Helicobacter pylori Chronic-Stage Inflammation Undergoes Fluctuations That Are Altered in tlpA Mutants.

Helicobacter pylori colonizes half of the world's population and is responsible for a significant disease burden by causing gastritis, peptic ulcers, and gastric cancer. The development of host inflammation drives these diseases, but there are still open questions in the field about how H. pylori controls this process. We characterized H. pylori inflammation using an 8-month mouse infection time course and comparison of the wild type (WT) and a previously identified mutant lacking the TlpA chemoreceptor that causes elevated inflammation. Our work shows that H. pylori chronic-stage corpus inflammation undergoes surprising fluctuations, with changes in Th17 and eosinophil numbers. The H. pylori tlpA mutant changed the inflammation temporal characteristics, resulting in different inflammation from the wild type at some time points. tlpA mutants have equivalent total and gland colonization in late-stage infections. During early infection, in contrast, they show elevated gland and total colonization compared to those by WT. Our results suggest the chronic inflammation setting is dynamic and may be influenced by colonization properties of early infection.

The degree of Helicobacter pylori-triggered inflammation is manipulated by preinfection host microbiota.

Helicobacter pylori infects over 3 billion people worldwide and is the primary risk factor for gastric cancer. Most individuals infected with H. pylori develop only asymptomatic gastritis; however, some develop ulcers or gastric adenocarcinoma. We demonstrate that one previously unappreciated parameter influencing H. pylori disease outcome is variation in the preinfection host microbiota. Utilizing a mouse model, we altered the microbiota by antibiotic treatment and found that these alterations resulted in significantly lowered H. pylori-triggered inflammation. Specifically, antibiotic pretreatment reduced CD4(+) T-helper cells and Ifnγ transcript levels in gastric tissue after H. pylori infection. The bacterial communities in mice with a reduced response to H. pylori displayed many differences from those in untreated mice, including significantly more cluster IV and XIVa Clostridium spp., bacteria known to influence inflammation via regulatory T cell populations. Our findings suggest that microbiota composition, perhaps Clostridium spp., contributes to the variable disease outcome of H. pylori infection by altering the recruitment of CD4(+) T cells to the gastric compartment. Our results suggest that gastric microbiota could be used as a diagnostic tool to determine which patients are at risk for developing severe disease.

Bacterial chemotaxis modulates host cell apoptosis to establish a T-helper cell, type 17 (Th17)-dominant immune response in Helicobacter pylori infection.

The host inflammatory response to chronic bacterial infections often dictates the disease outcome. In the case of the gastric pathogen Helicobacter pylori, host inflammatory responses result in outcomes that range from moderate and asymptomatic to more severe with concomitant ulcer or cancers. It was found recently that H. pylori chemotaxis mutants (Che(-)), which lack directed motility but colonize to nearly wild-type levels, trigger less host inflammation. We used these mutants to observe host immune responses that resulted in reduced disease states. Here we report that these mutants are defective for early gastric recruitment of CD4(+) T cells compared with wild-type infection. Furthermore, Che(-) mutant infections lack the T-helper cell, type 17 (Th17) component of the immune response, as measured by cytokine mRNA levels in gastric tissue via intracellular cytokine staining and immunofluorescence. We additionally find that a Che(-) mutant infection results in significantly less host cell apoptosis than does wild-type infection, in accordance with previous observations that T-helper cell, type 17 responses in Citrobacter rodentium infections are driven by concomitant bacterial and apoptotic cell signals. We propose that bacterial chemotaxis allows H. pylori to access a particular host niche that allows the bacteria to express or deliver proapoptotic host cell factors. This report indicates that chemotaxis plays a role in enhancing apoptosis, suggesting bacterial chemotaxis systems might serve as therapeutic targets for infections whose symptoms arise from host cell apoptosis and tissue damage.

Association of cervical cytology and HPV DNA status during pregnancy with placental abnormalities and preterm birth.

