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Law R.M.,ProPath | Fiman K.H.,Gastroenterology Consultants Southwest | Roberts C.A.,Pro Path
World Journal of Gastroenterology | Year: 2013

Esophageal involvement by lichen planus (ELP), previously thought to be quite rare, is a disease much more common in women and frequently the initial manifestation of mucocutaneous lichen planus (LP). Considering that the symptoms of ELP do not present in a predictable manner, ELP is perhaps more under-recognized than rare. To date, four cases of squamous cell carcinoma in association with ELP have been reported, suggesting that timely and accurate diagnosis of ELP is of importance for appropriate follow-up. In this case report, a 69-year-old female presented with dysphagia and odynophagia. She reported a history of oral LP but had no active oral or skin lesions. Endoscopic examination revealed severe strictures and web-like areas in the esophagus. Histologic examination demonstrated extensive denudation of the squamous epithelium, scattered intraepithelial lymphocytes, rare eosinophils and dyskeratotic cells. Direct immunofluorescence showed rare cytoid bodies and was used to exclude other primary immunobullous disorders. By using clinical, endoscopic, and histologic data, a broad list of differential diagnoses can be narrowed, and the accurate diagnosis of ELP can be made, which is essential for proper treatment and subsequent follow-up. © 2013 Baishideng. All rights reserved.


Lager D.J.,ProPath | Lewin M.,ProPath | Rendon G.,Texas Digestive Disease Consultants | Roberts C.A.,ProPath
American Journal of Gastroenterology | Year: 2014

OBJECTIVES:Eosinophilic esophagitis (EoE) is characterized clinically by dysphagia, chest pain, and food impaction, and morphologically by increased numbers of intraepithelial eosinophils and marked basal hyperplasia of the squamous mucosa. The consensus criteria for a diagnosis of EoE include the presence of ≥15 eosinophils/HPF in biopsies from both proximal and distal esophagus in the absence of other causes of esophageal eosinophilia, and the lack of clinical response to proton pump inhibitor therapy. Because of the variability in the distribution of intraepithelial eosinophils among biopsy fragments and the lack of standardized biopsy practices, we sought to determine the optimal number of esophageal biopsies from the mid and distal esophagus needed to reach the minimum morphologic criteria of ≥15 eosinophils/HPF. METHODS:From 5 January 2009 to 26 September 2011, 771 patients were diagnosed with EoE at our institution. From that patient population, 102 sequential cases were chosen for further study, all of whom had biopsies taken from the mid and distal esophagus. Cases with only gastric mucosa present and biopsies taken from patients with a previous diagnosis of EoE were excluded. The original H&E-stained slides were reviewed, and the number of biopsy fragments containing squamous mucosa was recorded. By using a × 40 objective and × 10 oculars (field diameter=0.52 mm, field area=0.21 mm 2), the number of eosinophils per high power field (EOS/HPF) in up to three HPFs was counted in each biopsy fragment.RESULTS:The EOS/HPF were counted in 1,342 biopsy fragments. The number of biopsy fragments obtained from the mid esophagus ranged from 1 to 20 (mean 7; median 7) and those obtained from the distal esophagus ranged from 1 to 18 (mean 6; median 5). There was no significant difference between the mean number of EOS/HPF from the mid (26) and lower (25) esophagus or between the mean peak number of EOS/HPF from the mid (69.1) and lower (60.4) esophagus. The probability of one, four, five, and six biopsy fragments containing >15 EOS/HPF was 0.63, 0.98, 0.99, and >0.99, respectively.CONCLUSIONS:From these data, at least four biopsy fragments should be submitted from the mid and/or proximal esophagus to optimize the chances of a positive diagnosis of EoE in populations not known to have undergone previous proton pump inhibitor therapy. However, the yield is not increased beyond six biopsy fragments. In order to morphologically exclude a diagnosis of reflux esophagitis as the cause of intraepithelial eosinophilia, distal esophageal biopsies, if obtained, must be accompanied by more proximal biopsies (i.e., mid esophagus or higher). © 2014 by the American College of Gastroenterology.


