Diagnosis of malignant mesothelioma by fine needle aspiration of a cervical lymph node. A case report.

BACKGROUND: Clinically documented distant metastases are rare in mesothelioma and tend to occur late in the course of the disease, well after the diagnosis has been made. In this instance, diagnosis was not made until a metastatic deposit was identified microscopically in the enlarged lymph node. CASE: A 65-year-old male with no definite history of occupational asbestos exposure presented with chest pain, pleural effusion and supraclavicular lymphadenopathy. Cytologic examination of material obtained by fine needle aspiration from his cervical lymph node revealed malignant mesothelioma. This was confirmed on histology. CONCLUSION: This was a particularly rare presentation and, as far as we are aware, was the first case in which mesothelioma was diagnosed by fine needle aspiration of a cervical lymph node. It serves to remind the pathologist that when confronted with a lymph node involved by tumor, the possibility of mesothelioma should be included in the differential diagnosis. The case also demonstrates the usefulness of fine needle aspiration in the diagnosis of metastatic tumor.

Metastatic liposarcoma in the adrenal gland: report of two cases diagnosed by fine-needle aspiration.

Fine-needle aspiration is now well established in the investigation of retroperitoneal masses. Many of these lesions are first detected in the course of radiological surveys of patients with known or suspected malignancy. It can be difficult to diagnose sarcomas on fine-needle aspiration material as many of these tumour do not show cytological features of malignancy. We describe two cases of metastatic liposarcoma confidently diagnosed on the basis of characteristic cytological features seen in material aspirated from metastatic adrenal tumours.

Cancer associated human papillomaviruses: perinatal transmission and persistence.

OBJECTIVE: To demonstrate the perinatal transmission and persistence of the cancer associated human papillomavirus types 16, 18, 31 and 33. DESIGN: Cervical swabs were taken from pregnant women between 20 and 38 weeks of gestation. Buccal and genital swabs were taken from infants at 24 h and at six weeks after delivery and examined for HPV-16, -18, -31 and -33 DNA by the polymerase chain reaction. SETTING: Maternity Unit at St Thomas's Hospital, London. SUBJECTS: Thirty-one pregnant women, 16 with a previous history of cervical intraepithelial neoplasia or genital warts, or both, and their 32 infants (one set of twins). RESULTS: Twenty of the 31 (65%) women were positive for HPV-DNA prior to delivery. Twelve of 32 (38%) and eight of 31 (26%) infants were HPV-DNA positive at 24 h and six weeks respectively. Swabs taken at 24 h demonstrated HPV type 16 in five mother-infant pairs and HPV type 18 in two mother-infant pairs. Dual infections with HPV types 16 and 18 were demonstrated in swabs from three mother-infant pairs. At six weeks, HPV-16 was demonstrated in swabs from six infants and HPV-18 in swabs from two infants. CONCLUSIONS: Perinatal transmission of human papillomavirus types 16 and 18 occurred in 55% cases. Persistent human papillomavirus infection was demonstrated at six weeks of age. Whether acquisition of human papillomavirus during the perinatal period predisposes to an increased risk of cervical intraepithelial neoplasia among female infants in later life remains to be established. Information on the persistence of perinatally acquired human papillomavirus is required before rational vaccination programmes can be considered.

Clinical utility of the immunocytochemical detection of p53 protein in cytological specimens.

In the important cytopathological distinction between benign and malignant lesions, there is always a residue of suspicious cases which cannot be satisfactorily diagnosed. Overexpression of the p53 tumor suppressor gene product has been consistently correlated with p53 missense gene mutation and is associated with malignancy. Therefore, assessment of p53 expression may assist in the cytopathological diagnosis of malignancy. Immunohistological assessment of p53 expression has been performed on a prospective series of 1333 nongynecological cytological specimens in the setting of a teaching hospital group. Evaluation of p53 staining was performed without knowledge of cytological diagnosis. Resultant p53 expression data were correlated with cytological diagnosis and clinical information. Of the 999 assessable cases, 956 had a clear cytological diagnosis. In these, p53 overexpression occurred in 108 cases of which 86 were malignant lesions. Of the 848 p53-negative cases, 119 were in fact neoplasms. The false positives were predominantly (19 of 22) reactive mesothelial proliferations, and overexpression occurred in only a small proportion of cells. While the sensitivity of p53 overexpression is low (p53 overexpression only occurring in 41.9% of tumors), the overall specificity is 97%. In the 43 cytopathologically suspicious cases, 7 were p53 positive, all of which proved to be malignant. In this prospective unselected series, we have conclusively demonstrated a close correlation between overexpression of p53 protein and neoplasia. Furthermore, we have shown the possible utility of p53 immunostaining in cytopathology. While there are important technical caveats and some cytological specimens are suboptimal for immunostaining, the data indicate that assessment of p53 is a valuable adjunct to morphological assessment in the analysis of cytopathologically suspicious cases.

