Diagnostic utility of immunohistochemistry in distinguishing trichoepithelioma and basal cell carcinoma: evaluation using tissue microarray samples

Trichoepithelioma is a benign neoplasm that shares both clinical and histological features with basal cell carcinoma. It is important to distinguish these neoplasms because they require different clinical behavior and therapeutic planning. Many studies have addressed the use of immunohistochemistry to improve the differential diagnosis of these tumors. These studies present conflicting results when addressing the same markers, probably owing to the small number of basaloid tumors that comprised their studies, which generally did not exceed 50 cases. We built a tissue microarray with 162 trichoepithelioma and 328 basal cell carcinoma biopsies and tested a panel of immune markers composed of CD34, CD10, epithelial membrane antigen, Bcl-2, cytokeratins 15 and 20 and D2-40. The results were analyzed using multiple linear and logistic regression models. This analysis revealed a model that could differentiate trichoepithelioma from basal cell carcinoma in 36% of the cases. The panel of immunohistochemical markers required to differentiate between these tumors was composed of CD10, cytokeratin 15, cytokeratin 20 and D2-40. The results obtained in this work were generated from a large number of biopsies and resulted in the confirmation of overlapping epithelial and stromal immunohistochemical profiles from these basaloid tumors. The results also corroborate the point of view that trichoepithelioma and basal cell carcinoma tumors represent two different points in the differentiation of a single cell type. Despite the use of panels of immune markers, histopathological criteria associated with clinical data certainly remain the best guideline for the differential diagnosis of trichoepithelioma and basal cell carcinoma. Modern Pathology (2012) 25, 1345-1353; doi: 10.1038/modpathol.2012.96; published online 8 June 2012

Breast imaging: is the sonographic descriptor of orientation valid for magnetic resonance imaging?

Purpose: To evaluate if the Breast Imaging Reporting and Data System (BI-RADS) ultrasound descriptor of orientation can be used in magnetic resonance imaging (MRI). Materials and Methods: We conducted a retrospective study to evaluate breast mass lesions identified by MRI from 2008 to 2010 who had ultrasound (US) and histopathologic confirmation. Lesions were measured in the craniocaudal (CC), anteroposterior (AP), and transverse (T) axes and classified as having a nonparallel orientation, longest axis perpendicular to Cooper's ligaments, or in a parallel orientation when the longest axis is parallel to Cooper's ligaments. The MR image data were correlated with the US orientation according to BI-RADS and histopathological diagnosis. Results: We evaluated 71 lesions in 64 patients. On MRI, 27 lesions (38.0%) were nonparallel (8 benign and 19 malignant), and 44 lesions (62.0%) were parallel (33 benign and 11 malignant). There was significant agreement between the lesion orientation on US and MRI (kappa value = 0.901). The positive predictive values (PPV) for parallel orientation malignancy on MR and US imaging were 70.4% and 73.1%, respectively. Conclusion: A descriptor of orientation for breast lesions can be used on MRI with PPV for malignant lesions similar to US. J. Magn. Reson. Imaging 2012; 36:13831388. (C) 2012 Wiley Periodicals, Inc.

In vitro influence of the extracellular matrix in myoepithelial cells stimulated by malignant conditioned medium

In order to investigate the role of myoepithelial cell and tumor microenvironment in salivary gland neoplasma, we have performed a study towards the effect of different extracellular matrix proteins (basement membrane matrix, type I collagen and fibronectin) on morphology and differentiation of benign myoepithelial cells from pleomorphic adenoma cultured with malignant cell culture medium from squamous cell carcinoma. We have also analyzed the expression of alpha-smooth muscle actin (alpha-SMA) and FGF-2 by immunofluorescence and qPCR. Our immunofluorescence results, supported by qPCR analysis, demonstrated that alpha-SMA and FGF-2 were upregulated in the benign myoepithelial cells from pleomorphic adenoma in all studied conditions on fibronectin substratum. However, the myoepithelial cells on fibronectin substratum did not alter their morphology under malignant conditioned medium stimulation and exhibited a stellate morphology and, occasionally focal adhesions with the substratum. In summary, our data demonstrated that the extracellular matrix exerts an important role in the morphology of the benign myoepithelial cells by the presence of focal adhesions and also inducing increase FGF-2 and alpha-SMA expression by these cells, especially in the fibronectin substratum. (C) 2011 Elsevier Ltd. All rights reserved.

