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BACKGROUND: Atypical naevi are common benign skin lesions but are also recognized both as precursors of and risk factors for melanoma. It is therefore imperative to excise those lesions that are either likely to progress or are already progressing to melanoma. Clinically, however, it may be difficult to distinguish these from benign atypical naevi with bland histology. OBJECTIVES: To analyse the clinical characteristics of excised melanocytic lesions and to identify the predictors of severe histological atypia/melanoma in situ and invasive melanoma. METHODS: The case notes of 434 patients who had melanocytic lesions removed at a pigmented lesion clinic were studied retrospectively. A single pathologist reviewed the excised lesions and clinical characteristics predictive of malignancy were identified. RESULTS: The best predictors of melanoma were older age, history of change and site on an extremity, but only older age was predictive of severe histological atypia/melanoma in situ as opposed to mild to moderate atypical histology. CONCLUSIONS: These results confirm the difficulty of differentiating accurately between benign atypical naevi and borderline lesions or early melanoma in a clinical setting. It is therefore necessary to have a sufficiently low threshold for excision to avoid missing early melanomas, particularly in older patients presenting with lesions on the extremities.

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BACKGROUND: Desmoplastic melanoma (DM) is an uncommonly encountered type of malignant melanoma. The clinical appearance of DM can be highly variable and thus, diagnosis of this tumour is difficult and very often may mislead the physician. OBJECTIVES: To make a critical review of the contemporary literature on DM, to pool the data from published studies and to evaluate the clinical and morphological characteristics of this neoplasm. METHODS: All studies or reports on DM including 10 or more participants with reported clinical and histological characteristics of the tumour were included. RESULTS: In the 17 studies that met the inclusion criteria a total of 856 patients with DM was reported. There was a male predilection, with a male/female ratio of almost 2 : 1 (63% of the lesions were diagnosed in males). The head and neck were the most common sites of DM for both sexes (53.2%). The data confirmed that DM usually has an advanced Breslow thickness at the time of presentation. Histopathological diagnosis of DM is sometimes difficult and the absence of pigmentation is probably the major cause for failure to recognize DM histologically. The pooled data from included studies showed that the incidence of nodal metastasis is lower in patients with DM than in patients with other forms of cutaneous melanoma. CONCLUSIONS: Prompt definitive surgical excision is the treatment of choice for DM. Improved knowledge of the clinical behaviour and histological features of DM is important for more effective management of patients with DM.

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PURPOSE: To assess image-guided peritoneal core biopsy for the diagnosis of tumor type and treatment of patients with peritoneal carcinomatosis. MATERIALS AND METHODS: Thirty-five women (age range, 47-85 years; mean age, 69 years) prospectively identified in a gynecologic oncology center underwent 18-gauge core biopsy in omental cake (n = 25), peritoneal (n = 7), or adnexal (n = 3) sites. No complications of biopsy occurred. Standard hematoxylin-eosin analysis of the biopsy cores was supplemented by immunohistochemical markers to CA-125, carcinoembryonic antigen, cytokeratin 7, and cytokeratin 20. Diagnoses were validated with further multidisciplinary review, subsequent surgery, and response to specific chemotherapy. RESULTS: In 27 (77%) of the 35 women, a confident primary site diagnosis was obtained with standard hematoxylin-eosin analysis of core biopsy material from the following sites: ovary (n = 22), breast (n = 2), colon (n = 2), and lymphoma (n = 1). The finding at hematoxylin-eosin analysis in another seven (20%) women was poorly differentiated adenocarcinoma with no definite primary site but with an immunohistochemical profile suggesting ovarian cancer (CA-125 positive, carcinoembryonic antigen negative, cytokeratin 7 positive, cytokeratin 20 negative). There was one false-negative biopsy result. CONCLUSION: Image-guided peritoneal core biopsy with hematoxylin-eosin analysis supplemented with immunohistochemical analysis is a simple, safe, and accurate technique for providing site-specific diagnoses in women with undiagnosed peritoneal carcinomatosis.

