 46 cases of typical carcinoid, nine cases of atypical carcinoids, 13 cases of large cell neuroendocrine carcinomas and six cases of small cell carcinomas were enrolled. Results: IMP3 was expressed in 50% of small cell carcinomas, 84% of large cell neuroendocrine carcinomas, 55% of atypical carcinoids and 10% of typical carcinoids. IMP3-positive cases showed significantly decreased overall and disease-free survival time compared with IMP3-negative cases. Nanog was expressed in 50% of small cell carcinomas, 31% of large cell neuroendocrine carcinomas, 33% of atypical carcinoids and 15% of typical carcinoids, and 68% of IMP3-positive tumors were also enriched for Nanog expression. Conversely, Oct3/4 expression could not be detected in all the analyzed series. When combining Ki67 and IMP3 expression we demonstrated that all the cases with a Ki67 index higher than 4% were also IMP3-positive, and their simultaneous expression was a poor prognostic factor. Conclusions: IMP3 is a marker of poor outcome in lung neuroendocrine tumors; its correlation with Nanog expression suggest an implication of IMP3 in stem cell processes and its association with a Ki67 labeling index higher than 4% stratifies a subset of atypical carcinoids with a higher risk of recurrence and mortality.

The Contrasting Role of p16Ink4A Patterns of Expression in Neuroendocrine and Non-Neuroendocrine Lung Tumors: A Comprehensive Analysis with Clinicopathologic and Molecular Correlations

Lung cancer encompasses a constellation of malignancies with no validated prognostic markers. p16Ink4A expression has been reported in different subtypes of lung cancers; however, its prognostic value is controversial. Here, we sought to investigate the clinical significance of p16Ink4A immunoexpression according to specific staining patterns and its operational implications. A total of 502 tumors, including 277 adenocarcinomas, 84 squamous cell carcinomas, 22 large cell carcinomas, 47 typical carcinoids, 12 atypical carcinoids, 28 large cell neuroendocrine carcinomas, and 32 small cell carcinomas were reviewed and subjected to immunohistochemical analysis for p16Ink4A and Ki67. The spectrum of p16Ink4A expression was annotated for each case as negative, sporadic, focal, or diffuse. Expression at immunohistochemical level showed intra-tumor homogeneity, regardless tumor histotype. Enrichments in cells expressing p16Ink4A were observed from lower- to higher-grade neuroendocrine malignancies, whereas a decrease was seen in poorly and undifferentiated non-neuroendocrine carcinomas. Tumor proliferation indices were higher in neuroendocrine tumors expressing p16Ink4A while non-neuroendocrine malignancies immunoreactive for p16Ink4A showed a decrease in Ki67-positive cells. Quantitative statistical analyses including each histotype and the p16Ink4A status confirmed the independent prognostic role of p16Ink4A expression, being a high-risk indicator in neuroendocrine tumors and a marker of good prognosis in non-neuroendocrine lung malignancies. In this study, we provide circumstantial evidence to suggest that the routinary assessment of p16Ink4A expression using a three-tiered scoring algorithm, even in a small biopsy, may constitute a reliable, reproducible, and cost-effective substrate for a more accurate risk stratification of each individual patient.

A case report of mesenteric mucinous cystoadenoma with review of the literature

BackgroundFew cases of primary retroperitoneal mucinous cystoadenoma, a rare benign tumor, have been reported in the literature so far. The pathogenesis of this tumour is not completely understood yet.Our case is particularly significant since the localization in the mesentery has been described only once before in the literature. Unless biologically benign, this tumour can cause relevant clinical symptoms related to the size and site (compression or obstruction of organs).Case presentationWe describe the case of a 52-years old woman who had presented with abdominal pain and underwent surgery in order to remove a palpable lump in the mesentery with histological diagnosis of primary mucinous cystoadenoma. The patient was followed-up for two years with no evidence of recurrence.ConclusionsMucinous cystoadenoma is more frequent in women, particularly when there is history of one or more pregnancies. A complete preoperative study with abdominal and pelvic tomographic images and an accurate physical examination are essentials for the management of the patient. Surgical resection is the only way to treat mucinous cystoadenomas, and to have the histological confirmation that the removed mass is a benign tumor.

