Dissociated overexpression of cathepsin D and estrogen receptor alpha in preinvasive mammary tumors.

The role of estrogen as a promoter agent of sporadic breast cancer has been considered by assaying, in benign breast disease (BBD) and in situ carcinomas (CIS), 2 markers, the estrogen receptor alpha (ERalpha) and cathepsin D (cath-D) involved in estrogen action on mammary tissue. ERalpha and cath-D were assayed by quantitative immunohistochemistry using an image analyzer in 170 lesions of varying histological risk (94 BBD and 76 CIS), and in "normal" glands close to these lesions. The ERalpha level increased significantly in proliferative BBD with atypia (P < .001), in non-high-grade CIS (P < .001), and in adjacent "normal" glands. ERalpha level was decreased in high-grade ductal CIS (DCIS) and also in adjacent "normal" glands. Cath-D level increased in ductal proliferative BBD (P < or = .01) and in high-grade DCIS (P < or = .003), but not in the other lesions. After menopause, ERalpha level was increased (P = .012) but not cath-D level. According to Mac Neman test, the high-grade DCIS were predominantly ERalpha negative and cath-D positive (P = .0017), and the other CIS were predominantly ERalpha positive and cath-D negative (P = .0002). The 2 markers are overexpressed early in premalignant lesions, but independently. This dissociation suggests a branched model of mammary carcinogenesis involving 1 estrogen-independent pathway with high cath-D and low ERalpha levels (including high-grade DCIS) and 1 estrogen-dependent pathway, with high ERalpha level (including proliferative BBD with atypia and low-grade DCIS). We propose that ERalpha-negative breast cancers may develop directly from high-grade DCIS and that ERalpha assay in preinvasive lesions should be considered in prevention trials with antiestrogens.

Ultrasonically guided aspiration biopsy in osteolytic bone lesions of the chest wall.

Sixteen consecutive patients with one or more osteolytic bone lesions of the chest wall radiologically confirmed underwent ultrasonically guided aspiration biopsy. Nine patients (56.2 percent) had bronchogenic carcinoma with a direct extension. Other diagnostic techniques had failed to diagnose disease in these patients. The lesion showed heterogeneous echogenicity (n = 16) caused by the hyperechoic signals of bone fragments. The interruption of the cortex bone was detected in all cases and extraosseous tumor portion in 14 of 16 patients (87.5 percent). No respiratory motions of the lesion could be demonstrated (n = 16). Definitive histologic diagnosis was made in 14 of the 16 patients (87.5 percent). In malignancy, diagnosis was established in 13 of 14 patients (92.8 percent). Of two confirmed benign lesions, one diagnosis of tuberculosis was obtained. No complication occurred. Sonography and consequently ultrasonically guided aspiration biopsy are a useful, accurate, safe, and low-cost technique for osteolytic lesions in thoracic diseases.

Ultrasonographic approach to diagnosing hydropneumothorax.

Ultrasound results for 11 patients with HPN confirmed by CXR were compared with those for 100 healthy subjects. The observation of the hyperechogenic line of the pleuropulmonary surface (normal subjects) showed back-and-forth respiratory movements in every case which we call the "gliding sign." Ultrasonographic signs were shown in all patients with HPN. Visualizing the gassy effusion above the pleural fluid, the disappearance of the "gliding sign" (n = 11) indicates PN. The image of the HPN allows in addition a "curtain sign" which depicts the movement of air/fluid level (n = 11), the pulmonary collapse being calculated across the liquid window whose echostructure is analyzed. A "polymicrobullous" image (n = 2) caused by air microbubbles within the fluid effusion, is reported. We conclude that echography appears to be a new approach to diagnosing HPN, which is particularly useful during or after ultrasonically guided procedures including pleural drainage, and should be recognized by sonographers.

Immunohistochemical study of tumor cell-associated plasminogen activators and plasminogen activator inhibitors in lung carcinomas.

