Neuroinvasive St. Louis Encephalitis Virus Infection in Solid Organ Transplant Recipients.

In summer 2015, three unrelated solid organ transplant recipients in Phoenix, Arizona, had meningoencephalitis suggestive of West Nile virus (WNV) infection. Testing was inconclusive but was later confirmed as St. Louis encephalitis (SLE). We retrospectively reviewed clinical manifestations, treatment, and outcomes of these transplant recipients. Common symptoms were fever, rigors, diarrhea, headache, and confusion. One patient died 3 days after hospitalization. Therapy for the other two patients was initiated with interferon α-2b (IFN) and intravenous IgG (IVIG; IFN plus IVIG in combination). Both patients tested positive for WNV by serologic assay, but SLE virus (SLEV) infection was later confirmed by plaque reduction neutralization test at a reference laboratory. Clinical improvement was observed within 72 h after initiation of IFN plus IVIG. SLEV has been an uncommon cause of neuroinvasive disease in the United States. Accurate, timely diagnosis is hindered because of clinical presentation similar to neuroinvasive WNV and SLE, serologic cross-reactivity, and lack of a commercially available serologic assay for SLEV. There is currently no approved therapy for flaviviral neuroinvasive disease. Anecdotal reports indicate varying success with IFN, IVIG, or IFN plus IVIG in WNV neuroinvasive disease. The same regimen might be of value for immunocompromised persons with neuroinvasive SLEV infection.

Adenomas and carcinomas missed in routine colonoscopy: a prospective study in resected colon segments.

Colonoscopy is the standard technique in the diagnosis and treatment of colorectal neoplasia, but small adenomas and even advanced lesions can be missed during the procedure. With large scale screening colonoscopy programs installed, information on quality of colonoscopy in primary care is essential, but scarcely available. Over a period of 45 months, we prospectively included all those patients in our study, who underwent major colonic surgery at our institution and who had undergone a colonoscopy within 42 days prior to the operation. 89 men and 100 women, median age 71 years, were included. The majority of these operations were performed for colorectal carcinoma (125), other malignant tumors (4), suspected malignancies (6) or large adenomas (14). The pathologist inspected the resected colonic segment, and we compared his findings with the colonoscopy report. Colonoscopies had been performed by 22 doctors in 13 institutions. Median length of the resected colonic segments was 20 cm (range 3 to 135 cm), total length was 41,21 metres. In 14 segments the pathologist identified 28 neoplastic lesions not described in the endoscopy report. Colonoscopy had missed 2 carcinomas, both in the right colon, and a 12 mm tubulo-villous adenoma with high-grade dysplasia. Another 25 tubular adenomas had been missed, 2 measuring 10 mm, 7 between 5 and 9 mm and 16 smaller than 5 mm. We conclude that primary care colonoscopy misses neoplastic lesions in a significant number of procedures. Most of the missed lesions in our high risk group of patients would have been of little clinical consequence. In a small, but clinically important number of cases, however, advanced adenomas and even colorectal carcinomas were missed by endoscopy.

Mesothelioma-like tumors of the pleura: a review of 72 autopsy cases.

The 72 mesothelioma-like tumors of the pleura (MLTP) found among 33 500 autopsy cases collected over more than 30 years are reviewed. MLTP have a worse prognosis than the 106 cases of pleural mesothelioma autopsied in our institutes with regard to survival time and metastatic spread. In MLTP, adenocarcinomas predominate with a wide range of histological and cytological variation and prominent development of connective tissue having its origin in the periphery of the lung. These intrapulmonary primary tumors often fulfill the criteria of pulmonary scar cancer. Etiologically, there is no correlation between the origin of this tumor and smoking or exposure to asbestos. The absence of mucus formation and glandular differentiation, together with the presence of spindle-shaped carcinoma components and strong mesothelial or stroma proliferation, can make the differential diagnosis between this tumor type and mesothelioma difficult. Immunohistological investigations were performed on 11 cases with antibodies against intermediate filament proteins, vascular endothelium, collagen IV, macrophage antigens, carcinoembryonic antigen (CEA), LeuM1, and the antibody BerEP4. Our investigation shows that a battery of several tumor markers, such as antibodies against LeuM1, CEA, and the antibody BerEP4, as well as staining with periodic acid/Schiff/diastase discriminate primary from secondary pleural neoplasms, whilst intermediate filament proteins alone are of little diagnostic value.

Cushing syndrome-associated pheochromocytoma and adrenal carcinoma. An immunohistological investigation.