The clinical implications of abnormal cervical cytology during pregnancy are unclear. Therefore, we performed the present study to determine the role of cervical cytologic screening during pregnancy in association with placental abnormalities and preterm birth. A review of 2,480 cases during 11 years revealed significant correlation of reactive, infectious, atypical, and dysplastic cytologic changes during pregnancy with abnormal placental findings. Also, all but dysplastic cytologic changes were significantly associated with preterm birth. Furthermore, we observed significant association of the presence of high-risk human papillomavirus (HPV) DNA with preterm birth and placental abnormalities. These findings indicate that cervical infection of HPV is a risk factor for preterm birth and that cervical cytology is an effective tool for screening women for infection and inflammation during pregnancy and predicting pregnancy outcome.

Gastrointestinal stromal tumors: a review of the literature.

Gastrointestinal stromal tumors are mesenchymal neoplasms with a spectrum of histologic appearances and biologic activity. The morphologic classification of these lesions has evolved over time, and molecular analysis has led to a better understanding of their nature. The histologic differential diagnosis for these lesions is broad and includes many spindle cell lesions of the gastrointestinal tract, including neoplasms of true smooth muscle and neural origin, proliferating fibrous lesions, metastatic neoplasms, and primary sarcomas of vascular and adipose origin. Immunohistochemical studies that include CD117 have become invaluable in the classification of mesenchymal lesions arising in the gastrointestinal tract. Treatment of gastrointestinal stromal tumors has historically been involved surgery, but the use of the chemotherapeutic agent imatinib mesylate for advanced disease has made accurate classification even more important. The molecular features have not only allowed us to understand the pathogenesis of these tumors but also have proven to be associated with response to kinase inhibitors.

Nonkeratinizing undifferentiated nasopharyngeal carcinoma: a case report.

BACKGROUND: Nasopharyngeal carcinoma, a malignant neoplasm of squamous origin, is an uncommon neoplasm in the United States, although it is a significant cause of morbidity and mortality in southeast Asia and northern Africa. These lesions arise most frequently from the lateral wall of the nasopharynx and may be locally aggressive or metastasize regionally or distantly. CASE: A 46-year-old African American male presented to our institution with a 5-month history of nasal congestion. Imaging studies revealed a mass filling the right sphenoid sinus and eroding into the adjacent sinuses and temporal bone. A biopsy was performed, and immediate imprint cytology showed two populations of cells, lymphoid cells and cohesive clusters of cells with prominent nucleoli. A diagnosis favoring nasopharyngeal carcinoma was rendered, and subsequent histology showed a nonkeratinizing undifferentiated nasopharyngeal carcinoma. CONCLUSION: Nasopharyngeal carcinoma, particularly in its nonkeratinizing undifferentiated form, may mimic inflammatory and lymphoproliferative disorders. Careful examination for the distinct cytologic features is necessary for accurate diagnosis and subsequent treatment.

Tricuspid valve and pacemaker endocarditis due to Pseudallescheria boydii (Scedosporium apiospermum).

We report a case of native valve and pacemaker endocarditis in a 78-year-old male with diabetes mellitus who died after cardiac surgery. At autopsy, tricuspid valve vegetations and lung abscesses containing thick, hyaline, septate, and branching hyphae were present. The culture identified Scedosporium apiospermum, an infrequent cause of opportunistic infections in immunocompromised hosts.

Diagnosis of linitis plastica-type gastric adenocarcinoma by endoscopic ultrasound-guided fine needle aspiration: a case report.

BACKGROUND: The diagnosis of linitis plastica-type adenocarcinomas of the stomach has traditionally been made by brush cytology and mucosal biopsy. These techniques may yield false negative results due to the often submucosal location of these lesions. CASE: A 46-year-old woman presented witb epigaseric abdominal pain and loss of abbetite. Computed tomography of her abdomen revealed diffuse thickening of a portion of the gastric wall. Subsequent endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) of the stomach yielded abundant single, discohesive malignant cells suspicious for lymphoma vs. poorly differentiated carcinoma. Special stains and immunohistochemical stains confirmed the diagnosis of poorly differentiated adenocarcinoma ofsignet ring cell type. CONCLUSION: As many linitisplastica-type adenocarcinomas are submucosal lesions, mucosal sampling by biopsy may yield nondiagnostic material in up to one third of cases. With its ability to sample deep submucosal lesions, EUS-FNA is an appropriate technique for establishing this diagnosis and guiding patient treatment.

