West Nile Virus encephalitis in intensive care: a small mosquito, a tremendous danger.

The authors describe two of three cases of West Nile virus (WNV) meningoencephalitis admitted to ICU in Ferrara (south of Po River) underlying the main common features. They focus on the difficulties in diagnosis, with key-points including seasonality (late summer in Italy), unspecific flu-like symptoms at the beginning, as hyperpyrexia, myalgia and asthenia, followed by neurological impairment, and use of steroids in the patient clinical history. Special attention is deserved to the poor outcome at both short and long term.

Solitary fibrous tumor of the orbit: a case report.

Solitary fibrous tumor is a very rare neoplasm affecting the head and neck. We present a case located in the orbit in which clinical, pathological and surgical features are reviewed.

Ectopic thymoma simulating a pericardial cyst.

We present a case of a 53 year old man with a thymoma near the pericardium, a rare ectopic localisation of thymoma. A round radiodensity found at the right cardiophrenic angle was initially suspected at the echocardiography to be a pericardial cyst. The diagnosis of thymoma was made only after histopathological examination of the surgically re-sected lesion.

Chronic lymphocytic leukemia with 6q- shows distinct hematological features and intermediate prognosis.

Cytogenetic and fluorescence in situ hybridization studies were successfully performed in 217 chronic lymphocytic leukemia (CLL). In all, 13 patients with 6q21 deletion were identified and characterized in comparison with 92 patients with 'favourable' karyotype (normal or 13q-), 69 cases with 'intermediate risk' (1-2 anomalies) and 43 cases with 'unfavourable' karyotype (complex, 11q- or 17p-). Six out of 13 cases with 6q- showed an excess of atypical lymphocytes, a finding confirmed at the histologic level; >20% CD38+ cells were seen in 5/6 cases. IGVH mutational status revealed >98% homology to the germline sequence in 4/10 cases. When compared with the 'favourable' group, patients with 6q- showed a higher white blood cell (WBC) count, frequent splenomegaly, atypical morphology, CD38+ and short time from diagnosis to first treatment and short survival. A higher median WBC count was found in the 6q- group vs the intermediate-risk group; survival was shorter in the unfavourable group. To ascertain if the 6q- anomaly was an independent factor predicting for an inferior outcome among those patients with 'favourable' cytogenetics, we performed an analysis of prognostic factors in 105 patients (92 'favourable' plus 13 with 6q-), showing that the 6q- chromosome maintained its prognostic significance at multivariate analysis (P=0.02) along with stage (P=0.01). We conclude that CLL with 6q- is characterized by a high incidence of atypical morphology, classical immunophenotype with CD38 positivity and intermediate incidence of IGVH somatic hypermutation. Clinicobiological features and outcome show that this cytogenetic subset of CLL should be allocated in an intermediate-risk category.

One case of immunotactoid glomerulopathy: morphological-ultrastructural aspects.

Starting from a group of 736 renal biopsy patients, evaluated by ultrastructural studies over a period of 22 years, the authors present a rare case of immunotactoid glomerulopathy, suggesting that these forms, until a few years ago considered in the same group as fibrillary glomerulonephritis, are in fact a separate entity; moreover, they may represent a very early manifestation of plasmacellular dyscrasia still at the initial stage.

Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability.