Infiltration of a mixture of immune cells may be related to good prognosis in patients with differentiated thyroid carcinoma

Objective Immune responses against differentiated thyroid carcinomas (DTC) have long been recognized. We aimed to investigate the role of immune cell infiltration in the progression of DTC. Design We studied 398 patients 253 with papillary and 13 with follicular thyroid cancers, as well as 132 with nonmalignant tissues. Patients and measurements Immune cell infiltration was identified using CD3, CD4, CD8, CD20, CD68 and FoxP3 immunohistochemical markers. In addition, we assessed colocalization of CD4 and IL-17 to identify Th17 lymphocytic infiltration and colocalization of CD33 and CD11b to identify infiltration of myeloid-derived suppressor cells (MDSC). Results Immune cells infiltrated malignant tissues more often than benign lesions. The presence of chronic lymphocytic thyroiditis (CLT) concurrent to DTC, CD68+, CD4+, CD8+, CD20+, FoxP3+ and Th17 lymphocytes but not MDSCs was associated with clinical and pathological features of lower tumour aggressiveness and a more favourable patient outcome. A log-rank test confirmed an association between concurrent CLT, tumour-associated macrophage infiltration, and CD8+ lymphocytes and an increased in disease-free survival, suggesting that evidence of these immune reactions is associated with a favourable prognosis. Conclusion Our data suggest that the tumour or peri-tumoural microenvironment may act to modify the observed pattern of immune response. Immune cell infiltration and the presence of concurrent CLT helped characterize specific tumour histotypes associated with favourable prognostic features.

Surgical management of dentigerous cyst and keratocystic odontogenic tumor in children: a conservative approach and 7-year follow-up

Dentigerous cyst (DC) is one of the most common odontogenic cysts of the jaws and rarely recurs. On the other hand, keratocystic odontogenic tumor (KCOT), formerly known as odontogenic keratocyst (OKC), is considered a benign unicystic or multicystic intraosseous neoplasm and one of the most aggressive odontogenic lesions presenting relatively high recurrence rate and a tendency to invade adjacent tissue. Two cases of these odontogenic lesions occurring in children are presented. They were very similar in clinical and radiographic characteristics, and both were treated by marsupialization. The treatment was chosen in order to preserve the associated permanent teeth with complementary orthodontic treatment to direct eruption of the associated permanent teeth. At 7-years of follow-up, none of the cases showed recurrence.

Myasthenia gravis and neuromyelitis optica spectrum disorder A multicenter study of 16 patients

Objective: To describe 16 patients with a coincidence of 2 rare diseases: aquaporin-4 antibody (AQP4-Ab)-mediated neuromyelitis optica spectrum disorder (AQP4-NMOSD) and acetylcholine receptor antibody (AChR-Ab)-mediated myasthenia gravis (AChR-MG). Methods: The clinical details and antibody results of 16 patients with AChR-MG and AQP4-NMOSD were analyzed retrospectively. Results: All had early-onset AChR-MG, the majority with mild generalized disease, and a high proportion achieved remission. Fifteen were female; 11 were Caucasian. In 14/16, the MG preceded NMOSD (median interval: 16 years) and 11 of these had had a thymectomy although 1 only after NMOSD onset. In 4/5 patients tested, AQP4-Abs were detectable between 4 and 16 years prior to disease onset, including 2 patients with detectable AQP4-Abs prior to thymectomy. AChR-Abs decreased and the AQP4-Ab levels increased over time in concordance with the relevant disease. AChR-Abs were detectable at NMOSD onset in the one sample available from 1 of the 2 patients with NMOSD before MG. Conclusions: Although both conditions are rare, the association of MG and NMOSD occurs much more frequently than by chance and the MG appears to follow a benign course. AChR-Abs or AQP4-Abs may be present years before onset of the relevant disease and the antibody titers against AQP4 and AChR tend to change in opposite directions. Although most cases had MG prior to NMOSD onset, and had undergone thymectomy, NMOSD can occur first and in patients who have not had their thymus removed. Neurology (R) 2012;78:1601-1607

