Novel complication of an emerging disease: Invasive Klebsiella pneumoniae liver abscess syndrome as a cause of acute respiratory distress syndrome.

Klebsiella pneumoniae is an increasingly recognized cause of a unique invasive syndrome manifesting as pyogenic liver abscess and hematogenous extrahepatic dissemination to a variety of sites, including the lung. Originally described only in Asia, this entity has now been reported across continents and ethnicities. Intrathoracic complications of invasive Klebsiella pneumoniae liver abscess syndrome (IKPLAS) have been characterized sporadically but have not been the subject of an all-encompassing investigation. Review of the English-language literature yields no reports of the acute respiratory distress syndrome as a consequence of IKPLAS. Herein we report what, to our knowledge, is the first such description.

Colorectal Cancer Associated with Strongyloides stercoralis Colitis.

Strongyloides stercoralis colitis is a severe but easily curable disease with a high mortality rate if left untreated. Strongyloidiasis can persist up to several decades and may lead to a chronic colitis similar to that seen in inflammatory bowel disease (IBD), and the two are often confused. Chronic colitis from IBD is associated with an increased risk of colorectal cancer, so it is plausible that chronic colitis from strongyloidiasis may carry a similar risk. Our case report associates chronic Strongyloides colitis and colorectal cancer.

Clinically occult primary fallopian tube carcinoma presenting as a malignant pleural effusion.

We report the first known case of malignant pleural effusion (MPE) as the sole presenting feature of clinically occult primary fallopian tube carcinoma (PFTC). A 57-year-old healthy woman was admitted with dyspnea. Evaluation demonstrated a right pleural effusion, fluid of which was malignant. The immunohistochemical profile, including negative calretinin, favored metastatic adenocarcinoma over mesothelioma but could not identify the primary tumour site. Pleural biopsy was not pursued as it would not have helped localize the primary. Chest, abdomen and pelvic computed tomography (CT) demonstrated only borderline lymphadenopathy in the left para-aortic lymph node chain that was hypermetabolic on positron emission tomography. Ultrasound and CT showed normal adnexal anatomy. These findings, coupled with an elevated serum CA-125, prompted empiric neoadjuvant chemotherapy targeting epithelial ovarian carcinoma (EOC) followed by surgery, which revealed a tiny left PFTC with negative peritoneal washings. Sampled left para-aortic lymph nodes were positive. The pleural effusion resolved after chemotherapy. Malignant pleural disease without peritoneal involvement is more characteristic of PFTC than of EOC, in which MPE is common but almost always accompanies peritoneal carcinomatosis. The extensive lymphatic supply of the fallopian tube promotes distant metastasis of small, seemingly localized tumours. This case is a reminder that the clinician should not be dissuaded from considering carcinoma of Müllerian origin, especially PFTC, as the cause of a MPE even in the face of normal gynecologic imaging. Appropriately broad immunohistochemical staining and careful attention to even minimal lymphadenopathy can be invaluable in pinpointing the primary tumour site in such patients.

Ectopic Anterior Mediastinal Pathology in the Chest: Radiologic-pathologic Correlation of Unexpected Encounters with the "Terrible Ts".

The complex embryology of the anterior mediastinum makes it home to an array of primary neoplasms tied to the presence of the thyroid and thymus glands in that compartment. While the occurrence of ectopic thyroid deposits in the extramediastinal thorax has not been convincingly established, the other three "Ts" of the classic "4T" mnemonic for the differential diagnosis of an anterior mediastinal mass have occurred in the lung parenchyma, pleural space, and endobronchially as primary tumors. Finding any of the three lesions - thymoma, teratoma, or B-cell lymphoma - in the chest outside the mediastinum is very unusual, but that possibility exists. Herein, we illustrate examples of this rare phenomenon.

Urinary bladder paraganglioma presenting as micturition-induced palpitations, dyspnea, and angina.