BACKGROUND: Widespread microsatellite instability (MSI) occurs in nearly 15% of sporadic colorectal cancers. Large bowel carcinomas with high-frequency MSI (MSI-H) (instability at > or = 30% of microsatellite loci) are believed to display distinctive pathologic features and to behave less aggressively than microsatellite-stable (MSS) tumors and carcinomas with low-frequency MSI (MSI-L) (instability at < 30% of microsatellite loci). The aim of the current study was to accurately define the clinicopathologic and biologic features of MSI-H sporadic colorectal carcinomas. METHODS: MSI status was evaluated in 216 large bowel adenocarcinomas using polymerase chain reaction (PCR) and 6 microsatellite markers. Tumors that showed instability with at least two microsatellite markers were classified as MSI-H, whereas the other tumors were classified as MSI-L (instability at one locus) or MSS (no instability). Expression of p53, hMLH1, and hMSH2 gene products was determined by immunohistochemistry, and DNA ploidy pattern was determined by flow cytometry. The prognostic significance of MSI status was assessed by univariate and multivariate survival analyses. RESULTS: The significantly different pathologic features of MSI-H carcinomas were proximal location; large size; mucinous and medullary histotype; poor differentiation; expanding pattern of growth; more frequent Crohn-like conspicuous lymphoid reaction; and low incidence of extramural vein invasion. Most MSI-H tumors were DNA diploid (33 of 40 tumors; 82.5%) and p53 negative (34 of 44 tumors; 77.3%). Conversely, DNA aneuploidy and p53 overexpression were observed in 82.3% (130 of 158 tumors; P < 0.0001) and 54.1% (93 of 172 tumors; P = 0.0002) of MSI-L/MSS tumors, respectively. Loss of hMLH1 or hMSH2 expression was detected in a high fraction of MSI-H carcinomas (86. 0%). Patients with MSI-H tumors showed a better clinical outcome than patients with MSI-L/MSS tumors (P = 0.0017). Furthermore, in multivariate analysis that included conventional clinicopathologic parameters, MSI status, and p53 expression as covariates, MSI status was a significant independent prognostic indicator of disease specific survival. CONCLUSIONS: Assessment of MSI status is an essential step in the genetic characterization of large bowel carcinomas and identifies a subset of tumors with distinct clinical, pathologic, and biologic features.

Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes.

Colon carcinomas with microsatellite mutator phenotype exhibit specific genetic and clinico-pathological features. This report describes the analysis of 63 "microsatellite instability-high" (MSI-H) tumors for the presence of mutations in microsatellites located in the coding regions (CDRs) of 6 genes: TGFbetaRII, BAX, hMSH3, hMSH6, IGFIIR, and BLM. The following frequencies of mutations were detected: TGFbetaRII (70%), BAX (54%), hMSH3 (36.5%), IGFIIR (22%), hMSH6 (17.5%), and BLM (16%). The overall picture revealed combinations of mutations suggestive of a progressive order of accumulation, with mutations of TGFbetaRII and BAX first, followed by frameshifts in hMSH3, hMSH6, IGFIIR, and BLM. Correlations with 12 clinico-pathological parameters revealed that tumors with frameshifts in 1 or 2 CDRs were significantly better differentiated than tumors with frameshifts in more than 2 CDRs. We also found that mutations in the hMSH3 gene were significantly associated with decreased wall invasiveness and aneuploidy, and frameshifts in the BLM gene were significantly associated with the mucinous histotype. A trend toward an association between hMSH3 and IGFIIR with the medullary and conventional adenocarcinoma histotypes, respectively, was seen. Our results strengthen the concept that mutations in target genes have a role in the tumorigenic process of MSI-H tumors, and indicate that frameshifts in microsatellites located in CDRs occur in a limited number of combinations that could determine distinct clinico-pathological traits.

Kaposi's sarcoma in renal transplant recipients: pathogenetic relation between the reduced density of Langerhans cells and cyclosporin-A therapy.

Patients treated with immunosuppressive drugs can develop cancers. The authors present two cases of Kaposi's sarcoma in kidney transplant patients who had been treated with azathioprine, steroids and cyclosporin-A; during this treatment the Langerhans cells decreased and Kaposi's sarcoma appeared. Discontinuation or reduction of the dosage of cyclosporin-A led to complete regression of the illness, and the Langerhans cells reappeared. We suggest that cyclosporin-A damages the immunological function of the epidermal Langerhans cells, and that this is the primary factor in the development of Kaposi's sarcoma.

H reflex excitability following voluntary muscle contraction of different duration.

The importance of the duration of contraction on the excitability of the motoneuronal pool was evaluated by measuring the H reflex from soleus muscle after short and long contractions at constant effort equal to 60% maximal voluntary contraction (MVC); the difference between the amplitude of H reflex at rest and after contraction of different duration was evaluated in 10 normal subjects and in one hemiparetic patient. The authors found a significant inhibition of H reflex after contraction of 10 seconds and after 40 seconds and a longer duration of the inhibition after 40 seconds. In the hemiparetic patient the H reflex did not show inhibition which suggests a possible reduction of the presynaptic inhibition, and a lack of modulation of the motoneuronal pool after contraction.

