Luisa Florez

Ovarian cancers overexpress the antimicrobial protein hCAP-18 and its derivative LL-37 increases ovarian cancer cell proliferation and invasion

The role of the pro‐inflammatory peptide, LL‐37, and its pro‐form, human cationic antimicrobial protein 18 (hCAP‐18), in cancer development and progression is poorly understood. In damaged and inflamed tissue, LL‐37 functions as a chemoattractant, mitogen and pro‐angiogenic factor suggesting that the peptide may potentiate tumor progression. The aim of this study was to characterize the distribution of hCAP‐18/LL‐37 in normal and cancerous ovarian tissue and to examine the effects of LL‐37 on ovarian cancer cells. Expression of hCAP‐18/LL‐37 was localized to immune and granulosa cells of normal ovarian tissue. By contrast, ovarian tumors displayed significantly higher levels of hCAP‐18/LL‐37 where expression was observed in tumor and stromal cells. Protein expression was statistically compared to the degree of immune cell infiltration and microvessel density in epithelial‐derived ovarian tumors and a significant correlation was observed for both. It was demonstrated that ovarian tumor tissue lysates and ovarian cancer cell lines express hCAP‐18/LL‐37. Treatment of ovarian cancer cell lines with recombinant LL‐37 stimulated proliferation, chemotaxis, invasion and matrix metalloproteinase expression. These data demonstrate for the first time that hCAP‐18/LL‐37 is significantly overexpressed in ovarian tumors and suggest LL‐37 may contribute to ovarian tumorigenesis through direct stimulation of tumor cells, initiation of angiogenesis and recruitment of immune cells. These data provide further evidence of the existing relationship between pro‐inflammatory molecules and ovarian cancer progression.

Postmortem findings in eight cases of influenza A/H1N1

In March and early April 2009, cases of a new swine-origin influenza A (H1N1) virus were diagnosed in Mexico and the United States. Influenza virus presents as a respiratory infection with high morbidity and mortality. We describe the postmortem findings of eight confirmed cases of influenza A/H1N1 in a medical examiner setting. The eight cases falling under the jurisdiction of the Harris County Medical Examiner (Houston, TX, USA) with confirmed influenza A/H1N1 infection between June and September 2009 were included in this study. All cases were males between 6 months and 54 years of age. All adult patients had a body mass index from 31 to 49.8 kg/m2. Five cases had comorbid conditions including one case with sleep apnea and mental retardation, three cases with chronic ethanolism, and one case with thymoma, sarcoidosis, and myasthenia gravis. The remaining three cases had no pre-existing medical conditions. All patients presented with severe flu-like symptoms; yet, only five were febrile. Rapid influenza diagnostic tests were performed in three cases by primary-care physicians, two of which were negative. None of the patients received antiviral medication. The average disease duration time was 8.2 days (3–14 days). A wide range of histopathological findings including tracheitis, necrotizing bronchiolitis, alveolitis, intra-alveolar hemorrhage, and hyaline membranes, both in a focal and in a diffuse distribution, were identified. Influenza A/H1N1 viral infection presents with a wide range of histological findings in a diffuse or focal distribution; most consistently with tracheitis, necrotizing bronchiolitis, and alveolitis with extensive alveolar hemorrhage. These histopathological findings at autopsy along with a clinical history of flu-like symptoms should raise suspicion for influenza A/H1N1 infection, and postmortem analysis by the reverse transcription-polymerase chain reaction (RT-PCR) is recommended for an accurate diagnosis.

Medulloepithelioma: Two unusual locations

Reported herein are two cases of medulloepithelioma (ME) occurring in very unusual locations. Case 1 involved a 44‐year‐old man who presented with leg pain and urinary incontinence. Spine magnetic resonance imaging (MRI) showed an enhancing epidural and intradural lumbosacral mass. He underwent L3–S2 laminectomy with partial tumor resection. Approximately 2 months following surgery, he developed leptomeningeal spread of the tumor, and died 2 months later. Case 2 involved a 22‐month‐old girl who presented with painless left proptosis. MRI demonstrated diffuse, fusiform, and contrast‐enhancing enlargement of the left optic nerve. Following biopsy, she was treated with chemotherapy. Histologically, the tumors in both cases consisted of primitive pseudostratified neuroepithelial cells, arranged in papillary, tubular, or trabecular configurations. A PAS‐stained external limiting membrane (ELM) of the neuroepithelia was present. In case 1 there were scattered cartilaginous nodules within the tumor, in keeping with the diagnosis of a teratoid ME. Immunohistochemically, the tumor cells were positive for synaptophysin, nestin, microtubule‐associated protein‐2, CD56, CD10, glial fibrillary acidic protein (focal), and S‐100 protein (focal). The main differential diagnoses include an immature teratoma and an optic nerve glioma in cases 1 and 2, respectively. Histological demonstration of the ELM by PAS stain is a simple but useful technique.

A web page to teach neurology and neuropathology to medical students.

