A comparative immunohistochemical study of malignant mesothelioma and renal cell carcinoma: the diagnostic utility of Leu-M1, Ber EP4, Tamm-Horsfall protein and thrombomodulin

Metastatic renal cell carcinoma has occasionally been reported to mimic malignant pleural mesothelioma. Morphologically, histochemically and immunohistochemically, similarities in the two tumours exist making their differentiation difficult, particularly in biopsy specimens. The aim of this study was to make a comparative immunohistochemical analysis of the two tumours by use of a panel of four antibodies (Leu M1; Ber EP4; thrombomodulin and Tamm-Horsfall protein). Their suitability in differentiating between the two tumours was assessed. We examined 20 cases of renal cell carcinoma and 20 cases of malignant pleural mesothelioma. On immunostaining with Leu M1, 14 of 20 renal cell carcinomas were positive, yielding 70% sensitivity and 95% specificity and one of 20 mesotheliomas. In comparison, Ber EP4 antibody stained only seven of 20 of the renal cell carcinomas. In addition, it was noted that four tubulopapillary pattern renal cell carcinomas stained positively with both anti-Leu M1 antibody and Ber EP4 antibody. Thrombomodulin immunostaining was present in 11 of 20 mesotheliomas (55% sensitivity and demonstrated 95% specificity) and one of 20 renal cell carcinomas. For epithelial mesotheliomas only, thromobomodulin staining was identified in 10 of 14 cases. In the differentiation of renal cell carcinoma from epithelial mesothelioma we recommend the use of Leu M1 and thrombomodulin as diagnostically useful markers. None of the antibodies used in this study was effective in distinguishing sarcomatoid renal cell carcinoma from sarcomatous mesothelioma. Tamm-Horsfall protein showed little diagnostic utility in differentiating the two tumours.     

Granular cell tumours of the lower respiratory tract

Granular cell tumours rarely involve the lower respiratory tract. We report eight cases surgically resected at our institution. There were four females and four males, aged between 18 to 56 years (mean 40). One tumour associated with a peripheral lung adenocarcinoma was asymptomatic. The other lesions presented with obstructive pneumonitis (3 cases), haemoptysis (2), dyspnea (1) or cough (1). These tumours were tracheal (1) or bronchial (6) and one case was located in the lung parenchyma. Four cases were multicentric with associated lesions located in a bronchus (2), the oesophagus (1) or a mediastinal lymph node (1). All tumours, with the largest diameter ranging from 0.5–4.5 cm, were histologically invasive. The tumours were positive for S-100 protein, neuron specific enolase, KP1 (CD68) and vimentin. No tumour expressed desmin, keratin or p53 oncoprotein. Our study demonstrates that, in spite of marked anatomical and clinical polymorphism, the rare granular cell tumours of the lower respiratory tract have a constant histological appearance. Our observations confirm that large tumours (> 8–10 mm) usually extend beyond the tracheo-bronchial cartilages and, therefore, only surgical treatment may avoid recurrence.     

Coronary Splinting in Cardiogenic Shock

An 84-year-old woman experienced an acute anterior wall myocardial infarction complicated by cardiogenic shock. Coronary angiography demonstrated a subtotal occlusion of the proximal left anterior descending artery. Conventional percutaneous transluminal coronary angioplasty, including a 15-minute perfusion balloon dilatation resulted in a persistent intraluminal filling defect with high grade stenosis and ongoing ischemia and hypotension. Coronary splinting was performed, using an autoperfusion balloon to achieve a 6-hour dilatation of the vessel in conjunction with balloon aortic counterpulsation. The patient remained hemodynamically stable during this lengthy dilatation without ECG evidence of ischemia. Angiography postdilatation demonstrated a minor residual stenosis with no evidence of intraluminal thrombus. The patient was discharged 8 days later without congestive heart failure. Follow-up at 3 months demonstrated normal left ventricular function with no evidence of anterior wall infarction or ischemia by thallium imaging . (J Interven Cardiol 1996;9:65–67)     