Nielsen J.A.,Research Division | Roberts C.A.,ProPath | Lager D.J.,ProPath | Putcha R.V.,Texas Digestive Disease Consultants | And 2 more authors.
Helicobacter | Year: 2014

Background: Lymphocytic gastritis (LG), characterized by marked intra-epithelial lymphocytosis in the gastric mucosa, has been frequently associated with both celiac disease (CD) and H. pylori gastritis. The aim of this study was to review and correlate the morphology of LG with the presence of CD and H. pylori. Materials and Methods: Gastric biopsies diagnosed with LG from 1/1/2006 to 8/1/2013 at our institution and corresponding small bowel biopsies, when available, were reviewed for verification of the diagnosis and to assess for the presence of H. pylori and CD. Immunohistochemical (IHC) staining for H. pylori was performed on all gastric biopsies. Demographic, clinical, and laboratory data were obtained from the medical record. Results: Fifty-four of the 56 cases that met inclusion criteria demonstrated significant intra-epithelial lymphocytosis as the predominant histologic abnormality; however, none were associated with H. pylori infection by IHC staining. Two cases that also showed a prominent intra-epithelial and lamina propria neutrophilic infiltrate were both positive for H. pylori and were excluded from further study. Of the 36 small bowel biopsies available, 19 (53%) showed changes in CD. Conclusions: LG is not a distinct clinicopathologic entity, but a morphologic pattern of gastric injury that can be secondary to a variety of underlying etiologies. When restricted to cases with lymphocytosis alone, LG is strongly associated with CD and not with active H. pylori infection. However, cases that also show significant neutrophilic infiltrate should be regarded as "active chronic gastritis" and are often associated with H. pylori infection. A morphologic diagnosis of LG should prompt clinical and serologic workup to exclude underlying CD. © 2014 John Wiley & Sons Ltd.


Yohe S.L.,University of Minnesota | Chenault C.B.,ProPath | Torlakovic E.E.,University of Toronto | Asplund S.L.,Miraca Life science | McKenna R.W.,University of Minnesota
Modern Pathology | Year: 2014

Four patients presented with acute leukemia of ambiguous or myeloid lineage in association with Langerhans cell histiocytosis and provide evidence suggesting a common origin of the two neoplasms. One patient had a non-constitutional trisomy 21 in both the leukemic blasts and the Langerhans cells indicative of a clonal relationship. A second case expressed CD2, CD13, and CD117 on both the Langerhans cells and the blasts suggesting a possible clonal relationship. All four cases exhibited geographic intermingling of the Langerhans cell histiocytosis and acute leukemia and shared unique features including extramedullary leukemia involving lymph nodes in all cases with Langerhans cell histiocytosis only present in sites involved by acute leukemia. T-cell antigen expression was present in all cases with one meeting criteria for mixed phenotype acute leukemia, T/myeloid, not otherwise specified. These findings support the concept that coexistent Langerhans cell histiocytosis and acute leukemia is clonally related in some cases. Furthermore, these cases of acute myeloid or acute leukemia of ambiguous lineage with Langerhans cell histiocytosis share some unique features suggesting a common underlying neoplastic hematopoietic stem cell. © 2014 USCAP, Inc.


Nielsen J.A.,Divisions of Research | Lager D.J.,ProPath | Lewin M.,ProPath | Weber J.J.,Texas Digestive Disease Consultants | Roberts C.A.,ProPath
American Journal of Clinical Pathology | Year: 2013

Objectives: To calculate the incidence of nondiagnostic (ND) colorectal (CR) polyp cases in which deeper tissue sectioning rendered new diagnostic information-particularly adenomas-in 2 laboratories staffed by the same pathologists. Methods: After initial diagnosis, 100 ND CR polyps from each laboratory were reexamined with 3 deeper levels to establish rates of diagnostic conversion based on biopsy specimen location and original observation(s). Results: Deeper sectioning rendered new diagnostic information in 43 (21.5%) of 200 biopsy specimens and specifically adenomas in 16 (8.0%) of 200 biopsy specimens. Conclusions: These results support routine ordering of deeper levels on ND CR polyps to improve adenoma detection rates, especially those cases without any histologic abnormality. If another biopsy in the same case already is adenomatous, examination of deeper levels may not be necessary, as it may not have any significant effect on the clinical management of the patient. © American Society for Clinical Pathology.


