Idiopathic Myointimal Hyperplasia of the Mesenteric Veins Diagnosed Preoperatively.

Idiopathic myointimal hyperplasia of the mesenteric veins (IMHMV) of the colon is a very rare disease that in previously reported cases was often mistaken for inflammatory bowel disease because of similar clinical characteristics. In our review of the literature, we found a total of 15 cases described, generally featuring sigmoid and rectal colitis and symptoms of abdominal pain, diarrhea, and hematochezia refractory to treatment with immunosuppressants. In all previously reported cases, the diagnosis was achieved only after surgical resection of the affected area. Herein, we report a case of IMHMV that was diagnosed preoperatively based on clinical information and endoscopy with biopsies. This led to the withdrawal of immunosuppression before a carefully planned surgical resection, with confirmation of the diagnosis in the resected tissue. To our knowledge, our case of IMHMV is the first to be diagnosed preoperatively.

Microenvironment-induced restoration of cohesive growth associated with focal activation of P-cadherin expression in lobular breast carcinoma metastatic to the colon.

Invasive lobular carcinoma (ILC) is a special breast cancer type characterized by noncohesive growth and E-cadherin loss. Focal activation of P-cadherin expression in tumor cells that are deficient for E-cadherin occurs in a subset of ILCs. Switching from an E-cadherin deficient to P-cadherin proficient status (EPS) partially restores cell-cell adhesion leading to the formation of cohesive tubular elements. It is unknown what conditions control EPS. Here, we report on EPS in ILC metastases in the large bowel. We reviewed endoscopic colon biopsies and colectomy specimens from a 52-year-old female (index patient) and of 18 additional patients (reference series) diagnosed with metastatic ILC in the colon. EPS was assessed by immunohistochemistry for E-cadherin and P-cadherin. CDH1/E-cadherin mutations were determined by next-generation sequencing. The index patient's colectomy showed transmural metastatic ILC harboring a CDH1/E-cadherin p.Q610* mutation. ILC cells displayed different growth patterns in different anatomic layers of the colon wall. In the tunica muscularis propria and the tela submucosa, ILC cells featured noncohesive growth and were E-cadherin-negative and P-cadherin-negative. However, ILC cells invading the mucosa formed cohesive tubular elements in the intercryptal stroma of the lamina propria mucosae. Inter-cryptal ILC cells switched to a P-cadherin-positive phenotype in this microenvironmental niche. In the reference series, colon mucosa infiltration was evident in 13 of 18 patients, one of which showed intercryptal EPS and conversion to cohesive growth as described in the index patient. The large bowel is a common metastatic site in ILC. In endoscopic colon biopsies, the typical noncohesive growth of ILC may be concealed by microenvironment-induced EPS and conversion to cohesive growth.

Traumatic arteriovenous fistula of the superficial temporal artery: a histopathologic report.

Traumatic aneurysms, pseudoaneurysms, and arteriovenous (AV) fistulas of the superficial temporal artery (STA) are uncommon, accounting for only 0.5% to 2.0% of all aneurysms subjected to surgery. In the literature that relates to the STA, the general term "aneurysm following traumatic injury" often includes a wide array of pathologic entities, including proper aneurysms, pseudoaneurysms, and AV fistulas. In 75% of cases, such aneurysms are due to blunt trauma. Within this group, STA AV fistulas constitute an exceedingly rare subset. The case presents the occurrence of a traumatic AV fistula of the STA following blunt trauma (karate kick) and provides the first description of the histologic appearance of this lesion.

A second-generation microRNA-based assay for diagnosing tumor tissue origin.

