Edward J. Wills

Intra-Abdominal Desmoplastic Small Round Cell Tumor

&NA; A rarely encountered but distinctive type of aggressive malignant tumor of childhood and adolescence has been recently described as occurring predominantly or exclusively intra‐abdominally. It is characterized by a generally diffuse pattern of growth of small cells with hyperchromatic nuclei, scanty cytoplasm, patchy epithelial differentiation, immunohistochemical co‐expression of keratin and desmin intermediate filaments and a focal but pronounced desmoplastic stromal component. It is regarded as yet another variant in the group of small round cell tumors (SRCT) of infancy and childhood. This case report of a mass in the greater omentum of a 15 yr‐old girl adds to the 33 cases already described in the English literature.

Burns, biofilm and a new appraisal of burn wound sepsis

PURPOSE Following a burn, the wound may become colonized and septic complications may ensue. Many organisms, commonly isolated from burn wounds produce biofilms, which are defined as a collection of organisms on a surface surrounded by a matrix. Biofilms are associated with development of antibiotic resistant organisms and are refractory to the immune system. The presence of biofilm in the burn wound has not been documented. METHODS A study was undertaken using light and electron microscopy to determine the presence of biofilm in the burn wound. Specific stains were used to detect the presence of micro-organisms and associated carbohydrate, a major constituent of the biofilm matrix. A concurrent microbiological study of the burn wound was also carried out. RESULTS Biofilm was detected in ulcerated areas of the burn wound. Bacterial wound invasion with mixed organisms was also commonly detected. CONCLUSIONS The finding of biofilm in the burn wound has significance in our understanding of burn wound sepsis and supports the evidence for early excision and closure of the burn wound. Due to the recalcitrant nature of biofilm associated sepsis and the difficulty in disrupting biofilm it has implications for the future development of wound care dressings.

THE APPLICATION OF ULTRASTRUCTURAL STUDIES IN THE DIAGNOSIS OF BLADDER DYSFUNCTION IN A CLINICAL SETTING

PURPOSE We examine the ultrastructural changes reported to be present in dysfunctional bladders and determine whether they can be used as a predictor of urodynamic diagnosis in a clinical setting. MATERIALS AND METHODS Subjects who required urodynamic diagnosis and cystoscopy as part of clinical management were recruited for this study. After urodynamic diagnosis cases were classified into 1 of 5 dysfunction groups as normal bladder outflow obstruction, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability. A detrusor muscle biopsy was taken from the lateral wall of the bladder at cystoscopy for subsequent electron microscopy. RESULTS Of the 27 cases 6 were normal, 9 had bladder outflow obstruction and detrusor instability, 8 had pure detrusor instability and 4 had idiopathic sensory urgency. The obstructed group showed the myohypertrophy pattern previously reported. In contrast to previous reports, abnormal junctions were found in all patients. For each patient the ratios of abnormal-to-normal junctions were calculated. Mean and standard error ratios were 1.1+/-0.1, 2.7+/-0.2, 6.1+/-1.2, 13.3+/-4.4 for normal, idiopathic sensory urgency, obstruction with detrusor instability and pure detrusor instability, respectively (p = 0.0003, 0.0042 and 0.04). CONCLUSIONS There are distinct morphological changes in the detrusor associated with bladder dysfunction. The ratio of abnormal-to-normal junctions is a novel measurement and can be used to predict urodynamic dysfunction. Ultrastructural studies may be useful as an adjunct in the diagnosis of bladder dysfunction.

Argyrophilia and endometrial carcinoma.

The incidence and patterns of argyrophilia in 25 endometrial carcinomas were analysed and correlated with other pathological features. In addition, the frequency with which argyrophilia was identified within nonneo-plastic endometrium and cervix from this carcinoma group was compared with that of a control group of 25 patients without malignant disease. Using the Grimelius stain, argyrophilia was observed in 68% of endometrial carcinomas, although in 28%, only rare positive cells were identified. Seven tumours (six argyrophilic carcinomas and one small-cell undifferentiated carcinoma) were examined by electron microscopy, which revealed neurosecretory granules. Argyrophilia was also found at the ultrastructural level. ACTH and calcitonin were revealed by the immunoperoxidase technique in four of the nine argyrophilic tumours examined. Argyrophilic cells in nonneoplastic endometrium were found in 10% of the carcinoma cases and 8% of the control cases; this has not been described previously. No correlation could be established between the presence or degree of argyrophilia and histological type or grade of carcinoma, extent of tumour infiltration, or argyrophilia in nonneoplastic endometrium or cervix. We conclude that argyrophilia in endometrial carcinomas has no clinicopathological significance. The histogenesis of endometrial and cervical argyrophilic cells is discussed.

Microvillous inclusion disease: report of a case with atypical features.

Microvillous inclusion disease is a rare lethal disorder characterized by intractable, severe, watery diarrhea beginning in early infancy. The underlying defect is thought to be an autosomal recessive genetic abnormality resulting in defective brush-border assembly and differentiation. Normally, this diagnosis is easily established through the electron microscopic demonstration of characteristic microvilli-lined inclusions lying within the apical cytoplasm of surface enterocytes. In a small number of patients appearing to have microvillous inclusion disease it has not proven possible to demonstrate the typical inclusions. The existence of another entity, termed intestinal microvillous dystrophy, has been proposed to account for such occurrences. This assertion was founded in large part upon the observation that the few subjects studied all displayed a slightly atypical clinical presentation. The case now being presented exhibited the morphologic features ascribed to intestinal microvillous dystrophy but had a clinical presentation that was entirely typical of microvillous inclusion disease. It serves thus to conceptually unite intestinal microvillous dystrophy with microvillous inclusion disease.

