Giant multilocular thymic cyst in an HIV-infected adolescent

A girl with vertically acquired HIV infection presented with a 6-month history of dyspnea and chest pain. Computed tomography of the thorax showed a heterogenous mass measuring 13 x 9 x 17 cm located in the anterior mediastinum. Complete surgical resection was accomplished with no complications. The final diagnosis was multilocular thymic cyst, a distinct pathologic entity that is morphologically distinguishable and unrelated to congenital thymic cyst. (C) 2011 Elsevier Inc. All rights reserved.

High-Resolution Genomic Mapping Reveals Consistent Amplification of the Fibroblast Growth Factor Receptor Substrate 2 Gene in Well-Differentiated and Dedifferentiated Liposarcoma

Well-differentiated liposarcoma (WDLS) is one of the most common malignant mesenchymal tumors and dedifferentiated liposarcoma (DDLS) is a malignant tumor consisting of both WDLS and a transformed nonlipogenic sarcomatous component. Cytogenetically, WDLS is characterized by the presence of ring or giant rod chromosomes containing several amplified genes, including MDM2, TSPAN31 CDK4, and others mainly derived from chromosome bands 12q13-15. However, the 12q13-15 amplicon is large and discontinuous. The focus of this study was to identify novel critical genes that are consistently amplified in primary (nonrecurrent) WDLS and with potential relevance for future targeted therapy. Using a high-resolution (5.0 kb) ""single nucleotide polymorphism""/copy number variation microarray to screen the whole genome in a series of primary WDLS, two consistently amplified areas were found on chromosome 12: one region containing the MDM2 and CPM genes, and another region containing the FRS2 gene. Based on these findings, we further validated FRS2 amplification in both WDLS and DDLS. Fluorescence in situ hybridization confirmed FRS2 amplification in all WDLS and DDLS tested (n = 57). Real time PCR showed FRS2 mRNA transcriptional upregulation in WDLS (n = 19) and DDLS (n = 13) but not in lipoma (n = 5) and normal fat (n = 9). Immunoblotting revealed high expression levels of phospho-FRS2 at 1436 and slightly overexpression of total FRS2 protein in liposarcoma but not in normal fat or preadipocytes. Considering the critical role of FRS2 in mediating fibroblast growth factor receptor signaling, our findings indicate that FRS2 signaling should be further investigated as a potential therapeutic target for liposarcoma. (C) 2011 Wiley-Liss, Inc.

Bites by the colubrid snake Philodryas patagoniensis: A clinical and epidemiological study of 297 cases

We retrospectively analyzed 297 proven cases of Philodryas patagoniensis bites admitted to Hospital Vital Brazil (HVB), Butantan Institute, Sao Paulo, Brazil, between 1959 and 2008. Only cases in which the causative animal was brought and identified were included. Part of the snakes brought by the patients was still preserved in the collection maintained by the Laboratory of Herpetology. Of the 297 cases, in 199 it was possible to describe the gender of the snake, and seventy three (61.3%) of them were female. The length of snakes (snout-vent length) ranged from 160 to 1080 mm. In 117 snakes their state of preservation enabled the dissection and examination of their stomach contents. The stomach was empty in 106 snakes (89.1%). Most bites occurred in the seasons of spring and summer (n = 196, 66.0%) and during warmer periods of the day. The mean age of the victims was 24.1 +/- 15.1 years old and 206 (69.4%) patients were men. Around 92% of the patients sought medical care within 6 h after the bite. Both lower (n = 188, 63.3%) and upper limbs (n = 102, 34.3%) were most frequently bitten, especially the feet and hands (n = 205, 69.0%). The local clinical manifestations were pain (n = 151, 50.8%), transitory bleeding (n = 106, 35.7%), erythema (n = 47, 15.8%) and edema (n = 39, 13.1%). Ecchymosis was not observed. Only 7 (2.4%) patients reported systemic symptoms characterized by mild dizziness and 88 patients (29.6%) showed no evidence of envenoming. The whole blood clotting time was performed in 76 (25.6%) patients on admission and all of them had coagulable blood. Supportive treatment was offered to only 13.4% of patients, namely administration of antihistamines (n = 19, 6.4%) and analgesics (n = 12, 4.1%). Eight patients (2.7%) were mistreated with Bothrops antivenom before their admission to HVB. No sequels or relevant complications were observed in patients, and the prognostic was benign. Therefore, although P. patagoniensis accidents can cause mild local symptomatology, it is very important that health professionals know how to make the correct diagnosis to avoid unnecessary use of antivenom. (C) 2010 Elsevier Ltd. All rights reserved.

