Skin erythrodiapedesis during chronic venous disorders

Background: Extravasation of erythrocytes (erythrodiapedesis [ED]) is currently included among causes of skin damage in legs with chronic venous disorders (CVD) and ascribed to venular hypertension. ED is followed by erythrocyte disruption, degradation of hemoglobin, and storing of ferric iron into hemosiderin. The aim of this study was to evaluate the occurrence of ED in the skin of legs with different clinical stages of CVD. Methods: One hundred eighteen skin biopsies from legs with CVD underwent histologic evaluation for ED and hemosiderin deposition (HD). Results: ED was found in only 21/118 specimens. In particular, it was found in ulcer samples, in tissues surrounding varicophlebitis and, finally, in acute eczematous skin. ED was found in only 15/30 samples showing HD. Conclusion: Our findings confirm the occurrence of ED during CVD. However, it was found only in concomitance of severe dermal inflammation. Hemosiderin deposition in the absence of actual ED could be explained with previous healed episodes of skin inflammation. However, ED is not likely the only cause of skin iron overload, which could also occur by a molecular mechanism. Further studies are needed to define the mechanism of iron deposition in the skin of legs afflicted with CVD. (J Vase Surg 2011;53:1649-53.

Primary vaginal leiomyosarcoma, a rare tumour: case report and review

Primary vaginal leiomyosarcomas (pvLMS) are rare, recurrent tumours accounting for ca. 2% of all vaginal cancers. The etiology is still unknown, the prognosis is poor and there is no consensus guideline on its management. Diagnosis is usually made during the 5th decade due to the presence of a vaginal mass or nodule [1-2]. Current medical literature reports about 200 cases (PubMed®); only 3 studies have considered the ultrastructure [2-4]. Herein a pvLMS is presented and discussed. A nodular, 25 x 23 x 28 mm-mass, infiltrating the urethra but not the rectovaginal septum, was widely excised from the superior vaginal wall of a 58-year-old previously hysterectomized woman. Macroscopic images and MRI were performed. Iliac lymph nodes and HMB45 were negative. The sample was fixed and prepared for light microscopy, transmission (TEM) and scanning (SEM) electron microscopy. Semithin sections showed a storiform pattern of spindle shaped cells with blunt-ended nuclei. Cells arranged in interwoven fascicles within a dense and richly vascularised stroma (neoangiogenesis). Some atypic mitotic figures and focal necrosis were seen. SEM evidenced a dense collagenous stroma with numerous microvessels. TEM showed neoplastic and pleomorphic cells with complex cytoplasm projections containing paranuclear crowds of dilated mitochondria, free ribosomes and a well-developed rough endoplasmic reticulum. Nuclei were large, mostly hyperchromatic, usually indented, with prominent nucleoli and nucleolonema. The dense intercellular space contained dense bundles of collagen fibers. A high and reactive endothelium lined blood vessels. After 4 follow-ups, the patient is fine and without recurrence. Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as it was for this case. As there are different kinds of LMS, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice. References [1] Umeadi et al. (2008) Vaginal leiomyosarcoma. J Obstet Gynaecol 28(5): 553-554. [2] Tobon et al. (1973) Primary leiomyosarcoma of the vagina. Light and electron microscopic observations. Cancer 32(2): 450-457. [3] Akhtar et al. (1978) Primary leiomyosarcoma of the vagina: light and electron microscopic study of a case with review of literature. Tex Med 74(9): 67-71. [4] Rastogi et al. (1984) Primary leiomyosarcoma of the vagina: a study of five cases. Gynecol Oncol 18(1): 77-86

Training the "clinical eye". Rubens' Three Graces: how many pathologies?