Prognostic significance of DNA ploidy in patients with stage II and stage III colon carcinoma: a prospective flow cytometric study.

BACKGROUND: The prognostic value of flow cytometric DNA ploidy in colorectal carcinoma has not been defined clearly. Most previous studies were conducted retrospectively using archival formalin fixed, paraffin embedded tumor samples. Conversely, few data on prospective studies employing fresh or frozen tissue specimens are available. There is general agreement that fresh/frozen material is more reliable than paraffin embedded tissue for DNA ploidy analysis by flow cytometry. METHODS: In the current investigation we evaluated the prognostic significance of nuclear DNA content in a prospective series of 191 patients with curatively resected TNM Stage II (n = 107) or Stage III (n = 84) sporadic colon carcinomas. DNA ploidy status was assessed by flow cytometry utilizing multiple frozen tumor samples. Mean follow-up in surviving patients was 48.5 months (median, 46.9 months; range, 29-77 months). The Cox proportional hazards model was used to adjust for several clinical and pathologic covariates. RESULTS: Of the 191 carcinomas examined, 47 (24.6%) were classified as DNA diploid and 144 (75.4%) as DNA aneuploid. DNA ploidy pattern was significantly related to tumor site (P < 0.0001), histologic type (P = 0.0002), and grade of differentiation (P = 0.009), but not to other clinical and pathologic variables. Patients with DNA diploid tumors showed a better disease free (P = 0.013) and overall survival (P = 0.021) than patients with DNA aneuploid adenocarcinomas. In particular, patients with Stage II DNA diploid tumors (n = 30) had an excellent clinical outcome, with an overall 5-year survival rate of 97%. When patients were analyzed according to the anatomic site of the tumor, a significant relationship between DNA ploidy status and disease free and overall survival was observed in the group of patients with carcinomas of the proximal colon (n = 84) (P = 0.004 and P = 0.002, respectively), but not among patients whose tumors were sited distally to the splenic flexure (n = 107). In multivariate analysis, nuclear DNA content was demonstrated to be an independent prognostic variable for both disease free and overall survival. Furthermore, in the group of patients with tumors of the proximal colon, DNA ploidy pattern was the single most important prognostic factor. CONCLUSIONS: Our results confirm that flow cytometric DNA ploidy status is a significant and independent prognostic factor in patients with colon carcinoma. These findings may have clinical implications for the management of affected patients, especially those with Stage II disease.

Lymphoepithelial cyst of the pancreas.

A rare case of lymphoepithelial cyst of the pancreas is reported. Microscopically the cyst content consisted of keratinous material and the walls were lined by mature squamous epithelium surrounded by dense lymphoid tissue. Immunohistochemistry showed diffuse reactivity for CD20 and CD3 in the lymphoid tissue and uniform positivity for cytokeratins in the squamous epithelium. Although the histogenesis of lymphoepithelial cysts of the pancreas is not understood, awareness of this lesion is helpful in differentiating it from other pancreatic cystic lesions.

p53 expression in colorectal cancer: relation to tumor type, DNA ploidy pattern and short-term survival.

p53 protein expression was evaluated in a series of 204 primary colorectal adenocarcinomas by immunohistochemistry using frozen tissue sections and monoclonal antibody DO-7. Nuclear staining of more than 5% of neoplastic cells was observed in 124 (60.8%) adenocarcinomas, which were classified as p53 positive. p53 immunoreactivity was found to he unrelated to several clinical and pathologic variables, including age and sex of patient, tumor site, tumor stage, grade of differentiation, pattern of growth, degree of peritumoral lymphocytic infiltration, and venous invasion. A strong association was demonstrated between p53 immunostaining and tumor type. Only 4 of 21 mucinous carcinomas examined (19%) were p53 positive. Conversely, 120 of 183 (65.6%) nonmucinous adenocarcinomas showed positive p53 immunostaining (P <.0001). p53 expression also was related to the flow cytometric DNA ploidy pattern, aneuploid carcinomas with DI >1.20 showing higher frequency of p53 overexpression than DNA diploid, and aneuploid tumors with DI < or = 1.20 (P = .0003). No relationship was found between p53 expression and the Ki-67 proliferation index. With respect to the total study population (mean follow-up 33.4 months; range 19-47 months) the duration of overall survival was independent of p53 expression. In the group of 141 patients with stage I, stage II, and stage III disease who had undergone curative resection, positive p53 immunostaining was associated with poorer overall survival (P = .029). Subgroup analysis showed that the reduced survival conferred by p53 overexpression was confined to patients with stage III tumors (P = .027). However, in multivariate analysis, p53 expression failed to demonstrate independent prognostic significance. Our results indicate that immunohistochemical analysis of p53 expression provides valuable information for the understanding of colorectal cancer biology and clinical behavior.