Different expression of protein kinase a (PKA) regulatory subunits in normal and neoplastic thyroid tissues

The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in both cell growth and cell differentiation control. Mutations of the PRKAR1A gene have been found in patients with Carney complex and in a minority of sporadic anaplastic thyroid carcinomas. The aim of the study was to retrospectively evaluate the expression of different PKA regulatory subunits in benign and non benign human thyroid tumours and to correlate their expression with clinical phenotype. Immunohistochemistry demonstrated a significant increase in PRKAR2B expression in both differentiated and undifferentiated (anaplastic) thyroid tumors in comparison with normal thyroid tissues. Conversely, a significant increase in PRKAR1A expression was only demonstrated in undifferentiated thyroid carcinomas in comparison with normal thyroid tissue and differentiated thyroid tumors. In thyroid cancers without lymph nodal metastases PRKAR1A expression was higher in tumours of more than 2 cm in size (T2 and T3) compared to smaller ones (T1). In conclusion, our data shows that an increased PRKAR1A expression is associated with aggressive and undifferentiated thyroid tumors.

A new mouse avatar model of non-small cell lung cancer

Introduction: Lung cancer remains the leading cause of tumor-related deaths, despite advances in the understanding of the disease pathogenesis and in its clinical treatment. It is crucial to develop novel technologies to discover disease biomarkers and predict individual therapy response. Materials and methods: We established 48 patients-derived tumor xenografts (PDTXs) implanted in the subrenal capsule of immunodeficient mice using thin, precision-cut tumor tissue slices, derived from five patients affected by non-small cell lung cancer. Twenty-six tissue slices were immediately processed and implanted at sample recovery [patients-derived tumor xenografts derived from fresh tissue (dPDTX)], whereas the remaining sections were cultured on specific organotypic supports at 37°C and 5% CO2 for 24 h before grafting [patients-derived tumor xenografts derived from cultured tissue (cPDTX)]. At sacrifice, xenografts tissue morphology, proliferation (Ki67), and histotype markers were analyzed. Oncogenic miRNAs profiles were assessed in PDTXs, human tumors, and serum from one patient. Results: Xenografts retained the original cancer features and there were no differences between dPDTXs and cPDTXs. Squamous cell carcinoma (SCC) xenografts showed a higher engraftment rate than adenocarcinoma (AC)-derived tumors. At basal time, Ki67 levels were higher in SCCs than in ACs, and the expression levels of genes associated to a stem cell-like phenotype were also more expressed in SCC samples. The analysis of oncogenic miRNAs showed that circulating miR-19b, -21, and -210 levels were correlated with higher Ki67 expression in xenografts. Conclusion: Our study implemented the PDTX model with thin, precision-cut tumor slices from small tumors, which could be useful for clinical applications and predictive purposes. The different engraftment success is likely determined by tumor histotype, high proliferation index, and the expression of genes essential for cancer stem cells maintenance. Our PDTXs model could be a valid tool to expand primary tumors for the discovery of new biomarkers and explore therapeutic options.

IMP3 expression in small-intestine neuroendocrine neoplasms: a new predictor of recurrence

PurposeSmall-intestine neuroendocrine neoplasms are heterogeneous neoplasms arising from endocrine cells of the intestinal mucosa. Ki-67 is the main determinant of prognosis in neuroendocrine neoplasms. However, the search for new prognostic makers represents a key point with regard to small-intestine neuroendocrine neoplasms. The oncofetal protein IMP3 plays a role in cell growth and its expression has a prognostic value in lung neoplasms.MethodsFrom January 1998 to August 2015, all the consecutive small-intestine neuroendocrine neoplasms patients suitable for surgery were included: 51 patients (32 males, median age 68 years) had small-intestine neuroendocrine neoplasms classified according to the WHO 2010 classification. In all the cases IMP3 expression was evaluated on primary tumors and, when available, on nodal and distant metastases. The medical records and pathological slides of these patients were used to determine the clinical characteristics, pathological diagnoses, and outcome information.ResultsThe overall 5-year and 10-year survival rate were 53.9 and 42% respectively. At Cox proportional hazards regression grading was the major factor influencing both OS and progression-free survival at univariate (p = 0.0002 and 0.0051, respectively) and multivariate analysis (p = 0.0004 and 0.0043, respectively). Also IMP3 expression at the nodal metastases resulted a factor significantly associated with progression-free survival at both univariate (p = 0.0066) and multivariate analysis (p = 0.0059, HR 3.58). IMP3 expression did not correlate with the Ki-67 (p = n.s.).ConclusionsIn this study, IMP3 at the nodal site resulted to be associated with low progression-free survival in small-intestine neuroendocrine neoplasms, independently of the Ki-67 index. We suggest that the integration of IMP3 and Ki-67 would help better stratify the risk of progression in small-intestine neuroendocrine neoplasms.