Isolated intestinal neurofibromatous proliferations in the absence of associated systemic syndromes.

Gastrointestinal tract involvement by neurofibromatous lesions is rare and occurs most frequently as one of the systemic manifestations of generalized neurofibromatosis type 1 (NF1). In this setting, the lesions may manifest as focal scattered neurofibromas or as an extensive diffuse neural hyperplasia designated ganglioneuromatosis. Occasionally, such lesions may be the initial sign of NF1 in patients without any other clinical manifestations of the disease. Rarely, cases of isolated neurofibromatosis of the large bowel with no prior or subsequent evidence of generalized neurofibromatosis have been documented. We present the case of a 52 year-old female with abdominal pain and alternating bowel habits. Colonoscopic evaluation revealed multiple small polyps in the cecum and the presence of nodular mucosa in the colon and rectum. Pathologic evaluation of the biopsies from the cecum, descending colon, sigmoid colon, and rectum revealed tangled fascicles of spindle cells expanding the lamina propia leading to separation of the intestinal crypts. Immunohistochemical stains helped confirm the diagnosis of diffuse intestinal neurofibromatosis. A thorough clinical evaluation failed to reveal any stigmata of generalized neurofibromatosis. This case represents a rare presentation of isolated intestinal neurofibromatosis in a patient without classic systemic manifestations of generalized neurofibromatosis and highlights the need in such cases for close clinical follow-up to exclude neurofibromatosis type I or multiple endocrine neoplasia type II.

Cytologic diagnosis of alveolar soft part sarcoma of the lower extremity by fine needle aspiration and correlation with core biopsy: a case report.

BACKGROUND: Alveolar soft part sarcoma is a rare soft tissue tumor of uncertain origin that is generally slow growing but unmistakably malignant due to its propensity for metastasis to lung, bone and brain early in the course of disease. Fine needle aspiration biopsy (FNAB) of these tumors and recognition of the characteristic cytologic features precludes more invasive diagnostic measures and facilitates appropriate treatment. CASE: A 54-year-old African-American man presented to our institution with a 2-week history of left leg pain. Imaging studies revealed a left leg soft tissue mass just below the popliteal fossa and multiple bilateral lung lesions suggestive of metastatic neoplasm. FNAB of the left lower extremity mass yielded uniform clusters of cells and sigle cells with large nuclei and single prominent nucleoli. Histologically, the biopsy showed nests of large polygonal cells with abundant eosinophilic cytoplasm, round regular nuclei and prominent nucleoli. A periodic acid-Schiff (PAS) stain highlighted intracytoplasmic rhomboidal crystals, a feature diagnostic of alveolar soft part sarcoma. CONCLUSION: Alveolar soft part sarcoma may be diagnosed by its unique morphologic characteristics and should be considered in the differential diagnosis of all cytologically sampled soft tissue lesions.

Giardia lamblia infection diagnosed by endoscopic ultrasound-guided fine-needle aspiration.

The protozoan Giardia lamblia is a major cause of gastrointestinal disease worldwide. We report the case of a 59-yr-old male who presented to his primary care physician with complaints of abdominal pain and weight loss. Imaging studies revealed a liver mass and a pancreatic head mass. Biopsy of the liver mass proved to be benign, and endoscopic ultrasound-guided fine-needle aspiration of the mass in the head of the pancreas showed no evidence of malignancy; however, numerous pear-shaped, binucleated, flagellated organisms morphologically consistent with trophozoites of Giardia lamblia were identified in the specimen. With the increasing use of endoscopic ultrasound-guided fine-needle aspiration for sampling of gastrointestinal, hepatobiliary, and pancreatic lesions, cytopathologists examining such specimens will need to be familiar with the diagnostic characteristics of this protozoal parasite.