ColoType: a forty gene signature for consensus molecular subtyping of colorectal cancer tumors using whole-genome assay or targeted RNA-sequencing.

Colorectal cancer (CRC) tumors can be partitioned into four biologically distinct consensus molecular subtypes (CMS1-4) using gene expression. Evidence is accumulating that tumors in different subtypes are likely to respond differently to treatments. However, to date, there is no clinical diagnostic test for CMS subtyping. In this study, we used novel methodology in a multi-cohort training domain (n = 1,214) to develop the ColoType scores and classifier to predict CMS1-4 based on expression of 40 genes. In three validation cohorts (n = 1,744, in total) representing three distinct gene-expression measurement technologies, ColoType predicted gold-standard CMS subtypes with accuracies 0.90, 0.91, 0.88, respectively. To accommodate for potential intratumoral heterogeneity and tumors of mixed subtypes, ColoType was designed to report continuous scores measuring the prevalence of each of CMS1-4 in a tumor, in addition to specifying the most prevalent subtype. For analysis of clinical specimens, ColoType was also implemented with targeted RNA-sequencing (Illumina AmpliSeq). In a series of formalin-fixed, paraffin-embedded CRC samples (n = 49), ColoType by targeted RNA-sequencing agreed with subtypes predicted by two independent methods with accuracies 0.92, 0.82, respectively. With further validation, ColoType by targeted RNA-sequencing, may enable clinical application of CMS subtyping with widely-available and cost-effective technology.

Severe but reversible pulmonary hypertension in scleromyxedema and multiple myeloma: a case report.

BACKGROUND: Scleromyxedema is a progressive, systemic connective tissue disorder characterized by fibro-mucous skin lesions and increased serum monoclonal immunoglobulin levels. Pulmonary involvement occurs in a subset of patients, though the overall prevalence of pulmonary lesions in scleromyxedema is unknown. Since pulmonary hypertension presumably occurs in these patients due to disease progression and development of additional conditions, treatment of the underlying plasma cell dyscrasia and connective tissue disorder may improve pulmonary hypertension symptoms. CASE PRESENTATION: An elderly patient with scleromyxedema developed pulmonary hypertension refractory to vasodilator and diuretic therapy and subsequently multiple myeloma that responded to a combination therapy of bortezomib, cyclophosphamide, and dexamethasone treatment. CONCLUSIONS: Treatment of the underlying disease(s) that contributed to pulmonary hypertension development with anti-neoplastic agents like bortezomib may improve cardiopulmonary symptoms secondary to reducing abnormal blood cell counts and paraprotein levels.

Hepatic Calcified Tumor-like Mass Complicating Umbilical Vein Catheterization in a Neonate.

Presented is a case of a hepatic calcified mass complicating umbilical vein catheterization in a neonate and diagnosed by wedge biopsy. Wedge biopsy of the hepatic mass, situated in proximity to the falciform ligament, revealed expansion of portal tracts by fibrosis and calcification. Some aggregates of calcified material appeared in ectatic vascular spaces. The biopsy findings accounted for the radiographic appearance of the mass and the constellation of features were deemed indicative of calcification secondary to umbilical vein catheterization. Umbilical vein catheterization in neonates may be complicated by a calcified mass that requires histologic evaluation for distinction from other space-occupying lesions. Such a calcified pseudotumor may develop after an umbilical catheter has been in place for only 5 days.

Oesophageal papillomatosis, not amenable to endoscopic therapies, treated with oesophagectomy.

Oesophageal papillomatosis is a very rare entity, with only 10 cases (including ours) reported in the literature. We report a 51-year-old man with a 25-year history of dysphagia with solids and liquids who failed a trial of proton pump inhibitors and fluticasone. His initial endoscopy revealed a viliform mass with dense eosinophilic infiltrate without neoplasia. Endoscopic ultrasound examination revealed a 4×1.6×0.7 cm mucosal hemicircumferential lesion without regional adenopathy. Pathological findings from the oesophagectomy specimen confirmed oesophageal papillomatosis with no malignancy. Surveillance endoscopy 4 months later revealed the lesion had increased in size. Additional ablative therapies failed, and the patient underwent oesophagectomy. Surveillance CT of the chest and abdomen at 3 months and oesophagogastroduodenoscopy at 6 months were negative. This case illustrates that oesophageal squamous papillomatosis not amenable to medical therapy requires surgical treatment.