STUDY OBJECTIVE: To compare the expression of plasminogen activators (PA) and plasminogen activator inhibitors (PAI) in normal lung mucosa and lung carcinomas. DESIGN: Immunohistochemical localization of urokinase-type PA (uPA), tissue-type PA (tPA), type 1 PAI (PAI-1), and type 2 PAI (PAI-2) in four normal lung biopsy specimens and in four adenocarcinomas (AC), four squamous carcinomas (SC), two large-cell carcinomas (LCC), and ten small-cell carcinomas (SCC) biopsy specimens. Qualitative immunostaining scoring system. RESULTS: tPA and uPA immunostaining scores from all specimens were statistically similar. The cellular staining for uPA and tPA was generally constant (normal epithelial layers, AC cells, SC cells) except for LCC cells (inconstant uPA staining, p < 10(-3). Both PAIs were detected in cells of the normal epithelial layer. The four carcinoma cell types stained for PAI in a statistically different pattern (p < 10(-3)). Cells of the peripheral cords of SCC were inconstantly PAI-1 and PAI-2 positive (p < 10(-3)). LCC were PAI-2 negative and inconstantly stained for PAI-1. SCC cells were PAI-1 and PAI-2 negative. CONCLUSION: Lung carcinomas of worst clinical prognosis no longer express PAI reactivity. The imbalance of the plasminogen activation pathway may favor the spreading of the more invasive histologic types of bronchogenic carcinomas.

Comparison of the diagnostic value of cardiac troponin I and T determinations for detecting early myocardial damage and the relationship with histological findings after isoprenaline-induced cardiac injury in rats.

Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. The purpose of this study was to investigate the diagnostic value of cTnI and cTnT with regard to creatine kinase (CK) and lactate dehydrogenase (LD) and to determine whether they can be used for early diagnosis of myocardial damage in rats, and to examine the relationship between cTnl and cTnT release with histological examinations, using isoprenaline-induced cardiac muscle damage as an experimental model in the rat. Eighteen Wistar rats per group were treated with a single dose of either isoprenaline (iso) or with normal saline as a control group. The anti-cTnI and cTnT monoclonal antibodies (mAbs) employed in the cTnI (Access) and cTnT (Elecsys) assays cross-react with cTnI and cTnT of the rat. A highly significant rise of cTnl or cTnT was found already 2 h after iso. The time-courses of cTnI and cTnT were monophasic in form. The highest cTnI (mean+/-S.D., 1.1+/-2.3 ng/ml) and cTnT (mean+/-S.D. 3.6+/-30 ng/ml) were found 4 h after iso. cTnI and cTnT significantly increased in iso-treated rats in comparison with controls whether the differences between 2-, 4- and 6-h levels and basal levels were considered or not. The areas under cTnl and cTnT curves (AUC) (0-6 h) and the maximal cTnI and cTnT (0-6 h) after iso were significantly different from the controls. For CK and LD, no elevation in comparison with controls could be detected (except a trend for LD whether or not the difference between 6-h levels and basal levels were considered (P=0.08) and for LD AUC (0-6 h) (P=0. 059)). Correlations between maximal cTnI and cTnT and AUC were 0.69 (P=0.0001) and 0.60 (P=0.0066), respectively. Histological examinations of iso-treated rats revealed acute focal or multifocal myofibrillar degeneration of the myocardial tissue in ten out of 14 rats and showed the earliest alterations 4 h after iso in one treated rat. Only four of the controls exhibited evidence of mild changes and slight mononuclear cell infiltration. cTnl and cTnT peak values to at least 0.35 and 1.3 ng/ml, respectively, were necessary to detect histological myocardial cell injury after iso. cTnI and cTnT were found to be early markers for diagnosing iso-induced myocardial damage in comparison with CK and LD. Elevations of cTnI and cTnT appeared to relate to the severity of histologic changes after myocardial injury. Although there was a difference in the absolute concentration of results between cTnI and cTnT assays, due to a lack of standardization and heterogeneity in the cross-reactivities of mAbs to various troponin I and T forms, cTnI and cTnT can be used as easily measurable target parameters for detection of cardiotoxic and/or cardiodegenerative effects in rats.

Evaluation of cardiac troponin I and T levels as markers of myocardial damage in doxorubicin-induced cardiomyopathy rats, and their relationship with echocardiographic and histological findings.

