bluuebunny/crossref_metadata_2025 huggingface dataset:
An Updated “Call Database” to Support Lab Consultation and Quality Improvement Projects
Authors: Krumm Niklas , Hoffman Noah
Published: September 2019

Clinical laboratories may have “on-call” residents and fellows, a practice that assists the laboratory in providing quality support to clinicians and provides valuable clinical experience to trainees. A Call Database may be used as a tool to facilitate call handoffs, as an educational resource and knowledge base for trainees, and as a call logging and review tool as required by the Accreditation Council for Graduate Medical Education (ACGME). The Call Database at our institution currently contains over 51,000 entries and is used by all clinical pathology residents and fellows while “on call.”

Prior versions of our Call Database (first developed in 2004 and updated in 2014) were self-hosted applications with limited feature sets that were difficult to support; moreover, they provided few guarantees around electronic protected health information (ePHI), a topic of increasing concern as HIPAA compliance among clinical laboratories is increasingly audited. A review of the current application also identified that it has limited usefulness in supporting faculty review of calls, does not easily allow structured data entry for quality improvement projects, and lacks features commonly seen in modern web applications (eg, rich text editing and file attachments). Here we describe the latest update to our existing Call Database addressing these feature limitations. In addition, we discuss our approach to using a modern cloud-based infrastructure design that address prior shortcomings in data security, user management, and ease of development.

The updated Call Database is a single-page web application, compatible with a wide range of local and cloud environments. We updated the user interface with features such as auto-saving of entries, rich text entry, file attachments, and topic tagging. Several new features facilitate the faculty review process: (1) a dedicated “review mode” for rapid viewing and commenting of relevant calls, (2) automated weekly emails by topic sent to faculty, and (3) a user “mention” feature so that trainees can solicit the opinion of faculty in the text of a call or comment itself. Finally, we provide support for customizing the structured data fields of call entries, which enables support of quality improvement and monitoring projects via the call database (eg, a customized entry for monitoring use of specific send-out tests, massive transfusion reactions, etc.).

Our application delivers a modern, performant, and easy to use call database for use by trainees and faculty alike. We utilize the Amazon Cloud (AWS) to host the application and have developed a specific set of compliance and risk review documents to address HIPAA compliance. Future work will incorporate user feedback and will focus on supporting the implementation of our application at other sites or clinical pathology residency programs.
Sample Dilution Is Not an Effective Mitigation for Hemolysis Interference in Anti-Xa Heparin Activity Assays
Authors: Khan Jenna , Chandler Wayne
Published: September 2019

The presence of hemolysis or icterus can interfere with chromogenic anti-Xa assays for unfractionated heparin monitoring (heparin activity), resulting in falsely lower estimates of heparin activity. Dilution is a common method for mitigating interference in spectroscopic assays that measure a single analyte by endpoint analysis and has been proposed as a solution for hemolysis interference in heparin activity assays. Heparin activity assays measure heparin/antithrombin complex activity using a chromogenic rate of absorbance change method. Heparin activity is a complex equilibrium of heparin binding to multiple proteins, including antithrombin, heparin cofactor II, platelet factor 4, histidine-rich glycoprotein, vitronectin, fibronectin, and others; some enhance while others neutralize heparin activity. The objective of this study was to determine how dilution affects heparin activity with different starting levels of antithrombin. First samples were diluted without interference (no hemolysis). Samples with 1 U/mL heparin in pooled normal plasma (PNP) and 50% PNP (to simulate 50% antithrombin levels) were diluted 1:1 with PNP versus OK buffer. Dilution resulted in nonlinear changes. Samples with 100% antithrombin recovered 88% of expected activity with PNP versus 74% with OK buffer; samples with 50% antithrombin recovered 111% with PNP versus 77% with OK buffer. Samples were then spiked with varying concentrations of hemolysate and 1:1 dilutions with PNP demonstrated nonlinear recoveries ranging from 41% to 84%. We were unable to recover the original heparin activity with or without hemolysis due to the complex interaction of initial heparin, antithrombin, and other binding protein concentrations with diluent antithrombin and other diluent heparin binding protein levels. When PNP is used as the diluent, the recovery will be lower when the initial antithrombin level is normal due to the addition of other heparin binding proteins; when the initial antithrombin level is low, the recovery is higher due to the addition of antithrombin from the diluent plasma. The recovery is always lower when buffer is used due to dilution of sample antithrombin. Careful consideration should be taken in evaluating the utility of sample dilution to mitigate interference from hemolysis and icterus in heparin activity assays, particularly in patients with fluctuating levels of antithrombin, such as those on extracorporeal life support or with liver failure.
Medium- and Short-Chain L-3-Hydroxyl-Acetyl-Coenzyme A Deficiency: A New Identified Mutation in Four Cases
Authors: Feng Sheng , Cooper Deborah , Tan Lu , Meyers Gail , Bennett Michael
Published: September 2019