Cytogenetic molecular delineation of a terminal 18q deletion suggesting neo-telomere formation

Deletion of the long arm of chromosome 18 is one of the most common segmental aneusomies compatible with life and usually involves a deletion of the terminal chromosomal region. However, the mechanisms implicated in the stabilization of terminal deletions are not well understood. In this study, we analyzed a girl with moderate mental retardation who had a cytogenetically visible terminal 18q deletion. In order to characterize the breakpoint in the terminal 18q region, we used fluorescence In situ hybridization (FISH) with bacterial artificial chromosomes (BACs) and pan-telomeric probes and also the array technique based on comparative genomic hybridization (array-CGH). FISH with pan-telomeric probes revealed no signal in the terminal region of the deleted chromosome, indicating the absence of normal telomere repeat (TTAGGG)n sequences in 18q. We suggest that neo-telomere formation by chromosome healing was involved in the repair and stabilization of this terminal deletion. (C) 2010 Elsevier Masson SAS. All rights reserved.

Predictive Factors for Positive Surgical Margins and Their Locations After Robot-Assisted Laparoscopic Radical Prostatectomy

Background: Positive surgical margin (PSM) after radical prostatectomy (RP) has been shown to be an independent predictive factor for cancer recurrence. Several investigations have correlated clinical and histopathologic findings with surgical margin status after open RP. However, few studies have addressed the predictive factors for PSM after robot-assisted laparoscopic RP (RARP). Objective: We sought to identify predictive factors for PSMs and their locations after RARP. Design, setting, and participants: We prospectively analyzed 876 consecutive patients who underwent RARP from January 2008 to May 2009. Intervention: All patients underwent RARP performed by a single surgeon with previous experience of > 1500 cases. Measurements: Stepwise logistic regression was used to identify potential predictive factors for PSM. Three logistic regression models were built: (1) one using preoperative variables only, (2) another using all variables (preoperative, intraoperative, and postoperative) combined, and (3) one created to identify potential predictive factors for PSM location. Preoperative variables entered into the models included age, body mass index (BMI), prostate-specific antigen, clinical stage, number of positive cores, percentage of positive cores, and American Urological Association symptom score. Intra-and postoperative variables analyzed were type of nerve sparing, presence of median lobe, percentage of tumor in the surgical specimen, gland size, histopathologic findings, pathologic stage, and pathologic Gleason grade. Results and limitations: In the multivariable analysis including preoperative variables, clinical stage was the only independent predictive factor for PSM, with a higher PSM rate for T3 versus T1c (odds ratio [OR]: 10.7; 95% confidence interval [CI], 2.6-43.8) and for T2 versus T1c (OR: 2.9; 95% CI, 1.9-4.6). Considering pre-, intra-, and postoperative variables combined, percentage of tumor, pathologic stage, and pathologic Gleason score were associated with increased risk of PSM in the univariable analysis (p < 0.001 for all variables). However, in the multivariable analysis, pathologic stage (pT2 vs pT1; OR: 2.9; 95% CI, 1.9-4.6) and percentage of tumor in the surgical specimen (OR: 8.7; 95% CI, 2.2-34.5; p = 0.0022) were the only independent predictive factors for PSM. Finally, BMI was shown to be an independent predictive factor(OR: 1.1; 95% CI, 1.0-1.3; p = 0.0119) for apical PSMs, with increasing BMI predicting higher incidence of apex location. Because most of our patients were referred from other centers, the biopsy technique and the number of cores were not standardized in our series. Conclusions: Clinical stage was the only preoperative variable independently associated with PSM after RARP. Pathologic stage and percentage of tumor in the surgical specimen were identified as independent predictive factors for PSMs when analyzing pre-, intra-, and postoperative variables combined. BMI was shown to be an independent predictive factor for apical PSMs. (C) 2010 European Association of Urology. Published by Elsevier B. V. All rights reserved.

