Loss of pulp sensitivity and pain as the first symptoms of a Ewing's sarcoma in the right maxillary sinus and alveolar process: report of a case

This case report describes the diagnosis and treatment of a Ewing's sarcoma in the right maxillary sinus and alveolar bone of a 19-year-old female patient. The first clinical symptoms were a loss of sensitivity of the premolars and first molar in the right maxilla and acute pain located in the area of these teeth. Initially, the referring dentist had treated these findings as an acute apical periodontitis with root canal medication. Because swellings on the palatal and buccal aspects of the teeth occurred and could not be treated with incision and drainage, the dentist referred the patient. Cone-beam computed tomography revealed a proliferation of soft tissue in the right maxillary sinus, with a radiopaque material at the tip of the mesiobuccal root of the first molar and resorptive signs of the mesiobuccal and distobuccal roots of the first molar. The palatal cortical bone of the right alveolar process seemed to be intact. After explorative surgery with biopsies from the buccal, palatal, and sinus proliferation areas, the pathologist diagnosed the lesion as a Ewing's sarcoma. Treatment of the patient consisted of initial chemotherapy, hemimaxillectomy, and postsurgical chemoradiotherapy.

Illusions of fusions: assessing cervical vertebral fusion on lateral cephalograms, multidetector computed tomographs, and cone-beam computed tomographs

INTRODUCTION The aims of this study were to compare lateral cephalograms with other radiologic methods for diagnosing suspected fusions of the cervical spine and to validate the assessment of congenital fusions and osteoarthritic changes against the anatomic truth. METHODS Four cadaver heads were selected with fusion of vertebrae C2 and C3 seen on a lateral cephalogram. Multidetector computed tomography (MDCT) and cone-beam computed tomography (CBCT) were performed and assessed by 5 general radiologists and 5 oral radiologists, respectively. Vertebrae C2 and C3 were examined for osseous fusions, and the left and right facet joints were diagnosed for osteoarthritis. Subsequently, the C2 and C3 were macerated and appraised by a pathologist. Descriptive analysis was performed, and interrater agreements between and within the groups were computed. RESULTS All macerated specimens showed osteoarthritic findings of varying degrees, but no congenital bony fusion. All observers agreed that no fusion was found on MDCT or CBCT. They disagreed on the prevalence of osteoarthritic deformities (general radiologists/MDCT, 100%; oral radiologists/CBCT, 93.3%) and joint space assessment in the facet joints (kappa = 0.452). The agreement within the rater groups differed considerably (general radiologists/MDCT, kappa = 0.612; oral radiologists/CBCT, kappa = 0.240). CONCLUSIONS Lateral cephalograms do not provide dependable data to assess the cervical spine for fusions and cause false-positive detections. Both MDCT interpreted by general radiologists and CBCT interpreted by oral radiologists are reliable methods to exclude potential fusions. Degenerative osteoarthritic changes are diagnosed more accurately and consistently by general radiologists evaluating MDCT.

Pathology working group review of histopathologic specimens from three laboratory studies of diclofenac in trout.

While the pathology peer review/pathology working group (PWG) model has long been used in mammalian toxicologic pathology to ensure the accuracy, consistency, and objectivity of histopathology data, application of this paradigm to ecotoxicological studies has thus far been limited. In the current project, the PWG approach was used to evaluate histopathologic sections of gills, liver, kidney, and/or intestines from three previously published studies of diclofenac in trout, among which there was substantial variation in the reported histopathologic findings. The main objectives of this review process were to investigate and potentially reconcile these interstudy differences, and based on the results, to establish an appropriate no observed effect concentration (NOEC). Following a complete examination of all histologic sections and original diagnoses by a single experienced fish pathologist (pathology peer review), a two-day PWG session was conducted to allow members of a four-person expert panel to determine the extent of treatment-related findings in each of the three trout studies. The PWG was performed according to the United States Environmental Protection Agency (US EPA) Pesticide Regulation (PR) 94-5 (EPA Pesticide Regulation, 1994). In accordance with standard procedures, the PWG review was conducted by the non-voting chairperson in a manner intended to minimize bias, and thus during the evaluation, the four voting panelists were unaware of the treatment group status of individual fish and the original diagnoses associated with the histologic sections. Based on the results of this review, findings related to diclofenac exposure included minimal to slightly increased thickening of the gill filament tips in fish exposed to the highest concentration tested (1,000 μg/L), plus a previously undiagnosed finding, decreased hepatic glycogen, which also occurred at the 1,000 μg/L dose level. The panel found little evidence to support other reported effects of diclofenac in trout, and thus the overall NOEC was determined to be >320 μg/L. By consensus, the PWG panel was able to identify diagnostic inconsistencies among and within the three prior studies; therefore this exercise demonstrated the value of the pathology peer review/PWG approach for assessing the reliability of histopathology results that may be used by regulatory agencies for risk assessment.