BACKGROUND: Cardiac troponins I (cTnI) and T (cTnT) have been shown to be highly sensitive and specific markers of myocardial cell injury. We investigated the diagnostic value of cTnI and cTnT for the diagnosis of myocardial damage in a rat model of doxorubicin (DOX)-induced cardiomyopathy, and we examined the relationship between serial cTnI and cTnT with the development of cardiac disorders monitored by echocardiography and histological examinations in this model. METHODS: Thirty-five Wistar rats were given 1.5 mg/kg DOX, i.v., weekly for up to 8 weeks for a total cumulative dose of 12 mg/kg BW. Ten rats received saline as a control group. cTnI was measured with Access(R) (ng/ml) and a research immunoassay (pg/ml), and compared with cTnT, CK-MB mass and CK. By using transthoracic echocardiography, anterior and posterior wall thickness, LV diameters and LV fractional shortening (FS) were measured in all rats before DOX or saline, and at weeks 6 and 9 after treatment in all surviving rats. Histology was performed in DOX-rats at 6 and 9 weeks after the last DOX dose and in all controls. RESULTS: Eighteen of the DOX rats died prematurely of general toxicity during the 9-week period. End-diastolic (ED) and end-systolic (ES) LV diameters/BW significantly increased, whereas LV FS was decreased after 9 weeks in the DOX group (p<0.001). These parameters remained unchanged in controls. Histological evaluation of hearts from all rats given DOX revealed significant slight degrees of perivascular and interstitial fibrosis. In 7 of the 18 rats, degeneration and myocyte vacuolisation were found. Only five of the controls exhibited evidence of very slight perivascular fibrosis. A significant rise in cTnT was found in DOX rats after cumulative doses of 7.5 and 12 mg/kg in comparison with baseline (p<0.05). cTnT found in rats after 12 mg/kg were significantly greater than that found after 7.5 mg/kg DOX. Maximal cTnI (pg/ml) and cTnT levels were significantly increased in DOX rats compared with controls (p=0.006, 0.007). cTnI (ng/ml), CK-MB mass and CK remained unchanged in DOX rats compared with controls. All markers remained stable in controls. Analysis of data revealed a significant correlation between maximal cTnT and ED and ES LV diameters/BW (r=0.81 and 0.65; p<0.0001). A significant relationship was observed between maximal cTnT and the extent of myocardial morphological changes, and between LV diameters/BW and histological findings. CONCLUSIONS: Among markers of ischemic injury after DOX in rats, cTnT showed the greatest ability to detect myocardial damage assessed by echocardiographic detection and histological changes. Although there was a discrepancy between the amount of cTnI and cTnT after DOX, probably due to heterogeneity in cross-reactivities of mAbs to various cTnI and cTnT forms, it is likely that cTnT in rats after DOX indicates cell damage determined by the magnitude of injury induced and that cTnT should be a useful marker for the prediction of experimentally induced cardiotoxicity and possibly for cardioprotective experiments.

Origin of malignant centrofacial granulomas: surface markers and gene rearrangement of malignant cells.

Malignant centrofacial granuloma (MCFG) is a clinical entity characterized by a relentless ulceration of the upper airway involving the nose, palate, and face, without any demonstrable etiology. The origin of 11 cases were analyzed with the help of cell-surface immunostaining in all and with T-cell receptor gene (TCR) rearrangement in 3. The results show that most of the cases of MCFG are in fact T-cell lymphomas with cell-surface antigens (CD2, CD7, CD3) consistent with either early or mature T lymphocytes. However, some cases exhibit B-lymphoid (CD19, CD20) or histiomonocytic (CD13, CD14) lineage-specific markers. In conclusion, despite its remarkable clinical unity, MCFG is a heterogeneous group of neoplastic diseases, most but not all of which may be classified as T-cell lymphoma.

Congenital muscular dystrophy with cerebral white matter spongiosis.

Two siblings affected with a slowly progressive congenital myopathy presented mental retardation, epilepsy and craniofacial dysmorphy. The cerebral necropsic study of one of these patients showed severe anomalies of the white matter, with spongiosis, astrogliosis and vascular hyperplasia, whereas a diffuse and marked hypodensity of white matter was observed at cerebral CT scan in the other patient. There were any lesion of cerebellar grey matter, heterotopy, micropolygyria or neuronal destruction. This syndrome seems to be an original variant of congenital neuromyopathy.

[Pericardial mesothelioma. Apropos of a case]. / Mésothéliome péricardique. A propos d'un cas.

A 74 year old woman without previous cardiovascular disease presented with pericardial effusion and tamponade. Two-dimensional echocardiography displayed a pericardial mass, but a diagnosis of tumour was not envisaged. Pericardiocentesis produced an exudative fluid with lymphocytes but no malignant cells. Pericardial biopsies through axillary thoracotomy indicated chronic progressive pericarditis. As the patient's haemodynamics deteriorated, sternotomy was carried out showing diffuse pericardial sclerosis corresponding, at histology, to a mixed, predominantly fibroblastic pericardial mesothelioma. The authors describe the main clinical characteristics of pericardial mesothelioma, always discovered belatedly at surgery or necropsy. They insist on the value of non-invasive methods (two-dimensional echocardiography, computed tomography) to diagnose a pericardial tumour, and on the poor prognosis of mesotheliomas, treatment still being uncertain due to the small number of cases and to the early occurrence of cardiac complications.