Automatic Implantable Cardioverter Defibrillator/Permanent Pacemaker Interaction: Loss of Pacemaker Capture Following AICD Discharge

A 78-year-old man treated with amiodarone for recurrent ventricular tachycardia, had sequential placement of a bipolar VVI pacemaker and an automatic implantable cardioverter defibrillator (AICD). During defibrillation threshold testing, there was failure to capture of the pacer in the post-shock period. The time of failure to capture appeared energy-related: the greater the energy delivered, the longer the failure to capture. Careful attention will be necessary in constructing combined AICD/pacemaker units.     

Autonomic Regulation of Voltage-Gated Cardiac Ion Channels

Altering voltage-gated ion channel currents, by changing channel number or voltage-dependent kinetics, regulates the propagation of action potentials along the plasma membrane of individual cells and from one cell to its neighbors. Functional increases in the number of cardiac sodium channels (Na_V1.5) at the myocardial sarcolemma are accomplished by the regulation of caveolae by β adrenergically stimulated G-proteins. We demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 channels specifically localize to isolated caveolar membranes, and to punctate regions of the sarcolemma labeled with caveolin-3. In addition, we show that Na_V1.5, Ca_V1.2a, and K_V1.5 channel antibodies label the same subpopulation of isolated caveolae. Plasma membrane sheet assays demonstrate that Na_V1.5, Ca_V1.2a, and K_V1.5 cluster with caveolin-3. This may have interesting implications for the way in which adrenergic pathways alter the cardiac action potential morphology and the velocity of the excitatory wave.     

Magnetic fields elicited by tones and vowel formants reveal tonotopy and nonlinear summation of cortical activation

A long-latency response component (N1m) and the sustained field (SF) of the auditory evoked magnetic field elicited by two composite stimuli (a two-tone combination and a two-formant vowel) and their individually presented components (a 600-Hz and a 2100-Hz pure tone and two single-vowel formants with formant frequencies matched to the tone frequencies) were recorded using a 37-channel magnetometer. The response to the composite stimuli differed from the linear sum of the responses to the respective components in latency, equivalent dipole moment, and equivalent dipole location, suggesting an interaction among the processes elicited by the constituents of composite stimuli. Nlm and SF source locations were more medial for the response to the high tone than to the low tone and more medial for the response to the high vowel formant than to the low vowel formant. The Nlm formant sources were more lateral than the Nlm tone sources. These findings suggest that, at the level of the auditory cortex, vowels are represented in terms of both the spectral pitches determined by their most prominent harmonics and, within the latency range of the Nlm, the virtual pitch determined by the spacing of the harmonics.     

Update on Catheter Ablation for Atrial Fibrillation

Atrial fibrillation (AF) is a common arrhythmia that can be treated with antiarrhythmic drugs and electrical cardioversion. New therapies such as the automatic implantable atrial defibrillator, multisite atrial pacing, and catheter ablation are being studied extensively. Ablation for AF is in its infancy. There are different mechanisms of AF, and, therefore, there can be no single approach to therapy. One question is whether radiofrequency electricity (RF) is the best source of energy for catheter ablation for AF. RF results have been disappointing for the treatment of ventricular tachycardia, presumably because of the small size of the lesions that are produced. Other sources of energy such as microwave energy, which produces larger and deeper lesions, may be necessary in the future. RF might be modified to produce a larger lesion, perhaps by cooling the ablating electrode so that neighboring myocardium does not become charred and a higher dose of electricity can be delivered with greater penetration into deeper layers of myocardium. These efforts at producing larger lesions must be tempered by close attention to maintaining a high level of safety. AF usually is not immediately life threatening, thus a risky therapy will not be acceptable. The procedure should not expose the patient to excessive procedural time or an excessive radiation dose. From laboratory and clinical evidence, it is clear that a catheter ablation cure for some forms of AF will become available in the future, as long as our understanding of the mechanisms of AF continues to increase and ablative techniques continue to evolve.