Rib fractures at postmortem computed tomography (PMCT) validated against the autopsy

To evaluate the sensitivity of postmortem computed tomography (PMCT) in rib fracture detection validated against autopsy. Fifty-one forensic cases underwent a postmortem CT prior to forensic autopsy. Two image readers (radiologist and forensic pathologist) assessed high resolution CT data sets for rib fractures. Correct recognition rates (CRR), sensitivity and specificity values were calculated over all observations as well as individually for every rib and region. Additionally, for partial rib fractures the sensitivity of autopsy was calculated vice versa. 3876 entries in each study protocol (autopsy, PMCT radiologist and PMCT forensic pathologist) were investigated. A total of 690 fractures (autopsy), 491 (PMCT and radiologist) and 559 (PMCT and forensic pathologist) were detected. The CRR was 0.85. Sensitivity and specificity of PMCT for rib fracture detection were 0.63 (0.58 radiologist, 0.68 forensic pathologist) and 0.97 (both readers 0.97), respectively. Low CRR and sensitivity values were obtained for antero-lateral fractures. Partial rib fractures were better detected by PMCT. PMCT has a rather low sensitivity for rib fracture detection when validated against autopsy and indicates that clinical CT may also demonstrate a reasonable number of false negatives. Partial rib fractures often remain undetected at autopsy.

Mitotic figure counts are significantly overestimated in resection specimens of invasive breast carcinomas

Several authors have demonstrated an increased number of mitotic figures in breast cancer resection specimen when compared with biopsy material. This has been ascribed to a sampling artifact where biopsies are (i) either too small to allow formal mitotic figure counting or (ii) not necessarily taken form the proliferating tumor periphery. Herein, we propose a different explanation for this phenomenon. Biopsy and resection material of 52 invasive ductal carcinomas was studied. We counted mitotic figures in 10 representative high power fields and quantified MIB-1 immunohistochemistry by visual estimation, counting and image analysis. We found that mitotic figures were elevated by more than three-fold on average in resection specimen over biopsy material from the same tumors (20±6 vs 6±2 mitoses per 10 high power fields, P=0.008), and that this resulted in a relative diminution of post-metaphase figures (anaphase/telophase), which made up 7% of all mitotic figures in biopsies but only 3% in resection specimen (P<0.005). At the same time, the percentages of MIB-1 immunostained tumor cells among total tumor cells were comparable in biopsy and resection material, irrespective of the mode of MIB-1 quantification. Finally, we found no association between the size of the biopsy material and the relative increase of mitotic figures in resection specimen. We propose that the increase in mitotic figures in resection specimen and the significant shift towards metaphase figures is not due to a sampling artifact, but reflects ongoing cell cycle activity in the resected tumor tissue due to fixation delay. The dwindling energy supply will eventually arrest tumor cells in metaphase, where they are readily identified by the diagnostic pathologist. Taken together, we suggest that the rapidly fixed biopsy material better represents true tumor biology and should be privileged as predictive marker of putative response to cytotoxic chemotherapy.

