Utility of cytokeratin 7 and 20 subset analysis as an aid in the identification of primary site of origin of malignancy in cytologic specimens.

This study was undertaken to assess the utility of combined cytokeratin (CK) 7/20 immunoprofile determination in malignant cytologic cell blocks as an aid to the identification of tumor primary site of origin. Fifty-one cases in which CK 7/20 immunocytochemistry was performed as part of the initial workup were retrieved. Their contribution to the final cytologic diagnosis of tumor primary site of origin was analyzed. CK reactivity patterns were 7+/20- (n = 34), 7-/20+ (n = 9), 7-/20- (n = 7), and 7+/20+ (n = 1). The CK 7+/CK 20- immunophenotype was the most common one obtained, and due to its wide expression in a number of common carcinomas, the least informative. The second most common immunophenotype was CK 7-/20+, which is associated with colorectal origin, and as such was very useful when obtained. The CK immunoprofile was more useful in the setting of a prior carcinoma, being a major diagnostic determinant in 13 cases (55%) from group 1 (those with a prior history of malignancy), compared to 8 cases (29%) from group 2 (those with no prior history of malignancy). In the setting of prior carcinoma, the CK immunoprofile is most useful when carcinomas under consideration have different expected immunoprofiles (e.g., CK 7+/CK20- carcinomas, including lung, breast, ovary, endometrium, and others, vs. CK 7-/CK 20+ carcinomas, primarily colorectal). When similar immunoprofiles are obtained, their usefulness is greater if they are immunoprofiles other than the most common 7+/20- pattern. Similarly, in newly diagnosed carcinomas, the CK immunoprofile either helps to narrow the differential diagnosis or points to a specific diagnosis.

Neuroendocrine differentiation in gastric adenocarcinomas. An immunohistochemical study.

BACKGROUND: The stomach contains a wide variety of neuroendocrine cells. Early studies with argyrophilic stains documented the presence of these cells in gastric adenocarcinomas. Immunohistochemical techniques for demonstrating hormones are more sensitive and specific and have been applied only sporadically to gastric adenocarcinomas. Thus, the true incidence of neuroendocrine cells in gastric adenocarcinomas is questionable. METHODS: Formalin-fixed, paraffin-embedded archival tissue specimens from 48 gastric adenocarcinomas were immunostained with antibodies to chromogranin A, synaptophysin, serotonin, gastrin, and neuron-specific enolase. The percentage of cells staining positively was evaluated semiquantitatively. RESULTS: Among 48 gastric adenocarcinomas, 36 (75%) stained positively for chromogranin A, 33 (69%) stained for synaptophysin, 29 (60%) stained for neuron-specific enolase, 17 (36%) stained for gastrin, and 15 (31%) stained for serotonin. The distribution of positivity was highest for chromogranin A (7 cases positive in 26% to 75% of cells) and lowest for serotonin (14 out of 15 cases stained in fewer than 1% of the cells present). CONCLUSIONS: Immunohistochemical evaluation of neuroendocrine markers in gastric adenocarcinomas indicates that a high percentage of tumors contain widely scattered single cells with neuroendocrine differentiation. Most often, however, such cells constitute only a small percentage of the total number of tumor cells present.

Myonecrosis due to Clostridium septicum in a patient with unexplained neutropenia: successful treatment with granulocyte colony-stimulating factor.

We report a case of sepsis due to Clostridium septicum successfully treated with granulocyte colony-stimulating factor (GCSF). This case prompted our review of clostridial sepsis and considerations regarding the use of GCSF in cases of drug-induced neutropenia.

Descending thoracic aortomyoplasty: effect of chronically conditioned muscle on heart failure.