Medium- and short-chain L-3-hydroxyacyl-coenzyme A dehydrogenase (M/SCHAD, SCHAD) deficiency is a mitochondrial fatty acid oxidation disorder (FAOD). This enzyme catalyzes the penultimate step in fatty acid oxidation, the NAD+ dependent conversion of L-3-hydroxyacyl-CoA to 3-ketoacyl-CoA for medium- and short-chain acyl-CoA intermediates (C4-C12). The clinical presentations of most patients are recurrent hypoglycemia associated with hyperinsulinism. We presented four infants with C4 acyl-carnitine elevation identified by newborn screening that also showed an unusual phenotype of congenital hypotonia and gross developmental delay. Enzymatic studies confirmed the disease. Sequencing analysis of all the HADH coding exons on the four patients revealed a homozygous variant of a novel change (c.908G>T, p.Gly303Val). Western blot analysis subsequently confirmed the lack of the SCHAD protein. In addition, there is another previously reported benign variant (c.257T>C) identified in three infants. Therefore, we postulate that the HADH variant (c.908G>T) is indeed pathogenic and associated with a severe phenotype as evidenced by the cases described herein. Population screening for the c.908G>T mutation suggests this mutation to be common among Puerto Ricans. We recommend that SCHAD deficiency is included as part of the differential diagnosis of all infants with congenital hypotonia.
Updates to a Lab-Developed Bioinformatics Pipeline and Application for Interpretation of Clinical Next-Generation Sequencing Panels
Authors: Christensen Paul , Subedi Sishir , Hendrickson Heather , Thomas Jessica , Li Zejuan , Long S Wesley , Olsen Randall
Published: September 2019

Objectives

Our goal was to enhance our next-generation sequencing (NGS) molecular oncology workflow from sequencing to analysis through improvements to our custom-built and previously described NGS application.

Methods

Over 1 year, we collected feedback regarding workflow pain-points and feature requests from all end users of our NGS application. The application consists of a series of scripted pipelines, a MySQL database, and a Java Graphic User Interface (GUI); the end users include molecular pathologists (MPs), medical technologist/medical laboratory technologists (MTs/MLTs), and the molecular laboratory manager. These feedback data were used to engineer significant changes to the pipelines and software architecture. These architecture changes provided the backbone to a suite of feature enhancements aimed to improve turnaround time, decrease manual processes, and increase efficiency for the molecular laboratory staff and directors.

The key software architecture changes include implementing support for multiple environments, refactoring common code in the different pipelines, migrating from a per-run pipeline model to a per-sample pipeline model, and key updates to the MySQL database. These changes enabled development of many technical and user experience improvements. We eliminated the need for the pipelines to be launched manually from the Linux command line. Multiple pipelines can be executed concurrently. We created a per-sample pipeline status monitor. Sample entry is integrated with our Laboratory Information System (LIS) barcodes, thus reducing the possibility of transcription errors. We developed quality assurance reports. Socket-based integration with Integrated Genomics Viewer (IGV) was enhanced. We enabled rapid loading of key alignment data into IGV over a wireless network. Features to support resident and fellow driven variant and gene annotation reporting were developed. Support for additional clinical databases was implemented.

Conclusions

The designed feature enhancements to our previously reported NGS application have added significant sophistication and safety to our clinical NGS workflow. For example, our NGS consensus conference can be held in a conference room over a wireless network, and a trainee can prepare and present each case without ever leaving the application. To date, we have analyzed 2,540 samples using three different assays (TruSight Myeloid Sequencing Panel, AmpliSeq Cancer Hotspot Panel, GlioSeq) and four sequencing instruments (NextSeq, MiSeq, Proton, PGM) in this application. The code is freely available on GitHub.
Procalcitonin as a Biomarker in Early Sepsis in Cancer Patients Presenting to the Emergency Department
Authors: Li Jieli , Meng Qing
Published: September 2019

Background

In the United States, sepsis is responsible for 9% of all cancer-related deaths. Patients with cancer presenting with sepsis have worse outcomes, which is probably because of immunosuppression, due to the disease burden itself or the effects of chemotherapy. Biomarkers are noninvasive rapid diagnostic tools, assisting in the early diagnosis of patients with suspected sepsis. The identification of a biomarker with reasonable sensitivity and specificity for early sepsis could potentially result in a beneficial effect on clinical outcomes in these patient populations. Procalcitonin (PCT) is a promising marker for identification of bacterial infections, but its role in oncology populations has less been studied. We investigated the performance characteristics of sepsis biomarkers for diagnosis of verified bacterial sepsis.

Methods

This was a retrospective study of patients admitted between June 1, 2018, and January 31, 2019, from the Emergency Department, MD Anderson Cancer Center. Approximately 51% adult patients were diagnosed with sepsis. Sepsis was defined by Surviving Sepsis Campaign (SSC) definitions. Three biomarkers were evaluated based on hospital records: (1) PCT ≥0.08 ng/mL, (2) C-reactive protein (CRP) ≥13 mg/L, (iii) white blood cells (WBCs) ≥11 K/µL. The diagnostic performances of the individual biomarkers were compared using the area under the receiver operating characteristic (ROC) curve (AUC).

Results

In total, 635 adult sepsis patients were included and investigated during the study period. For diagnosis of bacterial sepsis based on SSC criteria, the analysis yielded a CRP with sensitivity of 71% (95% CI, 56%-86%) and specificity of 22% (95% CI, 15%-29%), respectively. The area under the ROC curve was 52% (95% CI, 41%-68%). The sensitivity of WBCs was 18% (95% CI, 12%-24%), specificity was 84% (95% CI, 71%-97%), and the area under the ROC curve was 51% (95% CI, 43%-68%). However, the PCT reached the sensitivity of 77% (95% CI, 60%-93%) and specificity of 65% (95% CI, 48%-82%), respectively. The area under the ROC curve was 79% (95% CI, 67%-91%), significantly increased.