Bilateral pulmonary nodules and mediastinal lymphadenopathy in a patient with Sjogren's syndrome.

Bronchus-associated lymphoid tissue is a normal component of the lung's immune system and may be analogous to gut-associated lymphoid tissue, a form of mucosa-associated lymphoid tissue. Bronchial-associated lymphoid tissue lymphoma is a distinct subgroup of low-grade B-cell extranodal non-Hodgkin lymphoma, classified as marginal-zone lymphoma. It is a rare disorder and appears with a distinct clinical and radiological presentation. We report a case of a patient with a history of Sjogren's syndrome who presented with bilateral pulmonary nodules and mediastinal lymphadenopathy, and who was diagnosed as having bronchus-associated lymphoid tissue lymphoma.

Peripancreatic cystic lymphangioma diagnosed by endoscopic ultrasound/fine-needle aspiration: a rare mesenchymal tumour.

A 73-year-old man presented with a 5-month history of intermittent nausea, vomiting, central abdominal discomfort and a 17-pound weight loss over the past year. Laboratory testing, including a complete blood count with differential, liver function testing, amylase and lipase studies were normal. A CT scan showed a bilobed cystic lesion inferior to the body of the pancreas. An endoscopic ultrasound revealed a 5.3×3.9 cm, anechoic, bilobed cystic lesion, extrinsic to the body of the pancreas with a 1-2 mm septation and a normal pancreas. Fine-needle aspiration revealed a milky-white aspirate with negative cytology. Laboratory assessment of the cystic aspirant revealed carcinoembryonic antigen 1.7 ng/mL, amylase 148 units/L, cholesterol 300 mg/dL, and carbohydrate antigen 19-9 3 units/mL. He underwent resection of the mass, with the histopathology confirming a diagnosis of peripancreatic lymphangioma. He did well after the surgery with interval resolution of his symptoms.

Gastric antral vascular ectasia: case report and review of the literature.

Gastric antral vascular ectasia is the source of up to 4% of nonvariceal upper gastrointestinal bleeding. It can present with occult bleeding requiring transfusions or with acute gastrointestinal bleeding. It is associated with significant morbidity and mortality and has been associated with such underlying chronic diseases as scleroderma, diabetes mellitus, and hypertension. Approximately 30% of cases are associated with cirrhosis. We report two cases of gastric antral vascular ectasia with two strikingly different endoscopic appearances. We further describe the clinical, endoscopic, histologic, and therapeutic aspects of this entity.

Digital ischemia as a paraneoplastic consequence of squamous cell lung carcinoma.

We report the case of a 40-year-old man who presented with digital ischemia and squamous cell lung carcinoma. Based on review of the literature, to our knowledge this case represents the youngest patient with lung carcinoma associated with digital ischemia and the only one with this type of tumor. The patient's digital ischemia symptoms improved rapidly with systemic chemotherapy; however, he did eventually lose the distal portion of 1 finger to dry gangrene and mummification.

Multilocular thymic cyst with epithelioid granulomata of unknown etiology: a radiologic and histopathologic correlation.

Thymic cysts (congenital or acquired) are believed to account for 3% to 5% of all mediastinal masses. Multilocular thymic cysts are an acquired reactive inflammatory process arising within the thymus gland and are less common than the congenital unilocular type. Multilocular cysts have been reported in association with a variety of neoplastic, autoimmune, and infectious conditions. We report a case of a 23-year-old white man who presented with a 2-week history of progressive right-sided shoulder and chest pain. He was found to have an anterior mediastinal mass involving the thymus. This case of multilocular thymic cyst is particularly unique due to the presence of abundant epithelioid granulomata within the cyst, a finding that has not previously been emphasized as a histologic feature of these lesions, and one that expands the histopathologic differential diagnosis, warranting exclusion of infectious and autoimmune etiologies.

Dumping syndrome, a cause of acquired glycogenic hepatopathy.

