Reuben Baumal

Origin of the desmoplasia in desmoplastic malignant melanoma

Four cases of desmoplastic malignant melanoma were examined light microscopically and immunohistochemically. Electron microscopy was performed in three cases. Light microscopy showed that all tumors were composed of neoplastic spindle cells that infiltrated between mature collagen bundles in the reticular dermis. Some of the spindle cells had bizarre nuclei, whereas other spindle cells resembled normal fibroblasts. Melanin could not be demonstrated in any of the tumors by histochemical techniques. Electron microscopic examination of the spindle cells showed prominence of rough endoplasmic reticulum, which was dilated and filled with flocculent material and occasional collagen fibrils. The same cells contained aggregates of non-membrane-bound melanin granules and pre-melanosomes. Some cells also showed features of myofibroblasts. Immunoperoxidase staining with anti-S100 protein antibody demonstrated positivity of the spindle cells as well as of melanocytes in the basal layer of the epidermis. Scar tissue and fibroblasts did not stain. These findings show that the desmoplastic component of these malignant melanomas derives from melanocytes that have undergone adaptive fibroplasia. Therefore, in assessing depth of invasion in a malignant melanoma, measurements should include the desmoplastic areas.

Overcoming barriers to teaching the behavioral and social sciences to medical students.

Most U.S. medical schools offer courses in the behavioral and social sciences (BSS), but their implementation is frequently impeded by problems. First, medical students often fail to perceive the relevance of the BSS for clinical practice. Second, the BSS are vaguely defined and the multiplicity of the topics that they include creates confusion about teaching priorities. Third, there is a lack of qualified teachers, because physicians may have received little or no instruction in the BSS, while behavioral and social scientists lack experience in clinical medicine. The authors propose an approach that may be useful in overcoming these problems and in shaping a BSS curriculum according to the institutional values of various medical schools. This approach originates from insights gathered during their attempts to teach various BSS topics at four Israeli medical schools. They suggest that medical faculties (1) adopt an integrative approach to learning the biomedical, behavioral, and social sciences using Engels “biopsychosocial model” as a link between the BSS and clinical practice, (2) define a hierarchy of learning objectives and assign the highest priority to acquisition of clinically relevant skills, and (3) develop clinical role models through teacher training programs. This approach emphasizes the clinical relevance of the BSS, defines learning priorities, and promotes cooperation between clinical faculty and behavioral scientists.

Immunohistochemical and electron microscopic assessment of childhood rhabdomyosarcoma. Increased frequency of diagnosis over routine histologic methods.

Histologic examination was carried out in 65 cases of childhood rhabdomyosarcoma (RMS), 53 embryonal, and 12 alveolar. Cross‐striations were seen on light microscopy in 12 (23%) embryonal and 4 (33%) alveolar tumors. The capacity of immunohistochemical staining (PAP technique) to increase diagnostic accuracy was assessed, using antibodies against myoglobin, the MM isoenzyme of creatine kinase, desmin, calcium magnesium‐dependent ATPase of sarcoplasmic reticulum and calsequestrin. Myoglobin was detected in 16 (30%) embryonal and eight (67%) alveolar RMS, higher numbers than obtained by viewing cross‐striations on light microscopy. The creatine kinase antibody was slightly better than the antibody to myoglobin and 15 of 25 (60%) embryonal RMS were positive when both specificities were used. The remaining three antibodies were less useful. Of 13 (two alveolar and 11 embryonal) RMS studied by electron microscopy, four showed cross‐striations, contained late myoblasts, and were positive for myoglobin. Three additional cases showed only late myoblasts and one of these was positive for myoglobin. Thus, 16 of 25 (64%) of the embryonal and seven of nine (78%) of the alveolar RMS showed either positive immunostaining or ultrastructural features of RMS. This study indicates that a combination of immunohistochemical staining, using antimyoglobin and anticreatine kinase (MM isoenzyme) antibodies, and electron microscopy are useful markers in the diagnosis of childhood RMS.

A monoclonal antibody as a marker for carcinoma in situ germ cells of the human adult testis

Carcinoma in situ of the testis (CIS) is a precursor of invasive testicular germ cell tumours. The diagnosis of CIS is however often missed when conventional histological techniques are used. No specific immunological marker for CIS germ cells of the testis has been demonstrated previously. A novel monoclonal antibody, M2A, reacting with malignant germ cells of seminomas has recently been developed. Using the immunoperoxidase reaction on tissue sections, we tested the reactivity of M2A with CIS germ cells of the human adult testis. Positive reaction was found in 19 of 20 testicular specimens showing CIS, whereas no staining was found in 39 testicular biopsies without CIS. Thus, M2A may serve as a diagnostic marker in detection of CIS germ cells.