Vascular leiomyoma in the oral cavity

The aim of this study was to examine a case report of vascular leiomyoma located in the oral mucosa of the oral cavity. Vascular leiomyoma is a benign tumor arising from smooth muscle. One factor that makes vascular leiomyomas in the oral cavity rare is that there is little smooth muscle in the mouth. The most common histological subtype in the oral cavity is the vascular subtype. The greatest difficulty in histological diagnosis of this entity is the similarity in morphology with other malignancies, particularly of neural or fibroblastic lineage. Wide surgical resection is the only treatment reported in the literature with good results. The recurrence rate is very low if complete resection is achieved. The study of rare or unusual lesions is very important for the clinical diagnosis of vascular leiomyoma

Central giant cell granuloma

Background: Central giant cell granuloma is a benign condition of the jaws which may present an aggressive behavior. Case report: A 9-year-old boy was complaining of swelling in the floor of the mouth. A solid swelling was observed in the area of the lower incisors. From the radiographic exam, we observed a radiolucent image in the mandibular bone with well-defined limits extending from the apical region of tooth 33 to the apical region of tooth 42. Discussion: Due to the diagnosis and the age of the patient, we chose a conservative treatment, administering subcutaneous injections of calcitonin. During this treatment, no reduction to the lesion was observed. Therefore, we chose to treat the lesion with triamcinolone acetonide. Monthly follow-ups demonstrated good lesion reduction and the absence of any clinical symptoms during the first 2 years. After a 3-year follow-up, the patient returned, presenting mobility of the lower incisors. A significant increase in the size of the lesion was observed. After a biopsy, with the removal of tissuewhich had the appearance of a cyst capsule, microscopic analyses were found to be compatible with a secondarily infected cyst. Two months following this procedure, the patient did not present tooth mobility anymore and the oral mucosa presented a normal aspect. Following a radiographic exam, full lesion repair was observed. These conservative treatments should be the first option in cases of central giant cell granuloma and the patient must be observed for a long period of time, until no further clinical or radiographic signs of lesions are observed

Tratamiento conservador de tumor epitelial odontogénico calcificante asociado al canino inferior retenido: relato de caso clínico

The calcifying epithelial odontogenic tumour is a rare benign odontogenic neoplasm that accounts for approximately 1% of all odontogenic tumours. They are mainly located in the premolar/molar mandibular region, and are associated with an unerupted molar tooth. We present a literature review of the clinical, radiographic, pathological findings and treatment options of the calcifying epithelial odontogenic tumour, as well as describing the case of an calcifying epithelial odontogenic tumour associated with an impacted right mandibular in a 32-year-old male patient, who was treated conservatively, without no sign of recurrence of the lesion after five years.

Electroconvulsive therapy use in adolescents: a systematic review

Abstract Background Considered as a moment of psychological vulnerability, adolescence is remarkably a risky period for the development of psychopathologies, when the choice of the correct therapeutic approach is crucial for achieving remission. One of the researched therapies in this case is electroconvulsive therapy (ECT). The present study reviews the recent and classical aspects regarding ECT use in adolescents. Methods Systematic review, performed in November 2012, conformed to the PRISMA statement. Results From the 212 retrieved articles, only 39 were included in the final sample. The reviewed studies bring indications of ECT use in adolescents, evaluate the efficiency of this therapy regarding remission, and explore the potential risks and complications of the procedure. Conclusions ECT use in adolescents is considered a highly efficient option for treating several psychiatric disorders, achieving high remission rates, and presenting few and relatively benign adverse effects. Risks can be mitigated by the correct use of the technique and are considered minimal when compared to the efficiency of ECT in treating psychopathologies.