BACKGROUND: Sympathetic urinary bladder paragangliomas are rare catecholamine-secreting neuroendocrine tumors arising from neural crest cells. They are uncommon urinary bladder neoplasms. Symptoms classically include micturition-related or unrelated palpitations and syncope with hypertension, headaches, diaphoresis, and hematuria. Other than being attributable to vasovagal reactions, micturition-induced cardiovascular symptoms should prompt a search for catecholamine-secreting tumors such as a urinary bladder paraganglioma, as in this case. CASE REPORT: A 45-year-old asthmatic African-American female presented with episodic hematuria that began 4 years ago and episodes of micturition-induced palpitations, dyspnea, substernal tightness, sweating, and throbbing headaches. Computed tomography with contrast revealed an enhancing mass along the anterior urinary bladder wall, measuring 2.4×3.5 cm. On Positron emission Tomography with [18F] fluorodeoxyglucose integrated with computed tomography (18F-FDG PET/CT), the urinary bladder mass was 18F-FDG avid. Serum normetanephrine and supine plasma norepinephrine were significantly elevated and there was mild elevation of supine plasma epinephrine. Transurethral resection of the bladder mass revealed a neoplasm with microscopic features and immunohistochemical profile positive for synaptophysin and chromogranin, with negative screening cytokeratin AE1/AE3, suggesting a paraganglioma. Following resection of the paraganglioma, there was complete resolution of micturition-induced cardiovascular symptoms on long-term follow-up. CONCLUSIONS: Micturition-related cardiovascular symptoms are commonly attributed to vasovagal reactions. However, urinary bladder pathologies must be ruled out as a cause, as in this rare case of a urinary bladder paraganglioma exhibiting catecholaminergic symptoms.

Atypical presentation of an advanced obstructive biliary cancer without jaundice.

PATIENT: Female, 60 FINAL DIAGNOSIS: Cholangiocarcinoma Symptoms: Abdominal pain • abdominal discomfort MEDICATION: - Clinical Procedure: - Specialty: Oncology. OBJECTIVE: Unusual natural history/clinical course. BACKGROUND: Cholangiocarcinoma remains to be a challenging case to diagnose and manage as it usually presents in advanced stage and survival rate remains dismal despite the medical breakthroughs. It is usually classified as intrahepatic, perihilar or distal tumor which can lead to bile duct obstruction causing sluggish flow of bile through the biliary tract and promoting increased absorption of bilirubin, bile acids and bile salts into systemic circulation accounting for the occurrence of jaundice, dark-colored urine and generalized pruritus. It usually becomes symptomatic when the tumor has significantly obstructed the biliary drainage causing painless jaundice and deranged liver function with cholestatic pattern. Jaundice occurs in 90% of the cases when the tumor has obstructed the biliary drainage system. A markedly dilated gallbladder as initial presenting feature in the absence of other typical obstructive clinical manifestations of an advanced stage of the cholangiocarcinoma is rare. CASE REPORT: This case report presents an atypical case of an elderly woman who presented with advanced metastatic ductal cholangiocarcinoma with markedly dilated gallbladder and liver mass without other clinical manifestations and laboratory evidence of cholestatic jaundice. CONCLUSIONS: The mere presence of Courvoisier's sign, even in the absence of other signs of biliary obstruction, could be suggestive of advanced neoplastic process along the biliary tract. Laboratory evidence of cholestasis might lag behind the clinical severity of the biliary obstruction in cholangiocarcinoma.

Thyroglossal duct cyst carcinoma: case report and review of the literature.

Well-differentiated thyroid carcinoma of a thyroglossal duct cyst (TGDC) is a rare entity, found in about 1% of all TGDCs. Diagnosis is usually made incidentally after a Sistrunk procedure. Options for further therapy include total thyroidectomy, T4 suppression therapy, and radioactive iodine ablation. In a patient with a normal-appearing thyroid gland and no evidence of metastatic disease, the treatment course is controversial. The recent literature emphasizes the identification of risk factors that may prompt the clinician to pursue more aggressive treatment. We present the case of a 35-year-old woman who was found to have a 1-cm midline neck mass that showed atypical cells on fine-needle aspiration. Histologic analysis after a Sistrunk procedure revealed a small focus of papillary carcinoma within the TGDC. The patient subsequently underwent total thyroidectomy with no evidence of carcinoma on histologic examination.

An unusual cause of upper gastrointestinal bleeding: duodenal GIST. A case report and literature review.