Sir: We describe a computer-based module developed to teach neurology and neuropathology to sophomore medical students, made available on both CD-ROM and the World Wide Web. Student reaction to the module was encouraging and exam scores also appeared to improve in the class that used this module. A medical student must gain a working knowledge of the intricacies of the nervous system and its pathology in a very limited amount of time. In the United States, neuropathology is usually taught during the second year of medical school, over about a 1±3 week period. In recent years there also has been increasing pressure to advance relevant clinical knowledge in the allied ®elds of neurology, neuropsychiatry and neuroradiology within the teaching of neuropathology. Successful teaching of neuropathology involves several factors. Obviously, the main goal is that students learn the material. There are many ways to establish how well this has been accomplished, such as class exams, preceptor evaluations and performance in subsequent clinical rotations in areas such as neurology, neurosurgery and neuroradiology. Standardized exams, such as the National Board of Medical Examiners (NBME) shelf exam, can provide a reasonable means of comparison [6]. Although instructors would like their students to perform well on exams, neuropathology also should be an enjoyable and stimulating experience for the students. How best to accomplish these goals in the teaching of neuropathology has been the subject of research and debate [1,2]. Case-based approaches are increasingly popular [5], as is the use of computer technology [4]. In previous studies we have investigated what students found useful in a web page to teach pathology and have found that students generally like computer-based teaching modules [3]. Students like web pages that provide images and material in a format that is easily organized for review. Student complaints often focused on pages that loaded slowly, or that required complicated or memory-hungry plug-ins. The principles learned from these earlier surveys were applied to construct a web page to teach neuropathology to second year medical students. The same material was provided on a CD-ROM and distributed free to the students during their neuropathology block. The success of this venture was measured in two ways: by examining student scores on the neuropathology portion of the NBME shelf exam; and by surveying student opinions of the course, the web page and the neuropathology computer module. A module was constructed to cover the following topics: congenital malformations; hydrocephalus; brain herniation; intracranial haemorrhage; cerebrovascular disorders and cerebral haemorrhage; degenerative, demyelinating, and neuromuscular diseases; infectious diseases of the nervous system; and tumours and phakomatoses of the nervous system. This module included digital images, case presentations and review questions. All material was written in simple Hypertext Markup Language (HTML). Images were stored as industry-standard formats (jpg; joint expert photographic ®les or gif; graphic interface ®les) so that any web browser could be used. Material was made available to students at the following web address: Http://www.tmc.tulane.edu/ student/2002/neuropathology/start_here.htm. Material was also provided on CD-ROM. Student performance in neuropathology was compared by examining performance in the neuropathology section of the NBME shelf exam for the class that had access to the neuropathology module (class of 2002) to the previous years class (class of 2001). In order to protect the integrity of the NBME exam, and to correct for variations in the comparative dif®culty of different questions on exams from different years, scores are reported as normalized to the national average rather than as raw scores (Figure 1). After the neuropathology block, students were asked to ®ll out a survey that included their overall opinion of the neuropathology CD-ROM (Figure 2) and their preferred media for accessing neuropathology material outside of class (Figure 3). Students were also encouraged to write comments about the neuropathology module in general. Con®dence intervals for percentages were calculated for extrapolation to an in®nite population using an alpha of 0.95. Comparisons between groups were made by student t-test. Neuropathology and Applied Neurobiology (2001), 27, 142±144

Primary breast lymphoma with sudden death.

Primary breast lymphoma is a rare form of extranodal lymphoma. B cells constitute the most common type involving the breast. T cells represents only 3%. Even though lymphomas have a high predilection to metastasize to the heart, there are no specific clinical or radiological findings, and most of the cases are diagnosed at autopsy. We discuss the case of a 49-year-old woman with primary breast lymphoma who presented with sudden death. Autopsy revealed a primary T-cell lymphoma of the breast with tumoral infiltration of the atrioventricular node and transmural myocardial permeation with focal necrosis.

Vein of Galen aneurysmal malformations associated with high output cardiac failure: Report of three autopsy cases

Vein of Galen aneurysmal malformations (VGAMs) are rare congenital vascular, malformation. The malformation usually develops between the 6th to 11th wk of gestation. We report three autopsy cases, all prenatally diagnosed by ultrasound or fetal magnetic resonance imaging with VGAM with associated high-output cardiac failure. Prenatal fetal echocardiogram on two patients showed cardiomegaly, ventricular dilatation, pulmonary hypertension and reversed aortic flow. The cause of death in all the three patients was high-output cardiac failure due to VGAM. The autopsy findings confirmed feeding arteries from posterior cerebral arteries to VGAM in all patients. Other significant neuropathologic findings at autopsy were severe hydrocephalus, polymicrogyria, germinal matrix hemorrhage, periventricular leukomalacia, and microcalcification. The findings support that VGAM may be due to abnormal arterial venous communication and the most common cause of death in these patients is high-output cardiac failure. The presence of other associated brain abnormalities indicates a poor prognosis.