Thromboxane A2 mediates pulmonary hypertension after cardiopulmonary bypass in the rabbit.

Clinically, it is well established that cardiopulmonary bypass results in pulmonary dysfunction. Using a recently developed preparation for cardiopulmonary bypass in the rabbit, we have been able to mimic a similar, but more severe, condition. We found that, despite normal histologic structure of the myocardium, hearts could not be weaned from bypass because of a serious increase in pulmonary vascular resistance. Histologic studies of the lungs showed severe intravascular neutrophil aggregation and marked vasoconstriction. To identify the nature and origin of the mediator responsible for the changes in the pulmonary vasculature, we subjected groups of rabbits (n = 4 per group) to bypass with cooling to 18 degrees C, circulatory arrest for 1 hour, and rewarming on bypass to 33 degrees C. Pulmonary vascular resistance was measured at the same temperature before and after bypass. Four groups were studied: group I were untreated controls; group II received the cyclooxygenase inhibitor, indomethacin (0.2 mg/kg intravenously), before operation; group III received the thromboxane A2 synthetase inhibitor, Dazmegral (5 mg/kg intravenously), before operation together with the thromboxane A2 receptor blocker GR 32191B (2 mg/kg per 30 minutes intravenously); and group IV were treated with mustine hydrochloride (1.75 mg/kg intravenously) 3 days before the experiment to deplete the neutrophils by 90%. During circulatory arrest, the heart was protected with an initial infusion (10 ml at 4 degrees C over 1 minute) of St. Thomas' Hospital cardioplegic solution. At the end of the experiment, the heart and lungs were histologically examined. In the control group, a significant increase (+395% when compared with the value recorded before bypass) in pulmonary vascular resistance was observed after bypass. However, in none of the treated groups did pulmonary vascular resistance increase significantly (percentage changes in groups II, III, and IV were -24%, 0%, and +33%, respectively). Pulmonary histologic characteristics were normal in all treated groups, and all animals were successfully weaned from bypass. These results indicate that the increase in pulmonary vascular resistance that arises as a consequence of bypass in rabbits is primarily a result of the production of thromboxane A2, a process in which the neutrophil plays a pivotal role.

Early and late effects of leukopenic reperfusion on the recovery of cardiac contractile function. Studies in the transplanted and isolated blood-perfused rat heart.

BACKGROUND: Since there is considerable evidence that leukocytes contribute to tissue injury during ischemia and reperfusion, the present study was designed to: (1) determine whether reperfusion in vivo with leukopenic blood affords protection in a model of reversible hypothermic ischemia, (2) determine the duration of any protection, (3) characterize the relation between protection and duration of leukopenic perfusion, and (4) assess the effect of leukopenic reperfusion on myocardial glutathione content. METHODS AND RESULTS: Rat hearts (n = 12 per group) were excised, immediately arrested with an infusion (2 minutes at 4 degrees C) of St Thomas' cardioplegic solution, and subjected to 4 hours of global ischemia (4 degrees C). The hearts were then transplanted (1 hour additional ischemic time) into the abdomen of saline-treated or leukopenic recipients. Leukopenia was induced by intraperitoneal administration of mustine hydrochloride (2 mg/kg) 3 days before study. Hearts were then reperfused in situ for 1, 4, or 24 hours, after which they were excised and either processed for histological examination (n = 4 per group) or perfused aerobically with bicarbonate buffer for 20 minutes, and contractile function was assessed (n = 8 per group); at the end of this period, some hearts (n = 5 per group) were taken for metabolite analysis. After 1 hour of reperfusion, contractile function in the saline-treated control group was significantly reduced compared with aerobic controls that had not been subjected to ischemia (left ventricular developed pressure [LVDP], 108 +/- 5 vs 126 +/- 3 mm Hg at an end-diastolic pressure of 12 mm Hg; P < .05). However, in the hearts with leukopenic reperfusion, LVDP (119 +/- 2 mm Hg) was similar to that of aerobic controls. This benefit, however, was lost after 4 and 24 hours of reperfusion. Cardiac compliance was not influenced by leukopenia. Coronary flow recovered significantly better in the leukopenic hearts during the first 4 hours of reperfusion (11.8 +/- 0.5 vs 9.3 +/- 0.4 mL/min at 1 hour and 10.0 +/- 0.5 vs 8.0 +/- 0.4 mL/min at 4 hours, P < .05), but again this benefit was lost after 24 hours of reperfusion. The myocardial contents of reduced and oxidized glutathione after 1, 4, and 24 hours of reperfusion were similar in saline-treated and leukocyte-depleted animals. In additional studies, the period of ischemia was extended to 8 hours, and similar results were obtained, with improved recovery of contractile function and coronary flow but not cardiac compliance in the leukopenic group after 1 hour of reperfusion. In further studies with the isolated blood-perfused rat heart, ischemia was induced for 8 hours; this was followed first by reperfusion for 0, 2, 10, 30, or 60 minutes with leukopenic blood and then by perfusion with blood from saline-treated animals for 60, 58, 50, 30, or 0 minutes, respectively. Reperfusion with leukopenic blood for 2 minutes did not improve the recovery of LVDP (106 +/- 7 vs 96 +/- 10 mm Hg in controls; NS) but when continued for 10, 30, or 60 minutes resulted in significant improvements (137 +/- 5, 138 +/- 3, and 150 +/- 10 mm Hg, respectively). Although coronary flow tended to be greater in all leukopenic groups, by the end of 60 minutes of reperfusion, only those hearts reperfused with leukopenic blood for the entire reperfusion period showed a significant improvement (3.4 +/- 0.3 vs 2.5 +/- 0.2 mL/min in controls; P < .05). Histological studies revealed no intravascular aggregation of leukocytes or features of myocyte necrosis. CONCLUSIONS: Reperfusion with leukopenic blood accelerated the rate of recovery of cardiac function after reversible myocardial injury but did not lead to a sustained increase in the eventual extent of recovery. Reperfusion with leukopenic blood for the first 10 minutes of reflow is sufficient to obtain this benefit.