Lichen planus sialadenitis: a mucosal analog of lichen planopilaris and lichen planoporitis

Lichen planus (LP) is the most prevalent dermatological disorder with oral manifestation. Oral lesions comprise a broad spectrum of clinical presentations. We report the case of a 56-year-old woman who presented erosive LP on the buccal and lower lip mucosae. Besides typical erosions, small white keratotic papules on an erythematosus background on the lower lip mucosa were observed. Biopsy of lower lip lesions showed an unusual histopathological presentation consisting of a lichenoid inflammation targeted to salivary gland ducts. This is probably a salivary gland analog of lichen planopilaris and lichen planoporitis.

Extending the Phenotype of Monosomy 1p36 Syndrome and Mapping of a Critical Region for Obesity and Hyperphagia

Rearrangements of 1p36 are the most frequently detected abnormalities in diagnostic testing for chromosomal cryptic imbalances and include variably sized simple terminal deletions, derivative chromosomes, interstitial deletions, and complex rearrangements. These rearrangements result in the specific pattern of malformation and neurodevelopmental disabilities that characterizes monosomy 1p36 syndrome. Thus far, no individual gene within this region has been conclusively determined to be causative of any component of the phenotype. Nor is it known if the rearrangements convey phenotypes via a haploinsufficiency mechanism or through a position effect. We have used multiplex ligation-dependent probe amplification to screen for deletions of 1p36 in a group of 154 hyperphagic and overweight/obese, PWS negative individuals, and in a separate group of 83 patients initially sent to investigate a variety of other conditions. The strategy allowed the identification and delineation of rearrangements in nine subjects with a wide spectrum of clinical presentations. Our work reinforces the association of monosomy 1p36 and obesity and hyperphagia, and further suggests that these features may be associated with non-classical manifestations of this disorder in addition to a submicroscopic deletion of similar to 2-3 Mb in size. Multiplex ligation probe amplification using the monosomy 1p36 syndrome-specific kit coupled to the subtelomeric kit is an effective approach to identify and delineate rearrangements at 1p36. (C) 2009 Wiley-Liss, Inc.

Pituitary Apoplexy After a Single Dose of Long-Acting Octreotide

Pituitary apoplexy (PA) is a rare and potentially life-threatening syndrome resulting from an acute infarction or hemorrhage of the pituitary gland. Although the pathogenesis is not fully understood, some predisposing factors such as pituitary stimulation tests, diabetes mellitus, anticoagulant or antiplatelet aggregation therapy, head trauma, and high blood pressure may play a role in its pathophysiology. Octreotide is the mainstay of medical treatment for acromegaly. The majority of reported complications of octreotide therapy are gastrointestinal. We report the case of a 51-year-old acromegalic woman who developed pituitary apoplexy within the context of high blood pressure and a single dose of long-acting octreotide. Our data suggest that the combination of hypertension and octreotide therapy enhances the risk of pituitary apoplexy.

Primary retroperitoneal lipoma: A soft tissue pathology heresy? Report of a case with classic histologic, cytogenetics, and molecular genetic features

Adipose tissue tumors of the retroperitoneum showing no identifiable cytologic atypia are usually classified as lipoma-like well-differentiated liposarcoma. Whether a subset of these tumors represents true examples of retroperitoneal lipoma remains a controversial subject, because the diagnostic liposarcoma cells may be of difficult identification, even after extensive sampling. Herein, we describe a large retroperitoneal lipoma with classic histopathologic, cytogenetic, molecular cytogenetic, and molecular genetic features. Extensive morphologic inspection showed no evidence of cytologic atypia. Cytogenetic analysis performed on fresh tissue material revealed the classic lipoma chromosome t(3;12)(q27;q14-15). Fluorescence in situ hybridization on multiple sections excluded the presence of MDM2 and CDK4 amplification, but showed HMGA2 balanced rearrangement in most cells. Reverse-transcriptase polymerase chain reaction followed by sequencing analysis confirmed the presence of the HMGA2-LPP fusion gene, a characteristic and the most common fusion product found in lipoma. The patient has been followed for 2.5 years without evidence of recurrence or metastasis. These results indicate that retroperitoneal lipomata do exist, but their diagnosis must rely on stringent histologic, cytogenetic, and molecular genetic analysis.