Art can serve as a powerful resource for medical students to both train the so called “clinical eye” and to better understand disease [1]. Herein a paleopathological analysis is performed on one of Ruben’s final artworks, “The Three Graces” (1630- 1635; oil on oak panel; 220.5 x 182 cm; Museo del Prado, Madrid). Rubens depicts the three Graces beside a fountain, under a garland of flowers in a landscape. The circular rhythm and elegant undulation are based on classical sculpture. Painted shortly after his marriage, it bears witness to the happiness of the artist’s life. The figure on the left is directly inspired by his second wife, Hélène Fourment (23 years old); the central and right Graces probably illustrate Rubens’ sisters-in-law. Besides overweight, scoliosis, and hyperlordosis observed in all three Graces, the left Grace evidences flat feet; hyperextension of the right metacarpal joints; signs of rheumatoid arthritis (even fibromyalgia has been proposed); lateral deviation of the nipple (Mondor’s disease?); varicose thighs, and right hallux vagus. The central Grace (Clara Fourment?), in turn, shows cellulite and, interestingly, positive Trendelenburg sign. Finally, the Grace on the right -Susanna Fourment- has been subject of a long debate on signs of a locally advanced breast cancer in the left external upper quadrant. In fact, several specialists agree in the observation of signs of an open ulcer; redness of the surrounding skin (an inflammatory sign); nipple retraction; reduction of the left breast volume, and enlarged axillary lymph nodes [2-3]. Rubens was one of main Baroque and realist painters, i.e. he painted whatever his eyes captured. If the Graces were sisters, then they are likely to share genetic traits. The latter, together with all the other signs described, favour the working diagnosis of familial benign hypermobility syndrome. Observation has a key role in clinical medicine; the paleopathological observation in art show us how artists could record abnormalities long before doctors did [2]. Therefore, artworks still represent useful teaching tools for refining visual skills in traditional and innovative medical education. References [1] Hinojosa-Azaloa A. & Alcocer-Varela J. (2014) Art and rheumatology: the artist and the rheumatologist’s perspective. Rheumatology 53: 1725-1731. [2] Dequeker J. (2007) Medicine and the artist. Age and Ageing 37: 4-5. [3] Grau et al. (2001) Breast cancer in Rubens paintings. Breast Ca Res Treat 68: 89-93

Visual thinking strategy in the medical curriculum: training the “clinical eye” in classrooms and art museums

Medicine intertwines with arts as part of the wider field of humanities since its origin; they integrate creating a new synergy. Clinical diagnosis involves the observation, description and interpretation of visual information. These skills can be developed and trained by analysing visual art works. Visual thinking strategy (VTS) has been recognized as a legitimate cognitive tool (1,2). Thanks to a collaboration between our medical faculty (Sant’Andrea Hospital) and the Borghese Gallery and Museum we are piloting an innovative experience with small-group interactive sessions within the course of Methodology (3rd-year students). This activity is carried out under the tutelage of art education curators and faculty members. Sessions focused on the analyses of selected original paintings. Students were evaluated through pre- and posttest questionnaires and with short oral presentations. Discussion was warm and enthusiastic and students appreciated the interaction with faculty on a non-medical level. By engaging with art works, students learn a broader conception of human-ness, enhancing mindfulness, rendering learning enjoyable and meaningful. Museums as teaching labs are valuable resources for enhancing learning beyond the classroom walls. VTS in medicine encourages critical thinking and problem solving, thus improving clinical abilities by means of observation and clinical reasoning, promoting empathy and getting used with team work. These activities can be integrated with art works shown in the classroom as clinical triggers: several figurative paintings are shown within our course of human and clinical anatomy (first and second-year students), i.e. self-portraits of Piero della Francesca and Mantegna’s “Virgin and child” well illustrate goiter; Raphael’s La Fornarina and Rubens’ “The three graces” show breast cancer. Rombouts’ “Allegory of the five senses” is a nice introductory image for the sense organs as Bigot’s “A doctor examining urine” for the urinary tract. An art-based approach to teaching observational skills should be included continuously within required courses in the medical curriculum

Postgraduate eLearning satellite-based tutorials as a new approach to “teaching to teach” anatomy

Modern educational trends approach in a more innovative, learner-centered programs that rely on a combination of interactive didactic tools and individualized tutoring. In response to the increasing need for new professionals in the health sciences who are able to apply academic eLearning in Medicine, since 2005 Sapienza University of Rome is involved in and coordinates a multidisciplinary network formed by 11 Italian universities, aimed to deliver a Master (postgraduate) course on teleteaching applied to the health sciences (Matam). This program forms highly qualified professionals for distance teaching/eLearning in health sciences and management. University sites are activated through earth and satellite-based modules, thus creating real/virtual class-rooms or didactic communities. Matam is delivered in two semesters as either synchronous satellite-based or asynchronous pre-registered tutorials (posted on an intranet site). Learners can actively and autonomously follow these modules, interacting with teachers and colleagues, whereas teachers/tutors, in turn, are in a studio at the university. The program considers a total of 60 CFU and admits a maximum of 20 participants per site. The integrated course “Multimedia technologies and virtual reality in imaging diagnostics” (8 CFU) includes 3 two-hour tutorials of human gross and microscopic anatomy (digestive and reproductive tracts), of which one is sent synchronously and two asynchronously. Matam is a sharing of knowledge, allowing teachers and learners to have a continuous and real-time update. The use of eLearning as an innovative integration within a course considering either ex cathedra and tutorial teaching may be useful for the improvement of students’ motivation and self assessment aptitudes, specially in young undergraduate ones. In addition, eLearning can favour a wider use of computer animations, thus representing a valid complement to courses particularly belonging to health sciences degrees

Training the “clinical eye”. Rubens’ Three Graces: how many pathologies?