Conclusion

In this study, the diagnosis accuracy and specificity of PCT are much higher than those of CRP or WBC in cancer patients. PCT is a useful marker for early detection of sepsis in emergency department patients with suspected infection, especially in cancer patients with neutropenia. Further studies on the role of PCT in this population are warranted.
Anemia in Hidradenitis Suppurativa, Hepcidin as a Diagnostic Tool
Authors: Ghias Mondana , Cameron Sophie , Shaw Fiona , Soliman Yssra , Kutner Allison , Chaitowitz Mark , Cohen Steven , Gil Morayma Reyes
Published: September 2019

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease characterized by recurrent nodules, abscesses, and dermal tracts. We recently reported a high prevalence of anemia in HS patients. These data led to the hypothesis that chronic inflammation in HS predominantly causes anemia of chronic disease (ACD) through upregulation of IL-6 and hepcidin, a key regulator of iron homeostasis. Hepcidin is widely accepted as a marker distinguishing ACD from iron deficiency anemia (IDA) in inflammatory conditions. The purpose of this study was to measure serum hepcidin in HS patients to classify the type of anemia observed in this cohort. We measured hematologic data, inflammatory markers, and serum hepcidin using an enzyme-linked immunosorbent assay (ELISA; R&D Systems) in 55 patients with varying degrees of HS severity. Independent Student t tests and one-way ANOVA were used to compare hepcidin levels in HS patients with anemic and nonanemic states. Of 55 HS patients evaluated in this study, 42 (76%) were female and the average age was 37.6 ± 13.2 years. The mean hemoglobin (Hb) was 12.2 ± 2.0 g/dL and mean hepcidin was 19.5 ± 12.9 ng/mL. Anemic patients (n = 26) with reduced iron stores (ferritin ≤30 ng/mL) had significantly lower hepcidin than anemic patients with adequate iron stores (9.7 ± 15.8 ng/mL vs 23.8 ± 11.1, P = .03). Elevated hepcidin in this subset suggests that ACD is the predominant cause of anemia. Analysis by ANOVA also found that hepcidin levels were significantly greater in patients with more severe HS, as measured by HS-Physician Global Assessment scores (P = .005). Hepcidin may serve as a surrogate biomarker for active disease and inflammation in HS. These findings affirm the utility of hepcidin as a promising tool for distinguishing IDA from ACD and, in turn, help identify HS patients in whom dietary iron supplementation is unlikely to be beneficial.
Can We Predict the Number of Circulating CD34+ Cells From the Complete Blood Cell Count Before and After Plerixafor in Patients With Lymphoproliferative Disorders?
Authors: Fakhari Mahtab , Costa Luciano J , Williams Lawrence A , Marques Marisa B
Published: September 2019

Stem cell transplant is a common treatment for hematopoietic neoplasms. We use a standardized stem cell mobilization regimen consisting of the following: day 1, 6 mg of pegfilgrastim (pegylated formulation of granulocyte-colony stimulating factor); day 3, 24 mg of plerixafor (reversible CXCR4 antagonist) followed by peripheral blood stem cell collection (PBSC) on day 4 after collecting a sample to measure the circulating CD34+ cells by flow cytometry. Since the latter results are not available as quickly as a STAT complete blood count (CBC), we hypothesized that the difference in CBC parameters from DAY 3 TO DAY 4 could be useful to predict the final collection yield. To test our theory, we carried out the following process from September 2018 to February 2019: day 3, CBC with differential before plerixafor; day 4, CBC with differential and sample for CD34+ cells before starting PBSC. We collected the following data from the electronic medical records: gender, age, and CBC parameters preplerixafor (evening of day 3) and morning of day 4 (preapheresis) plus circulating CD34+ count. We used a paired Student t test to compare the results of each patient. Fifty-seven adults (35 males, 22 females) with a median age of 64 ± 13 years were included; 76% had the diagnosis of multiple myeloma. On day 3 (preplerixafor), the median hematocrit was 36 ± 8%, the WBC count was 29 ± 13 × 103/µL, and the platelet count was 189 ± 64 × 103/µL. On the next morning (day 4), the hematocrit and platelet counts were not significantly different at 36 ± 4% and 182 ± 60 × 103/µL, respectively (P > .05). However, the median WBC count was significantly higher with a median of 43 ± 16 × 103/µL (P = 2.5 × 10–20). In both CBCs with differential, neutrophils comprised the majority at 82% and 74% pre- and postplerixafor, respectively (P = .01), lymphocytes went from 7% to 8% (P > .05), and monocytes increased from 6% to 6.5% (P = .02). The median CD34+ count preapheresis was 40 ± 47 cells/µL. We did not find any strong correlation between day 3 and day 4 CBC parameters and the CD34+ count, with only a very weak trend for higher CD34+ cells with increasing day 4 WBC count (R2 = 0.225). We conclude that the precollection CD34+ cell count is the best way to predict the PBSC yield and must be performed in order to ensure the target number of CD34+ cells is met for a successful engraftment.
Verification of Access GI Monitor (CA 19-9) Assay on Beckman Coulter Unicel DXI 800
Authors: Ollila Eric , Cao Liyun , Wei Qing , Youssef Mariam
Published: September 2019