[Postvaccinal encephalitis in adult. A case with anatomo-clinical report (author's transl)]. / Encéphalite post-vaccinale de l'adulte, Etude anatomo-clinique d'une observation.

While post-vaccinal encephalitis in children is unfortunately well known, its occurrence in adults is rather exceptional. The calendar of a poly vaccination situated so close to each other, most probably account for such an evolution. The case reported concerns a man of 27 years who presented 10 days after a polyvaccination (7 vaccines in 2 months) altered consciousness, epileptic fits, right hemiplegia, vegetative dysfunctions and meningeal status. Evolutionary clinical course led to death in 21 days. Neuropathological findings showed lymphocytic infiltrates in the cortex and basal ganglia, congestive aspect with petechial areas in the white matter and inflammatory meningeal infiltrates. All viral investigations both in the blood, brain and cerebrospinal fluid remained negative. Post-vaccinal encephalitis is reviewed. Vaccination cannot be condemned, but in case of polyvaccination lapse of time in between vaccines should be longer so as to prevent such exceptional evolution and fatal course.

[Cleido-cranial dysostosis with malformation of the cervico-occipital junction]. / Maladie de Pierre Marie et Sainton avec malformation de la charnière cervico-occipitale.

A 66 years old man with cleido-cranial dysostosis suffered from a progressive ataxic gait for 45 years. Physical examination discovered cerebellar and pyramidal signs and altered deep sensibility in lower limbs. Roentgenograms showed skeletal dysostosis and a severe malformation of the cervico-occipital junction. The disease was transmitted with a dominant autosomic inheritance. The patient died from cardiac and respiratory distress. Post mortem examination confirmed radiologic anomalies: basilar invagination with a low-situated brain stem. The paucity of neurological complications of cleido-cranial dysostosis is emphasized. This is apparently the first reported case with clinical signs of cervico-occipital malformation.

[Occlusion of the basilar artery. A review with 17 personal cases (author's transl)]. / Occlusion du tronc basilaire.

Occlusion of the basilar artery is mainly of atherosclerotic origin; embolic occlusion, dissecting aneurysm, trauma and arteritis are less frequent. Pathologic and angiographic findings allow to classify basilar artery occlusions in three types: segmental (superior, medial or inferior), plurisegmental and extensive. The infarcted areas involve brain stem, especially pons and cerebellum, also diencephalon and cerebral hemispheres, in various combinations. Clinically, there is typically a prodromic stage, with transient ischemic attacks (vertigo, headaches, visual disturbances, motor deficit). Few weeks later, a decreased level of consciousness and motor anomalies are the most important signs. A fatal outcome is noted in 85,98 p. 100. Among laboratory examinations, only angiography proves the occlusion: it also shows the arterial supply (carotido-basilar reflux; inter-cerebellar anastomosis). Computed tomography usually eliminates an expanding mass of the posterior fossa. Management is only of general type. Surgical management of carotid arteries stenosis may ameliorate the anastomotic flow.

[Neurologic involvement in malignant mid-face granuloma]. / Atteintes neurologiques dans les granulomes malins centro-faciaux.

We report 4 cases with neurological disorders due to lethal centrofacial granulomas of unknown origin, and we review the relevant literature. This puzzling disease is characterized by a relentless ulceration of the nose progressing toward the base of the skull, and frequently involving the cranial nerves, the meninges and later the central nervous system. The main clinical point in such situations is to ascertain that no microorganism, no cancer, no specific disease is responsible for the centrofacial lesions, since the microscopic findings may be non-specific. When the entire work-up to exclude all differential diagnoses is completed, the clinician has to deal with lethal centrofacial granuloma. This seems to be a heterogeneous disease, in most of the cases close to malignant T lymphomas. Management is based on radiotherapy, chemotherapy and renutrition with treatment of frequent infectious complications. The prognosis is poor.

[Morphological aspects of parathyroid hyperplasia in patients with chronic renal insufficiency on dialysis]. / Aspects morphologiques de l'hyperplasie parathyroïdienne des insuffisants rénaux chroniques dialysés.

