Predictability of urinalysis parameters in the diagnosis of urinary tract infection: a case study.

Early diagnostic strategies to rule out uncomplicated urinary tract infections (UTI) or test of exclusion could significantly improve patient management in addition to providing optimal cost-effectiveness. We evaluated the predictability of dipstick parameters, with particular emphasis on leukocyte esterase (LE) and nitrite (NT) tests and microscopic urine sediment analysis as predictors of urinary tract infection in the setting of an urban university hospital. A total of 9,845 culture positive urine samples (7,095 females, 2,750 males; 8,938 clean catch, 907 catheterized specimens) collected over a period of twelve months from all patients seen at Temple University Hospital, Philadelphia, were included in this retrospective study. Dipstick and urinalysis data were independently correlated and compared with positive culture results. Either individually or in combination, LE and NT were positive in 30% (2,912/9,845), while both LE and NT were negative in 70% (6,933/9,845) of the total culture positive urine samples. There was no correlation of several other measured variables to culture positive urine samples. This study demonstrates that the uses of LE and/or NT are poor screening parameters as predictors of UTI, in the absence of additional clinical information.

CHAOS in the mirror: Ballantyne (mirror) syndrome related to congenital high upper airway obstruction syndrome.

In the mirror syndrome, maternal edema mirrors fetal edema. The pathogenesis is unknown. The most common etiologic associations are rhesus isoimmunization, twin-twin transfusion syndrome, and viral infections. Less than 10% of reported cases are associated with congenital anomalies. We report a case due to congenital laryngeal stenosis, which also caused congenital high airway obstruction syndrome (CHAOS), characterized by pulmonary hyperplasia and edema or anasarca, related to airway abnormality. The fetal manifestations of the mirror syndrome and CHAOS overlap, but occurrence of the two in the same patient does not seem to have been reported.

Aerosolized recombinant human lysozyme enhances the bactericidal effect of tobramycin in a hamster model of Pseudomonas aeruginosa-induced pneumonia.

Previous studies from this laboratory have shown that aerosolized recombinant human lysozyme (rhLZ) mitigates Pseudomonas aeruginosa (PA)-induced pneumonia. In the current investigation, our laboratory tested the hypothesis that aerosolized rhLZ can potentiate the effects of tobramycin (TBMN), thereby reducing the effective dose of this agent in the treatment of PA-induced pneumonia. Syrian hamsters were instilled intratracheally with PA, then exposed to an aerosol containing either 1% rhLZ, 3 µg TBMN, or a combination of both agents. In contrast to the initial studies with rhLZ, which involved 3 separate aerosol exposures, only a single treatment was used in the current investigation. Twenty-four hours after completion of the aerosol regimen, the following parameters were measured: (1) whole-lung colony-forming units (CFU), (2) total bronchoalveolar lavage fluid (BALF) CFU, (3) lung histopathology, and (4) total BALF neutrophils. The combination of rhLZ and TBMN significantly reduced whole-lung and BALF CFU, as well as the inflammatory index, compared to TBMN alone. Similar results were seen in vitro with regard to bactericidal activity. These findings provide a rationale for clinical testing of rhLZ as an adjunct to commercial antibiotic treatment.

Primary amyloidosis involving mesenteric lymph nodes: diagnosis by fine-needle aspiration cytology.

BACKGROUND: Mesenteric lymph node amyloid deposits are rare and may be seen in isolated or secondary amyloidosis. The diagnosis of mesenteric amyloidosis has conventionally relied on histopathological examination following an exploratory laparotomy or a biopsy. CASE: A 72-year-old male previously diagnosed with Waldenström's macroglobulinemia and multiple other malignancies was admitted for abdominal pain. An abdominal computed tomography (CT) scan revealed diffuse retroperitoneal and mesenteric lymphadenopathy associated with bowel wall thickening. A CT-guided fine-needle aspiration (FNA) cytology and core biopsies of mesenteric lymph nodes were performed. The FNA smears revealed irregular, waxy, basophilic clumps on a Diff-Quik stain and cyanophilic clumps of amorphous material on a Papanicolaou stain. The lymph node aspirates showed positivity for the Congo red stain, confirming it as amyloid. In situ hybridization studies revealed a predominance of λ light chains, and a diagnosis of primary amyloidosis involving mesenteric lymph nodes was made. Supplemental needle core biopsies showed positivity for Congo red and Crystal violet stains and exhibited the classic apple-green birefringence under polarized light. CONCLUSION: The involvement of lymph nodes in amyloidosis is not uncommon; however, the involvement of mesenteric lymph nodes in a setting of macroglobulinemia and its diagnosis by FNA cytology is novel to this case.