CA 19-9 antigen has been identified in patients with colorectal, pancreatic, bile duct, hepatocellular, stomach, and esophageal cancers. Noncancerous conditions that may elevate CA 19-9 levels include cirrhosis, cholangitis, hepatitis, pancreatitis, and nonmalignant gastrointestinal diseases. CA 19-9 antigen levels may be used as an aid in monitoring response to therapy or disease progression in cancer patients. The objective of this study was to assess the analytical performance of the Access GI Monitor assay on Beckman Coulter UniCel DXI 800. CA 19-9 was quantitatively determined on the Beckman Coulter UniCel DXI 800 following CLSI guidelines. The performance was evaluated for linearity, sensitivity, reference range, and precision. The within-run and between-run precisions were assessed by analyzing QC material at low and high levels of concentrations. Accuracy was assessed by comparison with the previously established Siemens ADVIA Centaur XP. Antigen level values were classified as positive or negative based on the upper limit of the reference range to assess concordance between the two analyzers. The accuracy of each analyzer was also assessed by correlating the discordant antigen values with the patients’ clinical history. For the Beckman Coulter DXI assay, the analytic measurement range was determined to be linear between 0.8 and 2,000 U/mL with a slope of 1.018 and intercept of 4.13. The limit of blank was determined as 0.09 U/mL. The reference range was verified as 0 to 35 U/mL. The within-run CVs for CA 19-9 were 3.7% at both the low level of 23.54 U/mL and high level of 262.56 U/mL. The between-run CVs at low and high levels were 4.34% and 6.36%, respectively. A total of 327 patient samples were analyzed in the comparison of CA 19-9 levels on Beckman Coulter DXI and Siemens ADVIA Centaur XP. On Deming regression, the slope was 0.665 with an intercept of 136.4 and correlation coefficient of 0.8964; there was wide scatter between the two methods. The mean bias between the two analyzers was –291.1 (–22.8%). The correlation coefficient was 0.8931, and the bias was –770.7 (–26.1%) when both were positive. The correlation coefficient was 0.7949, and the bias was –0.8 (–6.1%) when both were negative. The agreement of the two methods was 91% (n = 298) and disagreement was 9% (n = 29). After clinical analysis of 18 discordant values, six data points correlated better with the Siemens Centaur XP and the remaining 12 correlated better with the Beckman Coulter DXI. Our data demonstrate that CA 19-9 on Beckman Coulter DXI has good linearity and precision. There is poor to fair correlation between the two methods. Agreement based on clinical classification of positive and negative results is good. The Beckman Coulter DXI correlates with the patient clinical history better than the Siemens Centaur XP when comparing discordant values between the analyzers.
Exome Sequencing Identifies Glycosylation Defects as a Probable Cause of Immune-Mediated Thrombotic Thrombocytopenic Purpura
Authors: Basu Malay Kumar , Staley Elizabeth , Halkidis Konstantine , Sui Jingrui (Jean) , Kocher Nicole K , Gong Han , Williams Lawrence A , Marques Marisa B , Cao Wenjing , Zheng X Long
Published: September 2019

Background

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially fatal syndrome, resulting from autoantibodies against ADAMTS13. However, the mechanism underlying autoantibody formation is not known. Neither is known about the other genetic abnormality in the setting of severe deficiency of plasma ADAMTS13 activity.

Methods

Whole-exome sequencing (WES) was performed in 40 patients with iTTP who had plasma ADAMTS13 activity <10% and a positive inhibitor or elevated anti-ADAMTS13 IgG. Fifteen age- and ethnicity-matched subjects who never had iTTP were recruited as healthy controls.

Results

WES identified mutations in the genes involved in glycosylation, including O-linked glycosylation to be the major pathway affected in patients with iTTP. Mass spectrometry confirmed the changes in plasma levels of various glycoproteins in patients with acute iTTP when compared with those in the healthy controls. The altered glycosylation in glycoproteins may be responsible for the development of autoantibodies, susceptibility of von Willebrand factor to proteolysis by ADAMTS13, and the clearance of platelets in iTTP patients. Moreover, candidate gene analysis revealed that various genes involving in hemostasis, complement activation, platelet number and function, and inflammation were all affected in patients with iTTP, which may contribute to the onset, progress, severity, and long-term outcome of iTTP.

Conclusions

Our findings provide novel insight into a pathogenic mechanism underlying autoantibody production and the potential contribution of other genetic abnormalities in pathogenesis of iTTP in the individuals with severe deficiency of plasma ADAMTS13 activity.

Future Direction

Further studies are warranted to determine the specific glycosylation patterns of various plasma and cellular proteins in patients with iTTP and to determine the synergistic role of various gene mutations and severe ADAMTS13 deficiency in the pathogenesis of iTTP.
Adopting an Evidence-Based Approach for Folate Testing in a Tertiary Care Center
Authors: Rais Rehan , Szymanski Jeffrey , Jackups Ronald
Published: September 2019