The authors present an anatomic study of parathyroid hyperplasia in 15 patients presenting chronic renal failure treated by hemodialysis (mean time 6 years). The light microscopic examination (n = 56) confirms diffuse hyperplasia so occur in patients submitted to dialysis for a period inferior to 4 years while nodular hyperplasia occurs in patients submitted to dialysis for longer a time. Mixed hyperplasia may be considered a transitional form between diffuse and nodular hyperplasia. Electron microscopic examination (n = 31) reveals the secretory ability of chief cells containing lots of secretory granules, and the energetic power of oxyphil cells filled with mitochondria. The great amount of oxyphil and of vacuolized cells after long periods of dialysis means degenerative transformation of ancient chiefs cells. The authors emphasize the interest of per-operative identification of the type of hyperplasia in order to choose the fitting procedure of parathyroidectomy.

[Carcinoma of the pancreas with amyloid stroma and calcitonin secretion : ultrastructural study (author's transl)]. / Carcinome pancréatique à stroma amyloïde avec sécrétion de calcitonine. Etude ultrastructurale.

The authors report a case of anaplastic carcinoma with amyloid stroma, accompanied by the secretion of calcitonin, detected in a cervical lymph node and initially interpreted as being a metastasis from a medullary carcinoma of the thyroid. The actual pancreatic origin of the malignant tumour was proved only during the advanced stages. Ultrastructural study confirmed the endocrine nature of the tumour (neurosecretory granules). Despite its exceptional character, the existence of such a tumour is not surprising, if one accepts the concept of a diffuse endocrine system.

[Association of a secreting oncocytic tumor of the kidney and a parathyroid adenoma]. / Association d'une tumeur oncocytaire sécrétante du rein et d'un adénome parathyroïdien.

An unusual association of a secreting renal oncocytoma and a parathyroid adenoma is described. The high level of hypercalcemia and of blood parathormone (PTH 44-68), partially reduced by nephrectomy and totally normalized by parathyroidectomy, as well as the renal tumor PTH evaluation and the ultrastructural features showing secretory granules in oncocytic cells of kidney, advocate for a double site of PTH secretion. Removal of both tumors permits a complete recovering.

[Non-functional or silent endocrine tumors of the pancreas. Apropos of a case of cystic form]. / Les tumeurs endocrines "non fonctionnelles" ou silencieuses du pancréas. A propos d'une observation à forme kystique.

The authors report a new case of silent cystic pancreatic endocrine tumour discovered by chance on abdominal ultrasonography. This tumour was treated surgically by simple enucleation-resection. On the basis of the histological appearance and the absence of metastases, this tumour was considered to be benign, but only the long-term course will confirm the diagnosis.

[Towards another diagnostic approach of peripheral pulmonary masses. Ultrasound-guided puncture]. / Vers une autre approche du diagnostic des masses pulmonaires périphériques. La ponction échoguidée.

In a series of 50 patients with lung lesions touching the thoracic wall, percutaneous ultrasonically guided needle aspiration yielded a pathological diagnosis in 44 cases (sensitivity: 88%). The histological diagnosis of malignant lesion could be confirmed in 41 of these 44 patients. In this group of patients with neoplasia the diagnosis obtained by extemporaneous cytology was compared with that obtained by lung biopsy: the diagnostic sensitivity of cytology proved to be higher than that of biopsy (86.36% and 65.90% respectively). Using the two methods concomitantly increased sensitivity up to 93.18%. A pathological diagnosis could be obtained in 3 out of the 6 patients in this series who had benign lesions.

[Malignant pheochromocytoma. Apropos of a case report]. / Phéochromocytome malin. A propos d'une observation.

Pheochromocytoma was diagnosed in a male of 38 on the basis of severe and progressive hypertension associated with marked increases in urinary catecholamines and vanilmandelic acid. Left extra-adrenal topography was examined by tomography and confirmed by surgical treatment involving exeresis of the primary tumor and the metastatic latero-aortic lymph nodes, thus corroborating the diagnosis of malignancy. Complementary post-operative radiotherapy was performed on the abdomen. Eighty months later the patient is making good progress.

[Subacute ischemia of the lower leg caused by a popliteal synovial cyst. Apropos of a case]. / Ischémie subaiguë du membre inférieur par kyste synovial poplité. A propos d'une observation.

Based on the observation of a cyst compressing the popiteal artery, the authors discuss the characteristic clinical picture and radiology of this benign neoformation. They emphasize two possible causes: cystic degeneration of the arterial median or a cyst of articular derivation. Histological data from this observation supports the second hypothesis.