Protective action of taurine, given as a pretreatment or as a posttreatment, against endotoxin-induced acute lung inflammation in hamsters.

To assess the effect of taurine on lipopolysaccharide (LPS)-induced lung inflammation, oxidative stress and apoptosis, female Golden Syrian hamsters were intratracheally instilled with bacterial LPS (0.02 mg in phosphate buffered saline (PBS) pH 7.4), before or after a 3-day intraperitoneal treatment with a single dose of taurine (50 mg/kg/day in PBS pH 7.4), and bronchoalveolar lavage fluid (BALF) and lung tissue samples were collected at 24 hr after the last treatment. In comparison to BALF samples from animals receiving only PBS pH 7.4, and serving as controls, those of LPS-stimulated animals exhibited a higher count of both total leukocytes and neutrophils and increased expression of tumor necrosis factor receptor 1. In comparison to lungs from control animals, those from LPS-treated animals showed increased cellular apoptosis, lipid peroxidation, decreased glutathione levels, altered activities of antioxidant enzymes (catalase, glutathione peroxidase, superoxide dismutase) and focal inflammation confined to the parenchyma. A treatment with taurine was found to significantly attenuate all these alterations, with the protection being, in all instances, greater when given before rather than after LPS. The present results suggest that taurine is endowed with antiinflammatory and antioxidant properties that are protective in the lung against the deleterious actions of Gram negative bacterial endotoxin.

Aerosolized recombinant human lysozyme ameliorates Pseudomonas aeruginosa-induced pneumonia in hamsters.

As an alternative to conventional antibiotics, aerosolized recombinant human lysozyme (rhLZ) was used to treat experimentally induced pneumonia. Syrian hamsters were inoculated intratracheally with a nonmucoid strain of Pseudomonas aeruginosa (PA), then exposed to a 1.0% solution of rhLZ in water for 2 hours per day for 3 consecutive days (controls were treated with aerosolized water alone). Compared to controls, the rhLZ-treated group showed statistically significant reductions in the following parameters: (1) lung histopathological changes, (2) bacterial colony-forming units in whole lung and bronchoalveolar lavage fluid (BALF), (3) total BALF leukocytes, (4) percent BALF neutrophils, and (5) alveolar septal apoptosis. Exposure to aerosolized rhLZ also resulted in a large increase in BALF lysozyme activity. These findings indicate that aerosolized rhLZ may be potentially useful in reducing the level of bacterial colonization and inflammation in the lungs of patients with PA pneumonia.

Immunodeficiency-Related Lymphoid Proliferations: New Insights With Relevance to Practice.

PURPOSE OF REVIEW: Our understanding of risk factors and mechanisms underlying immunosuppression-related lymphoproliferative disorders continues to evolve. An increasing number of patients are living with altered immune status due to HIV, solid organ or hematopoietic stem cell transplant, treatment of autoimmune disease, or advanced age. This review covers advances in understanding, emerging trends, and revisions to diagnostic guidelines. RECENT FINDINGS: The tumor microenvironment, including interactions between the host immune system and tumor cells, is of increasing interest in the setting of immunosuppression. While some forms of lymphoproliferative disease are associated with unique risk factors, common mechanisms are also emerging. Indolent forms, such as Epstein-Barr virus positive mucocutaneous ulcer, are important to recognize. As methods to modulate the immune system evolve, more data are needed to understand and minimize lymphoproliferative disease risk. A better understanding of individual risk factors and common mechanisms underlying immunosuppression-related lymphoproliferations will ultimately enable improved prevention and treatment of these disorders.

Genetic Basis of Extramedullary Plasmablastic Transformation of Multiple Myeloma.