Spontaneous combined rupture of a pelvicalyceal cyst into the collector system and retroperitoneal space during the acquisition of computed tomography scan images: a case report

Abstract Introduction Pelvicalyceal cysts are common findings in autopsies and can manifest with a variety of patterns. These cystic lesions are usually a benign entity with no clinical significance unless they enlarge enough to cause compression of the adjacent collecting system and consequently obstructive uropathy. Few cases of the spontaneous rupture of pelvicalyceal renal cysts have been published and to the best of our knowledge there is no report of a combined rupture to collector system and retroperitoneal space documented during a multiphase computed tomography. Case presentation We report a case of a ‘real-time’ spontaneous rupture of a pelvicalyceal cyst into the collecting system with fistulization into the retroperitoneum. The patient was a 78-year-old Caucasian man with a previous history of renal stones and a large pelvicalyceal renal cyst who was admitted to our Emergency department with acute right flank pain. A multiphase computed tomography was performed and the pre-contrast images demonstrated a right pelvicalyceal renal cyst measuring 12.0 × 6.1cm in the lower pole causing moderate dilation of the upper right renal collection system. In addition, a partially obstructive stone on the left distal ureter with mild left hydronephrosis was noted. The nephrographic phase did not add any new information. The excretory phase (10-minute delay) demonstrated a spontaneous rupture of the cyst into the pelvicalyceal system with posterior fistulization into the retroperitoneal space. Conclusion In this case study we present time-related changes of a rare pelvicalyceal cyst complication, which to the best of our knowledge has fortunately not been previously documented. Analysis of the sequential images and comparison with an earlier scan allowed us to better understand the physiopathological process of the rupture, the clinical presentation and to elaborate hypotheses for its etiopathogenesis.

Trace elements as tumor biomarkers and prognostic factors in breast cancer: a study through energy dispersive x-ray fluorescence

Abstract Background The application and better understanding of traditional and new breast tumor biomarkers and prognostic factors are increasing due to the fact that they are able to identify individuals at high risk of breast cancer, who may benefit from preventive interventions. Also, biomarkers can make possible for physicians to design an individualized treatment for each patient. Previous studies showed that trace elements (TEs) determined by X-Ray Fluorescence (XRF) techniques are found in significantly higher concentrations in neoplastic breast tissues (malignant and benign) when compared with normal tissues. The aim of this work was to evaluate the potential of TEs, determined by the use of the Energy Dispersive X-Ray Fluorescence (EDXRF) technique, as biomarkers and prognostic factors in breast cancer. Methods By using EDXRF, we determined Ca, Fe, Cu, and Zn trace elements concentrations in 106 samples of normal and breast cancer tissues. Cut-off values for each TE were determined through Receiver Operating Characteristic (ROC) analysis from the TEs distributions. These values were used to set the positive or negative expression. This expression was subsequently correlated with clinical prognostic factors through Fisher’s exact test and chi-square test. Kaplan Meier survival curves were also evaluated to assess the effect of the expression of TEs in the overall patient survival. Results Concentrations of TEs are higher in neoplastic tissues (malignant and benign) when compared with normal tissues. Results from ROC analysis showed that TEs can be considered a tumor biomarker because, after establishing a cut-off value, it was possible to classify different tissues as normal or neoplastic, as well as different types of cancer. The expression of TEs was found statistically correlated with age and menstrual status. The survival curves estimated by the Kaplan-Meier method showed that patients with positive expression for Cu presented a poor overall survival (p < 0.001). Conclusions This study suggests that TEs expression has a great potential of application as a tumor biomarker, once it was revealed to be an effective tool to distinguish different types of breast tissues and to identify the difference between malignant and benign tumors. The expressions of all TEs were found statistically correlated with well-known prognostic factors for breast cancer. The element copper also showed statistical correlation with overall survival.