Plasma folate is a very commonly ordered test, despite evidence that folate deficiency is extremely rare following universal fortification of grains mandated in the United States in 1998. The objective of our study was to adopt an evidence-based approach for plasma folate testing and identify in what clinical and hospital settings folate may be an informative test. We performed a retrospective laboratory information system/patient chart review between 10/31/17 and 10/31/18 and identified folate-deficient patients. Folate testing data were collected over a 1-year period from a tertiary care hospital and associated allied centers. Data included total tests ordered, age and gender of patient, location of where testing was performed, plasma folate, vitamin B12, hemoglobin, and mean corpuscular volume (MCV). In addition, we looked at association in folate-deficient patients with history of alcohol use, immigrant status, gastric surgery, birth defects, and if any presented with neurological symptoms. Associated patient comorbidities and therapeutic interventions to treat folate deficiency were also noted. Our results show that 14,542 total tests were ordered during this time period, from which 408 patients (2%) had folate below the reference range of 5 ng/mL, with only 92 (0.6%) patients having results below 3 ng/mL (true folate deficiency). Five ICU patients were folate deficient, none of whom was below 3 ng/mL. The average age of folate-deficient patients was 58.3 (age range: 7-97), with a female predominance of 251 patients (61.5%). Hemoglobin results showed only 21 (5%) patients with values less than 7 g/dL, with 231 (56%) patients showing normal and 142 (34.8%) patients showing elevated MCV values (mean MCV: 93.1 fL, SD: 10.2). No clinically relevant association between concurrent folate deficiency and comorbid conditions was identified. Concurrent vitamin B12 testing performed in these patients showed normal levels in 299 (73.2%), while 27 (6%) and 70 (17%) patients showed B12 deficiency and elevation, respectively. Interestingly, only 176 (43%) of patients subsequently received folate supplementation. Our study highlights that folate testing following mandatory grain fortification is almost nonexistent. In addition, the vast majority of folate tests ordered provided no additional clinical information, particularly in the inpatient setting. In addition, our data suggest that elevated MCV values should not be used as a marker to suspect a diagnosis of folate deficiency. Folate testing should therefore be reserved for severely anemic patients without a clear etiology for anemia; however, even in this patient population, supplementation rather than testing may be a more effective option.
Esthesioneuroblastoma With Probable Paraneoplastic Hypertension: A Case Report
Authors: Haque Monira , Marbut Stephen
Published: September 2019

Objectives

Esthesioneuroblastoma or olfactory neuroblastoma (ONB) is a rare malignant neuroectodermal tumor accounting for 2% of all intranasal tumors with a reported incidence of 0.4 per million. We report an interesting case of ONB associated with hypertension, suspicious for paraneoplastic syndrome.

Methods

A 41-year-old male with clinical symptoms of chronic sinusitis presented with gradually worsening unilateral nasal obstruction. Computerized tomography demonstrated a 2.1-cm expansile mass in left ethmoid sinus. Examination revealed a swollen, erythematous middle turbinate. A left ethmoidectomy was performed.

Results

Histologic examination of the specimen revealed lobular nests of monomorphic small cells with round nuclei, salt and pepper chromatin, and indistinct cytoplasm embedded in a fibrillary stroma with abundant neuropil. Mitosis, necrosis, and nuclear pleomorphism were absent. Immunohistochemically, the neoplastic cells were positive for synaptophysin, chromogranin, CD56, and neuron-specific enolase and negative for pancytokeratin AE1/AE3, CAM 5.2, and CD45. S-100 focally highlighted the sustentacular cells. A diagnosis of ONB, Hyams grade 1 was made. Of note, the patient had a history of hypertension and the original surgery had been cancelled due to hypertensive urgency. With the suspicion of a paraneoplastic hypertension, his catecholamines were ordered; however, he failed to follow up for his scheduled testing. Five weeks postoperative, he was seen in the emergency department and found to be normotensive without antihypertensive medication. The clinical findings are strongly suggestive of paraneoplastic hypertension associated with ONB.

Conclusion

ONB is a rare tumor associated with a high recurrence rate due to its anatomical location. Survival rates are best with surgical resection followed by radiotherapy. ONB may rarely be associated with paraneoplastic syndromes. Review of available literature reveals only five reported cases of ONB with paraneoplastic hypertension. The rarity of this tumor and the clinical presentation highly suspicious for paraneoplastic hypertension make this case uniquely interesting.
A Rare Case of Desmoplastic Mesothelioma With Good Survival Despite Lymph Node Metastasis
Authors: Basu Atreyee , Pass Harvey , Zhou Fang , Narula Navneet , Moreira Andre
Published: September 2019

Introduction

Desmoplastic mesothelioma (DMM), a rare histological subtype of malignant pleural mesothelioma (MPM), is lethal and has very poor prognosis. Metastasis is commonly reported in DMM compared to other histological subtypes. Here we report a case of DMM with good survival (>1 year) despite lymph node metastasis.

Case Report

A 62-year-old female with a history of smoking and possible asbestos exposure presented with cough and wheeze in 2012. Computed tomography (CT) revealed left-sided pleural plaques and multiple ground-glass pulmonary nodules. In 2017, repeat CT showed increased diffuse left nodular pleural thickening. Positron emission tomography revealed hypermetabolic, nodular pleural thickening in the hemithorax, compatible with neoplasia. Needle biopsy in January 2018 showed pleural tissue with haphazard, nodular growth of spindled mesothelial cells, suspicious for desmoplastic mesothelioma. Definitive diagnosis was not possible due to lack of fat invasion and absence of supportive evidence by immunohistochemical stains. The patient underwent pleurectomy in February 2018. On histopathology, the majority of the tumor showed a desmoplastic pattern, composed of malignant spindled cells arranged haphazardly in a dense hyalinized stroma with chronic inflammatory infiltrate. AE1/AE3, calretinin, and D2-40 immunohistochemical stains highlighted the infiltrating neoplastic cells, which were negative for WT-1. BAP-1 was retained. The pattern of immunoreactivity supported the diagnosis of DMM. The tumor also involved visceral pleura, pulmonary parenchyma, and pericardium. It invaded into fat and displayed lymphovascular invasion. A metastatic focus of DMM was present in a lymph node. The tumor was staged as pT3N1. On recent examination, the patient only had complaints of mild breathlessness and stable hydro-pneumothorax, without any other comorbidities.