Art can serve as a powerful resource for medical students to both train the so called “clinical eye” and to better understand disease [1]. Herein a paleopathological analysis is performed on one of Ruben’s final artworks, “The Three Graces” (1630-1635; oil on oak panel; 220.5 x 182 cm; Museo del Prado, Madrid). Rubens depicts the three Graces beside a fountain, under a garland of flowers in a landscape. The circular rhythm and elegant undulation are based on classical sculpture. Painted shortly after his marriage, it bears witness to the happiness of the artist’s life. The figure on the left is directly inspired by his second wife, Hélène Fourment (23 years old); the central and right Graces probably illustrate Rubens’ sisters-in-law. Besides overweight, scoliosis, and hyperlordosis observed in all three Graces, the left Grace evidences flat feet; hyperextension of the right metacarpal joints; signs of rheumatoid arthritis (even fibromyalgia has been proposed); lateral deviation of the nipple (Mondor’s disease?); varicose thighs, and right hallux vagus. The central Grace (Clara Fourment?), in turn, shows cellulite and, interestingly, positive Trendelenburg sign. Finally, the Grace on the right -Susanna Fourment- has been subject of a long debate on signs of a locally advanced breast cancer in the left external upper quadrant. In fact, several specialists agree in the observation of signs of an open ulcer; redness of the surrounding skin (an inflammatory sign); nipple retraction; reduction of the left breast volume, and enlarged axillary lymph nodes [2-3]. Rubens was one of main Baroque and realist painters, i.e. he painted whatever his eyes captured. If the Graces were sisters, then they are likely to share genetic traits. The latter, together with all the other signs described, favour the working diagnosis of familial benign hypermobility syndrome. Observation has a key role in clinical medicine; the paleopathological observation in art show us how artists could record abnormalities long before doctors did [2]. Therefore, artworks still represent useful teaching tools for refining visual skills in traditional and innovative medical education

Looking is not seeing: visual art as a useful eLearning tool for teaching clinical anatomy

An old Chinese proverb reads “A picture paints a thousand words…”. Even though arts were used as a pedagogical tool as early as 1902, arts have not traditionally been part of medical education. Anatomy teaching is undergoing significant changes; long-distance education associated to web 2.0 tools have enlarged communication and interaction possibilities between users and virtual communities (1,2). We are developing a project consisting of a series of asynchronous (pre-registered) short video tutorials covering a wide range of clinical anatomy-related topics which can be posted on an internet/intranet site and then actively and autonomously be followed. Videos include short introductory remarks and legends which might be developed in different languages and which make them useful even to disable eLearners. The relationship between Art and: anatomy, thyroid gland, osteomuscular alterations, breast, ageing, artists’ diseases, as well as the presence of anatomists and physicians in Art, are some of the topics developed. Each tutorial considers numerous paintings and some sculptures covering a long time span, from Prehistory to the Classical period, Late Middle Ages, the rich Renaissance period up until modern times. Artworks were chosen in order to be narrative in nature and rich in detail, thus stimulating reflection and self-discussion. These video tutorials could be a valuable teaching/learning complement to theoretical knowledge within medical students’ education or even within a larger “art-loving” audience. eLearners are guided by the teacher’s voice and then get immersed in an artwork, discovering it. Clear and/or hidden clinical anatomical features can be enhanced and made easier to assimilate. This nontraditional format brings a new lens through which students can learn valuable visual skills on human clinical anatomy. It may favor critical thinking, opening the mind to alternative ways of seeing, thus enhancing medical students’ abilities to more deeply observe and to better understand real clinical situations

Introducing medical students to scientific research: an early electron-microscopy laboratory attendance experience