Genetic Control of Mosquitoes: population suppression strategies

Over the last two decades, morbidity and mortality from malaria and dengue fever among other pathogens are an increasing Public Health problem. The increase in the geographic distribution of vectors is accompanied by the emergence of viruses and diseases in new areas. There are insufficient specific therapeutic drugs available and there are no reliable vaccines for malaria or dengue, although some progress has been achieved, there is still a long way between its development and actual field use. Most mosquito control measures have failed to achieve their goals, mostly because of the mosquito's great reproductive capacity and genomic flexibility. Chemical control is increasingly restricted due to potential human toxicity, mortality in no target organisms, insecticide resistance, and other environmental impacts. Other strategies for mosquito control are desperately needed. The Sterile Insect Technique (SIT) is a species-specific and environmentally benign method for insect population suppression, it is based on mass rearing, radiation mediated sterilization, and release of a large number of male insects. Releasing of Insects carrying a dominant lethal gene (RIDL) offers a solution to many of the drawbacks of traditional SIT that have limited its application in mosquitoes while maintaining its environmentally friendly and species-specific utility. The self-limiting nature of sterile mosquitoes tends to make the issues related to field use of these somewhat less challenging than for self-spreading systems characteristic of population replacement strategies. They also are closer to field use, so might be appropriate to consider first. The prospect of genetic control methods against mosquito vectored human diseases is rapidly becoming a reality, many decisions will need to be made on a national, regional and international level regarding the biosafety, social, cultural and ethical aspects of the use and deployment of these vector control methods.

Case for diagnosis

Infantile digital fibromatosis or Reye's tumor is a benign fibroproliferative tumor, the etiopathogenesis of which has yet to be fully clarified. It typically presents at birth or in the first year of life and is characterized by a firm, flesh colored or erythematous nodule or nodules located on the digits. These lesions tend to regress spontaneously.

Underexpression of MMP-2 and its regulators, TIMP2, MT1-MMP and IL-8, is associated with prostate cancer

OBJECTIVE: Extracellular matrix homeostasis is strictly maintained by a coordinated balance between the expression of metalloproteinases (MMPs) and their regulators. The purpose of this study was to investigate whether MMP-2 and its specific regulators, TIMP-2, MT1-MMP and IL-8, are expressed in a reproducible, specific pattern and if the profiles are related to prognosis and clinical outcome of prostate cancer (PCa). MATERIALS AND METHODS: MMP-2, TIMP-2, MT1-MMP and IL-8 expression levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) in freshly frozen malignant and benign tissue specimens collected from 79 patients with clinically localized PCa who underwent radical prostatectomies. The control group consisted of 11 patients with benign prostate hyperplasia (BPH). The expression profile of the MMP-2 and its regulators were compared using Gleason scores, pathological stage, pre-operative PSA levels and the final outcome of the PCa. RESULTS: The analysis of 79 specimens of PCa revealed that MMP-2, TIMP-2, MT1-MMP and IL-8 were underexpressed at 60.0%, 72.2%, 62.0% and 65.8%, respectively, in malignant prostatic tissue in relation to BPH samples. Considering the prognostic parameters, we demonstrated that high Gleason score tumors (> 7) overexpressed MMP-2 (p = 0.048) and TIMP-2 (p = 0.021), compared to low Gleason score tumors (< 7). CONCLUSION: We have demonstrated that MMP-2 and its regulators are underexpressed in PCa. Alternatively, overexpression of MMP-2 and TIMP-2 was related to higher Gleason score tumors. We postulate that alterations in metalloproteinase expression may be important in the control of tissue homeostasis related to prostate carcinogenesis and tumor behavior.