Conclusion

Our finding is unusual, since among the mesothelioma subtypes, DMM has the shortest survival, usually not more than 6 months. We report an extremely rare case of DMM with survival of >1 year despite invasion of lung parenchyma and lymph node metastasis.
Endometriosis in an Indigenous African Women Population
Authors: Ohayi Samuel
Published: September 2019

Introduction

Endometriosis is a condition in which endometrial tissue exists outside the endometrial cavity. It has a high prevalence in women living in developed countries and is reportedly the third most common cause of gynecologic hospitalization in the United States. It is believed to be rare among indigenous African women, although studies on its prevalence in this population are few. This study aims to determine the prevalence and clinical presentation of the condition in an indigenous African population.

Methods

This is a retrospective study of gynecological specimens received in the Histopathology Laboratory of Enugu State University Teaching Hospital from January 1, 2014, to December 31, 2018. Laboratory request forms and histopathology reports archived in the laboratory were retrieved and relevant information about patients diagnosed with endometriosis was extracted and analyzed by simple statistical methods.

Results

There were 25 diagnosed cases of endometriosis representing 0.9% of gynecological specimens received in the period. Patients’ average age was 38.4 ± 8.4 years while the peak age range was 31 to 40 years (n = 10; 40%). Myometrium was the most common site (n = 16; 64%), followed by the ovary (n = 5; 20%). The umbilicus, round ligament, broad ligament, and suprapubic region constituted 1 (4%), respectively. The most common symptoms were pelvic pain (36%) and abnormal uterine bleeding (32%) while recurrent ascites occurred in 1 (4%). There was associated primary and secondary infertility in 20% and 16% of cases, respectively. Recurrent abortion occurred in 4 (8%) of cases. The umbilical and suprapubic masses had symptoms, bleeding, and tender swelling, respectively, that synchronized with the patient’s menstrual cycle.

Conclusion

Endometriosis has a low prevalence in our population but occurs in rare sites. Women presenting with chronic pelvic pain and infertility and menstrual disorders should be evaluated for endometriosis. Population-based study is required to properly determine the actual prevalence of the condition in this population.
Hemorrhagic Necrotizing Pneumonia Caused by Trichosporon asahii Suspected by Distinctive Histology in Tissue
Authors: Afsari Ali , Zhou Jiemin , Hassan Muhammad , Naab Tammey
Published: September 2019

Trichosporon spp. are yeast-like organisms most often responsible for superficial skin infections (white piedra) and may transiently colonize the respiratory tract. Trichosporon asahii can be an opportunistic pathogen, causing invasive disease and sometimes disseminated infections, usually in immunocompromised patients. They are the third most commonly isolated yeast species in clinical settings. They cause hemorrhagic and necrotizing bronchopneumonia due to vascular invasion; mycotic emboli are identified within hemorrhagic infarcts. Distinctive pleomorphic budding yeasts, true hyphae, and arthroconidia stain weakly with silver stain in tissue. A 53-year-old HIV-negative male with PMH of schizophrenia and intravenous drug abuse presented with shortness of breath and chest pain. Patient was admitted to the MICU for acute respiratory distress likely secondary to pneumonia. Chest CT scan revealed multiple ill-defined opacities in the lung periphery. The patient had neutrophilic leukocytosis and positive blood culture for methicillin-resistant Staphylococcus aureus and Candida glabrata. Broad-spectrum antibiotics and antifungal drugs (fluconazole, voriconazole, amphotericin B, micafungin) were started. Two weeks later, wedge lung biopsy revealed necrotizing pneumonia with abscess formation and pleomorphic budding yeast-like cells, measuring 3 to 6 microns in diameter; septated hyphae; and arthroconidia. Culture of a bronchial washing was confirmed to be T asahii by matrix-assisted laser desorption/ionization time of flight (MALDI-TOF). Unfortunately, the patient died and partial autopsy of his lungs showed the same pathogen. Invasive respiratory infections caused by T asahii have increased in frequency over the last two decades. Distinctive histology in tissue (pleomorphic yeasts, septated hyphae, and arthroconidia) can suggest the diagnosis, confirmed with MALDI-TOF. Risk factors for invasion include prior antibiotic therapy, central catheterization, malignancy (often hematologic), and intensive care unit admission. Thirty-day all-cause mortality has been reported to be 42% and has been linked to resistance to amphotericin B and echinocandins.
Rad-Path Correlate: Concordance and Discordance Rates in Danbury Hospital Patient Population
Authors: Olayinka Oluwaseyi , Kaur Gagandeep , Rebelo Ana , Chacho Mary , Vidhun Ramapriya
Published: September 2019

Objectives

Imaging-guided needle biopsy is a reliable alternative to surgical biopsy in the diagnosis of breast pathologies. However, false-positive results are common. Rad-Path correlation is crucial in identifying such results, thus allowing appropriate diagnosis and follow-up. We report our experience of Rad-Path correlation results in a community teaching hospital.

Methods

The tumor board data at Danbury Hospital were searched for Rad-Path conferences held from 2013 to 2018. Benign breast biopsies obtained from SNOMED, a monthly pathology list of imaging-guided needle biopsies performed at Danbury Hospital, were presented at these conferences. Data from the list were used for this research. Fibroadenoma cases were excluded in the analysis. The total number of cases presented and proportion of concordant and discordant cases were reviewed. Data on discordant cases were further reviewed to determine the reasons for discordance and follow-up outcomes.