Litz C.E.,ProPath | Cavagnolo R.Z.,ProPath
British Journal of Dermatology | Year: 2010

Background Tests commonly used in the diagnosis of onychomycosis include potassium hydroxide (KOH) preparation, histopathological examination with periodic acid-Schiff stain (PAS) and culture. These tests are either time-consuming or require specially trained personnel. A recently developed polymerase chain reaction (PCR) assay has the potential to provide a quick, inexpensive, operator-independent diagnosis of onychomycosis. Objective To determine the range of fungal species detected by the PCR technique and to compare this technique with KOH, PAS and culture on patient specimens. Methods A total of 176 dermatophytic and nondermatophytic fungal culture isolates were tested by PCR. Five hundred and fifty nail specimens from 550 patients with suspected onychomycosis were split and tested concurrently with PCR, PAS, KOH and culture. Results PCR was positive in 65 out of 66 dermatophyte culture isolates and negative in all 110 nondermatophyte and yeast isolates. Overall, PAS, PCR, KOH and culture were positive in 54%, 37%, 40% and 22% of specimens, respectively. Fifty-two per cent were positive for KOH and PCR. Conclusion PCR is a specific, relatively sensitive test for onychomycosis. When used in conjunction with KOH, PCR can produce positivity rates similar to those with PAS alone. © 2010 British Association of Dermatologists.


Chong B.F.,University of Texas Southwestern Medical Center | Tseng L.-C.,University of Texas Southwestern Medical Center | Kim A.,University of Texas Southwestern Medical Center | Miller R.T.,ProPath | And 2 more authors.
Journal of Dermatological Science | Year: 2014

Background: B-cell activating factor of the TNF family (BAFF) promotes the maturation and survival of B cells. Because BAFF levels are elevated in systemic lupus erythematosus (SLE) patients, BAFF has been the target of emerging therapies for SLE, such as belimumab. Levels of BAFF and its receptors in discoid lupus erythematosus (DLE) patients are unknown. Objective: To compare skin and blood mRNA and protein levels of BAFF and its receptors BAFF-R, TACI, and BCMA in DLE subjects with (DLE. +/SLE. + (N= 28)) and without SLE (DLE. +/SLE- (N= 35)), psoriasis subjects (N= 11), and normal subjects (N= 42). Methods: We used quantitative real-time PCR to measure blood and skin BAFF, BAFF-R, TACI, and BCMA mRNA, sandwich ELISAs to measure sera BAFF, and immunohistochemistry to evaluate BAFF and BAFF-R skin protein expression. Results: BAFF mRNA and protein levels were highest in DLE+/SLE+blood, followed by DLE+/SLE-, psoriasis, and normal blood. BAFF protein also correlated with anti-nuclear antibodies, and autoantibodies against double-stranded DNA, single-stranded DNA, and ribonucleoprotein, and Systemic Lupus Erythematosus Disease Activity Index scores in DLE patients. While showing no difference between DLE+/SLE+ and DLE+/SLE- skin, BAFF and its receptors mRNA were up-regulated in DLE skin vs. normal and psoriasis skin. DLE skin had higher percentages of BAFF-R+ inflammatory cells, likely T cells and macrophages, than psoriasis and normal skin. Conclusions: BAFF may be a serologic marker of systemic disease in DLE patients. BAFF and its receptors are elevated in DLE skin, suggesting that targeted therapies against these proteins could treat refractory DLE patients. © 2013 Japanese Society for Investigative Dermatology.


Chaux A.,Johns Hopkins Medical Institutions | Cohen J.S.,Kennedy Krieger Institute | Schultz L.,Johns Hopkins Medical Institutions | Albadine R.,Johns Hopkins Medical Institutions | And 5 more authors.
Human Pathology | Year: 2012

Epidermal growth factor receptor (EGFR) is a member of the erbB tyrosine kinase family reported to be overexpressed in a variety of solid malignancies. Mutations in exons 19 to 21 of the tyrosine kinase domain have been detected in a subset of these tumors and its presence associated with a better response to EGFR inhibitors. Several clinical trials are currently underway to evaluate the performance of such drugs in patients with bladder cancer, but data on EGFR mutation status are limited. The current study assesses EGFR immunohistochemical expression and the presence of mutations in exons 19 and 21 by polymerase chain reaction in 19 bladder urothelial carcinomas from formalin-fixed, paraffin-embedded tissues. Representative paraffin sections were microdissected for DNA extraction using a pinpoint isolation system. Parallel sections were immunostained using a monoclonal anti-EGFR antibody. No mutations in exons 19 and 21 of EGFR were identified in any of the cases. Immunohistochemical EGFR positivity was observed in 14 of 19 cases. In summary, we found EGFR protein expression in 74% of urothelial carcinomas, but we failed to detect EGFR mutations at exons 19 to 21, suggesting that EGFR overexpression is not related to the presence of mutations in the tyrosine kinase domain of the gene. Mutation analysis of EGFR exons 19 and 21 is feasible in microdissected paraffin sections from archival tissues. Immunohistochemical expression of EGFR may not be useful to predict therapeutic response to EGFR inhibitors in patients with urothelial carcinomas. To explain EGFR immunohistochemical overexpression, other mechanisms besides mutations in the EGFR kinase domain should be investigated in future studies. © 2012 Elsevier Inc.