In patients with multiple myeloma, plasmablastic transformation in the bone marrow is rare and associated with poor outcomes. The significance of discordant extramedullary plasmablastic transformation in patients with small, mature clonal plasma cells in the bone marrow has not been well studied. Here, we report the clinicopathologic, cytogenetic, and molecular features of 10 such patients (male/female: 6/4, median age: 65 y, range: 48 to 76 y) with an established diagnosis of multiple myeloma in the bone marrow composed of small, mature plasma cells in parallel with a concurrent or subsequent extramedullary plasmablastic transformation. Eight patients with available survival data showed an overall aggressive clinical course with a median survival of 4.5 months after the diagnosis of extramedullary plasmablastic transformation, despite aggressive treatment and even in patients with low-level bone marrow involvement. Pathologically, the extramedullary plasmablastic myeloma were clonally related to the corresponding bone marrow plasma cells, showed high levels of CMYC and/or P53 expression with a high Ki-67 proliferation index by immunohistochemistry and harbored more complex genomic aberrations including frequent mutations in the RAS pathway and MYC rearrangements compared with their bone marrow counterparts. In summary, although genetic and immunohistochemical studies were not uniformly performed on all cases due to the retrospective nature of this study, our data suggest that discordant extramedullary plasmablastic transformation of multiple myeloma has an aggressive clinical course and is characterized by frequent mutations in the RAS pathway and more complex genomic abnormalities.

Attenuating effect of taurine on lipopolysaccharide-induced acute lung injury in hamsters.

This study has evaluated the ability of the semiessential amino acid taurine to attenuate lipopolysaccharide (LPS)-induced lung inflammation, oxidative stress and apoptosis in a small animal model. For this purpose, bacterial LPS (0.02mg in phosphate buffered saline (PBS) pH 7.4) was instilled intratracheally into female Golden Syrian hamsters, before or after a 3-day intraperitoneal treatment with a single dose (50mg/kg in PBS pH 7.4) of taurine. At 24h after the last treatment, lung tissue and bronchoalveolar lavage fluid (BALF) samples were collected. In comparison to samples from animals receiving only PBS pH 7.4, serving as controls, those of LPS-stimulated animals exhibited a higher count of both total leukocytes and neutrophils in the BALF, and increased incidence of apoptosis, depletion of intracellular glutathione and evidence of inflammation confined to the parenchyma in the lung. In addition, LPS caused cells in the BALF to exhibit a higher expression of tumor necrosis factor-1, a higher activity of caspase-3, marked lipid peroxidation, and altered activities of catalase, glutathione peroxidase and superoxide dismutase relative to control samples. In contrast, a treatment with taurine was found to significantly attenuate all of the cellular and biochemical alterations induced by LPS, more so when given before rather than after the endotoxin. The present results suggest that taurine possesses intrinsic antiinflammatory and antioxidant properties that may be of benefit against the deleterious actions of LPS in the lung.

Endothelin-1 potentiates smoke-induced acute lung inflammation.

The current study examined the role of endothelin-1 (ET-1) in mediating acute lung inflammation induced by short-term cigarette smoke exposure. Hamsters received intraperitoneal injections of ET-1, followed by a 2-hour period of smoke exposure, for 3 consecutive days. The lungs were then evaluated for inflammatory changes, using the following parameters: (1) lung histopathology, (2) neutrophil content of bronchoalveolar lavage fluid (BALF), (3) percent tumor necrosis factor receptor 1 (TNFR1)-labeled BALF macrophages, and (4) alveolar septal cell apoptosis. Results indicate that ET-1 significantly amplified the effect of smoke on each of these inflammatory markers and that these responses could be blocked by pretreatment with a novel endothelin receptor A antagonist, HJP272. In particular, exogenous ET-1 induced a marked increase in BALF neutrophils, consistent with a role for this mediator as an inflammatory cell "gatekeeper."

Human Herpes Virus 6 (HHV-6)-associated Lymphadenitis: Pitfalls in Diagnosis in Benign and Malignant Settings.