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Patients attending the ear, nose and throat (ENT) department at St James's University Hospital, Leeds, UK, for evaluation of palpable head and neck lesions have a fine needle cytology (FNC) specimen taken and receive the result at the same out-patient visit. This study was designed to discover if there is a significant difference in the efficiency of the methods with and without suction. The method was chosen randomly on each occasion and the adequacy or otherwise of the specimen was determined taking into account the site and nature of the lesion and the total cellularity of the sample. The level of blood contamination was also compared by each method. When benign and malignant lesions from all sites were analysed together the method with suction produced a significantly higher number of adequate samples than the method without suction. The exception was in the case of samples from lymph node lesions measuring < 1 cm, where adequate specimens were only obtained without suction. The non-suction technique was particularly poor at sampling salivary gland lesions in the 1-1.5 cm category. There was no significant difference in the level of blood contamination between the two methods at any site. These results are at variance with most other similar studies and possible reasons for this are discussed.

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The purpose of this study was to determine the utility of prostate specific antigen (PSA) level and Gleason score in the prediction of disease stage in men with newly diagnosed prostate cancer. 102 consecutive men, newly diagnosed with prostate cancer and candidates for radical therapy, underwent contrast enhanced pelvic CT and skeletal scintigraphy. Staging examinations used the TNM classification and were reported prospectively with the radiologist blinded to the patient's Gleason score and level of PSA. Lymph node metastasis was confirmed by CT guided biopsy, lymphadenectomy or response to therapy in some cases of massive disease. There were significant differences between the mean PSA values of 18 men with and 84 men without skeletal metastases (p = 0.01) and between men with locally confined and non-confined disease (p = 0.02). There was no difference between PSA values of 13 men with and 89 men without lymph node metastasis (p = 0.9). Only one man with CT evidence of nodal metastasis (N + ve) had a PSA value below 20 ng ml-1. Two men with Gleason scores below 6 were N + ve and both had PSA values over 20 ng ml-1. One man with skeletal metastasis had a PSA value below 20 ng ml-1 but had bone pain. For this study group if only those men with PSA values over 20 ng ml-1 had been examined, sensitivity for lymphatic and skeletal metastasis would have been 92%. Using this threshold about one-third would have been spared imaging investigation. In conclusion, pelvic CT and skeletal scintigraphy are unlikely to show metastatic disease in a man newly diagnosed with prostate cancer who has no suggestive clinical features, a PSA level below 20 ng ml-1 and a Gleason score below 6.

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A slide circulation scheme measuring cervical screening performance of individual cytologists in 15 laboratories in Yorkshire Regional Health Authority is described. The advantages and disadvantages are compared with the current National Proficiency Testing (NPT) scheme. The results indicate that a slide circulation scheme can be successfully used in cervical cytology external quality assessment (EQA). Levels of participation are better than those currently achieved by regional variations of the NPT scheme, and the use of laboratory consensus in the selection of scoring slides appears to be no less valid than the use of a pre-selected slide pool assembled by an expert panel. The volume of data accumulated in one round is considerably greater than that achieved by proficiency testing and the educational value is regarded as high. However, the scheme is very time consuming for participants and consequently expensive for laboratories. The lack of external supervision increases the risk of unfair practices within individual laboratories. Because of these problems, Yorkshire has now switched to an NPT scheme.

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We have studied changes in the pattern of intrinsic hepatic innervation in sequential liver biopsies from 16 patients who underwent orthotopic liver transplantation. Seventy-one needle biopsies were used, including specimens obtained at the time of transplantation (time zero) and up to 4 years post-transplantation; five transplant hepatectomy tissue blocks removed 3-32 months after transplantation were also assessed. Paraffin sections were immunostained with anti-PGP 9.5 and anti-S-100 to identify nerve fibres. All 'time zero' biopsies contained portal nerves and all but two showed staining of parenchymal fibres. After 1 week, no subsequent biopsies contained parenchymal fibres. The disappearance of portal fibres was less rapid and showed greater variability between patients, but they had all disappeared by 6 weeks and there was no positive staining between 6 and 60 weeks. Thereafter, a minority of biopsies showed innervation of a few small portal tracts. Samples from the porta hepatis, hepatectomy specimens, and needle biopsies containing large tracts showed persistence of major nerve trunks at all stages. Abnormally large nerve bundles were seen in some of these areas. The pattern of nerve staining showed no obvious relationship to the intensity of rejection changes. Our results suggest that there is a limited, delayed capacity for regeneration of portal, but not parenchymal, fibres in the transplanted human liver. The physiological significance of this long-term parenchymal denervation in transplanted livers remains to be determined.

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Granulomas are thought to represent an immune reaction to antigenic stimulation. Bone marrow granulomas are uncommon, but in the following case report we show their transient appearance after interleukin 2 (IL-2) and autologous lymphokine-activated killer cell therapy. This is a previously unreported association, and may implicate IL-2 in the pathogenesis of granulomas.