A duodenal GIST is an unusual cause of upper gastrointestinal bleeding. Duodenal GISTs are rare and constitute 5% of all GISTs. A significant percentage of duodenal GISTs are located in the third and fourth portion of the duodenum and may not be detected on routine upper endoscopy. Push enteroscopy is necessary to locate these lesions. It is extremely important to differentiate a duodenal GIST from other submucosal tumors like leiomyomas, leiomyosarcomas or leiomyoblastomas which may present in a similar manner, because the treatment and prognosis differ significantly. Appropriate histological and immunohistiochemical staining is required to confirm the diagnosis. Surgical resection is the treatment of choice and may involve limited resection or a pancreaticoduodenectomy. Adjuvant therapy with Imatinib has been shown to prolong survival in patients with GIST in general.

Aggressive osteogenic desmoplastic melanoma: a case report.

A case of an osteogenic desmoplastic melanoma occurring on the sole of the foot of a 60-year-old African American man is described. The tumor measured 4.8 cm in greatest dimension, invaded to a thickness of 2.2 cm and metastasized to four of ten inguinal lymph nodes. The majority of the tumor had a classic desmoplastic phenotype with malignant spindle cells set in a sclerotic and myxoid matrix and foci of lymphocyte aggregation. In other areas, there were thick trabeculae of bone rimmed by malignant epithelioid melanocytes. There was a markedly atypical lentiginous hyperplasia in the overlying epidermis. Imaging showed no continuity with the underlying calcaneus. The tumor was characterized immunohistochemically by S100 positivity. Pathologists should be aware of this diagnosis and should differentiate it from osteosarcoma.

Successful tolerance induction under CD40 ligation in a rodent small bowel transplant model: first report of a study with the novel antibody AH.F5.

BACKGROUND: Intestinal transplantation has been hampered by high rates of intestinal allograft rejection. One mechanism of altering rejection in other organ transplant models has been blockade of second set T-cell costimulatory signals. AH.F5, a novel hamster anti-rat monoclonal antibody to CD154, blocks CD40-dependent T-cell costimulation. We hypothesized that blockade of this pathway might abrogate rejection in a rodent orthotopic survival model of intestinal transplantation. METHODS: Eight groups were studied with different dosing schema, including syngeneic transplants (group 1), untreated allogeneic transplants (group 2), allogeneic transplants plus multiple doses of AH.F5 alone given IV or s.c. (groups 3 and 4), allogeneic transplants plus donor splenocyte preconditioning with and without single dose AH.F5 (groups 5 and 6), and donor splenocyte preconditioning followed by multiple doses of AH.F5 with and without thymectomy (groups 7 and 8). RESULTS: Control animals all died within 12 days of transplantation, whereas antibody-alone and splenocytes-alone resulted in modest prolongation of survival to 16 days. Only animals treated with splenocytes before transplantation and AH.F5 survived long-term (>60 days, group 8). These animals tolerated donor-specific skin grafts, rejected third-party grafts, and fed normally. However, their weight gain was subnormal and they demonstrated intestinal muscular thickening, which might represent chronic rejection. Thymectomy prevented the induction of tolerance. CONCLUSIONS: AH.F5 prevents acute intestinal allograft rejection in combination with donor-specific splenocyte preconditioning. We achieved long-term survival and the animals appeared tolerant. Central conditioning is essential for success with this antibody when used alone. Further studies with different dosing regimens or second agents seem warranted.

Monoclonal antibody specific for histone H1 phosphorylated by cyclin-dependent kinases: a novel immunohistochemical probe of proliferation and neoplasia.