Fine needle aspiration cytology of a head and neck swelling in a child: a non-invasive approach to diagnosis.

A 12-year-old boy presented with a three-month history of a painful parotid swelling. Fine needle aspiration cytology indicated a pleomorphic adenoma--an uncommon lesion in a child. This diagnostic technique plays a useful role in the investigation of head and neck swellings.

Paper sections of macroenzymatically delineated myocardial necrosis.

Until now, the disadvantages of the nitroblue tetrazolium method of detecting myocardial necrosis have been that the colour reaction tended to fade and the wet heart slices were inconvenient for demonstration and storage. We have therefore modified the rapid technique of mounting sections of whole organs on paper to preserve the colour reaction. We can now show the extent of necrosis in permanent, readily portable, paper-mounted heart sections within 24 hours (although 48 hours is more convenient). Multiple preparations from multiple slices can be prepared for clinicopathological correlation, comparison with other cases, teaching, presentation at meetings, use in the case notes and distribution with the postmortem report.

Macroscopic enzyme histochemistry in myocardial infarction: use of coenzyme, cyanide, and phenazine methosulphate.

Transversely sectioned human heart slices, obtained at necropsy from normal subjects and from cases of recent myocardial infarction, were stained with the nitroblue tetrazolium (NBT) dehydrogenase macroreaction for the gross identification of recent myocardial infarction. The addition of nicotinamide adenine dinucleotide (NAD) to the incubating medium greatly improved the sensitivity of the method, while addition of cyanide caused just a modest improvement. Addition of the electron transfer mediator phenazine methosulphate (PMS) resulted in false non-selective staining and obscured areas of recent myocardial damage.

Macroscopic enzyme histochemistry in myocardial infarction: artefactual nature of the creatine phosphokinase reaction.

The histochemical creatine phosphokinase (CPK) tetrazolium test has been evaluated to detect recent human myocardial infarction in gross slices of the heart at necropsy. The demonstration of the lesion with this method has been assumed to result from local loss of CPK from the damaged myocardium. However, the present study indicates that the mechanism involved depends on localising NADPH tetrazolium reductase and not CPK. Phenazine methosulphate (PMS), when added to the incubating medium as an electron-acceptor to circumvent the tetrazolium-reductase (diaphorase) system, resulted in generalised false staining of the heart slice.

The non-specific nature of the myocardial wavy fibre.

Wavy myocardial fibres were found in about half each of a series of 28 normal and 31 infarcted human hearts, as well as in the normal heart of an infant. Such fibres were also seen in rather more than half of a series of normal rat hearts. Thus, the wavy fibre is not a specific feature of acute ischaemic heart disease. Some experimental evidence was obtained that patchy loss or preservation of ATP promotes the formation of wavy fibres.

Nitroblue tetrazolium test: early gross detection of human myocardial infarcts.

The hearts from 81 cases of suspected myocardial infarction were stained with the nitroblue tetrazolium (NBT) test to show damaged heart muscle in the gross at necropsy. Thirty-seven cases were of stated clinical age less than 12 h and 27 of these were less than 5 h. Seven out of 17 cases under 1 h were negative with NBT, but all other cases showed either focal diminution of staining with the dark blue diformazan or patchy red staining with the monogormazan of NBT. Thus the method may be of diagnostic value at necropsy from 1 h onwards after the time of apparent infarction (stated clinical onset). Satisfactory results were obtained up to 3 days at ambient temperature after death and for longer when the corpse was stored at 4 degrees C.