TEMOZOLOMIDE AND BEVACIZUMAB THERAPY IN ADVANCED HEMANGIOPERICYTOMA/ SOLITARY FIBROUS TUMOR

Tumors comprising the spectrum of hemangiopericytoma/ malignant solitary fibrous tumor (HPC/SFT) are thought to arise from fibroblasts and represent a small subset of soft tissue sarcomas. Surgery is typically the treatment of choice for localized disease, with reported 10-year overall survival rates of 54-89% after complete surgical resection. However, for the approximately 20% of HPC/SFT patients who eventually develop local recurrences and/or distant metastases, options for effective treatment are limited and are poorly defined. Alternative therapeutic options are therefore needed for improved palliation and disease control. We hypothesize that HPC/SFT are a spectrum of soft tissue tumors with unique clinical, pathological, and molecular makeup and clinical behavior. HPC/SFT respond to unique therapeutic agents that specifically target aberrations specific to these tumors. We retrospectively reviewed the characteristics and the clinical outcomes for all HPC/SFT patients whose tumor specimens have been reviewed at the MD Anderson Cancer Center from January 1993 to June 2007 by a MD Anderson pathologist and were treated at the institution with available electronic medical records. We identified 128 patients, 79 with primary localized disease and 49 with recurrent and/or metastatic disease. For the 23 patients with advanced HPC/SFT who received adriamycin-based, gemcitabine based, or paclitaxel chemotherapy as first- or second-line therapy, the overall RECIST response rate was 0%. Most patients achieved a brief duration of disease stabilization on chemotherapy, with median progression-free survival (PFS) period of 4.6 months. For the 14 patients with advanced HPC/SFT who received temozolomide and bevacizumab systemic therapy, the overall RECIST response rate was 14%, with the overall Choi response rate of 79%. The median PFS for the cohort was 9.7 months with a median 6-month progression free rate of 78.6%. The most frequently observed toxic effect of temzolomide-bevacizumab therapy was myelosuppression. We have designed a phase II study to evaluate the safety and efficacy of temozolomide-bevaciumab in locally advanced, recurrent, and metastatic HPC/SFT in a prospective manner. Combination therapy with temozolomide and bevacizumab may be a potentially clinically beneficial regimen for advanced HPC/SFT patients.

Pulsed versus continuous wave CO2 laser excisions of 100 oral fibrous hyperplasias: a randomized controlled clinical and histopathological study

BACKGROUND In experimental animal studies, pulsing the CO2 laser beam has been shown to reduce the thermal damage zone of excised oral mucosal tissue. However, there is still controversy over whether this is borne out under clinical conditions. OBJECTIVE To compare the outcome following excisional biopsies of fibrous hyperplasias using a pulsed (cf) versus a continuous wave (cw) CO2 laser mode regarding the thermal damage zone, duration of surgeries, intra- and postoperative complications, postoperative pain sensation, scarring and/or relapse during the initial 6 months. MATERIALS AND METHODS One hundred Swiss-resident patients with a fibrous hyperplasia in their buccal mucosa were randomly assigned to the cw mode (5 W) or the cf mode (140 Hz, 400 microseconds, 33 mJ, 4.62 W) group. All excisions were performed by one single oral surgeon. Postoperative pain (2 weeks) was recorded by visual analogue scale (VAS; ranging from 0 to 100). Intake of analgesics and postoperative complications were recorded in a standardized study form. The maximum width of the collateral thermal damage zone was measured (µm) in excision specimens by one pathologist. Intraoral photographs at 6-month follow-up examinations were evaluated regarding scarring (yes/no). RESULTS Median duration of the excision was 65 seconds in the cw and 81 seconds in the cf group (P = 0.13). Intraoperative bleeding occurred in 16.3% of the patients in the cw and 17.7% of the cf group. The median value of the thermal damage zone was 161(±228) μm in the cw and 152(± 105) μm in the cf group (P = 0.68). The reported postoperative complications included swelling in 19% and minor bleeding in 6% without significant differences between the two laser modes. When comparing each day separately or the combined mean VAS scores of both groups between Days 1-3, 1-7, and 1-15, there were no significant differences. However, more patients of the cw group (25%) took analgesics than patients of the cf group (9.8%) resulting in a borderline significance (P = 0.04). Scarring at the excision site was found in 50.6% of 77 patients after 6 months, and more scars were identified in cases treated with the cf mode (P = 0.03). CONCLUSIONS Excision of fibrous hyperplasias performed with a CO2 laser demonstrated a good clinical outcome and long-term predictability with a low risk of recurrence regardless of the laser mode (cf or cw) used. Scarring after 6 months was only seen in 50.6% of the cases and was slightly more frequent in the cf mode group. Based on the findings of the present study, a safety border of 1 mm appears sufficient for both laser modes especially when performing a biopsy of a suspicious soft tissue lesion to ensure a proper histopathological examination.