Monoclonal antibody 12D11 (MAb 12D11) has been shown to bind histone H1 isolated from human placenta and other tissues but not histone H1 that has been digested with bacterial alkaline phosphatase. We show here that phosphorylation of phosphatase-treated histone H1 with cyclin dependent-kinase (CDK) restores binding by MAb 12D11. We conclude that MAb 12D11 selectively binds histone H1 that has been phosphorylated by CDKs, and we have investigated the use of MAb 12D11 as an immunohistochemical probe of CDK activity in situ. Previous immunofluorescence studies have revealed strong nuclear staining by MAb 12D11 in proliferating cultured cells and the absence of staining in terminally differentiated cells. Immunohistochemical staining of frozen and formalin-fixed, paraffin-embedded sections of benign tissues with MAb 12D11 was nuclear and confined to recognized foci of cell proliferation. In lymphoid germinal centers, MAb 12D11 preferentially stained large lymphoid cells with a relative lack of staining in small cleaved cells, contrasting with a lack of cell size discrimination observed with the monoclonal antibody proliferation probe, MIB-1. Tumor tissues displayed strong albeit heterogeneous staining of malignant cells by MAb 12D11, with little or no staining observed in surrounding nonneoplastic stromal cells. Differential staining by MAb 12D11 of invasive and in situ carcinoma suggest applications in prognostication. MAb 12D11 may also be useful in identification of tumors more likely to respond to therapeutic CDK inhibitors.

Artificial neural networks distinguish among subtypes of neoplastic colorectal lesions.

BACKGROUND & AIMS: There is a subtle distinction between sporadic colorectal adenomas and cancers (SAC) and inflammatory bowel disease (IBD)-associated dysplasias and cancers. However, this distinction is clinically important because sporadic adenomas are usually managed by polypectomy alone, whereas IBD-related high-grade dysplasias mandate subtotal colectomy. The current study evaluated the ability of artificial neural networks (ANNs) based on complementary DNA (cDNA) microarray data to discriminate between these 2 types of colorectal lesions. METHODS: We hybridized cDNA microarrays, each containing 8064 cDNA clones, to RNAs derived from 39 colorectal neoplastic specimens. Hierarchical clustering was performed, and an ANN was constructed and trained on a set of 5 IBD-related dysplasia or cancer (IBDNs) and 22 SACs. RESULTS: Hierarchical clustering based on all 8064 clones failed to correctly categorize the SACs and IBDNs. However, the ANN correctly diagnosed 12 of 12 blinded samples in a test set (3 IBDNs and 9 SACs). Furthermore, using an iterative process based on the computer programs GeneFinder, Cluster, and MATLAB, we reduced the number of clones used for diagnosis from 8064 to 97. Even with this reduced clone set, the ANN retained its capacity for correct diagnosis. Moreover, cluster analysis performed with these 97 clones now separated the 2 types of lesions. CONCLUSIONS: Our results suggest that ANNs have the potential to discriminate among subtly different clinical entities, such as IBDNs and SACs, as well as to identify gene subsets having the power to make these diagnostic distinctions.

Hypermethylation of the p14(ARF) gene in ulcerative colitis-associated colorectal carcinogenesis.

The p14(ARF) protein directly inhibits the MDM-2 oncoprotein, which mediates degradation of the p53 protein. It has been shown that p14(ARF) expression is frequently down-regulated by p14(ARF) gene hypermethylation in colorectal cancer. To determine whether p14(ARF) inactivation was involved in ulcerative colitis (UC)-associated carcinogenesis, the frequency and timing of p14(ARF) methylation was investigated in four different histological stages of UC-associated carcinogenesis. Methylation-specific PCR and bisulfite sequencing were used to determine the prevalence of p14(ARF) gene methylation. p14(ARF) methylation was observed in 19 of 38 (50%) adenocarcinomas, 4 of 12 (33%) dysplasias, and 3 of the 5 (60%) nonneoplastic UC mucosae. In contrast, 3 of 40 (3.7%) normal tissues showed p14(ARF) methylation (chi(2) test: P = 0.0003). Bisulfite sequencing was used to analyze 28 CpGs of p14(ARF) gene in 20 samples. The number of methylated CpGs ranged from 0 to 4, 0 to 20, and 0 to 28 in the normal, dysplastic, and carcinomatous samples, respectively (Kruskall-Wallis test: P = 0.0005). Densely methylated alleles were detected only in carcinomas by bisulfite sequencing. In conclusion, our data suggest that methylation of p14(ARF) is a relatively common early event in UC-associated carcinogenesis. p14(ARF) offers potential as a biomarker for the early detection of cancer or dysplasia in UC. Finally, analyses of p14(ARF) methylation in other organs should explore not only frank cancers but other premalignant lesions.