Youens K.E.,Duke University | Hosler G.A.,ProPath | Washington P.J.,ProPath | Jenevein E.P.,ProPath | Murphy K.M.,ProPath
Journal of Molecular Diagnostics | Year: 2011

Testing for high-risk (HR) human papillomavirus (HPV) is a key component of current recommendations for cervical cancer screening. Herein is described our clinical experience using Cervista HPV HR, a testing platform recently approved by the US Food and Drug Administration for clinical use. Using data from a high-volume commercial laboratory, a retrospective analysis of cytologic and Cervista HPV HR test results from 56,501 samples was performed, and an indirect comparison was made with previous experience with 53,008 samples tested using the Hybrid Capture 2 platform. Of samples analyzed using Cervista HPV HR, 1.5% were of insufficient volume for testing and 1.1% yielded an insufficient signal from the internal control to be reported. In samples with a cytological interpretation of atypical squamous cells of undetermined significance, 48.5% (95% confidence interval [CI], 47.5 to 49.5) tested positive using Cervista HPV HR, compared with 59.4% (95% CI, 58.3 to 60.5) of samples using Hybrid Capture 2. Of samples from women aged 30 years or older with a negative cytological interpretation, 5.8% (95% CI, 5.6 to 6.1) tested positive using Cervista HPV HR, compared with 5.5% (95% CI, 5.3 to 5.7) of samples using Hybrid Capture 2. When stratified by five-year age groups between 30 and 65 years, positivity rates for high-risk human papillomavirus were similar in the Cervista HPV HR and Hybrid Capture 2 populations, and were consistent with expectations established by the literature. Copyright © 2011 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.


Banet N.,Johns Hopkins Medical Institutions | Descipio C.,Johns Hopkins Medical Institutions | Murphy K.M.,ProPath | Beierl K.,Johns Hopkins Medical Institutions | And 3 more authors.
Modern Pathology | Year: 2014

Immunohistochemical analysis of cyclin-dependent kinase inhibitor 1C (CDKN1C, p57, Kip2) expression and molecular genotyping accurately classify hydatidiform moles into complete and partial types and distinguish these from non-molar specimens. Characteristics of a prospective series of all potentially molar specimens encountered in a large gynecologic pathology practice are summarized. Initially, all specimens were subjected to both analyses; this was later modified to triage cases for genotyping based on p57 results: p57-negative cases diagnosed as complete hydatidiform moles without genotyping; all p57-positive cases genotyped. Of the 678 cases, 645 were definitively classified as complete hydatidiform mole (201), partial hydatidiform mole (158), non-molar (272), and androgenetic/biparental mosaic (14); 33 were unsatisfactory, complex, or problematic. Of the 201 complete hydatidiform moles, 104 were p57-negative androgenetic and an additional 95 were p57-negative (no genotyping), 1 was p57-positive (retained maternal chromosome 11) androgenetic, and 1 was p57-non-reactive androgenetic; 90 (85%) of the 106 genotyped complete hydatidiform moles were monospermic and 16 were dispermic. Of the 158 partial hydatidiform moles, 155 were diandric triploid, with 154 p57-positive, 1 p57-negative (loss of maternal chromosome 11), and 1 p57-non-reactive; 3 were triandric tetraploid, with 2 p57-positive and 1 p57-negative (loss of maternal chromosome 11). Of 155 diandric triploid partial hydatidiform moles, 153 (99%) were dispermic and 2 were monospermic. Of the 272 non-molar specimens, 259 were p57-positive biparental diploid, 5 were p57-positive digynic triploid, 2 were p57-negative biparental diploid (no morphological features of biparental hydatidiform mole), and 6 were p57-non-reactive biparental diploid. Of the 14 androgenetic/biparental mosaics with discordant p57 expression, 6 were uniformly mosaic and 8 had a p57-negative androgenetic molar component. p57 expression is highly correlated with genotyping, serves as a reliable marker for diagnosis of complete hydatidiform moles, and identifies androgenetic cell lines in mosaic conceptions. Cases with aberrant and discordant p57 expression can be correctly classified by genotyping.

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