Bilateral necrotizing sialometaplasia of the hard palate in a patient with bulimia: a case report and review of the literature.

Necrotizing sialometaplasia (NS) is a rare and benign lesion that mostly affects the posterior hard palate. Its importance resides in its clinical and microscopic characteristics, which can closely mimic malignant neoplasias, in particular oral squamous cell carcinoma and mucoepidermoid carcinoma. Accurate histopathologic evaluation of an incisional biopsy is considered as the diagnostic gold standard. NS lesions heal spontaneously within weeks, and no further treatment is necessary. We report a case of a bilateral palatal NS in a 22-yearold woman with bulimia, where an incisional biopsy confirmed the clinical diagnosis. The different clinical stages of the lesions from onset to resolution and the possible etiologic factors are described in detail, as well as a discussion of the differential diagnoses of palatal ulcers. When taking a biopsy from suspicious oral lesions, care has to be taken that an appropriate tissue sample is harvested, and the histopathologic analysis is performed by an experienced pathologist to establish a correct diagnosis.

Surgical treatments for esophageal cancers.

The following, from the 12th OESO World Conference: Cancers of the Esophagus, includes commentaries on the role of the nurse in preparation of esophageal resection (ER); the management of patients who develop high-grade dysplasia after having undergone Nissen fundoplication; the trajectory of care for the patient with esophageal cancer; the influence of the site of tumor in the choice of treatment; the best location for esophagogastrostomy; management of chylous leak after esophagectomy; the optimal approach to manage thoracic esophageal leak after esophagectomy; the choice for operational approach in surgery of cardioesophageal crossing; the advantages of robot esophagectomy; the place of open esophagectomy; the advantages of esophagectomy compared to definitive chemoradiotherapy; the pathologist report in the resected specimen; the best way to manage patients with unsuspected positive microscopic margin after ER; enhanced recovery after surgery for ER: expedited care protocols; and long-term quality of life in patients following esophagectomy.

Sudden cardiac death in forensic medicine – Swiss recommendations for a multidisciplinary approach

Sudden cardiac death (SCD) is by definition unexpected and cardiac in nature. The investigation is almost invariably performed by a forensic pathologist. Under these circumstances the role of the forensic pathologist is twofold: (1.) to determine rapidly and efficiently the cause and manner of death and (2.) to initiate a multidisciplinary process in order to prevent further deaths in existing family members. If the death is determined to be due to "natural" causes the district attorney in charge often refuses further examinations. However, additional examinations, i.e. extensive histopathological investigations and/or molecular genetic analyses, are necessary in many cases to clarify the cause of death. The Swiss Society of Legal Medicine created a multidisciplinary working group together with clinical and molecular geneticists and cardiologists in the hope of harmonising the approach to investigate SCD. The aim of this paper is to close the gap between the Swiss recommendations for routine forensic post-mortem cardiac examination and clinical recommendations for genetic testing of inherited cardiac diseases; this is in order to optimise the diagnostic procedures and preventive measures for living family members. The key points of the recommendations are (1.) the forensic autopsy procedure for all SCD victims under 40 years of age, (2.) the collection and storage of adequate samples for genetic testing, (3.) communication with the families, and (4.) a multidisciplinary approach including cardiogenetic counselling.

Nonlesions, misdiagnoses, missed diagnoses, and other interpretive challenges in fish histopathology studies: a guide for investigators, authors, reviewers, and readers.

Differentiating salient histopathologic changes from normal anatomic features or tissue artifacts can be decidedly challenging, especially for the novice fish pathologist. As a consequence, findings of questionable accuracy may be reported inadvertently, and the potential negative impacts of publishing inaccurate histopathologic interpretations are not always fully appreciated. The objectives of this article are to illustrate a number of specific morphologic findings in commonly examined fish tissues (e.g., gills, liver, kidney, and gonads) that are frequently either misdiagnosed or underdiagnosed, and to address related issues involving the interpretation of histopathologic data. To enhance the utility of this article as a guide, photomicrographs of normal and abnormal specimens are presented. General recommendations for generating and publishing results from histopathology studies are additionally provided. It is hoped that the furnished information will be a useful resource for manuscript generation, by helping authors, reviewers, and readers to critically assess fish histopathologic data.