The effect of descending thoracic aortomyoplasty using conditioned latissimus dorsi muscle on cardiac output in five mongrel dogs with pharmacologically induced congestive heart failure was evaluated. A neurovascular left latissimus dorsi flap was lifted and through a left thoracotomy placed around the proximal descending thoracic aorta. The flap was conditioned for 4-6 weeks with a neurostimulator using the following parameters: amplitude 0.5 V, pulse width 210 microseconds and frequency 2 Hz. The neurostimulator was then removed and a cardiomyostimulator inserted and programmed to burst-stimulate the muscle during diastole. Baseline measurements of central venous pressure, heart rate, mean arterial blood pressure, pulmonary capillary wedge pressure, and cardiac output were obtained with the cardiomyostimulator off and on (study 1). Heart failure was induced with a combination of propranolol and verapamil, and measurements again taken with the stimulator off and on. The neurostimulator was reimplanted to continue stimulation of the latissimus dorsi muscle, and another set of measurements taken at 6 weeks with the cardiomyostimulator off and on (study 2). Counterpulsation in control conditions (before cardiac failure) in both studies demonstrated no significant increase in cardiac output. However, mean(s.d.) cardiac output was significantly (P < 0.1) increased by muscle stimulation in dogs with heart failure (study 1: from 2.39(1.10) to 3.14(1.41)l/min; study 2: from 1.89(0.64) to 2.38(0.57)l/min). There was no significant difference in the increase in cardiac output associated with muscle stimulation between studies 1 and 2. The results indicate that the model can increase cardiac output in heart failure and that this improvement is constant over a 4-6 week period, suggesting that muscle fatigue may not occur.

Eosinophilia-myalgia syndrome (L-tryptophan-associated neuromyopathy).

Histopathologic study of skeletal muscle biopsy in a patient with eosinophilia-myalgia syndrome following L-tryptophan use showed prominent lymphocytic perineuritis, neuritis, and perimysial fasciitis. The presence of perineuritis and neuritis provides a histopathologic basis for clinical features of neuropathy in eosinophilia-myalgia syndrome and occurred in conjunction with a fasciitis or interstitial myositis that was predominantly perimysial and focally endomysial.

Endothelial morphology and plasma total and high density lipoprotein cholesterol changes in hypothalamically stimulated squirrel monkeys fed a modified atherogenic diet.

Experimental animals fed atherogenic diets show endothelial damage, impairment of endothelial regeneration and plasma lipid changes characterized by elevation of LDL and decrease of HDL cholesterol concentrations. Previous studies in this laboratory disclosed that chronic electrical stimulation of the lateral hypothalamus was associated with electron-microscopic evidence of endothelial injury in rats and squirrel monkeys maintained on basal (low fat/cholesterol-free) diets. In the present investigation squirrel monkeys fed similar diets supplemented with "modest" amounts of caloric fat and cholesterol were subjected to chronic lateral hypothalamic stimulation for periods as long as 20 months with the expectation that endothelial injury would be greater than in the absence of the supplements. The expectations were not substantiated. Endothelium was found to be surprisingly intact by electron microscopy and similar to that of implanted nonstimulated controls. A further observation of interest was the cholesterolemic response, notably in the HDL fraction, observed in both groups, but more striking in experimental animals. The data suggest that an interaction between a modified lipid/cholesterol diet and hypothalamic stimulation may lead to elevation of plasma HDL cholesterol concentration and preservation of endothelial integrity. Further investigation is required to determine whether these two events are causally related.

Muscular ventricular septal defects repaired with left ventriculotomy.

Between 1974 and 1979 nine patients, aged 10 months to 4 years, underwent left ventriculotomy for closure of single or multiple defects in the muscular ventricular septum. The vertical incision paralleled the anterior descending branch of the left coronary artery near the apex of the left ventricle and ranged from 2.5 to 3.5 cm in length. Four patients also had a right ventriculotomy with closure of a high perimembranous ventricular defect in two. Serial electrocardiograms indicated changes of myocardial ischemia or necrosis. Left bundle branch block did not develop in any patient. Three patients died in the early postoperative period. The six surviving patients are living and well 2 to 7 years later. There is apparent complete closure of the ventricular defects, which was documented by cardiac catheterization in four cases. Two patients had cardiomegaly and left ventricular dysfunction as assessed with echocardiographic and angiographic study, whereas four displayed good cardiac function. In three of the latter patients, cardioplegia or deep hypothermia techniques were utilized intraoperatively. The observations indicate that left ventriculotomy of limited size is an acceptable approach to the difficult problem of repair of muscular ventricular defects but may involve some risk of compromise of the coronary circulation.