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A fifty-year-old woman with a history of breast cancer presented with a clinically benign ovarian cyst. Laparoscopic aspiration of cyst fluid was performed and the cytology was suspicious of epithelial neoplasia. At subsequent hysterectomy and bilateral salpingo-oophorectomy, the specimen showed extensive metastatic breast carcinoma. Although the cytological examination of fluid from ovarian cysts is often unrewarding, this case shows that metastatic carcinoma may occasionally be diagnosed in this fashion.

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Five cases of central pontine myelinolysis (CPM) were detected by neuropathological examination in a series of 50 patients coming to necropsy after liver transplantation. One patient also had extrapontine myelinolysis. In no case was the diagnosis made during life. Only two patients showed rapid rises in serum sodium concentrations. The incidence of hyponatraemia, before and after transplantation, and rapid rises in serum sodium in patients with CPM was significantly greater than in the 45 patients showing no neuropathological evidence of CPM. It is concluded that there is a high incidence of CPM after liver transplantation, that clinical diagnosis is difficult, and that there is no simple direct correlation between rapid serum sodium changes and the development of this condition. Avoidance of major electrolyte fluctuations at the time of liver transplantation is recommended but it must be emphasised that CPM may occur without any rapid rise in serum sodium concentration.

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Between 1980 and 1989, 32 cases of invasive aspergillosis were identified out of 2315 consecutive necropsies, an incidence of 1.4%. The incidence in immunosuppressed "high risk" patients was 10.7%. Twenty out of 32 cases showed spread beyond the lungs, with the brain the most common site. There was an increase in cases in the second half of the decade, attributable to the start of a liver transplantation programme. Liver transplant recipients and patients with haematological malignancies were at significantly greater risk of acquiring aspergillosis than kidney transplant recipients or those with solid malignancies treated with chemotherapy. There was also a greater risk of haematogenous dissemination in liver transplant recipients than in all other groups, and this was significantly associated with the use of high dose steroids as anti-rejection treatment. Aspergillus was isolated during life in only eight cases, which indicates a continuing need for and emphasises the value of necropsy.

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Nine cases of cerebral aspergillosis were identified in a series of 44 brains obtained at necropsy from patients who had undergone liver transplantation. In two of these there was dual infection with Candida albicans. The primary focus of infection was invariably in the lungs. One case of pulmonary Aspergillus infection was found with no evidence of cerebral disease. Infection tended to occur in the period soon after transplantation, was associated with high dose steroids, retransplantation, and showed a significant seasonal incidence. Neurological findings were non-specific and only two cases were diagnosed before death. Aspergillus infection soon after transplantation indicates that this organism is a considerable nosocomial hazard, particularly in the winter and spring months. Positive cultures before death are rarely obtained and antifungal treatment should be started on clinical suspicion alone.

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The wheal-and-flare response to intradermal autologous serum in chronic urticaria offers a model for study of the pathogenesis of the disorder. Serial biopsies of autologous serum induced wheals were performed in 5 chronic urticaria patients to assess the evolution of the cellular inflammatory response and to look for evidence of mast cell degranulation. Perivascular neutrophils and eosinophils were seen as early as 30 min, becoming more intense and diffuse over 2 h. T lymphocyte numbers were increased by 2 h, CD4+ cells outnumbering CD8+ cells at 24 h. By 48 h, the neutrophils were clearing, but eosinophils and lymphocytes persisted. The histology of compound 48/80-induced wheals was similar to serum-induced wheals, but there was little or no response to physiological saline (0.16 M). Stainable mast cells were reduced in compound 48/80- and serum-induced wheals when compared to saline skin tests. Mast cell granules appeared swollen and had lost their characteristic lamellar substructure on electron microscopy of a serum-induced wheal biopsied at 10 min. Eosinophil degranulation was also observed at 2 h. The resemblance of the inflammation to the late phase of IgE-mediated immediate hypersensitivity reactions in atopics supports the concept that a circulating factor causes mast cell degranulation in chronic urticaria and may be important in the pathogenesis of the disorder.

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A patient with widespread livedo reticularis and transient cerebral ischaemia (Sneddon's syndrome) is described. She also had painful scarring ulcers of the lower legs resembling livedo vasculitis and a circulating anticardiolipin antibody. We suggest that Sneddon's syndrome and livedo vasculitis may be pathogenetically related.

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