Modulation of cutaneous inflammation induced by ticks in contrasting phenotypes of infestation in bovines

Tick saliva contains molecules that are inoculated at the site of attachment on their hosts in order to modulate local immune responses and facilitate a successful blood meal. Bovines express heritable, contrasting phenotypes of infestations with the cattle tick, Rhipicephalus (Boophilus) microplus: breeds of Bos taurus indicus are significantly note resistant than those of Bos taurus taurus. Tick saliva may contain molecules that interfere with adhesion of leukocytes to endothelium and resistant hosts may mount an inflammatory profile that is more efficient to hamper the tick`s blood meal. We show in vitro that adhesion of peripheral blood mononuclear cells to monolayers of cytokine-activated bovine umbilical endothelial cells was significantly inhibited by tick saliva. The inflammatory response to bites of adults of R. microplus mounted by genetically resistant and susceptible bovine hosts managed in the same pasture was investigated in vivo. The inflammatory infiltrates and levels of message coding for adhesion molecules were measured in biopsies of tick-bitten and control skin taken when animals of both breeds were exposed to low and high tick infestations. Histological studies reveal that cutaneous reactions of resistant hosts to bites of adult ticks contained significantly more basophils and eosinophils compared with reactions of the susceptible breed. Expression of the adhesion molecules - intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and P-selectin - was higher in adult-infested skin of susceptible hosts undergoing low infestations compared to resistant hosts; when host was exposed to high infestations expression of these adhesion molecules was down-regulated in both phenotypes of infestations. Expression of leukocyte adhesion glycoprotein-1 (LFA-1) was higher in skin from susceptible hosts undergoing low or high infestations compared to resistant hosts. Conversely, higher levels of E-selectin, which promotes adhesion of memory T cells, were expressed in skin of resistant animals. This finding may explain the resistant host`s ability to mount more rapid and efficient secondary responses that limit hematophagy and infestations. The expression profiles observed for adhesion molecules indicate that there are differences in the kinetics of the inflammatory reactions mounted by resistant and susceptible hosts and the balance between tick and host is affected by the number of tick bites a host receives. We show that the contrasting phenotypes of infestations seen in bovines infested with R. microplus are correlated with differences in the cellular and molecular composition of inflammatory infiltrates elicited by bites with adult ticks. (C) 2009 Published by Elsevier B.V.

Karyotype variability in KP1(+) and KP1(-) strains of Trypanosoma rangeli isolated in Brazil and Colombia

In the present study, the molecular karyotypes of 12 KP1(+) and KP1(-) Trypanosoma rangeli strains were determined and 10 different molecular markers were hybridized to the chromosomes of the parasite, including seven obtained from T. rangeli [ubiquitin hydrolase (UH), a predicted serine/threonine protein kinase (STK), hexose transporter, hypothetical protein, three anonymous sequences] and three from Trypanosoma cruzi [ubiquitin-conjugating enzyme E2 (UBE2), ribosomal RNA methyltransferase (rRNAmtr), proteasome non-ATPase regulatory subunit 6 (PSMD6)]. Despite intraspecific variation, analysis of the karyotype profiles permitted the division of the T rangeli strains into two groups coinciding with the KP1(+) and KP1(-) genotypes. Southern blot hybridization showed that, except for the hexose transporter probe, all other probes produced distinct patterns able to differentiate the KP1(+) and KP1(-) genotypes. The UH, STK and An-1A04 probes exclusively hybridized to the chromosomes of KP1(+) strains and can be used as markers of this group. In addition, the UBE2, rRNAmtr and PSMD6 markers, which are present in a conserved region in all trypanosomatid species sequenced so far, co-hybridized to the same T. rangeli chromosomal bands, suggesting the occurrence of gene synteny in these species. The finding of distinct molecular karyotypes in KP1(+) and KP1 (-) strains of T rangeli is noteworthy and might be used as a new approach to the study of genetic variability in this parasite. Together with the Southern blot hybridization results, these findings demonstrate that differences at the kDNA level might be associated with variations in nuclear DNA. (c) 2009 Elsevier BY. All rights reserved.