Human herpes virus 6 (HHV-6) is a member of the ß-herpesvirinae subfamily. Most people acquire HHV-6 primary infection early in life and reactivation may occur, most often in immunocompromised individuals, leading to various clinical manifestations. HHV-6 infected cells may be identified in lymph nodes in both reactive and neoplastic conditions. Cases were retrieved from the hematopathology consultation service archives at National Institutes of Health from 2003 to 2017 in which infection by HHV-6 had been documented by immunohistochemical stains to HHV-6 gp60/110 envelope glycoprotein. Five cases of reactive lymphadenitis and 3 cases of lymphoma; 2 angioimmunoblastic T-cell lymphoma and 1 classic Hodgkin lymphoma, positive for HHV-6 were identified. The reactive lymph nodes showed marked paracortical hyperplasia and admixed large atypical lymphoid cells exhibiting pleomorphic nuclei, vesicular chromatin, and prominent eosinophilic intranuclear inclusions. Vascular proliferation and necrosis were also present, raising suspicion of peripheral T-cell lymphoma. The 3 cases of lymphoma showed similar viral inclusions, in addition to the characteristic features diagnostic of the lymphoma. Staining for HHV-6 was positive with a membranous and Golgi pattern and was restricted to cells with evident inclusions on hematoxylin and eosin. HHV-6 infected cells were positive for CD3 and CD4. HHV-6 lymphadenitis can present with morphologic atypia creating a diagnostic pitfall for lymphoma. In such cases, careful attention to the characteristic viral inclusions can lead to immunohistochemical analysis highlighting the replicating virus. In cases of lymphoma, identification of the inclusions is key in detecting the associated infection as well as in avoiding misinterpretation of the lymphoma subtype.

KSHV-associated and EBV-associated Germinotropic Lymphoproliferative Disorder: New Findings and Review of the Literature.

We report 2 cases of Kaposi sarcoma-associated herpesvirus (KSHV)-and Epstein-Barr Virus (EBV) associated germinotropic lymphoproliferative disorder. Both cases arose in patients from regions endemic for KSHV, Cape Verde, and the Democratic Republic of the Congo, presenting as localized lymphadenopathy. The affected lymph nodes showed colonization of the follicles by clusters of large atypical plasmablasts, but also showed regressive changes with vascular proliferation and interfollicular plasmacytosis, both reminiscent of human herpesvirus 8 (HHV-8) positive multicentric Castleman disease. The atypical plasmablasts showed dual positivity for HHV-8 and EBV, being positive for LANA and viral interleukin 6, as well as Epstein-Barr virus-encoded small RNA by in situ hybridization. They showed a latency I phenotype, being negative for LMP1, EBNA2, and BZLF-1. The plasmablasts were negative for immunoglobulin light chains, and in 1 case with successful DNA amplification had a polyclonal immunoglobulin rearrangement pattern. Germinotropic lymphoproliferative disorder is a rare disorder, with only 6 cases reported in the literature. We demonstrate for the first time the expression of HHV-8 viral interleukin 6 and provide evidence for latency I phenotype for EBV. In addition, 1 case progressed to an EBV-positive diffuse large B-cell lymphoma, but interestingly was negative for KSHV/HHV-8, likely indicative of tumor derived from an independent clone.

Molecular diagnosis of prostate cancer: are we up to age?

Prostate cancer (PCa), a highly heterogeneous disease, is the one of the leading cause of morbidity and mortality in the developed countries. Historically used biomarkers such as prostatic acid phosphatase (PAP), serum prostate-specific antigen (PSA), and its precursor have not stood the challenge of sensitivity and specificity. At present, there is need to re-evaluate the approach to diagnose and monitor PCa. To this end, molecular markers that can accurately identify men with PCa at an early stage, and those who would benefit from early therapeutic intervention, are the need of the hour. There has been unprecedented progress in the development of new PCa biomarkers through advancements in proteomics, tissue DNA and protein/RNA microarray, identification of microRNA, isolation of circulating tumor cells, and tumor immunohistochemistry. This review will examine the current status of prostate cancer biomarkers with emphasis on emerging biomarkers by evaluating their diagnostic and prognostic potentials.

Myometrial cavernous hemangioma with pulmonary thromboembolism in a post-partum woman: a case report and review of the literature.