In the light of importance that “evidence-based medicine” has assumed in recent years (Snelgrove et al. 2009), we offer to the students of the first-year medical-degree the chance of an early exposure to the work in the ultrastructural research laboratory “Pietro M. Motta”. On an elective basis, students attended the laboratory in small groups. They were guided and supported by a qualified researcher, a post-graduate student, a graduate student and a technical-staff unit. During the week of attendance students performed several activities: at first they have visited the laboratory where the technicalities of the equipment were illustrated, than they have taken part to a lecture on the methods used to prepare the biological samples for Scanning and Transmission Electron Microscopy. In the following days preparation of samples for Scanning and Transmission Electron Microscopy was carried on and a guided discussion on scientific articles concerning the samples used in the experiments was conducted (Familiari et al. 2006). Later, samples were observed using a light microscope and both transmission and scanning electron microscope. At the end of the week students had taken hands-on in various stages of preparation, observation and analysis of the samples. The discussion with the researcher and the post-graduate doctors/ students provided the attendant students with key concepts regarding scientific work that are the basis of theory and practice of biomedical research projects, not only of ultrastructural type. The students’ early exposure to the work and methodology characteristic of ultrastructural research may prove useful, not only when promoting indepth understanding of microscopic anatomy, but also as a motivational base upon which to instil a correct approach to scientific research in future doctors

Primary vaginal leiomyosarcoma: A case report with complete morphological, immunohistochemical and ultrastructural study

Objective: Primary vaginal leiomyosarcomas (LMS) are rare, easily recurrent tumours with an unknown etiology; the prognosis is poor and there is no consensus guideline on their management. Case report: A nodular, 25 × 23 x 28 mm-mass, infiltrating the urethra, was found in a 58-year-old woman. A biopsy showed a LMS of the vagina that was positive for vimentin, alpha-smooth muscle actin, caldesmon, desmin, p16 and p53. An anterior pelvic exenteration was performed. The sample was fixed and prepared for light microscopy, transmission and scanning electron microscopy, confirming the diagnosis of LMS. Conclusions: Best outcomes occur when the tumour is small, localized, and can be removed surgically with wide, clear margins, as in this case. As there are different kinds of malignant mesenchymal tumours, biopsy followed by immunohistochemistry and electron microscopy still represents a good diagnostic choice and surgical resection is generally the gold standard in these cases. Keywords: Electron microscopy, Immunohistochemistry, Leiomyosarcoma, Light microscopy, Vagin

Intima neovascularization studied on epoxy-resin semithin sections in a rare case of carotid recurrent in-stent restenosis

Introduction. Restenosis after carotid endarterectomy (CE) has been described in 8-19% of patients (1). In-stent  restenosis (ISR) after stenting has been reported in a few cases (2). Here we report an extremely rare case of recurrent ISR after CE and wallstent.  Materials and methods. An atherosclerothic plaque belonging to a patient who underwent recurrent ISR after both CE and wallstent has been studied. Semithin sections (0,850 µm thick) obtained from epoxy-resin embedded samples were stained as reported (3). Light microscopy observations were performed at magnifications of 400X and 1000X, within an area of 3,8mm2 corresponding to 10 microscopic field at 400X. The morphological characteristics considered were: cells number and type; presence, number and type of neovessels; calcifications, and inflammatory cells. Results. The plaque appeared mostly fibrous, with an internal rupture and hemorrhagy. Very few foam cells (N= 12/3,8mm2) were observed whereas vascular smooth muscle cells (VSMCs) were abundant (n=160/3,8mm2) and often entrapped in a thick coat of self-secreted collagen. Lipid laden VSMCs were present (n=18/3,8mm2); three of them showed intracellular microcalcifications. Marked signs of inflammation were found, macrophage (n=50/3,8mm2), mast cells (n=8/3,8mm2), lymphocytes (n=5/3,8mm2) as well as granulocytes (n=4/3,8mm2). There was a marked neovascularization, 24 sections of circular regular vessel and 6 sections of flattened but patent vessels were found in 3,8mm2. Neovessels had intact endothelium and likely derived from the underneath media. Discussion. Histopathological diagnosis is usually carried out on paraffin-embedded 4µm-thick sections. The observation of semithin sections has allowed us to achieve a better morphological characterization than that routinely obtained. The cellular population observed is that of an active remodelling plaque, susceptible of rupture, both for the presence of mast cells and extensive neovascularization. Mast cells secrete effector molecules that affect endothelial cells and VSMCs activity, the presence of neovessels weakens the plaque, thus producing cleavage planes. 1. Counsell et al., 2011. Carotid stenting for restenosis after endarterectomy. Cardiovasc Intervent Radiol. 34(3):488-92. 2. Willfort-Ehringer et al., 2002. Single-center experience with carotid stent restenosis. J Endovasc Ther. 9(3):299-307. 3. Relucenti et al., 2010. Detecting microcalcifications in atherosclerotic plaques by a simple trichromic staining method for epoxy embedded carotid endarterectomies. Eur J Histochem. 54(3):e33