BACKGROUND: Cancers of unknown primary origin (CUP) constitute 3%-5% (50,000 to 70,000 cases) of all newly diagnosed cancers per year in the United States. Including cancers of uncertain primary origin, the total number increases to 12%-15% (180,000 to 220,000 cases) of all newly diagnosed cancers per year in the United States. Cancers of unknown/uncertain primary origins present major diagnostic and clinical challenges because the tumor tissue of origin is crucial for selecting optimal treatment. MicroRNAs are a family of noncoding, regulatory RNA genes involved in carcinogenesis. MicroRNAs that are highly stable in clinical samples and tissue specific serve as ideal biomarkers for cancer diagnosis. Our first-generation assay identified the tumor of origin based on 48 microRNAs measured on a quantitative real-time polymerase chain reaction platform and differentiated 25 tumor types. METHODS: We present here the development and validation of a second-generation assay that identifies 42 tumor types using a custom microarray. A combination of a binary decision-tree and a k-nearest-neighbor classifier was developed to identify the tumor of origin based on the expression of 64 microRNAs. RESULTS: Overall assay sensitivity (positive agreement), measured blindly on a validation set of 509 independent samples, was 85%. The sensitivity reached 90% for cases in which the assay reported a single answer (>80% of cases). A clinical validation study on 52 true CUP patients showed 88% concordance with the clinicopathological evaluation of the patients. CONCLUSION: The abilities of the assay to identify 42 tumor types with high accuracy and to maintain the same performance in samples from patients clinically diagnosed with CUP promise improved utility in the diagnosis of cancers of unknown/uncertain primary origins.

Gastrointestinal pathologic findings of teriflunomide associated diarrhea.

BACKGROUND: Diarrhea is generally a benign and self-limited adverse effect of teriflunomide. Small intestinal pathology has yet to be described with teriflunomide associated diarrhea. OBJECTIVE: To report small intestinal pathology in teriflunomide associated diarrhea. METHODS: Small intestinal and colonic biopsies were obtained from a patient with teriflunomide associated diarrhea. RESULTS: Small intestinal biopsy demonstrated blunting of villi, increased intraepithelial lymphocytes and expansion of lamina propria. Gliadin and t-transglutaminase antibodies were negative. Diarrhea resolved following elimination of teriflunomide with cholestyramine. CONCLUSION: This is the first reported case of small intestinal inflammation similar to celiac disease in teriflunomide associated diarrhea.

Effective control of recurrent and metastatic GU SCC by employing a multimodal approach in a patient with a history of radiation and transscrotal surgery for stage I seminoma.

This 68-year-old male, with a history of treated testicular seminoma, developed scrotal SCC 30 years later, with a metastatic SCC recurrence following another interval of 10 years. He exhibited good response to multimodal therapy, though subsequently underwent orchiectomy, revealing SCC invading his solitary testicle. This case presents a unique danger of adjuvant radiation in testicular cancer survivors, demonstrates the efficacy of multimodal therapy with GU SCC, and describes a highly unusual histologic finding.

Presence of Erdheim-Chester disease and Langerhans cell histiocytosis in the same patient: a report of 2 cases.

The histiocytic disorders Langerhans cell histiocytosis (LCH) and Erdheim-Chester disease (ECD), can both present with multisystem involvement, with the central nervous system and the bone, skin, neuroendocrine, cardiac, respiratory, and gastrointestinal systems potentially affected. The 2 entities occasionally can be difficult to distinguish. Both rarely affect the orbit and the central nervous system, and although there are rare reports of patients with coexistent LCH and ECD, there are no reported cases of the 2 diseases that involve both the orbital and neuroendocrine systems. We report 2 such cases, and review the literature of cases of LCH and ECD occurring in the same patient. The presentation of LCH and ECD in certain patients suggests a possible abnormality in the common CD34 progenitor cell. The coexistence of the 2 disease states should be suspected in patients with atypical presentations of either disorder.

Peripheral intrapulmonary lipoma in a 26-year-old woman - a case report.

Rare in occurrence, the following case of intrapulmonary lipoma is only the fifth known case in a female patient reported in the literature. Importantly, the incorporation of this lesion into the differential diagnosis during frozen section of a predominantly adipocytic lesion limited the extent of surgical intervention and provided the patient with an optimal standard of care.

Endoscopic and Histological Assessment, Correlation, and Relapse in Clinically Quiescent Ulcerative Colitis (MARQUEE).