INTRODUCTION: Cavernous hemangiomas of the uterus are rare benign vascular lesions. Nine cases of diffuse cavernous hemangioma of the gravid uterus have been reported, most of which diffusely involved the myometrium. These vascular malformations are clinically significant, and may cause pronounced bleeding resulting in maternal or fetal demise. Thrombosis of cavernous hemangiomas of the uterus has been previously reported. We here report the first case in which a thrombosed cavernous hemangioma of the myometrium resulted in a fatal pulmonary embolism in a post-partum woman. CASE PRESENTATION: A 25-year-old obese African-American woman who had one pregnancy and was delivered of twins by cesarean section was admitted 1 week after the successful delivery. The 12-day clinical course included ventilator-dependent respiratory failure, systemic hypertension, methicillin-resistant Staphylococcus aureus in the sputum, leukocytosis and asystole. A transabdominal ultrasound examination showed heterogeneous thickened and irregular products in the endometrial canal. The laboratory values were relevant for an increased prothrombin time, activated partial thromboplastin time, ferritin and a decrease in hemoglobin. The clinical cause of death was cited as acute respiratory distress syndrome. At autopsy, a 400g spongy, hemorrhagic uterus with multiple cystic spaces measuring approximately 0.5 × 0.4cm filled with thrombi within the myometrium was identified. Immunohistological examination with a CD31 stain for vascular endothelium associated antigen confirmed several endothelium-lined vessels, some of which contained thrombi. These histological features were consistent with cavernous hemangioma of the myometrium. A histological examination of the lungs revealed multiple fresh thromboemboli in small- and medium-sized pulmonary arteries in the right upper and lower lobes without organization, but with adjacent areas of fresh hemorrhagic infarction. CONCLUSION: This case underscores the importance of a high index of suspicion in a pregnant or post-partum woman presenting with respiratory symptoms. Thrombosis of the cavernous hemangiomas of the gravid or post-partum uterus is a rare entity. This case is of interest because it indicates that this condition can be fatally complicated by embolization of the thrombi in the cavernous myometrial hemangiomas. Although delivery by conservative methods, as well as cesarean section, is possible without resorting to hysterectomy, occasionally, the consequences could be fatal as in this case.

Collision metastasis of urothelial and prostate carcinomas to the same lymph node: a case report and review of the literature.

INTRODUCTION: A collision tumor is the meeting and eventual intermingling of two malignant neoplasms arising from independent topographical sites. Collision metastasis of carcinomas in the lymph nodes is a rare event. A literature search revealed only three cases of such a collision metastasis of prostatic and urothelial carcinoma, and only one of those cases had used immunohistochemical stains to distinguish the two tumors. CASE PRESENTATION: We encountered a case of this rare entity in an 83-year-old African-American man who presented to our facility with increasing pelvic pain after a transurethral resection of a high-grade bladder tumor and a negative metastatic computed tomography chest, abdomen and pelvic scan investigation. A radical cystoprostatectomy was subsequently performed revealing a multi-centric, high-grade, ill-defined infiltrating urothelial carcinoma infiltrating the right pericystic soft tissue. A histopathological examination of the prostate revealed a multi-centric adenocarcinoma (Gleason 4 + 4) involving two pelvic lymph nodes. Interestingly, while the right pelvic lymph node was positive for metastatic prostatic adenocarcinoma alone, immunohistochemical studies of the left pelvic lymph node revealed a dual metastatic urothelial (cytokeratin-7 and pan-cytokeratin positive, prostate-specific antigen and cytokeratin-20 negative) and prostatic (prostate-specific antigen and pan-cytokeratin positive, cytokeratin-7 and cytokeratin-20 negative) carcinoma. CONCLUSIONS: The collision of metastatic urothelial carcinoma and prostatic adenocarcinoma is unusual, and their biological behavior remains uncertain. A high index of suspicion along with thorough clinical examination and immunohistochemical stain results are an integral part of differentiating collision of urothelial carcinoma from prostate carcinoma, particularly when the two tumors are in close proximity with overlapping histological features.

Diagnostic Approach to a Patient With Paraneoplastic Neurological Syndrome.

Herein, we discussed a case of an otherwise healthy man who presented with progressive gait imbalance and ataxia, found to have small cell lung cancer. Based upon our clinical findings and laboratory data, a diagnosis of paraneoplastic cerebellar degeneration was made. Paraneoplastic neurological syndromes (PNS) are relatively rare but diverse and always should be considered in differentials. A diagnostic algorithm along with appropriate work up is discussed here.