Intraperitoneal therapy of malignant ascites associated with carcinoma of ovary and breast using radioiodinated monoclonal antibody 2G3

Abstract A phase I/II study of intraperitoneal (ip) radioimmunotherapy was conducted in ovarian or breast cancer patients with symptomatic chemotherapy-resistant ascites using a novel anti-mucin monoclonal antibody (mAb) 2G3 labeled with 131 I. Tracer doses of 2 mCi [ 131 I]2G3 were given by ip injection to 11 patients, followed by increasing therapeutic doses up to 150 mCi (cumulative) in 9 patients. There was no serious toxicity. Temporary palliation of ascites was observed in 3 of 4 patients who received doses greater than 50 mCi. Total body elimination half-life of the radiolabeled antibody assessed by gamma scintigraphy ranged from 95 to 250 hr, longer than data previously reported in patients without ascites treated with ip administered radiolabeled antibodies. However, uptake of radiolabel by tumor nodules was small and variable (2 × 10 −4 − 2 × 10 −2 % ID/g), and preferential uptake by tumor compared to normal peritoneum was observed in only 2 of 5 patients in whom biopsies were obtained. These results suggest that the observed palliation of ascites is due to prolonged retention of radiolabeled antibody in the peritoneal cavity even in the absence of specific targeting.

Enhancing self-awareness in medical students: an overview of teaching approaches.

Self-awareness is an individuals tendency to pay attention to his or her own emotions, attitudes, and behavior in response to specific situations. In the case of physicians, self-awareness is their insight into how their emotional makeup influences patient care. Conceivably, such insight may improve doctors’ professional performance. The authors review published approaches aimed at enhancing the self-awareness of medical students and draw attention to some problems in these approaches that call for further research. Published teaching programs of self-awareness may be classified as direct or indirect. The primary objective of direct programs is to promote students’ insight into their own feelings and attitudes by classroom instruction or small-group discussions, during which students share with their peers their emotional responses to various clinical experiences. The primary objective of indirect approaches is to teach clinical skills, such as patient interviewing, patient counseling, and self-assessment. It has been claimed that these programs also enhance self-awareness by drawing students’ attention to differences between students’ assessment of their own performance and the assessments of their instructors and patients. Both types of programs should be given consideration for inclusion into the medical curriculum. However, since presently available evidence does not allow educators to identify an optimal teaching program, more study is needed concerning the effectiveness of the various approaches to teaching self-awareness. Specifically, an effort should be made to ascertain that the benefit of the direct approaches exceeds their cost in terms of time, teacher training, and—possibly—student embarrassment.

Categorization of pediatric neoplasms by immunostaining with antiprekeratin and antivimentin antisera.

Forty‐six tumors in children were examined using light microscopy and subsequently frozen sections were stained with antiprekeratin and antivimentin antisera, so that the tumors could be classified by tissue of origin. Except for two adrenal cortical carcinomas and four liver tumors, most epithelial neoplasms continued to produce prekeratin filaments, a characteristic of normal epithelial cells. Tumors and cells of epithelial origin did not produce vimentin filaments, whereas normal and neoplastic mesenchymal cells did. Tumors with both epithelial and mesenchymal components produced vimentin filaments in mesenchymal areas and prekeratin in epithelial areas. Tumors of lymphoid origin showed variable production of vimentin filaments, depending on the amount of cell cytoplasm, but did not contain prekeratin filaments. Of the neuroectodermal tumors, only the ganglioneuroma contained vimentin filaments and none contained prekeratin filaments. Thus, antibodies to both prekeratin and vimentin filaments are useful in diagnosing childhood neoplasms and studying their histogenesis.

Xanthogranulomatous Pyelonephritis in Children Etiology, Pathogenesis, Clinical and Radiologic Features, and Management

matous pyelonephritis was likely first described by Schlagenhaufer’ in 1916, and the term itself was coined by Osterlind’ in 1944. It is a chronic inflammatory lesion of the kidney characterized by destruction of the renal parenchyma, which is replaced by granulomatous tissue containing lipid-laden macrophages (foam cells). Once regarded as uncommon, the condition has been reported with increasing frequency in the last few

Sources of distress during medical training and clinical practice: Suggestions for reducing their impact

Background: Medical students and doctors experience several types of professional distress. Their causes (“stressors”) are commonly classified as exogenous (adapting to medical school or clinical practice) and endogenous (due to personality traits). Attempts to reduce distress have consisted of providing students with support and counseling, and improving doctors’ management of work time and workload. Aim: To review the common professional stressors, suggest additional ones, and propose ways to reduce their impact. Method: Narrative review of the literature. Results and conclusion: We suggest adding two professional stressors to those already described in the literature. First, the incongruity between students’ expectations and the realities of medical training and practice. Second, the inconsistencies between some aspects of medical education (e.g., its biomedical orientation) and clinical practice (e.g., high proportion of patients with psychosocial problems). The impact of these stressors may be reduced by two modifications in undergraduate medical programs. First, by identifying training–practice discrepancies, with a view of correcting them. Second, by informing medical students, both upon admission and throughout the curriculum, about the types and frequency of professional distress, with a view of creating realistic expectations, teaching students how to deal with stressors, and encouraging them to seek counseling when needed.

Prognostic Significance of Urinary Findings and Renal Biopsies in Children with Henoch-Schönlein Nephritis

Clinical course and renal biopsy were evaluated as predictors of renal outcome in 21 children with Henoch-Schönlein nephritis. Persisting heavy proteinuria and severe glomerular changes most accurately predicted those patients who were likely to develop renal failure. Renal biopsy is recommended only in patients with a nephrotic or nephritic/nephrotic picture.