Results

In the last 6 years, 64 Rad-Path meetings were held. A total of 393 benign breast biopsies were presented. Of the 393 cases, 24 (6.1%) were discordant. The radiologic findings for the discordant cases were as follows: mass/nodule, 15; calcifications, 7; linear nonmass enhancement, 1; and duct debris, 1. All the suspicious radiologic findings received a benign pathologic diagnosis. These discrepancies in Rad-Path findings were discussed in detail during the multidisciplinary tumor board. Out of 24 discordant cases, 5 (20.8%) were reviewed by the sign-out radiologist and their BI-RADS updated accordingly, another 5 (20.8%) cases had excisional biopsies, 9 (37.5%) cases were recommended for 6- or 12-month radiology follow-up, and the remaining 5 (20.8%) cases were lost to follow-up.

Conclusion

Rad-Path correlation is a key component of imaging-guided breast biopsy reporting. It facilitates detection of discordant radiologic and pathologic findings, and it prevents misdiagnosis and unnecessary repeat interventional procedures. This practice ultimately results in improved patient management.
Cancrum Oris(Noma): An Early Sign of Acute Lymphoblastic Leukemia Relapse
Authors: Madabhavi Irappa , Modi Mitul , Sarkar Malay , K S Sandeep , Shah Mansi , Mallikarjuna Vinay Sakaleshpura
Published: September 2019

Cancrum oris is an infectious disease, which involves the orofacial tissues and adjacent neighboring structures in its fulminant course. Cancrum oris can occur rarely in chemotherapy-induced neutropenic patients with acute lymphoblastic leukemia. This rare case report reveals that cancrum oris can be a sign of acute lymphoblastic leukemia relapse. It is characterized by gangrenous lesions on skin with fine-needle aspiration cytology smear from the lesion showing infiltration of lymphoblasts. Cancrum oris can occur rarely in chemotherapy-induced neutropenic patients with acute lymphoblastic leukemia, but the presentation as an early sign of extramedullary disease relapse has not been documented in literature. Here we report a case of cancrum oris in a 27-year-old woman who presented with redness and swelling of the upper lip and infranasal area. She had a known case of acute lymphoblastic leukemia diagnosed 6 months back and was on regular multiagent chemotherapy for the same. Clinical examination revealed gangrenous lesions on infranasal, intranasal, and area involving the upper lip. Complete blood count, bone marrow aspiration, and cytology did not show any lymphoblasts. Blood culture and swab culture from the gangrenous area were sterile. Patient did not get better even after 7 days of broad-spectrum antibiotic treatment. With a high degree of clinical suspicion of isolated extramedullary relapse, fine-needle aspiration cytology from marginal and gangrenous area was taken and revealed infiltration of soft tissues by lymphoblasts. After receiving four cycles of multiple chemotherapy drugs, the skin lesions resolved. Treatment of cancrum oris involves the correction of the underlying immune status, antibiotics, and surgical reconstruction. The rare possibility of relapse of acute lymphoblastic leukemia presenting as cancrum oris should be kept in mind in patients with acute lymphoblastic leukemia on chemotherapy with skin manifestations.
Metastatic Pulmonary Calcification With Coexisting Nonspecific Interstitial Pneumonia: A Case Report
Authors: Inamdar Arati , Pulinthanathu Rajiv
Published: September 2019

Patients with underlying chronic kidney disease (CKD) often have elevated serum calcium and parathyroid hormones due to compromised kidney function. We present a case of a 63-year-old female nonsmoker with surgical history of three renal transplants (at age 47, 51, and 58) along with thyroidectomy and parathyroidectomy who came to the emergency department with complaint of persistent dry cough and shortness of breath for the last 2 months. The patient had been on immunosuppressive drugs, tacrolimus, prednisolone, and mycophenolic acid since her first renal transplant as well as on cinacalcet after parathyroidectomy (at age 54). Initial computed tomography (CT) scan demonstrated ground-glass opacities in bilateral upper lobes while bronchoscopy revealed few inflammatory cells without any fungi or bacteria. Repeat CT scan performed 5 days later due to rapid progression of her clinical symptoms showed worsening of ground-glass opacities in bilateral upper lobes and new nodules in right middle and lower lung lobes. The wedge lung biopsy revealed metastatic pulmonary calcification (MPC) in the right upper lobe while nonspecific interstitial pneumonia (NISP) in the right lower lobe confirmed the coexistence of two different pathological processes most likely complicating the patient’s clinical symptoms. Despite comprehensive medical therapy, patient’s symptoms have been progressively worsening and she is currently undergoing evaluation for both renal and lung transplants. Our case report not only presents a rare case of MPC coexisting with NSIP but also sheds light on the associated morbidity due to pulmonary diseases in CKD patients.
Concordance of Intradepartmental Consultations of Barrett’s Dysplasia
Authors: Chen Fengming , Liu Yongjun , Ruggiero Francesca
Published: September 2019

Introduction

Barrett’s esophagus (BE) is a well-known precursor to esophageal adenocarcinoma (EAC). Simple BE has an annual rate of progression to EAC of only up to 0.5%, while BE with low-grade dysplasia (LGD) or with high-grade dysplasia (HGD) has a higher progression rate of ~10% and ~40%, respectively. Therefore, accurate diagnosis and grading of dysplasia in BE are critical for optimal patient management. However, grading dysplasia is not well defined in practice, which often results in poor interobserver and/or intraobserver reproducibility. In this study, we aim to (1) investigate the concordance of intradepartmental consultations of BE dysplasia and (2) compare consultant diagnosis with final diagnosis and follow-up diagnosis.