Myosin storage (hyaline body) myopathy: a case report.

Myosin storage myopathy/hyaline body myopathy is a rare congenital myopathy, with less than 30 cases reported in the literature. It is characterised by the presence of subsarcolemmal hyaline bodies in type 1 muscle fibres and predominantly proximal muscle weakness. Recently, a single mutation (Arg1845Trp) in the slow/beta-cardiac myosin heavy chain gene (MYH7) was identified in four unrelated probands from Sweden and Belgium. The clinical severity and age of onset was variable, despite the same disease-causing mutation and similar histological findings. Here, we report the clinical and morphological findings of two brothers of English/Scottish background with the Arg1845Trp mutation in MYH7. This case report adds to the clinical description of this rare disorder and confirms that Arg1845Trp is a common mutation associated with this phenotype, at least in the White European population.

Electron Microscopy in the Diagnosis of Percutaneous Fine Needle Aspiration Specimens

Five years experience in the application of electron microscopy to fine needle aspiration biopsy specimens is reviewed. In an initial evaluation, 200 consecutive unselected specimens were examined; 89 proved diagnostic and, in a third of these, electron microscopy gave additional information that was often essential to diagnosis. Negative specimens resulted almost entirely from failure to obtain an adequate amount of material. Results were improved by the adoption of a preparation technique involving concentration of the cells in bovine serum albumin and by the inspection of a rapidly stained smear at the time of the aspiration procedure, with a further needle pass for electron microscopy being performed if necessary. Despite the small size of specimens, adequate examination was usually possible and electron microscopy has proved of value in the diagnosis of tumor samples acquired by fine needle aspiration in the same way as has been established with the larger sized specimens obtained by conventional biopsy and surgical resection.

Parachordoma is not distinguishable from axial chordoma using immunohistochemistry

Parachordoma is a rare soft tissue tumor that morphologically resembles chordoma of the axial skeleton but occurs in a peripheral site. A recent study reported immunohistochemical differences between chordoma and parachordoma. While both tumors were positive for cytokeratin (CK) 8/18 (as recognized by the antibody Cam5.2), S100 and epithelial membrane antigen (EMA), only the chordoma was positive for CK7, CK20, CK 1/5/10/14 (as recognized by the antibody 34βE12) and carcinoembryonic antigen (CEA). It has since been suggested that tumors indistinguishable from chordoma that involve the periphery should be termed chordoma periphericum and that these tumors are distinct from parachordoma. In the current study, the clinical, radiological, pathological, immunohistochemical and ultrastructural features of a chordoma‐like tumor involving the deep soft tissues of the lower leg of a 69‐year‐old woman are presented. Microscopically, the tumor had a pseudolobulated growth pattern and consisted of sheets, nests and cords of epithelioid cells, some with a physaliferous appearance, separated by abundant myxoid stroma. The tumor cells were positive for CK 8/18, EMA and S100, showed focal staining for CK7, and were negative for CK20, CK 1/5/10/14 and CEA. On the basis of these results a diagnosis of parachordoma was favored. For comparison, an immunohistochemical analysis of five axial chordomas was also performed. The chordomas showed positivity for CK 8/18 (5 of 5 cases), EMA (5 of 5 cases), S100 (5 of 5 cases), CK 1/5/10/14 (1 of 5 cases) and CK7 (1 of 5 cases). Stains for CK20 and CEA were negative in all five chordomas. The results of the present study suggest that the expression of antigens for CK 1/5/10/14, CK7, CK20 and CEA in chordoma might not be as common as what has been previously reported. The results also suggest that parachordoma might not be easily distinguished immunohistochemically from axial chordoma (and therefore also from so‐called chordoma periphericum).

Features of squamous and adenocarcinoma in the same cell in a xenografted human transitional cell carcinoma: Evidence of a common histogenesis?

SummaryUltrastructural features of squamous differentiation have been found in adenocarcinomatous cells in a xenografted line (UCRU-BL-17) established in nude mice from a primary human bladder transitional cell carcinoma (grade III, stage T4) with a tetraploid DNA component. The line has been characterized by light and electron microscopy, flow cytometry and immunocytochemistry. The initial xenograft showed predominantly adenocarcinomatous differentiation with mucin secretion, whilst the subsequent passages also contained cells showing squamous differentiation. A xenograft subline established from a cell culture of the initial xenograft shows the emergence of a population of cells with near triploid DNA, which are less differentiated, grow more quickly, show decreased expression of carcinoembryonic antigen, and a change in the distribution of staining with peanut lectin from cell surface to cytoplasm. These lines offer an unusual opportunity to study the histogenetic relationships between the histological subtypes of bladder cancer.

Generalized pustular psoriasis responsive to PUVA and oral cyclosporin therapy

A patient with acute generalized pustular psoriasis was successfully treated with a combination of oral cyclosporin (6 mg/kg per day) and photochemotherapy (PUVA). Although early inpatient treatment with weak topical steroids and PUVA produced initial improvement, the patients clinical condition fluctuated, with the subsequent development of erythroderma. The addition of oral cyclosporin produced dramatic improvement within 1 week of its commencement. The patient remained in remission 12 months following cessation of therapy.