The Right to Die Debate: The Demonization of Dr. Kevorkian and the Creation of a Moral Panic Surrounding Physician-Assisted Suicide in the United States

The Right to Die Debate is a recent but highly controversial moral matter. In particular, physician-assisted suicide (PAS) is an issue that has been evaded by the medical community for years. As of 1990, most states had never encountered the issue before and therefore did not have any laws in place to prohibit PAS (Strate et. al, 2005). Dr. Jack Kevorkian, a retired pathologist from Royal Oak Michigan was the first to publicly address PAS. He brought the issue into the limelight through a bizarre and crude series of assisted deaths that had a lasting impact on not only the Right to Die Debate as whole, but on public policy and both federal and state governmental agendas. This study focuses on the way in which the media, in particular the New York Times (NYT) has portrayed Dr. Jack Kevorkian as incompetent, morally culpable and in an overall negative light in the past twenty years. Applying Stanley Cohen’s 1972 theory of moral panic, a content analysis of NYT media publications between 1990 and 1999 supports Cohen’s theory and reveals that the media has created a moral panic surrounding Kevorkian. This has in turn led to public policy that prevents both terminally ill individuals and their doctors from having a desirable choice; that of voluntary euthanasia and PAS.

Infrared microspectroscopy of inflammatory process and colon tumors.

According to the last global burden of disease published by the World Health Organization, tumors were the third leading cause of death worldwide in 2004. Among the different types of tumors, colorectal cancer ranks as the fourth most lethal. To date, tumor diagnosis is based mainly on the identification of morphological changes in tissues. Considering that these changes appears after many biochemical reactions, the development of vibrational techniques may contribute to the early detection of tumors, since they are able to detect such reactions. The present study aimed to develop a methodology based on infrared microspectroscopy to characterize colon samples, providing complementary information to the pathologist and facilitating the early diagnosis of tumors. The study groups were composed by human colon samples obtained from paraffin-embedded biopsies. The groups are divided in normal (n=20), inflammation (n=17) and tumor (n=18). Two adjacent slices were acquired from each block. The first one was subjected to chemical dewaxing and H&E staining. The infrared imaging was performed on the second slice, which was not dewaxed or stained. A computational preprocessing methodology was employed to identify the paraffin in the images and to perform spectral baseline correction. Such methodology was adapted to include two types of spectral quality control. Afterwards the preprocessing step, spectra belonging to the same image were analyzed and grouped according to their biochemical similarities. One pathologist associated each obtained group with some histological structure based on the H&E stained slice. Such analysis highlighted the biochemical differences between the three studied groups. Results showed that severe inflammation presents biochemical features similar to the tumors ones, indicating that tumors can develop from inflammatory process. A spectral database was constructed containing the biochemical information identified in the previous step. Spectra obtained from new samples were confronted with the database information, leading to their classification into one of the three groups: normal, inflammation or tumor. Internal and external validation were performed based on the classification sensitivity, specificity and accuracy. Comparison between the classification results and H&E stained sections revealed some discrepancies. Some regions histologically normal were identified as inflammation by the classification algorithm. Similarly, some regions presenting inflammatory lesions in the stained section were classified into the tumor group. Such differences were considered as misclassification, but they may actually evidence that biochemical changes are in course in the analyzed sample. In the latter case, the method developed throughout this thesis would have proved able to identify early stages of inflammatory and tumor lesions. It is necessary to perform additional experiments to elucidate this discrepancy between the classification results and the morphological features. One solution would be the use of immunohistochemistry techniques with specific markers for tumor and inflammation. Another option includes the recovering of the medical records of patients who participated in this study in order to check, in later times to the biopsy collection, whether they actually developed the lesions supposedly detected in this research.