OBJECTIVE: It is difficult to predict relapse in quiescent ulcerative colitis (UC), but newer endoscopic and histological indices could improve this. This study aimed to determine in UC patients in clinical remission (1) the prevalence of active endoscopic and histological disease; (2) the correlation between endoscopic and histological scores; and (3) the predictive power of these scores for clinical relapse. DESIGN: This multicenter prospective cohort study conducted by the Crohn's and Colitis Foundation Clinical Research Alliance included 100 adults with UC in clinical remission undergoing surveillance colonoscopy for dysplasia. Endoscopic activity was assessed using the Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), and ulcerative colitis colonoscopic index of severity (UCCIS). Histology was assessed with the Riley index subcomponents, total Riley score, and basal plasmacytosis. RESULTS: Only 5% of patients had an MES of 0, whereas 38% had a score of 2 to 3; using the UCEIS, the majority of patients had at least mild activity, and 15% had more severe activity. Many patients also had evidence of histological disease activity. The correlations among endoscopic indices, histological subcomponents, and total score were low; the highest correlations occurred with the subcomponent architectural irregularity (ρ = 0.43-0.44), total Riley score (ρ = 0.35-0.37), and basal plasmacytosis (ρ = 0.35-0.36). Nineteen patients relapsed clinically over 1 year, with the subcomponent architectural irregularity being the most predictive factor (P = 0.0076). CONCLUSIONS: This multicenter prospective study found a high prevalence of both endoscopic and histological disease activity in clinically quiescent UC. The correlations between endoscopy and histology were low, and the power to predict clinical relapse was moderate.

Mitochondrial dysfunction in inflammatory bowel disease alters intestinal epithelial metabolism of hepatic acylcarnitines.

As the interface between the gut microbiota and the mucosal immune system, there has been great interest in the maintenance of colonic epithelial integrity through mitochondrial oxidation of butyrate, a short-chain fatty acid produced by the gut microbiota. Herein, we showed that the intestinal epithelium could also oxidize long-chain fatty acids, and that luminally delivered acylcarnitines in bile could be consumed via apical absorption by the intestinal epithelium, resulting in mitochondrial oxidation. Finally, intestinal inflammation led to mitochondrial dysfunction in the apical domain of the surface epithelium that may reduce the consumption of fatty acids, contributing to higher concentrations of fecal acylcarnitines in murine Citrobacter rodentium-induced colitis and human inflammatory bowel disease. These results emphasized the importance of both the gut microbiota and the liver in the delivery of energy substrates for mitochondrial metabolism by the intestinal epithelium.

70-year-old female presenting with rectosigmoid (colonic) xanthoma and multiple benign polyps - case report.

Xanthomas are benign lesions frequently described in the upper gastrointestinal tract, most commonly in the stomach. In the stomach, these lesions are usually associated with chronic gastritis, intestinal metaplasia, H. pylori infection and duodenogastric reflux following gastric surgery, but are otherwise indolent. Xanthomas in the upper gastrointestinal tract occur in a broad age range, 45-82 years (mean: 65 years). Rare cases have also been described in the esophagus, duodenum, small intestine, colon and rectum. Rectosigmoid location of xanthomas have been described in rare cases. We present a case of polypoid xanthoma in the rectosigmoid colon occurring in a 70-year-old female with a history of hyperplastic polyps.

Classification of Inflammatory Bowel Disease from Formalin-Fixed, Paraffin-Embedded Tissue Biopsies via Imaging Mass Spectrometry.

PURPOSE: Discrimination between ulcerative colitis (UC) and Crohn's disease (CD) by histologic features alone can be challenging and often leads to inaccurate initial diagnoses in inflammatory bowel disease (IBD) patients. This is mostly due to an overlap of clinical and histologic features. However, exact diagnosis is not only important for patient treatment but it also has a socioeconomic impact. It is therefore important to develop and improve diagnostic tools complementing traditional histomorphological approaches. EXPERIMENTAL DESIGN: In this retrospective proof-of-concept study, the utilization of MALDI imaging is explored in combination with multi-variate data analysis methods to classify formalin-fixed, paraffin-embedded (FFPE) colon biopsies from UC (87 biopsies, 14 patients), CD (71 biopsies, 14 patients), and normal colonic (21 biopsies, 14 patients) tissues. RESULTS: The proposed method results in an overall balanced accuracy of 85.7% on patient and of 80.4% on sample level, thus demonstrating that the assessment of IBD from FFPE tissue specimens via MALDI imaging is feasible. CONCLUSIONS AND CLINICAL RELEVANCE: The results emphasize the high potential of this method to distinguish IBD subtypes in FFPE tissue sections, which is a prerequisite for further investigations in retrospective multicenter studies, as well as for a future implementation into clinical routine.

Malignant tumors and forensics--dilemmas and proposals.