A 2-year-old boy, having undergone fundoplication for gastroesophageal reflux disease and fed by gastrostomy, presented with recurrent emesis, syncope with hypoglycemia, and persistently elevated serum liver transaminase levels. Liver biopsy revealed hepatocellular glycogenosis by light and electron microscopy. Further evaluation showed no evidence of diabetes mellitus, glycogen storage disease, or corticosteroid use. Since the hyperglycemic-hyperinsulinemic state of dumping syndrome would provide a mechanism for hepatocellular glycogenosis, the biopsy findings prompted consideration of dumping syndrome. Metabolic evaluation confirmed the diagnosis of dumping syndrome, and appropriate dietary management led to sustained resolution of symptomatology and hypertransaminasemia. Dumping syndrome is proposed to be a cause of hepatocellular glycogenosis, the latter representing a form of acquired glycogenic hepatopathy.

Prostate carcinoma metastatic to the stomach: report of two cases and review of the literature.

We report two cases of prostate carcinoma metastatic to the stomach. In the first case, the patient had indolent disease before presenting with gastric metastasis. The patient responded to treatment with resolution of gastrointestinal bleeding and other symptoms. In the second case, the patient developed aggressive prostate carcinoma while on immunosuppressive therapy following kidney transplant. His tumor became widely systemic, and he ultimately died of his disease. Although rare, the possibility of prostate carcinoma metastatic to the stomach should be considered when a patient with a history of prostatic adenocarcinoma presents with gastrointestinal symptoms.

Barrett's esophagus: incidence and prevalence estimates in a rural Mid-Western population.

BACKGROUND AND AIMS: Barrett's esophagus (BE) predisposes to adenocarcinoma of the esophagus and survival in esophageal adenocarcinoma is low. We studied patients diagnosed with BE in the Marshfield Epidemiologic Study Area (MESA). Our objectives were to estimate the prevalence of diagnosed BE, estimate the annual incidence of initial diagnosis of BE, and characterize the demographics of patients diagnosed with BE. METHODS: We retrospectively reviewed medical records of patients diagnosed with BE until December 31, 2002. The esophagogastroduodenoscopy (EGD) reports were reviewed to establish the presence of columnar epithelium. All slides were retrieved and reviewed by a gastrointestinal pathologist to establish the presence of intestinal metaplasia and dysplasia. Chart abstraction was conducted using a standardized form. RESULTS: BE was histologically confirmed in 216 patients. All were white, 165 (76%) were male, and 81% had a hiatal hernia. Median age at diagnosis was 65.5 yr (range 17-94). Long-segment BE (LSBE) was present in 112 (51.9%) patients. The prevalence of histologically confirmed BE in MESA was 261.8 (95% CI 222.5-301.1) per 100,000 people. The incidence of an initial diagnosis of BE between 1996 and 2002 was 32.7 per 100,000 person-years (95% CI 27.1-38.2) and did not change significantly over the study period despite an increase in EGD rates. At the initial diagnosis, 41.7% of the patients were on proton pump inhibitors. Dysplasia was present in 24.5% of patients. CONCLUSION: The incidence of initial diagnosis of BE in a stable white population did not change significantly over a 7-yr period, despite an increase in EGD rates.

Esophageal adenocarcinoma arising from Barrett's dysplasia: a case report of double occurrence and prolonged survival after chemotherapy.

A relatively young patient with chronic gastroesophageal reflux disease (GERD), obesity, smoking, and alcohol intake presented with widespread metastatic disease in lymph nodes, liver and lungs from a lower esophageal adenocarcinoma extending into the gastroesophageal junction associated with Barrett's mucosa and dysplasia.A complete response was achieved with six cycles of chemotherapy that sustained for more than 4 years without further recurrence. Unfortunately, there was presence of esophageal metaplasia after complete response which eventually converted to low to high grade dysplasia and ultimately to a second primary localized lower esophageal adenocarcinoma that was treated with thoracoabdominal esophagectomy and lymphadenectomy. No evidence of disease recurrence was seen 2 years later. The pathogenesis of a recent increase in the incidence of GERD, Barrett's esophagus and lower esophageal adenocarcinoma are discussed. Surgery, radiotherapy and combination chemotherapy are effective in the early stages leading to tumor shrinkage and prolongation of life and even cure in some cases. Lower esophageal adenocarcinoma is frequently associated with Barrett's high-grade dysplasia. Since there has been a dramatic increase in the incidence of Barrett's dysplasia, appropriate surveillance with upper gastrointestinal endoscopy and preventive strategies, such as the use of aspirin, cyclo-oxygenase II inhibitors and other nonsteroidal antiinflammatory drugs known to be chemopreventive agents against colon, esophagus, gastric and bladder cancers, need to be studied.