Infective endocarditis at autopsy: a review of pathologic manifestations and clinical correlates.

The frequency of autopsies appears to be declining, and the usefulness has been challenged. We reviewed cases of autopsied active infective endocarditis (IE) during 2 periods based on the availability of high-tech 2-dimensional echocardiograms: Period 1 (P1) included 40 cases studied from 1970 to 1985, and Period 2 (P2) included 28 cases seen from 1986 to 2008--that is, before and after the introduction of echocardiograms in our institution. We conducted the study to reassess the pathology of IE and to determine how frequently diagnosis is not made during life.The age of patients increased 10 years on average between the 2 periods, and comorbidities were significantly more frequent in P2. While the frequency of rheumatic valve disease and prosthetic valve endocarditis (PVE) decreased, degenerative valve disease increased. Isolated mitral or aortic valve IE was most common. Right-sided IE was observed in patients with Staphylococcus aureus bacteremia from infected venous lines. In most cases IE involved only the cusps of cardiac valves. "Virulent" microorganisms caused ulcerations, rupture, and perforation of the cusps and necrosis of chordae tendiniae and perivalvular apparatus. In PVE the lesions were located behind the site of attachment, and vegetations were seen on the sewing ring in both metallic and biologic prostheses. Infection spread to adjacent structures and myocardium with ring abscess observed in 88% of cases. Prosthetic detachment causing valve regurgitation was associated with abscesses in 76% of cases; these patients developed persistent sepsis and severe cardiac failure. Obstruction occurred in patients with PVE of the mitral valve. Acute purulent pericarditis was observed in 22% of cases, mainly in patients with aortic valve IE and myocardial abscesses.Gross infarcts were seen in 63% of cases but were asymptomatic in most instances. The spleen, kidneys, and mesentery were the sites most frequently involved. Myocardial infarctions were found in less than 10% of cases. Abscesses were also frequently found and were a common source of persistent fever and bacteremia. Glomerulonephritis was more common in the first period. Brain pathology consisted of ischemic and hemorrhagic infarcts and abscesses. Cerebral bleeding was more frequent in patients with PVE on anticoagulant therapy. Neutrophilic meningitis was observed in S. aureus IE.Diagnosis of IE was not made during life in 14 (35%) cases during P1 and 12 (42.8%) cases in P2. Overall, diagnosis was missed until autopsy in 38.2% of cases. IE was hospital acquired in 28 instances. While a clinical diagnosis was made in all but 4 cases of early-onset PVE (23.5%), the diagnosis was not made during life in 22 of 51 patients with native-valve IE (43.1%). Of these 22 patients, IE was hospital acquired in 11 (50%). The absence of fever, cardiac murmurs, and many of the typical stigmata of endocarditis may have led to the diagnosis being overlooked clinically.Brain bleeding, cardiac failure and less frequently acute myocardial infarct were the most common causes of death.IE continues to be missed frequently until autopsy. Postmortem examination is an important tool for evaluating the quality of care, and for guiding teaching and research related to cardiovascular infections.

Nodular lung schistosomiais lesions after chemotherapy for dysgerminoma.

We report an unusual case of pulmonary schistosomiasis in a traveler to Mali that was diagnosed 16 months after primary infection, one month after she finished chemotherapy for a malignant tumor. Serologic analysis showed marked eosinophilia. Our case emphasizes the need to detect parasitic infections in cancer patients with unexplained eosinophilia, particularly in immigrants and travelers to tropical countries.

Generalized livedo reticularis associated with monoclonal cryoglobulinemia and multiple myeloma.

Cryoglobulins are detected in a wide variety of diseases, including malignancies, infections and systemic autoimmune diseases. Classically, monoclonal cryoglobulinemia is associated with hematologic malignancies, whereas mixed cryoglobulinemias are reported in association with hepatitis C virus infections or autoimmune diseases. We present a patient with generalized livedo reticularis as the first manifestation of monoclonal cryoglobulinemia and multiple myeloma. Histopathology demonstrated that nearly all small blood vessels of the upper and deep dermis, as well as the capillaries of the fat lobule, were filled with homogeneous, eosinophilic material that corresponded to monoclonal cryoglobulin deposits within the vascular lumina. Our case of livedo reticularis associated with monoclonal cryoglobulinemia and multiple myeloma was exceptional, because the mottled cyanotic discoloration of the skin with a reticular pattern was generalized, covering most of the skin surface. We have not found previous report of similar cases. Therefore, we recommend that dermatologists be made aware of the significance of this diagnosis.