AIM: To evaluate the effect of genetic instability and degradation in archived histology samples from cancerous tumors and to investigate the validity of short tandem repeat (STR) typing of these samples and its potential effect on human identification. METHODS: Two hundred and twenty eight slides of archival pathology tissues from 13 different types of malignant tumors were compared with healthy tissues from the same individuals. DNA analysis was performed using standard techniques for forensic STR analysis, PowerPlex16 and Identifiler on 2 distinct sample sets. Genetic instability was assessed by comparing reference tissues with cancerous tissues derived from the same individual. Loss of heterozygosity, a > or =50% reduction in heterozygosity ratio between healthy and diseased samples, and microsatellite instability, the presence of an additional allele not present in reference tissue, were assessed. The quality of profiles obtained with respect to completeness among the archived samples and degradation using the 2 platforms were also compared. RESULTS: Profiles obtained using the Identifiler system were generally more complete, but showed 3-fold higher levels of instability (86%) than those obtained using PowerPlex 16 (27%). Instances of genetic instability were distributed throughout all loci in both multiplex STR systems. CONCLUSION: After having compared 2 widely used forensic chemistries, we suggest individual validation of each kit for use with samples likely to exhibit instability combined with fixation induced degradation or artifact. A "one size fits all" approach for interpretation of these samples among commercially available multiplexes is not recommended.

Isolated Intraocular Rosai-Dorfman Disease.

BACKGROUND/AIMS: To report a case of Rosai-Dorfman disease (RDD) presenting as a solitary, choroidal mass, initially suspicious for uveal melanoma, in a 72-year-old woman. METHODS: Retrospective case report of a single patient. RESULTS: A 72-year-old woman presented with sudden vision loss in the right eye. A month prior, visual acuity was 20/40, but she was noted to have a choroidal mass confirmed with B-scan ultrasonography. Patient's vision deteriorated significantly a month later and a shallow retinal detachment was newly noted. Magnetic resonance imaging was obtained, demonstrating a hyperintense intraocular tumor on TI imaging. Patient underwent enucleation of the right eye for suspicion of a uveal melanoma. Pathology revealed a mixed cellular infiltrate with histiocytes, some exhibiting emperipolesis. Macrophage immunohistochemical stains were positive, while melanocytic markers were negative. A diagnosis of RDD was made. Subsequently, the patient had a negative workup for systemic involvement. A final diagnosis of intraocular RDD without extraocular and systemic involvement was determined. CONCLUSION: We describe a rare presentation of RDD as a solitary choroidal mass in an elderly patient with overlapping features of uveal melanoma. Definitive diagnosis could only be made on histology. RDD should be considered in the differential diagnosis of a choroidal lesion in the elderly.

Cold-stored whole blood: A better method of trauma resuscitation?

BACKGROUND: Cold-stored whole blood (CWB) provides a balance of red blood cells, plasma, and platelets in less anticoagulant volume than standard blood component therapy (BCT). We hypothesize that patients receiving CWB along with BCT have improved survival compared with patients receiving only BCT. METHODS: We performed a dual-center case-match study of trauma patients who received CWB and BCT at two urban, Level-I Trauma Centers. Criteria to receive CWB included boys 16 years of older, women older than 50 years, SBP less than 90 mm Hg, and identifiable source of hemorrhage. We performed a 2:1 propensity match against any trauma patient who received 1 unit or greater of packed red cells during their initial trauma bay resuscitation. Endpoints included trauma bay mortality, 30-day mortality, laboratory values at 4 hours and 24 hours, and overall blood product utilization. Comparisons were made with Wilcoxon-ranked sum and Fisher's exact test, p less than 0.05 was significant. RESULTS: Between both institutions, a total of 107 patients received CWB during the study period with 91 being matched to 182 BCT patients for analysis. Hemodynamic parameters of the patients in both groups at the time of presentation were similar. The CWB patients had higher mean hemoglobin (10 ± 2 g/dL vs. 11 ± 2 g/dL; p < 0.001) and hematocrit (29.2 ± 6.1% vs. 32.1 ± 5.8%; p < 0.001) at 24 hours. Importantly, trauma bay mortality was less in CWB patients (8.8% vs. 2.2%;p = 0.039). Thirty-day mortality was not different in CWB patients, and there were no differences in the total amount of blood products transfused at the 4-hour and 24-hour periods. CONCLUSION: Cold-stored whole blood offers the benefit of a balanced resuscitation with improved trauma bay survival and higher mean hemoglobin at 24 hours. A larger, prospective study is needed to determine whether it has a longer-term survival benefit for severely injured patients. LEVEL OF EVIDENCE: Therapeutic, level III.