Methods

We retrospectively reviewed 856 intradepartmental consultation records obtained from May 2017 to March 2018. For cases of Barrett’s dysplasia in biopsy specimens, H&E-stained slides were re-reviewed and the corresponding clinical information was retrieved from the electronic medical record.

Results

Twenty intradepartmental consultation cases of Barrett’s dysplasia were identified (involving 2 females and 18 males, mean age 67.8 ± 8.6 years, ranging 50-81 years). The most frequent reasons for consultation were indefinite dysplasia (IND) vs LGD and LGD vs HGD. Half of the cases showed concordance between referring pathologist and consultant pathologist(s), while 10% of the case showed a major discrepancy (resulting in significant changes in patient management and/or prognosis) and 40% showed a minor discrepancy (resulting in no significant impact on patient management and/or prognosis). The final diagnoses were changed after consultation for cases with major discrepancy, while 60% of cases with minor discrepancy remained the original diagnoses.

Conclusions

Intradepartmental consultations are strongly recommended for the challenging cases of BE dysplasia, which can effectively prevent over- or underdiagnosis. For challenging cases such as IND vs LGD, two or more consultants are usually needed to reach an agreement.
Retrorectal Cystic Hamartoma (Tail Gut Cyst): An Institutional Experience
Authors: Kaseb Hatem , Zhang Xuchen
Published: September 2019

Objectives

Tailgut cyst (TGC) is a rare congenital benign cystic lesion arising from a remnant of the embryonic postnatal hindgut. TGCs are typically multinodular, uncapsulated, but usually well circumscribed. TGCs are generally rare in adults and the majority of the lesions are benign. Malignant transformation is rare and malignancies reported include adenocarcinomas and neuroendocrine tumors.

Methods

A retrospective database search was conducted and coded as “tailgut cyst or retrorectal cystic hamartoma” to identify cases of possible TGC between January 2005 and January 2019. The search utilized the pathology files of Yale-New Haven Hospital using CoPath laboratory information system. Clinical and surgical data were gathered from the surgical pathology report and surgical operative note when available.

Results

A total of 13 cases (10 women) were identified with a median age of 51 years. All the specimens were obtained by surgical excision. Most of the cases were excised from the presacreal area (11 cases), and two cases were excised from the retrorectal area. The two cases resected from the retrorectal area had a malignant component. The first case was a 33-year-old female who had a 1.5-cm tailgut cyst that showed a multifocal neuroendocrine tumor (carcinoid); the resection margin was also positive. The second case was a 59-year-old female who had a tailgut cyst that showed mucinous adenocarcinoma; the resection margin was also positive.

Conclusion

Diagnosis of tailgut is sometimes challenging. Possible differential diagnoses in this location include teratoma, dermoid cyst, anterior sacral meningocele, and presacral abscess. Imaging is an important component of the initial workup. Surgical resection is the treatment of choice when the cyst grows in size and if a solid component is present. Exclusion of other benign entities and malignant transformation/component on histological examination is crucial.
High-Output (HO) Ostomy With Histopathologic Abnormality: Examination of 78 Stoma Specimens
Authors: Cordeiro-Rudnisky Fernanda , Sheuka Natallia , Lee Edward , Lee Hwajeong
Published: September 2019

Background

HO (>2,000 mL output/day) is a serious complication following ostomy procedure. HO may be associated with variable underlying conditions or idiopathic. We encountered an ileostomy case with diffuse subepithelial collagen deposits resembling collagenous colitis from a patient with history of HO without underlying cause. A subset of idiopathic HO may be associated with histopathologic abnormalities of the bowel.

Methods

Resected stomas from ostomy malfunction were searched using ICD-9 and CPT codes (2003-2018). Archived pathology materials were reviewed and activity, villous blunting, pyloric metaplasia (PM), and subepithelial collagen deposits were assessed. Trichrome stain was performed when necessary. Clinical history was obtained from medical records.

Results

Sixty-one ileostomies and 17 colostomies were retrieved from 69 patients. Types of ostomy malfunction were stricture/obstruction (n = 21), hernia (n = 10), ischemia/necrosis (n = 4), leak (n = 4), abscess/adhesion (n = 3), skin breakdown (n = 3), prolapse (n = 3), retraction (n = 2), reepithelialization (n = 1), and unclear/not specified (n = 15). Thirty-two patients had inflammatory bowel disease (IBD; 19 Crohn disease [CD], 13 ulcerative colitis [UC]). All HOs were from ileostomy, and 16 had risk factors for HO, including IBD (n = 9 [56%]; 7 CD, 2 UC), short bowel (n = 6, 3 with CD), pelvic/intra-abdominal abscess (n = 2), sepsis (n = 2), and prokinetic (n = 1). Five ileostomies from CD showed PM, while 11 lacked significant histologic abnormalities. Among 5 (24%) idiopathic HOs, 1 was the index case with diffuse subepithelial collagen deposits with subtotal villous blunting, 1 showed PM, and 1 had focal activity. Remaining 2 ileostomies from idiopathic HO were unremarkable. Stomas from patients with other types of ostomy malfunction showed compatible histologic changes. Fifteen cases without ostomy malfunction did not show histologic abnormality.

Conclusion

Most HO represents functional abnormality without histopathologic abnormality except in IBD. However, idiopathic HO may be associated with histopathologic abnormalities in the stoma suggestive of acute/chronic enteritis and scarring, which may be underrecognized and treatable.