Evidence for androgen receptor gene expression in human thyroid cells and tumours.

Androgen-binding activity has been identified in normal and pathological thyroids, but evidence for the expression of the canonic androgen receptor (AR) in the thyroid has not been provided so far. In this study we have used reverse transcription (RT)-PCR to examine RNA expression of the canonic AR gene in human thyroid tissues, in primary cultures of human thyrocytes and in a variety of neoplastic thyroid cell lines (NPA, TPC and WRO). An AR cDNA fragment with the expected size of 262 bp was detected in normal tissues and cultured thyrocytes as well as in neoplastic cell lines, demonstrating that the gene for AR is indeed expressed in thyroid follicular cells. Immunocytochemical analysis revealed the presence of the AR protein in cancer cell lines and androgen treatment increased nuclear positivity to AR. In a survey of 35 thyroid tissues AR cDNA was detected in all the non-neoplastic samples (6 normal and 3 goitrous) and in 19 of 26 neoplastic samples. AR cDNA was not detected in 4 of the 9 follicular adenomas and in 3 of the 12 papillary carcinomas. AR was revealed by immunohistochemistry in 1 of 2 normal thyroids, in 1 goiter and in 1 of 2 neoplastic thyroids. These findings show the presence of the canonic AR in the human thyroid.

Analogs of cord red blood cell membrane components displayed on placenta, amnion and amniotic cells in culture.

Placenta and amnion were analyzed to ascertain the presence of antigens in common with red blood cells (RBC) from cord or fetuses. The expression of distinct antigens displayed on a subpopulation of cord RBC and detected by anticord RBC membrane antibodies was particularly investigated, concomitantly with the presence of transferrin receptors (TR) by employing immunohistochemistry. The placenta showed both cord antigen and TR; on the contrary, amnion--which was labelled by anti-cord RBC membrane antibodies--was not stained by the anti-TR antibody. The results of inhibition and double labelling assays further excluded TR as the relevant antigen in the labelling of both placenta and amnion. The staining of fetal membranes disappeared after absorption of antibodies with cord RBC membranes. These results suggest that the antigens externally expressed on a subpopulation of cord RBC are shared by amnion and placenta.

[Clinico-pathological features and biological characterization of mucoid colorectal carcinoma]. / Aspetti clinico-pathologici e caratterizzazione biologica del carcinoma mucoide del colon-retto.

The clinical, pathological and biologic features of 79 mucinous colorectal carcinomas were compared with those of 602 non-mucinous adenocarcinomas. The two groups did not show appreciable differences in patients' age, stage distribution, extent of lymph node involvement, grade of differentiation, pattern of growth and venous invasion. Mucinous carcinomas occurred more frequently among female patients (P < 0.05) and in the proximal colon (P < 0.01). Moreover, mucinous carcinomas more often demonstrated origin within villous adenomas (P < 0.0001) and lacked pronounced peritumoural lymphocytic infiltration (P < 0.001). A strong association was found between tumour type and flow cytometric nuclear DNA content. A high proportion of mucinous carcinomas showed DNA index (DI) values < or = 1.20 (26/38, 68.4%); conversely only 103 of 322 (32%) non-mucinous carcinomas had a DI < or = 1.20 (P < 0.0001). In addition mucinous carcinomas were characterized by infrequent p53 overexpression (4/21, 19% versus 120/183, 65.6%; P < 0.001) and higher levels of proliferative activity (P < 0.0001) compared to non-mucinous adenocarcinomas. Our data support the hypothesis that mucinous carcinoma represents a distinct clinicopathologic and genetic entity.