Effect of hypothalamic stimulation on the endothelial morphology of the aorta in the conscious squirrel monkey.

The role of neurogenic factors in the development of atherosclerosis has not previously been studied in detail. In recent years evidence has accumulated to implicate endothelial injury as a primary stimulus for the proliferation of myo-intimal cells resulting in the formation of the early morphologic lesion. In the present investigation, the effect on aortic endothelial morphology of repetitive electrical stimulation of the lateral hypothalamus in the conscious, unrestrained squirrel monkey, maintained on a cholesterol-free low-fat diet, has been studied. Stimulation was performed with a self-powered, miniaturized electronic stimulator connected to indwelling electrodes. Implanted nonstimulated animals served as controls. Endothelial injury in the form of cell degeneration, denudation, with plasma insudation and partial junctional separation were observed electron-microscopically in stimulated animals compared with controls. These alterations were found to be independent of hypercholesterolemia and/or hypertension. Possible pathways for the induction of injury in this neurogenic model are: (1) direct, through neural circuits from the brain to the vessel wall, and (2) indirect, by elaboration of angiopathic substances inside or outside of the CNS, released into the circulation and transported to the vessel wall where they exert their effects. Reversibility of the endothelial injury progression to established lesions and mechanisms involved remain to be determined in further investigations.

Cardiac fibromatosis: an ultrastructural study.

The fine structure of a surgically resected cardiac fibroma is described. The tumor consisted primarily of fibroblasts set in a matrix composed of acid mucopolysaccharide and collagen. Many of the fibroblasts contained abundant myofilaments and dense bodies, suggesting differentiation or transformation of these cells to myofibroblasts. No striated muscle was identified. This study confirms the fact that the cardiac fibroma is derived from connective tissue elements and should not be considered either a hamartoma or a mesoblastic tumor. Structurally, as well as biologically, the cardiac fibroma closely resembles soft tissue fibromatoses and should be considered an example of cardiac fibromatosis.

Recommended site and depth of newborn heel skin punctures based on anatomical measurements and histopathology.

The heels of 40 children (0.56--13.15 kg), 35 of whom were newborn infants and 28 of whom had 2--20 visible skin punctures, were examined at necropsy, and the thickness of the tissue layers was measured with a metric vernier caliper. Histological examination showed that uncomplicated skin-puncture wounds heal with minimum scarring and no neuroma formation. 1 infant had an infected puncture track extending into the calcaneus and resulting in cellulitis and focal calcaneal necrotising chondritis. The skin's primary blood-supply is located at the junction of the dermis and subcutaneous tissue, and the distance from the surface of the heel to this junction was quite constant (0.35--1.6 mm). However, the distance from the skin surface to the calcaneus increased with infant weight (in the smallest infant it was 2.4 mm), and at the posterior curvature of the heel it was half that from the plantar surface to the calcaneus. The calcaneus rarely extended lateral to a line drawn posteriorly from a point midway between the 4th and 5th toes and running parallel to the lateral aspect of the heel or medial to a line extending posteriorly from the middle of the great toe and running parallel to the medial surface of the heel. Therefore, in order to avoid calcaneal puncture and the risk of osteochondritis, heel puncture in the newborn should be done: (1) on the most medial or lateral portions of the plantar surface of the heel; (2) no deeper than 2.4 mm; (3) not on the posterior curvature of the heel; and (4) not through previous puncture sites that may be infected.