Treinamento de habilidades sociais com universitários da área de fonoaudiologia: análise de conteúdo

Além do aprendizado de conhecimentos básicos e técnicos, promover competência social e habilidades interpessoais de universitários da área da Saúde torna-se fundamental para o desenvolvimento de relações saudáveis e produtivas no contexto acadêmico e na linha do cuidado. O campo das Habilidades Sociais, uma área da Psicologia, tem fornecido fundamentação desde a metodologia de avaliação de repertório social, até programas de Treinamento de Habilidades Sociais (THS) em contextos educacionais. Atualmente, é crescente o interesse em pesquisas qualitativas na Saúde por englobar o universo de significados, motivos, crenças, valores e atitudes, correspondendo a um espaço mais profundo das relações humanas. Objetivos: Investigar do ponto de vista qualitativo o programa de THS com universitários, oferecido pela disciplina de Psicologia III no Curso de Fonoaudiologia; descrever as potencialidades e dificuldades do repertório de HS conforme a autopercepção dos universitários; identificar os ganhos percebidos pelos universitários ao longo do programa de THS; analisar a relação entre o THS com o autoconhecimento nas relações interpessoais e na relação profissional-paciente. Metodologia: Participaram desta pesquisa 22 universitários, com faixa etária entre 19 e 21 anos de ambos os sexos, que cursavam o segundo ano do Curso de Fonoaudiologia de uma Instituição de Ensino Superior do interior paulista. Empregaram-se abordagem qualitativa e análise de conteúdo dos relatos produzidos pelos universitários no 1o, 8o e 15o encontros do THS e das sínteses (8o e 15o). Resultados: Foram identificadas três temas para análise: \"A importância do conhecimento teórico/técnico para a formação do fonoaudiólogo\", \"A importância do THS no contexto acadêmico e para a prática clínica\" e \"Avaliação dos universitários sobre os efeitos do THS\". No que se refere ao conhecimento teórico/técnico, os relatos apontaram a importância de que este seja desenvolvido de maneira contínua, valorizando as metodologias ativas empregadas. Quanto ao treinamento, os participantes descreveram maior prevalência de potencialidades e dificuldades das habilidades assertivas nos relacionamentos interpessoais do contexto acadêmico. Também foi apontada maior dificuldade de empatia com colegas e na comunicação com professores. No contexto profissional, as dificuldades permearam a ansiedade de falar em público e ser assertivo ao trabalhar em grupo. Quanto aos ganhos identificados, prevaleceu a assertividade com os dois interlocutores envolvidos nesta pesquisa; porém, todas as habilidades sociais tiveram resultados considerados positivos nos dois contextos, destacando a comunicação empática com paciente como facilitadora do processo terapêutico. O THS foi avaliado positivamente, pois permitiu a identificação de potencialidades, dificuldades e ganhos no repertório de HS no contexto acadêmico, sendo apontado como uma forma de preparação para a prática clínica, promovendo o autoconhecimento, o desenvolvimento de comportamentos socialmente habilidosos e a generalização para outros contextos. Conclusão: A inserção do THS na formação profissional de universitários na Fonoaudiologia mostrou-se bastante promissora ao ampliar o repertório de habilidades e competências para além do conhecimento teórico/técnico, tendo o autoconhecimento papel central neste processo, culminando com mudanças de comportamento na vida pessoal e profissional. Salienta-se a relevância do THS em cursos de graduação na área da Saúde, pelo contexto da relação profissional-paciente.

Post-mortem CT and MR brain imaging of putrefied corpses

INTRODUCTION Putrefaction of the brain is a challenge to a forensic pathologist because it may lead to considerable organ alterations and restrict documenting reliable autopsy findings. OBJECTIVES This study aims to present a new and systematic evaluation of possible benefits of post-mortem MR Neuroimaging (1.5 Tesla, sequences: T1w, T2w) in putrefied corpses in comparison to PMCT and autopsy. METHODS A post-mortem MRI brain examination was conducted on 35 adult, putrefied corpses after performing a whole body CT scan prior to a forensic autopsy. Imaging data and autopsy findings were compared with regard to brain symmetry, gray and white matter junction, ventricular system, basal ganglia, cerebellum, brain stem, and possible pathological findings. RESULTS At autopsy, a reliable assessment of the anatomical brain structures was often restricted. MR imaging offered an assessment of the anatomical brain structures, even at advanced stages of putrefaction. In two cases, MR imaging revealed pathological findings that were detectable neither by CT scans nor at autopsy. CONCLUSIONS Post-mortem MR imaging of putrefied brains offers the possibility to assess brain morphology, even if the brain is liquefied. Post-mortem MR imaging of the brain should be considered if the assessment of a putrefied brain is crucial to the evaluation of a forensic autopsy case.