Seven adrenal carcinomas and seventeen pheochromocytomas (PHs), two of which were clinically associated with a Cushing's syndrome and one associated with multiple endocrine neoplasia Type II (MEN-II), were investigated immunohistologically with a panel of antibodies against intermediate filament proteins, a proliferation-associated nuclear antigen (Ki-67), neuroendocrine tumor markers, and different hormones on paraffin-embedded tissue sections and, from 19 cases, also on frozen tissue sections. Synaptophysin proved to be the most reliable tumor cell marker on both snap-frozen and paraffin-embedded tissue but, like antibodies against NSE, yielded unspecific stainings in the carcinomas. The two Cushing-associated pheochromocytomas (CaPH) showed the same immunohistological profile as the other PHs, except one chromogranin-negative tumor. Five PHs showed weak reactivity for calcitonin, one for serotonin, and two for a-HCG in small amounts. All PHs lacked other hormone expression, including ACTH. The average growth fraction was small (2.2%) in 13 cases, but 80% of the tumor cells were proliferating in one case of CaPH. Adrenal carcinomas showed only weak or no expression of keratin in one case, a homogenous or droplet, non-filamentous cytoplasmic staining with antibodies against neurofilament in frozen tissue section, and they were completely chromogranin-negative. The average growth fraction was 7.6% in 5 cases.

[Age determination of venous thrombi by ultrasound]. / Altersbestimmung venöser Thromben im Ultraschall.

In addition to diagnosing deep-vein thrombosis of the lower limb and pelvis, determination of the age of the thrombus is of considerable importance in guiding treatment. The present study was done to find out whether thrombus age can be determined by ultrasound morphology. 138 examinations were carried out on 76 lower limbs with phlebographically demonstrated thrombosed veins. Diameter of the thrombosed vein, echogenicity of the thrombus and demarcation of the venous wall from its surroundings were determined by colour-coded duplex sonography. The results were compared with histological evidence or with the age of the thrombus as determined by history and clinical course. The diameter of the thrombosed vein in conjunction with the history and clinical data makes it possible to determine the age of a thrombus. Echogenicity of the thrombus and demarcation of the venous wall do not provide any reliable information on thrombus age.

Epstein-Barr virus and carcinomas: undifferentiated carcinomas but not squamous cell carcinomas of the nasopharynx are regularly associated with the virus.

The Epstein-Barr virus (EBV) is consistently associated with undifferentiated nasopharyngeal carcinoma (NPC). There is, however, conflicting evidence as to whether squamous cell NPCs are also EBV-associated. Moreover, it has been proposed that other epithelial tumours, particularly thymomas and thymic carcinomas, should be included in the group of EBV-associated neoplasias. However, since the viral DNA in these studies was demonstrated only in extracted DNA, the cellular origin of the viral DNA is uncertain. We have therefore investigated 152 epithelial tumours from various sites for the presence of EBV-DNA by in situ hybridization with 35S-labelled probes. Sixty-eight of 77 undifferentiated NPCs showed an EBV-specific autoradiographic signal, thus confirming the strong association of this tumour type with EBV even in geographical areas where undifferentiated NPC is not endemic. None of eight squamous cell NPCs showed an EBV-specific signal. All of 15 carcinomas with a similar morphology to undifferentiated NPC but from different anatomic sites (thymus, tonsil, breast) were EBV-negative as were 9 thymomas, 26 squamous cell carcinomas of the palatine tonsil, and 14 cervical carcinomas. Our results therefore suggest a unique association of EBV with undifferentiated NPC and support concepts assigning different biological properties to undifferentiated NPC as compared with squamous cell NPC.

[Diagnosis of deep leg vein thrombosis with color-coded duplex sonography and sonographic determination of the duration of the thrombosis]. / Diagnostik tiefer Beinvenenthrombosen mit der farbcodierten Duplexsonographie und sonographische Altersbestimmung der Thrombose.

In a prospective study, 188 patients with suspected deep venous thrombosis were examined by color-coded duplex sonography. In 114 patients the diagnosis of deep venous thrombosis was based on the criteria of 1) compressibility, 2) blood flow changes during compression, and 3) pelvic level during Valsalva maneuver. In all patients the results were compared with data from contrast venography. Venography was performed by an investigator, who was blinded to the prior findings. Sensitivity and specificity of the color-coded duplex sonography in diagnosing deep vein thrombosis were 96% and 97%, respectively. In the other 74 patients, in which the diagnosis of deep vein thrombosis was made by phlebography and/or ultrasound, a follow-up by color-coded duplex sonography was performed to determine the age of thrombosis. Criteria considered to determine the thrombus age included 1) margin of the vessel, 2) echogenicity; and 3) venous diameter. In 20 patients the results were compared to the age of thrombus that had been determined by histologic criteria (group I). In 54 patients the results were compared with the age that had been determined by patient history and symptoms (group II). A significant correlation was found between the age of thrombosis and the venous diameter (p less than 0.001). When thrombosis was less than 10 days old, the venous diameter was at least twice that of the diameter of the accompanying artery. The two other criteria, echogenicity and margin of the venous wall, however, did not prove to be accurate criteria to determine the age of deep venous thrombosis.

So-called fibroepithelial polyps of the vagina exhibiting an unusual but uniform antigen profile characterized by expression of desmin and steroid hormone receptors but no muscle-specific actin or macrophage markers.