Epicardial coronary artery intimal smooth muscle hyperplasia in a cocaine user.

Accelerated epicardial coronary artery atherosclerosis has been well-documented in cocaine users. There are only two reported cases of cocaine-associated diffuse intimal expansion by proliferated smooth muscle cells causing significant coronary luminal compromise. This type of lesion histologically resembled chronic transplant arteriopathy. Here, we report a third such case.

Littoral cell angiomas of the spleen associated with solid pseudopapillary tumor of the pancreas.

Littoral cell angiomas (LCA) of the spleen are vascular tumors of unknown etiology arising from the littoral cells of the splenic red pulp sinuses. Usually a benign and incidental finding, LCA have been repeatedly reported in association with a variety of visceral malignancies and hold the potential for dissemination per se. We encountered a case of a 30 year old female who was diagnosed with solid pseudopapillary tumor of the head and distal pancreas by fine needle aspiration cytology. A distal pancreatectomy with splenectomy was performed in addition to a pylorus-preserving Whipple's procedure and cholecystectomy. Histopathological examination confirmed solid pseudopapillary tumor of the pancreas and showed multiple well-circumscribed anastomosing vascular channels in the spleen. The diagnosis of LCA of the spleen was confirmed by immunohistochemistry that revealed co-expression of endothelial cell marker, CD31 and CD34, along with histiocytic marker, CD68 by the vascular lining cells. LCA has been previously reported in association with colorectal and pancreatic adenocarcinoma, malignant lymphoma, myelodysplasia and autoimmune disorders. We report the first case of LCA associated with solid pseudopapillary tumor of the pancreas.

An unusual case of a microscopic alveolar adenoma coexisting with lung carcinoma: a case report and review of the literature.

INTRODUCTION: Alveolar adenomas are extremely rare, benign, primary lung tumors of unknown histogenesis that are characterized by proliferative type II alveolar epithelium and septal mesenchyma. Mostly incidental, they are clinically important as they can imitate benign primary and secondary malignant tumors and at times are difficult to differentiate from early-stage lung cancer. We describe the case of a 59-year-old man with an incidental microscopic alveolar adenoma coexisting with poorly differentiated lung carcinoma. CASE PRESENTATION: A 59-year-old Caucasian man with a medical history of smoking and chronic obstructive pulmonary disease was incidentally found to have a right upper lobe mass while undergoing a computed tomographic chest scan as part of a chronic obstructive pulmonary disease clinical trial. Our patient underwent a right upper lobectomy after a bronchoscopic biopsy of the mass revealed the mass to be a carcinoma. A pathological examination revealed an incidental, small, 0.2 cm, well circumscribed lesion on the staple line margin of the lobectomy in addition to the carcinoma. Histopathological and immunohistochemical examinations revealed the lesion to be an alveolar adenoma. CONCLUSIONS: We report the rare presentation of a microscopic alveolar adenoma coexisting with lung carcinoma. Alveolar adenoma is an entirely benign incidental neoplasm that can be precisely diagnosed using immunohistochemical analysis in addition to its unique histopathological characteristics.

Retroperitoneal cystic lymphangioma in an adult: A case report and review of the literature.

Lymphangiomas are rare benign cystic tumors of the lymphatic system. Retroperitoneal lymphangiomas account for 1% of all lymphangiomas, and approximately 186 cases have been reported. They may clinically present as a palpable abdominal mass and can cause diagnostic dilemmas with other retroperitoneal cystic tumors, including those arising from the liver, kidney and pancreas. This report describes the rare case of a cystic retroperitoneal lymphangioma in a 54-year-old male patient. The lymphangioma had progressed to the point of inducing clinical symptoms of abdominal distention, abdominal pain, anorexia, fever, nausea and diarrhea. Radiological imaging revealed a large multiloculated cystic abdominal mass with enhancing septations involving the upper retroperitoneum and extending into the pelvis. Surgical removal of the cyst was accomplished without incident. A benign cystic retroperitoneal lymphangioma was diagnosed on histology and confirmed with immunohistochemical stains.