Multicavitated left atrial myxoma mimicking a hydatid cyst.

A 67 year-old asymptomatic patient was referred to our echo-lab because of hypertension. Transthoracic 2D-echocardiogram showed a non-prolapsing ovoid mass attached to the left side of the interatrial septum. Transesophageal echocardiography evidenced an ovoid cavitated mass with internal areas of calcification. Color Doppler revealed flow inside the cavities. At surgery, a multicavitated mass was observed attached to interatrial septum. Macroscopically revealed cavities filled with blood, as well as partially calcified areas. Microscopically there were collections of "lipidic" cells embedded in the myxoid matrix, typical of cardiac myxoma. Cardiac hydatid cysts usually have a rounded shape. Most myxomas are solid masses without a cystic architecture or cavitations. Calcification is usually identified at a microscopic level. The combination of a polycystic appearance of the mass and macroscopic areas of calcification is more frequently observed in hydatid cysts than in cardiac myxomas. This appearance of the mass leads us to consider a cardiac echinococcal cyst as the first diagnostic possibility. This peculiar structure of cardiac myxoma, to the best of our knowledge, has never been documented. Transthoracic echocardiography and particularly transesophageal imaging, enable us to delineate this kind of tumors. Surgical resection is the appropriate treatment for these tumors, even in asymptomatic patients.

Tumor-induced endothelial cell activation: role of vascular endothelial growth factor.

Proangiogenic, proliferative effects of tumors have been extensively characterized in subconfluent endothelial cells (EC), but results in confluent, contact-inhibited EC are critically lacking. The present study examined the effect of tumor-conditioned medium (CM) of the malignant osteoblastic cell line MG63 on monolayer, quiescent bovine aorta EC. MG63-CM and MG63-CM + CoCl(2) significantly increased EC survival in serum-starved conditions, without inducing EC proliferation. Furthermore, MG63-CM and MG63-CM + CoCl(2), both containing high amounts of vascular endothelial growth factor (VEGF), induced relevant phenotypic changes in EC (all P < 0.01) involving increase of nucleoli/chromatin condensations, nucleus-to-cytosol ratio, capillary-like vacuolated structures, vessel-like acellular areas, migration through Matrigel, growth advantage in reseeding, and factor VIII content. All these actions were significantly inhibited by VEGF and VEGF receptor (VEGFR2) blockade. Of particular importance, a set of similar effects were detected in a human microvascular endothelial cell line (HMEC). With regard to gene expression, incubation with MG63-CM abolished endogenous VEGF mRNA and protein but induced a clear-cut increase in VEGFR2 mRNA expression in EC. In terms of mechanism, MG63-CM activates protein kinase B (PKB)/Akt, p44/p42-mitogen-activated protein kinase (MAPK)-mediated pathways, as suggested by both inhibition and phosphorylation experiments. In conclusion, tumor cells activate confluent, quiescent EC, promoting survival, phenotypic, and gene expression changes. Of importance, VEGF antagonism converts MG63-CM from protective to EC-damaging effects.

Chloracne: histopathologic findings in one case.

BACKGROUND: Chloracne is an acneiform eruption due to poisoning by halogenated aromatic compounds having a specific molecular shape. This condition is always a symptom of systemic poisoning by chemical chloracnegens and not just a cutaneous disorder. METHODS: We have studied a patient with severe chloracne who showed cutaneous lesions involving mostly the face and the axillae. RESULTS: Histopathologic study of the facial lesions demonstrated that almost every vellus hair follicle was involved, showing a dilated infundibulum filled by a keratotic plug. This keratotic material was mostly composed of orthokeratotic basket-weave basophilic corneocytes, namely infundibular keratin, although there were also some dilated infundibula containing eosinophilic laminated or granular sebum at their center. Small infundibular cysts were more numerous than comedones. Mature and well-developed sebaceous glands were seen at the base of many of the dilated infundibula and no squamous metaplasia of the sebaceous glands or ducts could be demonstrated. Hyperpigmentation of the lesions resulted from hyperproduction of melanin by a normal number of melanocytes along the basal layer of the epidermis and infundibular epithelium. Abundant melanin granules also impregnated the corneocytes of the infundibular plugs. CONCLUSIONS: Our findings support the notion that tiny infundibular cysts rather than comedones represent the basic lesions of chloracne.