The nature of the atypical, often multinucleated stromal cells proliferating in the so-called fibroepithelial polyps of the vagina (FEPV) is obscure. The authors therefore investigated immunohistochemically four polyps of this type with a panel of monoclonal and polyclonal antibodies, including those directed against intermediate filaments, steroid hormone receptors, and macrophage antigens. The authors found that the atypical stromal cells of FEPV expressed vimentin, desmin, and receptors for estrogen and progesterone but lacked all the other markers studied. The homogenous antigen profile strongly suggests that FEPV form a disease entity whose characteristic cells are special hormone-sensitive stromal cells with a myoid component of differentiation. Morphologically similar stromal cells expressing steroid hormone receptors but lacking desmin were found in myxomatoid subepithelial regions of the vaginal wall and the cervix.

Thymic carcinoma. Report of five cases and review of the literature.

Among 54 mediastinal tumours we examined in the past 20 years, there were 5 cases of primary thymic carcinomas, each with widespread metastases. Histological features in three cases were consistent with lymphoepithelioma-like carcinoma. One case showed an epidermoid pattern with keratotic pearls resembling Hassall bodies. One undifferentiated carcinoma developed from a cortical thymoma. Epstein-Barr virus could not be detected in tumour tissue with in situ hybridization. A review of the literature revealed only 94 well-documented cases of thymic carcinoma. Both thymic carcinomas and thymomas are neoplasms of the thymic epithelial cells, but thymic carcinomas are obviously histologically malignant and usually not associated with any parathymic syndromes. Epidermoid and lymphoepithelioma-like carcinomas are described along with special forms, such as small- and clear-cell carcinomas, basaloid, sarcomatoid, mucoepidermoid, and adenocystic carcinoma. Compared to the other forms, lymphoepithelioma-like carcinoma has a poor prognosis in regard to metastases and rate of survival. Some thymic carcinomas may develop from pre-existing thymomas.

[Demonstration of DNA tumor viruses in carcinomas of the upper respiratory tract]. / Nachweis von DNS Tumorviren in Karzinomen des oberen Respirationstraktes.

In situ hybridization (ISH) using 35S-labeled probes was applied to the detection of viral DNAs in 115 epithelial tumours from various sites. Epstein-Barr virus (EBV) DNA was detected in 83% of undifferentiated nasopharyngeal carcinomas (NPC) while none of seven squamous cell NPC displayed an EBV-specific autoradiographic signal. Also, all other tumours investigated, including thymomas, thymic carcinomas, tonsillar carcinomas and medullary breast carcinomas were negative upon ISH to EBV-specific probes. These results suggest a unique association of undifferentiated NPC with EBV. 28 tonsillar carcinomas were further analyzed for the presence of human papillomavirus (HPV) DNA. Six carcinomas showed an HPV16-specific signal while hybridization to HPV6- and HPV11-specific probes yielded negative results. No HPV-DNA was detected in any of 30 tonsils with chronic inflammation, thus excluding that the finding of HPV16 in a proportion of tonsillar carcinomas is merely circumstantial. These results point to a possible etiologic role of HPV16 in the pathogenesis of some tonsillar carcinomas.

Pulmonary blastomas. Immunohistochemical investigations of three cases.

Three cases of pulmonary blastoma (PB) were investigated microscopically with conventional stainings and immunohistochemically with monoclonal antibodies to cytokeratin, vimentin, desmin and neurofilament protein. The tumors differed in terms of morphology as well as of immunohistochemistry. Two were epithelial and mesenchymal mixed tumors, and the remaining one was a monophasic tumor of a typical blastemic character. The two mixed tumors also differed from each other. In one of them, the epithelial and mesenchymal component expressed cytokeratin and vimentin in a clear-cut manner without any transition. The other mixed tumor displayed a gradual epithelial-to-mesenchymal transition accompanied by a switch in the expression of cytokeratin and vimentin. The third tumor was of pure mesenchymal origin, expressing vimentin in the majority of cells and desmin in few cells. It is concluded that the PB is a morphologically and histogenetically heterogeneous tumor. Metaplastic changes may take place within a PB and make the recognition of embryogenesis more difficult.

[Cryosurgery of the healthy rat liver]. / Kryochirurgie an der gesunden Rattenleber.

Cryosurgical treatment was applied to normal liver tissue of 13 clinically intact rats, with a view to investigating effects of freezing temperatures upon normal liver tissue. The animals were sacrificed after different intervals from surgery, and their liver tissue was macroscopically and histologically examined. Major postoperative complications were not observed but for one animal which died of wound healing disorder. The method seems to be suitable also for treatment of liver cell carcinoma or liver metastases.

[Animal experiment studies of cryosurgical treatment of DS sarcomas and Morris hepatomas implanted in the liver]. / Tierexperimentelle Untersuchungen über die kryochirurgische Behandlung von in die Leber implantierten DS-Sarkomen und Morris- Hepatomen.

Cryosurgical treatment was applied to solid liver tumours of rats with a view to studying the effects of freezing temperatures upon liver carcinoma. Such treatment was applied to twelve rats to which carcinomas, 0.5 cm to 3.0 cm in size, had been implanted. Cryosurgical treatment was successful in one case. Many of the animals died of complications which resulted from freezing of surrounding organs, such as stomach or greater liver vessels.