Mars is close to venus - Female reproductive proteins are expressed in the fat body and reproductive tract of honey bee (Apis mellifera L.) drones

Vitellogenin (Vg) and lipophorin (Lp) are lipoproteins which play important roles in female reproductive physiology of insects. Both are actively taken up by growing oocytes and especially Vg and its receptor are considered as female-specifically expressed. The finding that the fat body of in honey bee (Apis mellifera) drones synthesizes Vg and is present in hemolymph has long been viewed as a curiosity. The recent paradigm change concerning the role played by Vg in honey bee life history, especially social division of labor, has now led us to investigate whether a physiological constellation similar to that seen in female reproduction may also be represented in the male sex. By means of Western blot analysis we could show that both Vg and Lp are present in the reproductive tract of adult drones, including the accessory (mucus) glands, but apparently are not secreted. Furthermore, we analyzed the transcript levels of the genes encoding these proteins (vg and lp), as well as their putative receptors (Amvgr and Amlpr) in fat body and accessory glands. Whereas lp, vg and Amlpr transcript levels decreased with age in both tissues. Amvgr mRNA levels increased with age in fat body. To our knowledge this is the first report that vitellogenin and its receptor are co-expressed in the reproductive system of a male insect. We interpret these findings as a cross-sexual transfer of a social physiological trait, associated with the rewiring of the juvenile hormone/vitellogenin circuitry that occurred in the female sex of honey bees. (C) 2010 Elsevier Ltd. All rights reserved.

Polyploidy in atypical grade II choroid plexus papilloma of the posterior fossa

Cytogenetic studies of choroid plexus tumors, particularly for atypical choroid plexus papillomas, have been rarely described. In the present report, the cytogenetic investigation of an atypical choroid plexus papilloma occurring at the posterior fossa of a 16-year-old male is described. Comparative genome hybridization analysis demonstrated gains of genetic material from almost all chromosomes. Chromosome losses involved 19p, regional losses at chromosome X and loss of chromosome Y. The presence of polyploid cells was confirmed by fluorescence in situ hybridization analysis with probes directed to centromeric regions. Furthermore, the microscopic analysis of cultures showed nuclear buds, nucleoplasmic bridges, and micronuclei in 23% of tumor cells suggesting the presence of complex chromosomal abnormalities. Previous cytogenetic studies on choroid plexus papillomas showed either normal, hypodiploid or hyperdiploid karyotypes. To the best of our knowledge, this is the first report of polyploidy in choroid plexus papilloma of intermediate malignancy grade. Although the mechanisms beneath such genome duplication remain to be elucidated, the observed abnormal nuclear shapes indicate constant restructuring of the tumor`s genome and deserves further investigation.

Assessing Interethnic Admixture Using an X-Linked Insertion-Deletion Multiplex

In this study, a PCR multiplex was optimized, allowing the simultaneous analysis of 13 X-chromosome Insertion/deletion polymorphisms (INDELs). Genetic variation observed in Africans, Europeans, and Native Americans reveals high inter-population variability. The estimated proportions of X-chromosomes in an admixed population from the Brazilian Amazon region show a predominant Amerindian contribution (congruent to 41%), followed by European (congruent to 32%) and African (congruent to 27%) contributions. The proportion of Amerindian contribution based on X-linked data is similar to the expected value based on mtDNA and Y-chromosome information. The accuracy for assessing interethnic admixture, and the high differentiation between African, European, and Native American populations, demonstrates the suitability of this INDEL set to measure ancestry proportions in three-hybrid populations, as it is the case of Latin American populations. Am. J. Hum. Biol. 21:707-709, 2009. (C) 2009 Wiley-Liss, Inc.

Translocations t(X;14)(q28;q11) and t(Y;14)(q12;q11) in T-cell prolymphocytic leukemia

P>We report a case of T-cell prolymphocytic leukemia (T-PLL) in a 41-year-old male. Classical cytogenetic, spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) studies of a blood sample obtained at diagnosis revealed the co-existence of t(X;14)(q28;q11), t(Y;14)(q12;q11) and a ring chromosome derivated from i(8)(q10). Immunophenotypic studies revealed involvement of T-cell lineage, with proliferation of CD4(-) CD8(+). The co-existence of two translocations involving both sex chromosomes in a case of T-PLL is rare. Chromosomal instability associated with the disease progression may have allowed the emergence of cell clones with translocations involving the sex chromosomes and the ring chromosome observed.