A voluntary oral ethanol-feeding rat model associated with necroinflammatory liver injury.

BACKGROUND: The intragastric (IG) ethanol infusion model results in fatty liver, necrosis, inflammation and fibrosis. This model was utilized to study the pathogenesis of alcoholic liver disease (ALD). Disadvantages of the IG model include maintenance of the animals and equipment expense. To develop a voluntary feeding model for ALD, we took advantage of two important observations in the IG model: (i) female rats demonstrate greater severity of alcohol-induced liver injury than males and (ii) rats fed fish oil as a source of fatty acids develop more severe alcoholic liver injury than rats fed other fatty acids with ethanol. METHODS: Female Wistar rats (205 to 220 g) were fed for 8 weeks a diet containing 8% ethanol, fish oil (30% of calories), protein, and dextrose. Pair-fed controls (FD) received dextrose in amounts isocaloric to ethanol. The following measurements were made: liver pathology [fatty liver (0 to 4), necrosis, inflammation and fibrosis by Sirius Red], endotoxin and alanine aminotransferase (ALT) in plasma, urine ethanol, lipid peroxidation, nuclear factor kappa-B (NF-kappaB) and mRNA levels for tumor necrosis factor-alpha (TNF-alpha), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Protein levels for iNOS and nitrotyrosine were evaluated by immunohistochemistry and Western Blot analysis. Liver proteasome and cytochrome P450 2E1 activity and protein levels of asialoglycoprotein receptor (ASGPR) were also evaluated. In addition, mRNA levels of fibrogenic markers were assessed. RESULTS: All animals lost weight for the initial 2 to 3 weeks but then gained weight until killing at 8 weeks. There was, however, a significant difference (p < 0.05) in weight between the ethanol-fed (Etoh) and (FD) groups at the end of the experiment. The mean urine ethanol levels ranged between 190 and 240 mg/dl. The severity of pathological changes was greater (p < 0.01) in Etoh vs. FD: fatty liver, 3.0 +/- 1.2 vs. 1.2 +/- 0.4; necrosis (foci/mm(2)), 3.9 +/- 2.3 vs. 0.4 +/- 0.3; inflammation (cells/mm(2)), 19.0 +/- 6.3 vs. 1.8 +/- 0.6. Centrilobular collagen deposition (% area), assessed by Sirius Red staining, was greater in Etoh vs. FD. Levels of endotoxin, ALT, CYP2E1 and lipid peroxidation markers were also higher (p < 0.01) in Etoh vs. FD. Levels of NF-kappaB and mRNA of pro-inflammatory mediators (TNF-alpha, COX-2, iNOS) and procollagen-I were increased (p < 0.05) in ethanol-fed rats. Immunohistochemical analysis showed more intense staining for both iNOS and nitrotyrosine in the centrilobular areas in the Etoh vs. FD groups. The greater area of positive staining for iNOS and nitrotyrosine in Etoh vs. FD was confirmed by Western Blot analysis. An increase in the expression of mRNA for profibrogenic genes (p < 0.05) was seen in ethanol-fed rats. CONCLUSIONS: A voluntary feeding regimen consisting of fish oil and ethanol in female rats is technically less demanding yet produces pathological and biochemical changes similar to those observed with the IG model. Pathological changes include fatty liver, necrosis and inflammation. Increased NF-kappaB and mRNA and protein levels of the pro-inflammatory mediators TNF-alpha, COX-2 and iNOS, coincided with the presence of necroinflammatory changes. The voluntary feeding regimen is proposed as an alternative to the IG model in the study of alcoholic liver injury.

Intraosseous glomus tumor of the great toe: a case report with review of the literature.

We report a case of intraosseous glomus tumor that presented as a painful lesion in the distal phalanx of the left great toe in a 21-year-old male. The radiographic appearance showed a well-circumscribed osteolytic lesion, and histological examination revealed solid nests of polygonal cells surrounding branching vasculatures consistent with a glomus tumor. Partial toe amputation resulted in complete alleviation of the patient's pain. Although glomus tumors commonly occur in the distal soft tissue of the extremities, they very rarely localize to bone. To the best of our knowledge, this is the first published report of a case of intraosseous glomus tumor localized to the toe.