The Oncofetal Protein IMP3: A Novel Grading Tool and Predictor of Poor Clinical Outcome in Human Gliomas

Morphologic criteria illustrated in WHO guidelines are the most significant prognostic factor in human gliomas, but novel biomarkers are needed to identify patients with a poorer outcome. The present study examined the expression of the oncofetal protein IMP3 in a series of 135 patients affected by high-grade (grade III and IV) gliomas, correlating the results with proliferative activity, molecular parameters, and clinical and follow-up data. Overall, IMP3 expression was higher in glioblastomas (68%) than in grade III tumors (20%, P < 0.0001), and IMP3-positive high-grade gliomas showed a shorter overall and disease-free survival than negative ones (P = 0.0002 and P = 0.006, resp.). IMP3 expression was significantly associated with the absence of mutations of IDH1 gene (P = 0.0001) and with the unmethylated phenotype of MGMT in high-grade gliomas (P = 0.004). High Ki67 levels were correlated with better prognosis in glioblastomas but IMP3 expression was not correlated with the proliferation index. These findings confirm the role of IMP3 as a marker of poor outcome, also in consideration of its association with IDH1 wild-type phenotype and MGMT unmethylated status. The data suggest that IMP3 staining could identify a subgroup of patients with poor prognosis and at risk of recurrence in high-grade gliomas.

Primary urothelial cell carcinoma of the vagina.

doi:10.1016/j.ijgo.2011.07.028 A 27-year-old female presented with hallucinations, excessive speech, disorientation, and hyperthermiawithout evidence of infection. Neuroleptic treatment did not improve the clinical picture. Cranial CT was negative. Hyperthermia was complicated by muscular rigidity and seizures that progressed to status epilepticus. The patientwas intubated emergently and admitted to the Intensive Care Unit. Orofacial dyskinesia, catatonic-like behavior, frequent multifocal myoclonus, high blood pressure, tachycardia, diaphoresis, and hypoventilation/desaturation episodes complicated the clinical picture further. The response to 5 different antiepileptic agents was suboptimal. Cranial MRI showed bilateral focal lesions along the frontoparietal subcortical white matter, with no restriction to diffusion. Abdominal CT detected a left adnexal cyst. A paraneoplastic encephalitis was suspected and treated with corticosteroids, immunoglobulins, and plasmapheresis. Anti-NMDA receptor antibodies were positive in cerebrospinal fluid. The cyst was surgically excised. A total intravenous anesthetic including propofol, remifentanil, and rocuronium was used. No complications, unexpected events, or temperature derangement occurred perioperatively and agents such as ketamine, nitrous oxide, and tramadol were avoided. Pathology revealed a mature teratoma. The patients clinical picture improved over the following 2 weeks, but subtle mental changes such as poor communication and retrograde amnesia remained. In a review of 100 cases, the median age of patients with antiNMDA receptor encephalitis was 23 years [6]. These patients initially showed psychiatric symptoms or memory derangements; 76% had seizures, 88% had decreased consciousness, 86% had dyskinesia, 69% had autonomic instability, and 66% suffered hypoventilation. Of the cases, 60% had tumors—most frequently ovarian teratoma, but also mediastinal teratoma. Patients who received early immunotherapy and surgical treatment had better outcome and fewer neurological relapses. Seventy-five patients recovered or had mild deficits, whereas 25 had severe deficits or died. In conclusion, a standard anesthetic, either intravenous or inhaled, demonstrated adequate performance for patients with antiNMDA receptor encephalitis. NMDA antagonists such as ketamine, nitrous oxide, xenon, tramadol, and dextropropoxyphene should be judiciously avoided perioperatively because of the uncertainty about the pharmacodynamic response of an abnormal NMDA receptor.